Clinical Nephrology: miscellaneous
P: Clinical Nephrology: miscellaneous
HYPOKALEMIA WITHOUT HYPERTENSION: LICORICE
ABUSE OR GITELMAN’S SYNDROME?
A Mercieri, P Faranna, G Cozzi, M Mercieri
Nephrology and Dialysis Unit, “S. Isidoro” Hospital, Trescore
Balneario, Bergamo, Italy
Beta-Glycyrrhetic acid blocks renal 11-beta-hydroxysteroid dehydrogenase, which normally inactivates cortisol. Cortisol can
thus stimulate renal tubular mineralcorticoid receptors and a
picture of “Pseudoaldosteronism” with suppression of reninangiotensin-aldosterone (RAA) axis and isolated hypokalemia
without hypertension may develop. In case of elevated renin
and aldosterone levels Gitelman’s syndrome should be suspected. Gitelman’s syndrome is a familiar disorder characterized by hypokalemia, hypomagnesemia and hypocalciuria. Patients are normotensive. A 43-year-old woman with history of
hypokalemia due to suspected liquorice ingestion was admitted because of deep asthenia. The patient denied misuse of
diuretics and laxatives. No symptoms due to water and salt
retention were found and her blood pressure remained constantly
normal or low. We confirmed serum potassium depletion (2.7
mmol/L). Plasma renin activity and plasma aldosterone were
found surprisingly raised: Renin: supine 53 pg/ml (3-19) and
upright 64.1pg/ml (3-40); Aldosterone: supine 299 pg/ml (40105) and upright 496 pg/ml (70-195). Laboratory findings
showed metabolic alkalosis, hypomagnesaemia (0.5 mmol/L),
hyperuricemia (540 mmol/L), and the 24-hour calciuria was
strikingly low (0.5 mmol/24 h), despite normocalcemia and
normal creatinine clearance. These findings were consistent with
the diagnosis of Gitelman’s syndrome, which mimics the effects
of thiazides diuretics on distal nephron. Molecular defects are
inherited and most are single amino acid substitutions that alter
conformational structure of the renal thiazide-sensitive Na-Cl
cotransporter (TSC). In case of chronic liquorice abuse we propose to confirm a clear suppression of RAA axis, in order to
investigate tubular disease like Gitelman’s syndrome.
KIDNEY FUNCTIONS AFTER CHEMOTHERAPY IN CANCER PAEDIATRIC PATIENTS
L Kopecna, Z Dolezel, H Hrstkova
Dept. of Pediatrics, Univ. Child. Hosp., Brno, Czech Republic
The common side effect of chemotherapy is reversible or non
reversible nephrotoxicity. The parameters which are usually evaluated for renal damage are serum creatinine (Cr), urea, uric acid,
and creatinine clearence (Ccr). In many cases there are no
pathologic changes evident until the damage occures.
We examined a group of 36 children (M:F 21:15, age range 5.516.5 yr, average age 6.9 yr, average period which past since the
treatment was finished were 48 months). The following parameters were examined: urinalysis, proteinuria (Pr)/24 hrs, urine
protein analysis (albumin, transferin, alfa-1-microglobulin,
Tamm-Hosfall protein), Ccr, and ADH test.
65% of these patients had tubular patterns of lesions, 17.5% had
glomerular patterns, and 17.5% had mixed patterns. Decreased
Ccr was evident in 13.8% patients and reduced concentration
capacity in 52.7%. After the therapy none of ALL patients were
on renal replacement therapy.
We can assert, on the basis of obtained results and statistic
evaluation, that nephrotoxicity of the protocol ALL BFM 90
usually shows late manifestations that can be seen months or
even years after the chemotherapy has finished. The most frequent symptom showing a damage on kidneys is Pr, which can
see glomerular (PrG), tubular (PrT) or mixed (PrM). Patients
with persistent complete PrT and mixed PrG/PrT were found to
have a high risk for irreversible renal damage and should be
periodically controlled.
Nephrology Dialysis Transplantation
Vol. 16 n.6
Abstracts
FASTING PLASMA ACYLATION STIMULATING PROTEIN (ASP) AND
LEPTIN CONCENTRATIONS IN PATIENTS WITH UNTREATED NEPHROTIC SYNDROME
M Ozata, C Oktenli, M Gulec, T Ozgurtas, K Caglar, N Bingol, F Bulucu, D
Gungor, A Vural
Gulhane Military Medical Academy, Ankara, Turkey
Acylation stimulating protein (ASP) is an adipocyte-derived protein that has
recently been suggested to play an important role in the regulation of lipoprotein metabolism and triglyceride (TG) storage. In addition to its role as a hormonal regulator of body weight and energy expenditure, leptin is now implicated as a regulatory molecule in lipid metabolism. Moreover, hyperlipidemia
is one of the most striking manifestations of the nephrotic syndrome. However,
little information has been published regarding the levels of fasting ASP and its
relation with leptin and/or lipids in nephrotic syndrome. Thus, we consider
that nephrotic syndrome is a good model to investigate the alteration of fasting
ASP and leptin levels and their relation with lipid profile. 25 patients with
untreated nephrotic syndrome and 25 age-, sex- and body mass index (BMI)matched healthy controls included the study. Fasting plasma lipoproteins, TG,
lipoprotein (a) (Lp(a)), apoAI, apoB, urinary protein (Upro), plasma albumin,
ASP and leptin levels were measured. Plasma ASP concentrations were measured by RIA with a sensitivity of < 40 ng/ml. Plasma leptin levels were determined by RIA with a sensitivity of 0.10 ng/ml. Upro, total cholesterol, TG, LDL
and VLDL cholesterol, and apoB levels were found to be increased, while plasma
albumin, HDL cholesterol and apoAI levels were decreased compared to the
control group (p<0,001). Plasma ASP was significantly higher in the nephrotic
patients compared to the control subjects (1350,2411092,12 ng/ml vs
266,41112,94 ng/ml, p<0,001), whereas leptin levels were not significantly
different between nephrotic patients and controls (2,6912,06 ng/ml vs 3,9912,99
ng/ml, p=0,118). Plasma leptin levels were correlated with body mass index in
both nephrotic syndrome patients (rs=0.866, p<0.001) and controls (rs=0.983,
p<0.001). Fasting ASP concentrations were not correlated with BMI, proteinuria, plasma albumin, leptin or any lipid parameters. We conclude that regulation of fasting plasma ASP concentration is mediated by factors other than
BMI, proteinuria, plasma albumin, lipid levels or leptin in patients with nephrotic syndrome. Thus, further studies are needed to elucidate the mechanisms
that regulate fasting plasma ASP concentrations and its physiological role in
lipid metabolism in nephrotic syndrome.
SYNERGIC EFFECTIVENESS OF ANGIOTENSIN-CONVERTING ENZYME
(ACE) - INHIBITORS AND BIOFLAVONOIDS IN PATIENTS (pts) WITH
CHRONIC GLOMERULONEPHRITIS (CGN)
T Ospanova, A Khalanskyy
Dept. of Internal diseases, Kharkiv State Medical University, Clinic of Nephrology and Hemodialysis of Region Nephro-Urologic Center, Kharkiv, Ukraine
This study was undertaken to compare the effectiveness of the ACE-inhibitors
monotherapy and combined therapy of ACE-inhibitors and bioflavanoids
(Quercetine as typical bioflavonoid and Solidago Canadensis extract (SC) as a
bioflavonoid complex).
131 pts with CGN were examined (M - 58.5%, F - 41.5%, pts age ranged from 16
to 56 yrs). 34 pts had arterial hypertension: systolic blood pressure (SBP) =163.04
± 6.15 mm Hg and diastolic blood pressure (DBP) = 103.33 ± 3.29 mm Hg, the
rest of pts had SBP < 140 mm Hg and DBP < 90 mm Hg. 26 pts had proteinuria
> 3.5 g/24 h, the rest of pts had mean propteinuria level less than 0.8 g/24 h).
62.5% pts had gross hematuria with dysmorphic urinary erythrocytes. All of
pts had normal serum creatinine (Scr) level and Glomerular Filtration Rate
(GFR).
56 pts (1st group) were treated with Captopril (50 -150 mg/day), 24 pts (2nd
group) were treated with Quercetin (500-1000 mg/day), 22 pts (3rd group)
were treated with SC (150 mg/day) and 20 pts (4th group) were treated with
combined therapy of ACE-inhibitors and SC.
An antihypertensive and antiproteinuric effects were found in 1st, 3rd and 4th
groups. More significant decreasing of SBP (-20.8% of baseline level) and DBP
(-19.6% of baseline level) were found in patients with arterial hypertension.
More significant decreasing of proteinuria was found in 1st group (-65.8% of
baseline level), 3rd group (- 61.2% of baseline level) and 4th group (-71.4% of
baseline level) in pts with proteinuria level > 3.5 g/24 h. 73.3% pts with marked
hematuria had favorable effect after Quercetine treatment.
In conclusion, our study demonstrates that synergic effectiveness of CGN pts
treatment can be expected in case combination of ACE-inhibitors and Quercetine
in pts with proteinuria and hematuria and ACE-inhibitors and SC in pts with
high BP and proteinuria.
2001
A101
Abstracts
Clinical Nephrology: miscellaneous
JUVENILEPRIMARYHYPERPARATHYROIDISMASSOCIATEDTOFAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH) AND RENAL GLYCOSURIA
A. Mercieri, R.M. Penna*, P. Faranna, M. Mercieri
Nephrology and Dialysis Unit, Cardiology Unit* , Azienda Ospedaliera
“Bolognini” di Seriate, Bergamo, Italy
Primary hyperparathyroidism (PHP) is more commonly seen in the fifth and
sixth decades of life, but it is infrequent in adolescents and youngsters. Some
investigators report possible dual renal tubular re-absorption deficits in children evaluated for renal glycosuria, in whom idiopathic hypercalciuria was
identified without hypercalcaemia and hyperparathyroidism. It has been speculated that, in children with renal glycosuria, there is defective re-absorption of
glucose and calcium in the strait portion of the proximal tubule or in the collecting duct. A 27-year-old male was referred because of persistent hypercalcaemia (13 mg/dl) and dehydration, after a symptomatic paroxysmal supraventricular tachycardia was successfully treated only with volume expansion. No
frequent cause of secondary hypercalcaemia, such as hyperthyroidism, neoplasia or sarcoidosis, was present. Patient’s history revealed a previously diagnosed familial renal glycosuria. None of his parents was ever assessed for
calcium balance. In order to exclude a possible FHH we decided to evaluate the
24-hour-calcium excretion together with PTH immuno-radiometric assay. We
found a surprisingly elevated PTH (234 pg/ml) with hypercalciuria (874 mg/
24h) and hypophosphoraemia (1,7 mg/dl). Hypocalciuria, with a slightly elevated serum calcium and normal PTH, was confirmed in five family members. A radionuclide scanning revealed a left parathyroid adenoma which was
treated successfully by surgery. Furthermore, we investigated our patient for
other endocrine tumours and this allowed us to exclude multiple endocrine
neoplasia (MEN) syndrome. Our experience confirms that no case of hypercalcaemia should be labelled as “idiopathic” or left unexplained without a detailed investigation to exclude PHP, even in cases of demonstrated FHH and in
young people. Whether there is any relationship between PHP, glycosuria and
FHH in our patient is still under investigation but it seems unlikely that three
different diseases may exist in the same patient.
CLINICAL SIGNIFICANCE OF α-SMA AND CD34 EXPRESSION IN MESANGIAL CELLS IN GLOMERULONEPHRITIS.
Tchebotareva N., Proppe D., Rudolph P., Koslovskaja L.
Moscow Sechenov Medical Academy, Russia, Clinic of
Nephrology CAU, Kiel, Germany
The purpose of this study was to assess the clinical significance
of α-SMA and CD34 expression as markers of mesangial activation and transformation.
Materials and methods: 47 needle biopsy specimens were obtained from the patients with the different types of glomerulonephritis (GN) and 9 specimens (healthy renal tissue from removed kidney) were used as a control group. The expression of
α-SMA and CD34 was examined immunohistochemically using
APAAP complex. The mean number of staining mesangial cells
in one glomerulus was calculated. Results: Expression of αSMA was higher in patients with proliferative types of GN
(mesangial proliferative GN, mesangiocapillar GN, lupus GN,
chronic transplantat nephropathy) (11,0±3,5) compared with
nonproliferative types (membranous GN, minimal change disease, focal sclerosis) (8,0±2,0) and control (8,6±2,3). Expression
of α-SMA in proliferative types group correlate with severity of
GN (erythrocyturia, hypertension, serum creatinin). There were
no difference in CD34 expression between proliferative (11,3±2,7)
and nonproliferative (11,1±2,7) types of GN. CD34 expression
in control group was comparable with those in nephritis group
(10,5±2,7). The expression of CD34 was elevated (14,2±4,0) in
specimens with high degree of glomerulosclerosis (> 50%
glomerula) compared with those with moderate sclerotic changes
(8,9±.2,0). Conclusion: Examining of α-SMA and CD34 expression in renal biopsy specimens may be useful for assessing the
GN activity and possibly as prognostic factor.
A102
SELECTIVE STENTING FOR ATHEROSCLEROTIC RENOVASCULAR NEPHROPATY
A Campo, R Boero*, P Stratta, D Savio§, F Quarello*, G Piccoli
Nephrology Units, Molinette and S.G. Bosco* Hospitals, and
Service of Vascular Radiology§, Molinette Hospital, Turin, Italy
Despite achieving high rate of arterial patency, percutaneous
revascularisation not always has favourable effects on clinical
course of atherosclerotic renovascular nephropathy (ARN).
52 cases of ARN (mean age 67.8 years, mean BCrC 33.8 ml/
min) treated by selective stenting (SS) after 1991 at our institutions (mean follow up 22.3 months before and 24.6 after the
procedure) were studied retrospectively.
SS was technically successful in 92.3%, with a restenosis rate of
17.3%, but 42% of cases suffered for complications (12%
atheroembolism, 14% contrast nephropathy) and early mortality was 3.8%. SS achieved sustained increase of BCrC (more
than 10% of basal value) in 30% of cases and slowed in the
whole group mean BCRC decline rate from 0.9 ml/min*month
to 0.19 (p 0.007). Bilateral stenosis or stenosis of a single
functional kidney (p 0.02), absent or low grade (<1g/day) proteinuria (p 0.01-0.02), serum creatinine (sCrs) < 4 mg/dl (p
0.04) and normal (< 0.81) dopplersonography resistance index
(RI, p 0.05) were all associated with a better outcome in univariate
analysis.
The efficacy of SS on blood pressure, however, was poor, with
no change in amount of drug therapy and no cure of hypertension.
Kaplan-Meier survival at 5 years was 69.4% for the kidney (better if basal sCr < 4 mg/dl: 89.2% vs 21.2% p < 0,001) and 68.9%
for the patient (better in dialysis-free cases: 81.7% vs 45% p
0,08), with a gross mortality of 4.5/100 patient-years.
Our data suggest that progression of renal failure in ARN is
rapid and can be reduced by SS, but the risk of revascularisation
is not negligeable. Some findings (low or absent proteinuria, RI
< 0.81, SCr < 4 mg/dl, bilateral stenosis or stenosis of a single
functional kidney) are associated with better outcome after SS,
and must be taken into account when ARN revascularisation is
planned.
STEVENS-JOHNSON SYNDROME ; THE LIFE THREATENING COMPLICATION OF SYSTEMIC CORTICOSTEROID THERAPY
B.S. Cho, H.J. Hong, H.H. Kang, T.W. Lee*, C.G. Ihm*
East-West Kidney Diseases Research Institute, College of Medicine*, KyungHee University, Seoul, Korea
Stevens-Johnson syndrome (SJS) is an acute inflammatory disease with an
autoimmune pathogenesis clinically expressing in a severe mucocutaneous illnesses that can be a life-threatening emergency, occurs primarily in young adults.
A considerable number of factors of different nature have been reported as
etiologic agents of SJS, range from multiple pharmacologic agents to viral infections, but most of them are not well documented. Corticosteroid has been
used to treat the SJS, but paradoxically the use of systemic corticosteroid for the
treatment of other disease might be closely related to the development of severe
SJS.
Nine children ( from 3 years old to 19 years old) with SJS were seen at the
department of pediatrics in our institution during last two years since 1998.
Diagnosis of SJS were done by pediatrician and dermatologists, with typical
cutaneous lesions. No patients were taken sulfonamides, anticonvulsants, penicillin, barbiturates and other related drugs with SJS. Bacterial and viral studies were done.
Of the 9 patients, eight patients were suffered from severe renal diseases, who
were taken 3 cycles of methylprednisolone pulse therapy ( 1 cycle, 30mg/kg /
day for three days). Of the 8 patients six cases were IgA nephropathy with heavy
proteinuria and two cases were minimal change nephritic syndrome with frequent relapsers. No uniform etiologic agents were associated with SJS, one case
was associated with Adenovirus, Four cases were associated with mycoplasma
infection and two cases were associated with Herpes virus. One case involved
whole body include scalp area and the others did not involved scalps. All
patients resolved within 2 weeks by conservative treament, however macular
lesions were persisted more than 6 months.
As yet corticosteroid related SJS was not reported rather corticostroid has been
used as a therapeutic measure although efficacy remains still controversial,
however SJS might be regarded as one of the serious complications of corticosteroid theapy.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
Clinical Nephrology: miscellaneous
APOLIPOPROTEIN-E POLYMORPHISM AND LIPID LEVELS IN END STAGE RENAL
DISEASE PATIENTS IN TURKEY
H Sari, M Koc, A Beserli1, I Guney1, Y Oymak2, B Cirakoglu1, E Akoglu, C Ozener.
Division of Nephrology and Departments of Medical Biology1, and Biochemistry2, Marmara
University School of Medicine, Istanbul, Turkey.
Background: Lipid and lipoprotein abnormalities are frequently found in end-stage renal
disease (ESRD). Previous investigators have reported that apolipoprotein E (apoE) has an
important role in lipoprotein metabolism and that the process of lipoprotein catabolism
varies according to the apoE phenotype. In addition the relative frequency of the apoE
alleles is different among the race. In this study, we investigated the allele frequency of
apoE phenotypes and evaluated the impact of apo E polymorphism on lipid profile in
Turkish population undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) treatment.
Methods: Apolipoprotein E phenotypes were determined using polymerase chain reaction (PCR) in 63 ESRD patients [19 HD, 44 CAPD] and 35 controls. Allele frequency and
apoE phenotype distribution were estimated by the gen-counting method. Serum lipid
parameters related to lipid metabolism and other biochemical parameters were measured
after a 12-hour fasting period.
Result: Since this research is a preliminary study and still goes on. The allele frequency of
the three major apoE phenotypes (apoE2, apoE3 and apoE4) in 63 ESRD patients (E2: 0,19,
E3: 0,70, E4: 0,11) was almost identical to that of control population (E2: 0,16, E3: 0,75, E4:
0,08). The dominating genotypes were E3/E3, E2/E3, E4/E3 and only a few subjects were
found with E2/2, E4/4, E2/4 genotypes. We found a similar phenotype distribution and
allele frequency between ESRD patients and healthy controls. Serum levels of total cholesterol (T-Chol), triglyceride (TG), LDL-cholesterol (LDL-Chol), HDL-cholesterol (HDLChol), Lpa, apoAI, and apoB were similar in all subgroups of apoE phenotypes of ESRD
patients. Patients in CAPD group had significantly higher levels of T-Chol and LDL-Chol
than that of HD patients (T-Chol, 236 ± 61 vs 168 ± 42mg/dl P<0,0001; LDL-Chol, 153 ±
43 vs 99 ± 34mg/dl, P<0,0001) and control group (T-Chol, 236 ± 61 vs 202 ± 47 mg/dl
P<0,0001; LDL-chol, 153 ± 43 vs 125 ± 38mg/dl, P<0,0001). The distributions of Apo-E
phenotypes were similar among the different etiologies of ESRD.
Conclusion: ApoE polymorphism modulates cholesterol metabolism in ESRD patients but
a meaningful relationship between apoE and lipid, lipoprotein levels could not be observed. We did not found a relation between apoE-phenotypes and lipid and lipoprotein
levels in ESRD patients.
ESTIMATION OF RENAL FUNCTION FROM BODY COMPOSITION ANALYSIS AND PLASMA CREATININE IN PEDIATRIC PATIENTS
C Donadio1, A Lucchesi1, M Ardini1, L Calisti2, M Massimetti2
1
Unità Nefrologia, Dip. Medicina Interna; 2Divisione Pediatria, Dip. Medicina
procreazione ed età evolutiva, Università di Pisa, Italy
The aim of this study was to evaluate, in pediatric patients, a new method to
predict creatinine clearance (Ccr) from plasma creatinine (Pcr) and from the
analysis of body composition.
The values of fat-free mass (FFM) and of body cell mass (BCM) were measured
using a tetrapolar impedance plethysmograph (Akern, Firenze) in 39 pediatric
patients (17 f, 22 m, aged 3.4-18 years, mean 11.6; Pcr 0.25-1.18 mg/dl, mean
0.71).
In the same patients 24h urinary creatinine (Ucr) was measured twice collecting the 24h urine. 24h Ucr was strictly correlated with the values of FFM and
BCM, independently from age, BMI and body surface of patients. The mean
ratio (±SD) of 24h Ucr over FFM was 23.5±5.3 mg/kg and that of 24h Ucr over
BCM was 50.0±10.8 mg/kg, without differences between males and females.
On the basis of these ratios and of values of FFM and BCM, 24h Ccr was predicted in individual patients with the following formulas:
FFM Ccr (ml/min) = FFM (kg) x 23.5 (mg/kg)
Pcr (mg/ml) x 1440 min
BCM Ccr (ml/min) = BCM (kg) x 50.0 (mg/kg)
Pcr (mg/ml) x 1440 min
In the same patients, Ccr was predicted according to Schwartz (Sch Ccr), and
was measured by collecting 24h urine (24h Ccr).
FFM Ccr
BCM Ccr
Sch Ccr
correlation with 24h Ccr
0.697
0.697
0.672
difference vs 24h Ccr, ml/min 2.1±25
1.6±25
29±28
Good correlation and concordance were found between Ccr predicted from
FFM and BCM and the values of Ccr measured collecting the 24h urine. To the
contrary, Ccr predicted according to Schwartz formula significantly overestimated the values of 24h Ccr.
In conclusion, in pediatric patients renal function can be predicted from body
composition and plasma creatinine. This method is more accurate than
Schwartz formula to estimate 24-hour creatinine clearance.
Nephrology Dialysis Transplantation
Vol. 16 n.6
Abstracts
GLOMERULAR FILTRATION RATE CAN BE PREDICTED FROM PLASMA
CREATININE AND BODY COMPOSITION ANALYSIS IN OVARIAN CANCER PATIENTS
C Donadio, A Lucchesi, M Ardini, S Cosio, A Fanucchi, A Gadducci
Dept Internal Medicine, Division of Nephrology, Dept Reproductive Medicine,
Division of Gynecology,University of Pisa, Pisa, Italy
The dosage of drugs, in particular cisplatin and carboplatin, to administer for
chemotherapy of ovarian cancer must be calculated on the basis of individual
values of renal function. The aim of this study was to evaluate, in ovarian cancer
patients, a new method to predict glomerular filtration rate (GFR) from plasma
creatinine (Pcr) and from the analysis of body composition.
The values of fat-free mass (FFM) and of body cell mass (BCM) were obtained,
using an impedance plethysmograph (ST-BIA Akern, Firenze), in 51 ovarian
cancer patients without evidence of renal failure (Pcr 0.5-1.16 mg/dl). In all
patients, GFR was measured as the renal clearance of 99mTc-DTPA. In the same
patients GFR was predicted from Pcr and individual values of FFM (FFM GFR)
and of BCM (BCM GFR), with the following formulas, derived from the relationships found between FFM, BCM and Pcr with GFR:
FFM GFR (ml/min) = 1.20 x FFM / Pcr
BCM GFR (ml/min) = 2.35 x BCM / Pcr
For comparison, in the same patients, GFR was predicted according to Cockcroft
and Gault formula (CG GFR).
In the range of measured GFR (37 to 112 ml/min, mean 66.2) the values obtained with formulas derived from body composition analysis were better
correlated with GFR than those obtained with CG formula.
Versus GFR
FFM GFR
BCM GFR
CG GFR
correlation
0.689
0.711
0.657
mean difference, ml/min
-0.4
-0.6
+15.3
range of agreement, ml/min
+22.7/-23.6 +22.1/-23.3
+47.1/-16.5
Other parameters of body composition, useful to evaluate the balance of fluid
compartments and the nutritional status of cancer patients, were obtained in
the meantime from body impedance measurement.
In ovarian cancer patients, GFR can be predicted from body composition analysis and plasma creatinine. Thanks to its simplicity and reproducibility, this
method is suitable to the repeated measurements of renal function, which are
necessary during platin-based chemotherapy.
CYSTATIN C, ß2-MICROGLOBULIN, AND PLASMA CREATININE AS INDICATORS OF GFR IMPAIRMENT IN PATIENTS WITH OVARIAN CANCER
C Donadio, M Ardini, A Lucchesi
Dept Internal Medicine, Division of Nephrology, University of Pisa, Italy
The aim of this study was to compare the accuracy of serum levels of cystatin
C (Cys), ß2-microglobulin (ß2M) and creatinine (Creat) as indicators of impairment of glomerular filtration rate (GFR), in patients with ovarian cancer.
GFR (renal clearance of 99mTc-DTPA), Creat (autoanalyzer method), Cys (particle enhanced immune-nephelometry), and ß2M (immune-enzymic method)
were measured in 47 patients (age 42-80 years, body weight 43.5-96.0 kg) affected by ovarian cancer. Furthermore, the values of plasma Creat were adjusted for the amount of fat-free mass (FFM) and of body cell mass (BCM) of
individual patients. The rationale for this correction is that muscle mass, which
produces Creat, is an important constituent of FFM and BCM. FFM and BCM
were measured with an impedance plethysmograph (ST-BIA, Akern, Firenze).
The values of GFR ranged 37-112 ml/min, mean 66.6. A poor correlation was
found between GFR and serum levels of Creat (r=0.472), Cys (r=0.296), and
ß2M (r=0.493). Closer correlation with GFR was fond for modified Creat. The
r values were 0.712 for Creat/FFM and 0.742 for Creat/BCM.
The accuracy of Creat, ß2M, Cys and adjusted values of creatinine as indicators
of different degrees of GFR impairment was tested using receiver-operating
characteristics (ROC) analysis. In the table are reported the values of the areas
under the curve of the ROC plot.
GFR
N
Creat
Cys
ß2M
Creat/FFM
Creat/BCM
<80
38 0.751
0.596 0.670
0.801
0.845 +
<70
28 0.802
0.617 0.711
0.835 +
0.841 +
<60
16 0.749
0.641 0.771
0.897 + *
0.930 ++ * §
*= p<0.05 vs Creat; +=p<0.05 and ++=p<0.01 vs Cys; §=p<0.05 vs ß2M
No statistically significant difference was found between Creat, Cys and ß2M.
Creat/FFM was more accurate than Creat and Cys; Creat/BCM was more accurate than Creat, Cys and ß2M.
In conclusion, plasma creatinine, modified on the basis of FFM and BCM, is a
better indicator of GFR impairment than creatinine, cystatin C and ß2microglobulin in ovarian cancer patients.
2001
A103
Abstracts
Clinical Nephrology: miscellaneous
OXIDATIVE STRESS AND ANTIOXIDANTS IN IDIOPATHIC IgA NEPHROPATHY
L Ong-ajyooth1, S Ong-ajyooth2, P Parichatikanon3, S Vasuvattakul1
1
Department of Medicine, 2Department of Biochemistry, 3Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok,
Thailand
COMPARISON OF CALCULATED CREATININE CLEARANCE
BY COCKCROFT AND GAULT AND SERUM CYSTATIN C
A Kuhn, S Markau, E Lotterer*, B Osten, T Langer
Depts. of Nephrology and Gastroenterology*, Martin-LutherUniversity Halle-Wittenberg, Halle/Saale, Germany
Reactive oxygen free radicals have been suggested as important mediators of
glomerular injury in IgA nephropathy. The levels of free radicals are dependent
not only on the activity of oxidant enzymes but also on the antioxidant defense
mechanisms. We therefore measured the extent of lipid peroxidation product
(malondialdehyde, MDA), the antioxidants (glutathione, glutathione peroxidase (GSH-Px), catalase, vitamin E, superoxide dismutase (SOD) activities,
cofactor of SOD (Zn, Cu), of GSH-Px (selenium), and aluminium which was the
inhibitor of SOD. These parameters were analysed in 50 patients with idiopathic IgA nephropathy and 32 age-matched controls.
Significantly higher concentrations of plasma MDA was found in IgA patients
compared to the controls (18.35±9.72 vs 7.29±3.39, p<0.0001) Plasma MDA
was significantly higher in patients with serum creatinine greater than 1.5 mg/
dl (23.76±8.97 vs 16.65±9.42, p<0.0001). GSH-Px, catalase, erythrocytes vitamin E levels were significantly low in the patients than in controls (p<0.0001).
Also zinc and selenium were decreased while copper and aluminium were
increased significantly in patients group. However, SOD activity in erythrocytes tended to be high in patient group but insignificantly (2074.6±634 vs
2106.5±505.3, p>0.05). Erythrocytes vitamin E correlated with plasma MDA,
(r=-.44, p=.014), GSH-Px (r=.34, p<.05) catalase (r=.60, p=.0003), Al (r=-.55,
p=.001) and Cu (r=-.42, p =.02).
We concluded that diminished antioxidant activities and altered status of trace
elements result in increased lipid peroxidation in patients with IgA nephropathy. The vulnerability of glomerular injury in these patients might play role in
the progressive renal damage. Moreover, erythrocytes vitamin E levels are
more important and sensitive marker than plasma vitamin E for early detection of impaired defense mechanisms of oxidative stress in IgA patients.
Recently the measurement of serum cystatin C, a protein produced at constant rate by all nucleated cells and freely filtrated
by renal glomerula, is in the focus of interest regarding the assessment of the glomerular filtration rate.This prospective study
was designed to evaluate different methods in determination
glomerular filtration rate. 108 patients (50 m, 58 f; age 55 ± 11.6
yrs) were included and the following parameters were estimated:
parameter
mean ± standard deviation
inulin clearance,
108.86 ± 37.94 ml/min
„single-shot method“
serum creatinine
89.53 ± 53.9 µmol/l
creatinine clearance
80.9 ± 36.6
ml/min
calculated creatinine
91.24 ± 34.55 ml/min
clearance by
Cockcroft and Gault
serum cystatin C
1.14 ± 0.52
mg/l
renal sorbitol
77.16 ± 37.12 ml/min
clearance
Our investigation shows serum cystatin C and calculated creatinine clearance to correlate to the same extent to inulin clearance
as “gold standard” of measuring glomerular filtration rate (correlation coefficient: 0.69, p<0.01 versus 0.67, p<0.01). The other
parameters appear to correlate only at the 95% confidence level
exposing a weaker relationship.
Conclusion: Surprisingly, the measurement of serum cystatin C
seems to have no significant benefit compared to the calculated
creatinine clearance by Cockcroft and Gault in estimating glomerular filtration rate.
ATHEROSCLEROSIS IN PATIENTS WITH END-STAGE RENAL FAILURE PRIOR TO INITIATION OF HEMODIALYSIS
1
R Hojs, 2T Hojs-Fabjan T, 1B Pecovnik Balon
1
Clin. Dept. of Internal medicine, Dept. of Nephrology and 2Dept.
of Neurology, Teaching Hospital Maribor, Maribor, Slovenia
In dialysis patients cardiovascular mortality is 10 to 20 times
higher than in general population. It remains uncertain whether
atherosclerosis of dialysis patients is effectively accelerated because many of dialysis patients have more or less marked vascular lesions already at the start of dialysis treatment.
Using B-mode ultrasonography (ATL HDI 3000), we compared
intima-media thickness (IMT) and plaque occurrence (indicators of atherosclerosis) in the common carotid arteries (CC), in
the area of bifurcation (CB) and in the proximal part of internal
carotid arteries (CI) in 28 hemodialysis patients (14 men and 14
women; mean age 49,4 years; mean duration of HD treatment
66,6 months) with that in 28 age-sex matched patients prior to
initiation of hemodialysis. We also investigated possible differences in atherosclerotic risk factors in both groups. Diabetic
patients were excluded from the study.
The IMT values of CC (0,71 versus 0,70 mm; P=0,937), CB (0,81
versus 0,77 mm; P=0,423) and CI (0,72 versus 0,71 mm; P=0,935)
were not significantly different in dialysis patients and patients
starting dialysis treatment. We also found no difference in plaque
occurrence (61% versus 54%; P=0,597) and in atherosclerotic
risk factors (hypertension, smoking, lipids) between both groups.
In our study we found no difference in atherosclerotic lesions in
carotid arteries between dialysis patients and patients with endstage renal failure starting dialysis treatment. Patients with
chronic renal failure are at high risk for cardiovascular diseases
so we should intervene earlier and more actively before dialysis
treatment in order to reduce the atherosclerotic risk factors.
A104
ELEVATED HOMOCYSTEINE LEVELS IN MAINTENANCE DIALYSIS
(CAPD-HD) PATIENTS AND IN RENAL TRANSPLANT (Tx) RECIPIENTS.
RELATION WITH OTHER CARDIOVASCULAR RISK FACTORS
D. Garofalo, V. Sirolli, L. Di Liberato, P. Cappelli, T. Piacenza, M. Bonomini
Institute of Nephrology, G. D’Annunzio University, Chieti, Italy
Several risk factors can worsen and accelerate the evolution of atherosclerotic
disease in uraemic patient. Recent studies show a close correlation between
homocysteine blood levels and cardiovascular disease. In the present study we
measured plasma levels of homocysteine in patients on renal replacement therapy
and examined the correlation between such levels and both clinical and biochemical parameters. Table shows the demographic characteristics and clinical documentation parameters of study population:
HD
CAPD
Tx
Number
32
12
20
Age
64.8±11
55.5±14.5
46±10.1
Gender (F/M)
12/20
6/6
8/12
Treatment (months)
40.5±44.2
29.5±18.9
92.3±79.3
BMI (kg/m2)
24.2±4.5
24.6±2.7
23.4±3.2
Hypertension, n (%)
14(44%)
9(75%)
17(85%)
Diabetes, n (%)
5(16%)
0
0
Lp(a) (mg/dl)
34.9±27.7°
54.9±68.5°
22.9±27
Total Chol. (mg/dl)
176.4±40.9
216.4±22.1* 210.8±34.3*
TG (mg/dl)
171.5±62.1°
197.5±53.2° 142.9±69°
HDL Chol. (mg/dl)
40.8±11.5^
47.4±9^
67.8±19.3
LDL Chol. (mg/dl)
101.2±34
129.3±17.6* 114±32.4
APO A1 (mg/dl)
128.9±33.1
152.5±22.3 170.8±44.4
APO B (mg/dl)
105.5±99.2
110.9±21.2 102.7±23.8
Albumin (g/L)
3.9±0.3°
4±0.3°
4.1±0.3°
Haematocrit (%)
34.6±4°
33.6±3°
38±4.4°
Significantly different (p<0.05) °vs normal, *vs HD and Normal,
^vs Tx and Normal
NORMAL
15
51.5±10
8/7
=
24±2.1
0
0
12±3.1
184.3±17.8
97.7±19
60.4±9.9
104.2±22.9
153.3±25.5
98.8±17.9
4.4±0.3
42±1.2
Plasma homocysteine levels (mmol/L) were significantly (p<0.05) increased in
HD (22.3±8), CAPD (31.2±6.6) and Tx (15.3±3.2) patients compared to healthy
subjects (9.6±2.1). Significant differences (p<0.05) in homocysteine levels were
also noted between each pair of renal replacement groups. No correlation between homocysteine levels and any of the other parameters examined was found.
In conclusion, high homocysteine levels in CAPD-HD patients could be an additional atherogenic factor not completely reversed by Tx.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
Clinical Nephrology: miscellaneous
Abstracts
PREVALENCE OF CHRONIC RENAL FAILURE (CRF) IN
GENERAL POPULATION. AN EPIDEMIOLOGICAL APPROACH.
F Aguero, Pl Santacruz, D Urbina, O Zarraga, C Aguero
Central Hospital of Maracay, Aragua, Venezuela.
THE MICROANGIOPATHIC AND MACROANGIOPATHIC COMPLICATIONS IN
BOTH TYPES OF DIABETES MELLITUS AND SIGNIFICANCE OF ASSESSMENT OF
ACE GENE POLYMORPHISM
Rosochová I.1, Šufliarska A . 2, Podracká L.1, Kovács L. 2
Department of Internal Medicine, University Hospital Košice 1 Slovak Republic. Children’s University Hospital, Laboratory of Molecular Diagnostics Bratislava 2, Slovak Republic.
With the aim of estimating the magnitude of the CRF on anyone
of its phases in the general population a sample of 1436 peoples
(623 males and 813 females) with age > 15 years old (average
age was 38.4±17.6 years old) of the Choroni community, a coast
town of the Aragua State in Venezuela. The 12.5% were catalogued as white, 18.7% as black and 68.8% as mixed race. On all
of them a survey was done, which included arterial pressure
measure (mmHg), weight (Kg), size (cm) and blood sample in
order to measure the serum creatinine (SCr, mg/dl). As diagnosis of CRF was considered each person with SCr>1.5 mg/dl in
two consecutive measures with a 4 weeks interval in the absence
of instigating factors of acute renal damage for at least one year
before. In 6 cases, the diagnosis of CRF was established and 5 of
them (83.3%) did not know they had the disease. One case
presented end stage kidney disease (ESKD). The average age of
the patients with CRF was 54.3±23.6 years old significantly
superior (p<0.01) to the studied population and the male sex
was the most affected. The etiology of the CRF was hypertensive
nephropathy and polycystic kidney (2 cases each) and diabetic
nephropathy and primary glomerulopathy (1 case each). The
prevalence rate of CRF on all of its phases was 4178.3 per million population (pmp), while for ESKD was 696.3 pmp.
The factors leading to the onset of diabetic nephropathy still remain unexplained. Besides
glycaemic control, genetic predisposition seems to play an important role in development
of diabetic nephropathy. Genes of the renin – angiotensin system are the potential candidate genes. An insertion/deletion polymorphism in the gene coding for the angiotensin
I converting enzyme (ACE) has been extensively examined, but results are controversial.
The aim of this study was to analyse the relation between ACE gene variants in diabetic
nephropathy and major cardiovascular diseases, such as ischaemic heart disease, myocardial infarction and arterial hypertension.
Patients and methods: ACE gene polymorphism was examined in a group of 102 patients
with type 2 diabetes mellitus, lasting more than 10 years, and in 59 patients with diabetes
1. type, lasting more than 20 years. Patients were divided into two groups according to
the significance of proteinuria: A group – patients with proteinuria, B group – patients
without proteinuria. In the whole group we followed – up quantity (age, duration of both
types of diabetes, HbA1c, cholesterol, creatinine, blood pressure) and quality parameters
(significance of proteinuria, incidence of ischaemic heart disease and myocardial infarction, presence of arterial hypertension and diabetic retinopathy). The type of ACE gene
polymorphism was examined by PCR method in the Laboratory of Molecular Diagnostics
of the Children’s University Hospital, Bratislava. Unpaired t–test was used for comparison
of quantitative data and χ2 test to compare qualitative data. Multiple comparison method
(Tukey – Kramer) was used for mutual comparison of all the parameters in followed – up
patients.
Results: In patients with proteinuria a higher prevalence of cardiovascular diseases was
found in diabetics with type 2 diabetes (incidence of myocardial infarction in A group was
33.13% vs. 17.4% in B group, and arterial hypertension in A group 86.56% vs. 74.28% in B
group, and finally incidence of diabetic retinopathy 71.6% in A vs. 57.1% in B group).
Analysing the quantitative data in patients with dia betes 2. type we found a significant
relation of DD genotype to cholesterol level (p = 0.03) and ID genotype to diabetic retinopathy (p = 0.008). In patients with diabetes 1. type, there was a significant relation of ID
genotype to diabetic retinopathy (p = 0.04). It has been not found any relation between
diabetic nephropathy and and DD genotype and also D allele of ACE gene polymorphism.
Conclusion: The preliminary results of this study showed only higher incidence of diabetic
retinopathy in patients with ID genotype in both types of diabetes mellitus. There was no
association between diabetic nephropathy and DD genotype as well as D allele.
An interesting finding is relation of cholesterol level to DD genotype in patients with DM
2. type. Significance of this finding is unknown. Up to now we have not found any
information about this, and so for the explanation we will need more patients.
SENSITIVITY ASSESSMENT OF DRASTIC-DERIVED CLINICAL PREDICTION RULE IN ATHEROSCLEROTIC RENOVASCULAR NEPHROPATY (ARN)
A Campo, R Boero*, P Stratta, F Quarello*, G Piccoli
Nephrol. Units, Molinette and S.G.Bosco* Hospitals, Turin, Italy
Atherosclerotic renal artery stenosis (ARAS) is usually detected
by means of first line imaging tests and then confirmed with
arterial angiography. The preangiographic pathway is still to
expensive for screening purpose, however, even more in suspected ARN, which reduces single test sensitivity and needs
often additional diagnostic steps.
We retrospectively assessed sensitivity of a clinical prediction
rule (adapted from that of Drastic Study Group, Ann Int Med
1998; 129: 715-711) in 54 cases of ARN recruited after 1991 for
selective stenting outcome analysis (98.1% hipertensive, 84.4%
with Cockcroft-Gault BCrC < 70 ml/min). Diagnosis of functional relevant ARAS was always confirmed by renal angiography (narrowing of arterial lumen > 70%). Our modified rule
(mDrastic) gives a score to 7 items (age, sex, spread of vascular
disease, body mass index, recent onset of hypertension, serum
creatinine, hypercholesterolemia): based on Krijnen and coll. (see
reference above) score > 13 are positive (risk of RAS > 30%), 1211 are indetermined, and > 10 are negative.
The mDrastic in our cohort have an 86% sensitivity, better than
colordopplersonography (77,1%) and renal ACE-scintigraphy
(66,7%), but lower than their association (96,3%). Classic picture of ARN instead was quite uncommon: only 13 % had an
history of acute renal failure after ACE inhibition, and 7.4% of
acute pulmonary edema without heart disease.
The mDrastic high sensitivity (better in ours than in Drastic
patients, probably because of the higher prevalence of renal failure due to ARN) and low costs make the method adapte to
screening purpose. We need more studies in unselected patients
to assess specificity and know if positive predictive value is high
enough to avoid other imaging tests before angiography.
Nephrology Dialysis Transplantation
Vol. 16 n.6
TC-99M EC: A RAPID PROCEDURE TO EVALUATE THE
RENAL PARENCHYMA IN ACUTE PYELONEPHRITIS;
COMPARATIVE STUDY WITH TC-99M DMSA
O. Soylemezoglu, T. Atasever, O. Ozkaya, E. Abamor, O.U.
Akdemir, N. Buyan, M. Unlü
Dept. of Pediatric Nephrology and Nuclear Medicine, Gazi
University Ankara, Turkey
Tc-99m DMSA renal parenchymal scintigraphy is accepted as a
gold standart in the diagnosis and follow-up of pyelonepritis.
The purpose of this study is to investigate whether, a relatively
new agent, Tc-99m Ethylene cysteine (Tc-99m EC), can determine renal cortical parenchymal defects in the early phase (1-3
minutes) of a renal function study. In 43 children with acute
pyelonephritis (APN), aged between 4 months and 11 years old
(median: 21.5 ± 32 months) both Tc-99m DMSA and Tc-99m
EC studies performed within five days of acute infection. Both,
Tc-99m DMSA and Tc-99m EC scans were visually interpreted
using four point semiquantitative rating (0; normal, I; mild
hypoactivity, II; moderate hypoactivity with partial loss of
margins, III marked hypoactivity with loss of cortical margins).
Split renal functions were also evaluated for both Tc-99m DMSA
and Tc-99m EC scans. A total of 109 lesions identified in 43
patients. In Tc-99m DMSA; there were 43 Grade I, 40 Grade II
and 26 Grade III lesions. Tc-99m EC scans detected 90 lesions
with a sensitivity of 82.0 %; of these 26 were Grade I; 38 were
Grade II and 26 were Grade III lesions. In regarding lesion site
and grade, 78 (72 %) lesions showed head to head match on
both scans. Tc-99m EC scintigraphy was unable to recognize 19
lesions identified on the Tc-99m DMSA study. Seventeen of
these were grade I lesions and 2 were grade II lesions
We can conclude that Tc-99m EC early phase images (1-3 min)
is reliable in detecting cortical parenchymal lesions. Thus, by
using a single agent it is possible to obtain information about
both cortical parenchymal and renal function. The other advantage of this procedure is lower radiation exposure.
2001
A105
Abstracts
Clinical Nephrology: miscellaneous
ATHEROSCLEROTIC ISCHEMIC RENAL DISEASE IN THE AGED POPULATION
Coen G., Ferrannini M., *Cianci R., Calabria S., Lifrieri F.,Dinnella A., *Lai S.,
**Montesanti **T., Ronga, ***Zaccaria C., ♦Marziale P., ♦♦Nofroni I..
Renal Pathoph. and Hypertension Unit, *6th Medical Clinic, **Nuclear Med.
Unit, ***2ndVascular Surg., ♦ 2nd Chair of Radiol., ♦♦ Dep.Exper.Med.Pathol.,
La Sapienza University, Rome
Atherosclerotic ischemic renal disease (AIRD) is recognized as a distinct and
frequent cause of renal insufficiency in the elderly leading to dialysis. Nevertheless its real prevalence is unknown and screening investigations on large cohorts of subjects, based on non-invasive diagnostic tools, are rare.
We have enrolled 269 subjects with the inclusion criteria of hypertension and/
or chronic renal failure, unrelated to other known causes of renal disease, starting after 50 years of age. The patients were studied with renal scintigraphy and
colour-duplex sonography of renal arteries. 39 patients, found to have renal
artery stenosis, were subjected to 3D-contrast enhancement Magnetic Resonance Arteriography (3D-CE-MRA) and/or Digital Selective Angiography
(DSA). In addition 23 cases, who were negative both to scintigraphy and to the
ultrasound study, accepted to undergo a renal angiography. Colour-duplex
sonography, carried out in 238 patients, showed 49 cases of renal artery stenosis. MRA or DSA carried out in 35 cases, confirmed the diagnosis in 33. Colourduplex sonography was 91.7% sensitive and 90.9% specific, with PPV of 94.2%
and NPV of 86.9%. Specificity and sensitivity of renal scintigraphy, carried out
in 225 patients, was significantly lower (50% and 52% respectively).
Renal artery stenosis, based on the color-duplex sonography studies, was present
in 11% of patients in the age group 50-59, 18% in the 60-69 and 22.8% at age 70
or higher. Patients with renal artery stenosis showed a higher degree of renal
insufficiency compared to non stenotic patients; an average similar degree of
proteinuria is present in both groups.
In conclusion a large percentage of the elderly population with renal insufficiency is affected by AIRD and is at risk of end-stage renal failure. The presence
of proteinuria does not exclude AIRD. Color-duplex ultrasonography is a valid
routine method of investigation of population at risk of renal artery stenosis.
DIAGNOSTIC CRITERIA FOR SYSTEMIC AL AND AA
AMYLOIDOSIS
Sarkissova I., Mukhin N., Koslovskaja L.
Clinic of Nephrology and Internal Diseases, Moscow Sechenov
Medical Academy, Moscow, Russia
According to our investigation (from 1994 to 1998) the median
frequency of amyloidosis was 0.56% among the patients of Clinic
of Nephrology and Internal Medicine. The goal of this study was
to assess the clinical and diagnostic criteria for systemic AL and
AA amyloidosis. Two groups of patient were examined: Group
I (12 patients with AL amyloidosis) and Group II (20 patients
with AA amyloidosis). All patients had biopsy verified amyloidosis. The patients were assigned to the groups on the basis of
classical signs: the diagnosis of multiple myeloma, identification of immunoglobulin light chain in urine and/or serum, the
plasma cell percentage on bone-marrow biopsy for Group I and
an underlying disease, renal involvement for Group II. The predominant (39%) underlying disease pro-cesses were inflammatory arthritides (rheumatoid arthritis, ankylosing spondylitis,
psoriatic arthritis), followed by familial Mediterranean fever
(30%), chronic inflammatory and infection disorders (27%). The
features of cardiac involvement in patient with AL amyloidosis
were cardiomegaly (33%), low voltage (42%), atrial conduction
abnormality (33%) on ECG and thickening of left ventricular
wall (80%), interventricular septum (50%), diastolic dysfunction (30%) on echocardiography. Whereas cardiac involvement
may occur with AA amyloidosis as well, in patients of Group II
we noted ECG abnormalities (80%) and diastolic dysfunction
(27%) on echocardiography in the absence of previous cardiovascular disease. The high frequency of renal involvement was
found in patients with AL amyloidosis as compared with manifestation of renal involvement in AA amyloidosis: 58% of patients in Group I had the nephrotic syndrome and 33% had renal
failure; in Group II – 75% and 45%, respectively. The results of
this study showed the high specificity for AL amyloidosis such
uncommon diagnostic criteria as hypotension (50%), weight loss
(42%), macroglossia (25%), identification of immunoglobulin
light chain (92%). The method of typing with alkaline guanidine
is more specific for identification of AA amyloidosis.
A106
LEFT VENTRICULAR HYPERTROPHY IN NON-DIALYSED PATIENTS
WITH CHRONIC RENAL FAILURE
M. Resuli, M. Tase, A. Idrizi, M. Barbullushi
Department of Nephrology-Hypertony, University Hospital Center “Mother
Teresa”, Tirana, Albania
Left ventricular hypertrophy (LVH) is an important marker of risk for cardiac
death in patients (pts) with chronic renal failure (CRF). Many authors have
studied the causes and the significance of the LVH in the dialyzed pts. We
decided to study the LVH in non-dialyzed pts with CRF, and also the impact of
anemia and hypertension on it.
50 non-dilysed pts with CRF admitted at our service were included in the study.
They were divided in three stages as regard the seric creatinine: first stage of
creatininemia < 4 mg/dl; second stage of creatininemia 4-7 mg/dl and third
stage of creatininemia > 7 mg/dl. LVH evaluation was performed by
echocardiography, using the criteria of the American Society of
Echocardiography. The left ventricular mass index (LVMI) was determinated
according to the method of Devereux and Reichek.
LVH was present in 78.8% of pts: 66.6% in the pts of the first stage of CRF, 90%
in the pts of the second stage of CRF, and 80.7% in the pts of the third stage of
CRF. All pts that presented LVH had also different stages of anemia, and only
80.7% of them presented hypertension. On the other hand, 57.1% of pts with
anemia and without hypertension presented LVH. 22.2% of pts with LVH presented concentric ventricular hypertrophy. 14.4% of pts of the first group had
eccentric ventricular hypertrophy without dilatation, and 62.9% of the pts of
the third group presented eccentric ventricular hypertrophy with left ventricular dilatation.
We conclude that LVH is very common in non-dialyzed pts with CRF. Hypertension and anemia are very important LVH-induced factors, moreover, the
presence of left ventricular hypertrophy in some pts of the first group, with
anemia but without hypertension, supports the role of anemia in left ventricular
hypertrophy. The very high rate of pts, especially those of the third group who
present eccentric ventricular hypertrophy with left ventricular dilatation can
be as result of the absence of the dialysis.
FOODS RICH IN ADVANCED GLYCATION END PRODUCTS (AGEs) INDUCE MICROALBUMINURIA IN HEALTHY PERSONS
I Wittmann1, Z Wagner1, I Mazák1, L Pótó2, R Schinzel3, A Heidland4, J Nagy1
1 nd
2 Department of Medicine and 2Central Research Laboratory, Pécs University, Hungary, 3Physiologische Chemie I.,4Dept. of Internal Medicine, Universität
Würzburg, Germany
The aim of this study was to elucidate whether a chronic dietary AGE-load
exerts detrimental effects on renal function in healthy subjects. A cross-over
study was carried out in 19 healthy volunteers. We compared the effect of heated
(AGE-rich) foods to the effect of non-heated (AGE-poor) foods. Protein content
of diet was 3 g/bw. kg/day. Volunteers were divided into 2 groups. After a
baseline (1st) week Group A consumed the AGE-rich diet for one week (2nd).
After the wash-out period of the 3rd week they consumed the AGE-poor diet
during the 4th week. In Group B the sequence of the diets was reversed. Serum (S)
and urinary (U) Nε-(carboxymethyl)lysine (CML as an AGE, ELISA) and Ualbumin excretion (UAE, immunoturbidimetry) were determined. Body weight
(BW), GFR (creatinine clearance), S-insulin (RIA), S-leptin (RIA) and blood
pressure (BP, ABPM) were also measured.
Baseline S-CML and U-CML averaged 291±10 ng/ml and 1.3±0.1 mg/day,
respectively in Group A, which did not differ significantly from Group B. The
AGE-rich diet increased S-CML (p=0.03) and U-CML excretion (p=0.02) in
both groups. In Group A the AGE-rich diet elevated UAE (baseline vs. AGE-rich
diet, 7±1 vs. 33±13 mg/day; p=0.04), whilst all other changes in UAE were
insignificant. GFR and BP were unchanged but BW was increased by the AGErich diet (deltaBW=0.9±0.4 kg) and decreased by the AGE-poor diet (deltaBW=
–0.8±0.4 kg) by the 4th week (p=0.005). S-insulin levels were increased by the
AGE-rich diet (Group A: 24±6 vs. 32±6 mU/l and Group B: 23±6 vs. 31±2 mU/
l; baseline vs. AGE-rich diet; p=0.04). S-leptin was unchanged.
The results of our study suggest that a chronic elementary AGE-rich proteinoverload induces a rise in S-CML, S-insulin, UAE and BW, indicating the potentially harmful effects of diet containing heated food.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
Clinical Nephrology: miscellaneous
THE INFLUENCE OF GLOMERULAR FILTRATION RATE,
CALCULATED BY THE COCKROFT-FORMULA, ON HOMOCYSTEINE PLASMA LEVELS
Karshelova E., E. Andreev, L. Lambreva, A. Tconcheva
Medical University Sofia
Hyperhomocysteinemia, a consistent finding in uremic patients,
is now widely recognized as an independent risk factor for vascular disease. The aim of the study is to evaluate the influence of
early GFR changes on homocysteine metabolism. In 121 pts (104
male, 17 female), without history of renal disease, homocysteine
plasma levels were determined by the Abbott IMx Homocysteine
Assay. The group was subdivided relating to individual Ccr,
calculated by the Cockcroft-Gault formula, as follows:
Gr. A - 72 pts with normal Ccr > 80 ml/ min, mean Ccr=111,47
ml/min (SD±27,11)
Gr. B - 49 pts with reduced Ccr < 80 ml/min, mean Ccr=65,17
ml/min (SD±21,43) (including 6 pts with plasma creatinine
above the normal limit 133,4 µmol/l)
The mean plasma homoctysteine level of Gr. B-18.09 µmol/l
was slightly higher then that of Gr. A-15, 28 µmol/l (p=0,061)
We found a correlation between Individual Ccr and individual
homocysteine plasma levels in the entire group as well as in the
gr. B, but not in gr. A. This correlation was stronger in gr. B and
it was largely accounted for by data from pts with increased
creatinine plasma levels.
ent. gr (N 121) gr. B (N 49)
gr. A (N 72)
r
-0,227
-0,465
0,024
p
0,012
0.001
0.843
The mean homocysteine plasma level (31,40±14,89µmol/l) of
the six pts with elevated creatinine was higher then that
(15,70±6,86µmol/l) of the others (p<0,01). Our results suggest
that GFR reductions, only when provoke hypercreatininemia could
produce significant hyperhomocysteinemia.
ACUTE FOCAL BACTERIAL NEPHRITIS (AFBN) - INTERESTING DOPPLER RESULTS
R. Djerassi, M. Ljubomirova, B. Bogov, M. Stojanova
University Hospital “Alexandrovska’, Clinic of Nephrology
Because of the good visualisation of the parenchyma circulation
with Power Doppler (PWD), the examination of the diffuse
cortical or focal defects of perfusion is now a lot easier. Twenty
two pts with AFBN were examined - 16 females and 6 males,
average 32.43 (SD +/-13.29) year, M=33, by Conventional Ultrasound (CU), Colour (CFM) Pulse (PD) and Power Doppler.
Systolic peak (Vp) and Diastolic velocity (Vd) were measured,
and the Resistive index (RI), a parameter of the vascular resistance, vas calculated. Triangular hypoehogenic (13 pts),
hyperehogenic (4 pts) and heterogenic (5 pts) focal areas, sized
from 15 up to 49 mm, single in 17 and multiple in 5 pts were
revealed on CU. Areas of decreased or even missing perfusion
were diagnosed by PWD on the same side, on which were previously seen by CU. PD shows higher RI (0.66 SD ± 0.042, p=
0.001) of the intrafocal arcuate artery, than the mean RI (0.059
SD± 0.024). Vp and Vd in the focal areas were lower than average Vp and average Vd (p<0.014). The diagnostic value of Power
Doppler in the diagnosis of AFBN are:the sensitivity - 94%,
specificity -100%, positive predictive - 94% and negative predictive value of 100% and almost same are the probability of scarring.
Power Doppler sonography seems to be significantly more sensitive than CU for the diagnosis of AFBN. It should be able to
replace CT for the detection of acute pyelonephritis.
Nephrology Dialysis Transplantation
Vol. 16 n.6
Abstracts
END STAGE RENAL FAILURE AND REFERRAL FOR DIALYSIS IN THE REPUBLIC OF
MACEDONIA
Stojceva-Taneva O, Sikole A, Zafirovska K, Gjulsen S, Grozdanovski R.
Department of Nephrology, Clinical Center, University “St. Cyril and Methodius” Skopje,
Macedonia
The study presents the epidemiology of ESRD patients in the Republic of Macedonia.A
total of 168 ESRD patients have been accepted for renal replacement therapy (RRT), 156
in Skopje and 12 in Struga. Complete data have been obtained from the medical records
of the 156 patients in Skopje. 16 patients died during their hospitalization after initiating
hemodialysis (HD). There have been 140 patients left starting maintenance HD in Skopje,
and 12 in Struga, a total of 152, or an incidence of 76 patients/milion population. The M/
F ratio was 45.5/54.5 %, Albanians comprised 33.97% and the rest were Macedonians. The
number of late referrals was unbelievably high, 79.5%, compared to early ones, 20.5%. The
causes for ESRD were: undetermined nephropathy as a leading cause 23.72%, probably
due to the high number of late referrals, diabetes 19.86% (but true diabetic nephropathy
in only 14.1%), interstitial nephritis in 18.6%, glomerulonephritis in 17.95%,
nephroarteriosclerosis in 12.82%, ADPKD in 5.13%, renal grafts in 1.28% and malignancies
in 0.64%. The early referrals had a significantly higher measured and calculated creatinine
clearance at start of RRT, 7.7+3.5 and 9.2+5.4 ml/min respectively, compared to late
referrals, 6.1+4.3 and 7.02+3.9 respectively, p<0.05. Also, male gender had significantly
higher serum creatinine and calculated creatinine clearance at start of RRT compared to
female, 1091.1+415.3 micromol/l and 7.9+3.7 ml/min respectively, compared to 924.5+340.0
micromol/l and 7.1+4.8 ml/min respectively, p<0.05. The group of patients deceased
during hospitalization were significantly older than those survived, 61.1+15.8 years, compared to 54.3+14.2 and had lower albumin levels, 30.6+6.5 g/l compared to 34.7+6.4,
p<0.05. Of the 16 patients deceased during hospitalization, 14 were from the late referrals
and only 2 from the early ones. Patients with diabetic nephropathy started RRT with a
significantly higher measured and calculated creatinine celarance, 8.4+3.3 and 11.7+6.5
respectively, compared to other causes of ESRD, 5.7+4.2 and 6.3+2.6 respectively, p<0.01
and p<0.000000.There has been a total of 936 patients on hemodialysis in the Republic of
Macedonia in 1999, and 111 died. There have been 15 new living donor transplantations
and 2 patients started CAPD. Taking into consideration these numbers, the increase in the
number of ESRD patients requiring HD will be 24 per year, for 1999. In conclusion, there
is an insignificant number of CAPD patients and low rate of renal transplantation, from
living donors only, in the Republic of Macedonia, and therefore, a rapidly increasing
number of new ESRD patients requiring HD. Efforts have to be made to increase the
number of CAPD patients and renal transplantation, and particularly to initiate cadaveric transplantation.
RENAL FUNCTION AND CARDIOVASCULAR RISK FACTORS IN AN
ITALIAN ELDERLY POPULATION: RESULTS OF THE “ILSA” STUDY.
B. Baggio, A. Budakovic, E. Perissinotto 1, S. Maggi2, S. Cantaro, G. Enzi, F.
Grigoletto1.
Medical-Surgical Science Department, 1Environmental Medicine and Public
Health Department, University of Padua. 2 CNR, Study Center on Aging.
The relation of cardiovascular risk factors and physiological loss of renal function with senescence is still unclear. The aim of this work was to evaluate in an
italian elderly population the prevalence of elevated serum creatinine (SCr)
levels and cardiovascular risk factors related.
The multicentric study ILSA (Italian Longitudinal Study on Aging) was
perfomed on a random sample of 5462 individuals aged 65-84 years. After
leaving out 100 elderly people affected by renal diseases, we identified 3994
subjects with complete clinical information on their cardiovascular risk factors. Into this group we singled out a subset of 678 “healthy” subjects without
every pharmacological treatment and not affected by hypertension, diabetes or
cardiovascular diseases. The 3416 individuals left over and positive to one of
the chosen criteria were called “unhealthy” subjects.
With available SCr of 211 male and 160 female “healthy” subjects we estimated the 95th percentiles (cutpoints) equal to 1.4 mg/dl in men and to 1.1 mg/
dl in women. We applied these cutpoints to 2625 “unhealthy” subjects (1271
females and 1354 males) with SCr; the prevalence of values over the cutpoints
was 5.4% in men and 9.8% in women. Multiple logistic regression identified,
as correlate variables of over SCr cutpoint, in men age >75 yrs (Odd Ratio “OR”
=3.1; Confidence Interval “CI” 95%=1.6-5.7), atherosclerosis at lower limbs
(OR=2.5;CI 95%=1.24.9), fibrinogen > 350 mg/dl (OR=2.1;CI 95%=1.13.9), antihypertensive medications (OR=1.8; CI 95%=1.0-3.5); and in women antihypertensive medications (OR=2.1; CI 95%=1.2-3.5), history of stroke (OR=1.9; CI
95%=1.0-3.5), age >75 yrs (OR=1.8;CI 95%=1.2-2.8) and fibrinogen >350 mg/dl
(OR=1.7;CI 95%=1.1-2.6). Coronary disease, diabetes, hypertension, smoke and
dyslipidemia did not result as being significant independent variables. When
we carried out logistic regression analysis with alimentary habit as independent variable, we obtained, only in women, an significant regression model with
potatoes (>2 times/week) (OR=0.52;CI 95% = 0.30-0.89) and fish (>2 times/
week) (OR=0.54; CI 95% = 0.34-0.89) consumption as significantly protective
predictors, while meat consumption (>7 times/week) (OR=1.52; CI 95% = 1.052.22) was significant risk predictor of elevated SCr levels.
Our results demonstrate that coexisting cardiovascular diseases and risk factors could be playing an important role in increasing the decline of kidney
function with aging.
2001
A107
Abstracts
Clinical Nephrology: miscellaneous
HIGH ERYTHROCYTE Na,Li COUNTERTRANSPORT (CNT)
ACTIVITY STRONGLY PREDICTS ADVERSE OUTCOME IN
IgA NEPHROPATHY (IgAN)
R. Boero, A. Fabbri*, M. Ferro, E. Degli Esposti*, R. Cocchi*, A.
Sturani*, C. Rollino, F. Quarello
Divisione di Nefrologia e Dialisi, Ospedale G. Bosco, Torino e
*Ospedale S.M. delle Croci, Ravenna, Italy
THE CORRELATION BETWEEN THE RISK FACTORS FOR CARDIOVASCULAR DISEASE AND KIDNEY AND CARDIAC FUNCTION IN VERY ELDERLY PATIENTS
J. Dulawa, T. Fojt, A. Kurek, W. Wojakowski, T. Francuz, W. Garczorz, A. Danch,
J. Gmiñski
Dept. Int. Med and Metab. Dis., Dept. Geriatrics, Dept. Experim. and Clin. Biochemistry Silesian Medical Academy, Katowice, Poland
Aim of this study is to evaluate whether high erythrocyte CNT is
a marker of poor prognosis in IgAN. Forty-six patients (34 males,
12 females, mean age at baseline 38±2 years) with biopsy proven
IgAN were studied.
At baseline we evaluated: CNT, creatinine (Scr, mg/dl), 24h
proteinuria (Uprot, g/day), cholesterol (Chol, mg/dl),
tryglycerides (TG, mg/dl), blood pressure (hypertension when
DBP=>95 mmHg or when taking antihypertensive drugs). In 18
patients CNT was remeasured after 3 years and resulted stable
(0.27±.08 vs 0.26±.08 mM/l RBC/h; r=0.96, p<0.0001). After a
mean follow up of 118±4 months all 46 patients were evaluated
for the following end-points: dialysis (6 cases), doubling of Screat
(3 cases), development of renal insufficiency (1 case).
End-points were significantly more frequent in patients with
CNT above median value (all end-points 9 vs 1, Fisher p=0.01;
dialysis 6 vs 0, p=0.02). Similar results were obtained using a
cut-off value for CNT of 0.3. Baseline values of other variables
(mean±SEM or n° of cases) for patients who reached or not an
end-point were respectively: M/F 9/1 vs 25/11, age 40±4 vs
38±2, hypertension/normotension 7/3 vs 9/27, p=0.02, CNT
0.36±.04 vs 0.25±.01, p=0.002; SCr 1.3±.05 vs 1.0±.04, p=0.001;
Uprot 2.1±.3 vs .76±.2, p=0.001; Chol 249±10 vs 196±8, p=0.002;
TG 236±54 vs 119±11, p=0.002. Multiple stepwise logistic regression analysis showed an independent association with endpoint status for CNT (p=0.04) and Uprot (p=0.03).
These results, the first obtained in a longitudinal long-term prospective study, show that CNT, a genetically inherited marker
stable over time, is associated with the prognosis of IgAN.
The insulin resistance, elevated homocysteine (Hcy) concentration,
dyslipidaemia, hyperuricaemia, hypertension and genetic polymorphisms of
methylenetetrahydrofolate reductase (MTHFR) gene are the important risk
factors for cardiovascular diseases (CVD). The plasma Hcy concentrations is
determined by renal function and is associated with the genetic polymorphisms
of the MTHFR gene. Aging has profound effect on kidney and cardiac function.
The aim of the study was to correlate the creatinine clearance (CC), left ventricular ejection fraction (LVEF) with CVD risk factors in very elderly patients. The
study population comprised of 16 patients, aged > 75 years, 10 women and 5
men. The fasting serum concentrations of uric acid, creatinine, HDL-, LDLcholsterol and triglycerides were assayed using standard diagnostic kits. The
fasting insulin levels were measured using RIA kit and the concentration of Hcy
using HPLC. Creatinine clearance and insulin resistance index were calculated
as described elsewhere. The genotyping for MTHFR polymorphisms was performed using PCR-RFLP (digestion with restriction enzymes MboII for A1298C
and HinfI for C677T). Blood pressure measurements (mean SBP and DBP, SBP
and DBP variability were performed according to approved protocols. The
ejection fraction (EF), left ventricle mass (LVM) and left ventricle mass index
(LVMI) were measured using echocardiography. All patients were overweight
(n=10) or obese (n=5) and had insulin resistance index > 0.3. The serum Hcy
levels in all subjects were normal (<15 µM/L). No patient had hyperuricaemia.
The GFR did not influence the insulin resistance indices. The mean SBP was
significantly higher in men than in women (p<0.05). In age group > 80 years the
LVM and LVMI were significantly lower in comparison to age group 75-80
years (p<0.05). The positive correlation was found between the DBP variation
and BMI (r=0.68), negative between creatinine clearance and SBP variation (r=0.55), uric acid and EF (r=-0,56). No differences in tested parameters were found
out between carriers and non-carriers of T677 and C1298 allele.
Conclusion: The Hcy and other tested CVD risk factors did not correlate with
kidney and cardiac function parameters in very old patients.
THE ROLE OF NON-ENZYMATIC GLYCATION AND OXIDATIVE STRESS ON THE PROGRESSION OF IGA NEPHROPATHY
1
T Vas, 1Z Wagner, 1T Kovács, 1I Wittmann, 2R Schinzel, 3A
Heidland, 1J Nagy
1
Second Department of Medicine and Nephrological Center,
University of Pécs, Hungary, 2Physiologische Chemie I, 3Dept.
of Internal Medicine, University of Würzburg, Germany
IgA nephropathy (IgA NP) is the most common form of primary glomerulonephritis and is characterized by high levels of
serum IgA and circulating immune complexes in half of the
patients (probably due to a delayed removal) as well as enhanced oxygen radical levels in erythrocytes. Up to now there is
no systematic data on potential alterations in serum AGE levels
in this form of NP. We investigated this question with especial
attention to renal function (as evaluated by creatinine clearance)
and to oxidative stress. Two IgA NP groups were formed: patients with normal (GFR=104±21 ml/min, n=54) and those with
decreased renal function (GFR=50±19 ml/min, n=34). As control 97 subjects (GFR=105±21 ml/min) were used. AGE levels
were measured by carboxymethyl-lysine (CML, using competitive ELISA) as well as by means of AGE-specific fluorescence
intensity (ex. 370 nm, em. 440 nm). Oxidative stress was evaluated by determination of TBA-reactive substances. In our study,
even in IgA NP patients with normal GFR, there was a small, but
statistically significant increase in AGE-specific fluorescence intensity and CML (2026±704 a.u. vs. 1703±505 a.u. and 438±136
ng/ml vs. 334±121 ng/ml, p<0,001); and in those with decreased
renal function, a further rise in AGE-specific fluorescence and
CML was observed (2628±1013 a.u. and 563±215 ng/ml,
p<0,001). Serum TBARS levels averaged 1,00±0,62 µmol/l in
patients with normal GFR vs. 1,15±0,61 µmol/l in patients with
decreased renal function, while in control subjects, levels of
0,49±0,27 µmol/l were documented (p<0,001). A significant
correlation was found between AGE-specific fluorescence intensity and creatinine clearance in patients with decreased renal
function (r=-0,52, p<0,05). We conclude that the AGE levels as
well as the oxidative stress parameter are elevated in patients
with IgA NP, even in the presence of normal or slightly decreased GFR, which may contribute to the progression of IgA
NP.
A108
ABNORMALITES OF GLUCOSE METABOLISM AND CARDIOVASCULAR
EVENTS IN PATIENTS WITH HYPERTENSIVE NEPHROSCLEROSIS AND
MILD RENAL FAILURE.
L. Zingaro, C. Catena, D. Casaccio, S. De Marchi, L.A. Sechi.
Hypertension Unit, Internal Medicine, DPMSC, University of Udine, Udine,
Italy.
Abnormalities of glucose metabolism and hyperinsulinemia have been demonstrated in patients with end-stage renal disease and may contribute to the development of atherosclerotic complications in these patients. This study was
performed in hypertensive patients with mild to moderate impairment of renal
function to investigate at what stage of renal failure abnormalities of glucose
metabolism develop and whether these abnormalities are associated with increased prevalence of cardiovascular events. In 321 untreated essential hypertensive patients recruited at a hypertension clinic and 92 matched normotensive controls we assessed the renal function by measurement of 24-hour creatinine clearance, urinary protein excretion, and microalbuminuria, the cardiovascular status by clinical and laboratory tests, and measured plasma glucose,
insulin, and C-peptide levels at fast and following a 75-g oral glucose tolerance
test (OGTT). Patients with creatinine clearance less than 30 ml/min/1.73 m2,
severe hypertension, obesity, and diabetes or family history of diabetes were
excluded. Hypertensive patients had significantly greater fasting plasma insulin and C-peptide levels and glucose and insulin responses to OGTT as compared to normotensive controls. In 116 of 321 hypertensive patients we found
creatinine clearance less than 90 ml/min/1.73 m2 which was caused by hypertensive nephrosclerosis. Analysis of patients with different degree of renal function impairment demonstrated increased plasma glucose response to OGTT,
hyperinsulinemia, and decreased fasting glucose/insulin ratio only in those
patients with creatinine clearance less than 50 ml/min/1.73 m2.
Parameters of glucose metabolism were not correlated with creatinine clearance and microalbuminuria. Prevalence of atherosclerotic cardiovascular
events was significantly related to reduction of creatinine clearance, but parameters of glucose metabolism were comparable in patients with and without
evidence of atherosclerotic damage. In conclusion, in patients with hypertensive nephrosclerosis and mild renal failure, abnormalities of glucose metabolism become evident only when creatinine clearance is less than 50 ml/min/
1.73 m2 and do not seem to be related to microalbuminuria and cardiovascular complications.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
Clinical Nephrology: miscellaneous
ABNORMALITIES OF COAGULATION IN HYPERTENSIVE PATIENTS
WITH EARLY RENAL FAILURE: ASSOCIATION WITH CARDIOVASCULAR
EVENTS.
C. Catena, L. Zingaro, D. Casaccio, S. De Marchi, L.A. Sechi.
Hypertension Unit, Internal Medicine, DPMSC, University of Udine, Udine,
Italy.
A prothrombotic state has been demonstrated in uremic patients undergoing
conservative treatment or dialysis and could act as a cardiovascular risk factor in these patients. This study was performed in hypertensive patients with
mild to moderate impairment of renal function to investigate at what stage of
renal failure abnormalities of the coagulation system develop and whether
these abnormalities are associated with increased prevalence of cardiovascular events in these patients. Renal function was assessed in 382 essential hypertensive patients by measurement of 24-hour creatinine clearance (Cr Cl), urinary protein excretion, and microalbuminuria. In these patients we assessed
the prevalence of atherosclerotic disease and evaluated the overall function of
the coagulation system by measurement of platelet counts, PT, PTT, antithrombin
III, fibrinogen, D-dimer, and prothrombin fragment 1+2 (F1+2). Mild renal
failure, as indicated by Cr Cl from 30 to 89 ml/min/1.73 m2 of body surface
area, was found in 168 of 382 patients.Age, blood pressure, duration of hypertension, and plasma concentrations of fibrinogen, D-dimer, and F1+2 were
significantly greater in hypertensive patients with mild renal failure than in
those with normal renal function and this difference persisted after adjustment
for potential confounders. Cr Cl was significantly and inversely correlated
with plasma fibrinogen (rho=0.260, P<0.001), D-dimer (rho=0.334, P<0.001),
and F1+2 (rho=0.196, P<0.001) levels. Multiple regression analysis showed
that plasma fibrinogen (F=6.31, P=0.009) and D-dimer (F=9.347, P=0.003) levels were correlated to renal function independent of age, blood pressure, duration of hypertension, triglyceride levels, urinary protein excretion, and erythrocyte sedimentation rate. The prevalence of coronary artery, cerebrovascular,
and peripheral vascular disease was significantly greater in patients with mild
renal failure than in those with normal renal function. Elevated levels of fibrinogen and D-dimer were associated with the presence of atherosclerotic
disease independent of renal function and other risk factors. Thus, increased
plasma levels of fibrinogen, D-dimer, and F1+2 are present in hypertensive
patients with mildly decreased creatinine clearance, suggesting a prothrombotic
state that may contribute to the risk for ahterosclerotic disease at all levels of
renal function.
Abstracts
HAEMOLYTIC UREMIC SYNDROME IN A NEWBORN WITH
METHYLMALONIC ACIDURIA, HOMOCYSTEINEMIA AND ALTERATION
OF VITAMIN B12 METABOLISM
T. De Palo, R.Bellantuono, M.Giordano, F. Palumbo,F. Casino, D.A.Caringella,
M.G. Burattinié, N. Laforgia*, A. Mautone*
UO Nefrologia e dialisi Pediatrica, Ospedale Giovanni XXIII*Sezione di
Neonatologia, Università degli Studi, Bari
The methyl-malonic acidaemiae are a heterogeneous group of diseases caused
by a reduced methylmalonyl-CoA-mutase activity or by alteration of its cofactor (Vit. B12) of which, according to complementation tests, we identify tree
types: Cb1C and Cb1D deficiency with the blockage of adenosylcobalamin and
methylcobalamin synthesis and methyl-malonic acid and homocysteina increasing; Cb1A and Cb1B deficiency, similar to methylmalonyl-CoA-mutase
deficiency; Cb1F deficiency with lisosomial cobalamin altered relapse. We
report on a case of haemolytic uremic syndrome (HUS) in newborn with methyl-malonic aciduria and iperhomocysteinemia caused by Cb1C deficiency.
L.M., 29 days old male, born by spontaneous delivery at the 41st week (3.1 Kg;
Apgar 8-9), presented with arrested growth (3.3 Kg), poor feeding, vomiting
and hepatomegalia. Laboratory results on admission revealed: metabolic acidosis, megaloblastic anaemia (Hb 10.5 %), low platelet count (38,000/ml), LDH
1037 U/l, negative Coomb’s tests, microematuria, microproteinuria, regular
renal function. During the following days, the infant presented diuresis reduction and after 5 days, congestive heart failure, generalised convulsive attack
that needed a sudden transfer to the Intensive Care Unit and mechanic respiration. The diagnosis of HUS, caused by Cb1C deficiency, was made according to
the following results: acute renal failure with severe anaemia (Hb 6.3 %), low
platelet count (10,000/ml), LDH 8800 U/l, hyperomocysteinemia (95,4 mM),
high levels S Cobalamin (930 pg/ml), high urinary metyl-malonic acid (>1000
mMol/MoleCrea) and complementation tests (Cb1C deficiency). The patient
underwent Continuous Veno-Venous Haemodiafiltration (CVVHD) and two
plasmapheresis sessions and was treated with hydroxycobalamin (1mg/die
i.v.) and barbiturics. Thanks to a gradual general conditions improving and to
a restored renal function, we gave up the substitutive treatment and dismissed
the patient with the only oral vitamin therapy (1mg/die). The association between Cb1C deficiency and HUS, extremely rare during infancy, is pathogenically correlated to the high plasmatic levels of homocysteine, an amino-acid
that is able to start a HUS for its endothelium toxicity. The prognosis, both
quoad vitam and for the severe neurological consequence, is usually unfavorable
even with hydroxycobalamin treatment. Despite that, after 6 months follow up,
our patient mantains good renal and neurological function.
RENAL BIOPSY IN THE ELDERLY
J. Buturovic Ponikvar, A. Urbancic, M. Malovrh, R. Ponikvar
Department of Nephrology, University Medical Center Ljubljana,
Slovenia
The aim of our report is to present the technique, safety and
efficacy of ultrasound guided renal biopsy in the elderly.1766
renal biopsies were performed at our Department from January
1990 to December 2000, 212 of them (12 %) in the patients aged
65 years or more (65-85 yrs, mean 71+-4). All biopsies were
performed with the same technique: single operator (nephrologist), real-time ultrasound guidance (ultrasound monitor
Acuson XP/10, Mountain View, CA, USA), 3.5 MHz vector
probe, Biopty gun (Biopty, Radiplast AB, Sweden) and 18-gauge
modified Tru-Cut needles. A minimum of two tissue specimens
were required. The major indications were acute/rapidly progressive renal failure and nephrotic syndrome. All patients with
advanced renal failure were hemodialyzed before the biopsy.
Normal blood pressure, normal hemostatic parameters and
hemoglobin > 100 g/L were required. Ultrasound examination
of the punctured kidney was performed in all patients at least
24/48 hours after the biopsy and according to clinical course
thereafter. Peak serum creatinine ranged from 59-1900 umol/l
before the biopsy (mean 310+-230). In the majority of patients
(194/212-92 %) left kidney was punctured. Only one out of 212
biopsies (0.5 %) was unsuccessful (without renal tissue to establish diagnosis). Number of passes ranged from 2-4 (mean
2.4+-0.7), number of tissue specimens 1-3 (mean 2.1+-0.5). The
number of glomeruli in histologic specimen ranged from 5-31
(mean 16+-7). In 8/212 patients (3.7 %) macrohematuria was
observed after the biopsy, in 5/12 (2.4 %) perirenal hematoma
was detected by ultrasound and in 1/212 (0.5 %) AV fistula
was found by Doppler. No death or nephrectomy occurred as a
consequence of biopsy. Real-time ultrasound guided renal biopsy with Biopty-gun and 18-gauge needle is safe and successful procedure in the elderly, even in the presence of advanced
renal failure.
Nephrology Dialysis Transplantation
Vol. 16 n.6
GLOMERULONEPHRITIS IN THE ELDERLY - DO WE USE RENAL BIOPSY
IN NEPHROTIC SYNDROME AGE OVER 60?
P. Legrady, B. Ivanyi 1,Gy. Abraham, A. Letoha, Z. Ondrik2, E. Kemeny 1,S.
Sonkodi
1st Dept. of. Med., 1Inst. of Histopathology, 2Acute Dialysis Center, University
of Szeged, Faculty of Medicine, Szeged, Hungary
In the last decade the use of renal biopsy has increased resulting more discovery
of glomerulonephritis (GN) even in higher age. It is difficult to interpret the
histological finding in elderly patients because changes are often may related
to the aging. Retrospectively we investigated data of 39 nephrotic patients aged
over 60 divided into two groups. Patients in group A were 60-70 years old at
the time of biopsy (age: 66.1±0.6 yrs, BMI: 29.2±1.2 kg/m2, blood pressure
(BP)syst: 162.6±3 mmHg, BPdiast: 92±1.9 mmHg, duration of nephrosis (DN):
25,5± 15.5 mo; mean±SEM). Patients in group B were over the age of 70 (age:
73.4±0.8 yrs, BMI: 27.1±0.9 kg/m2, BPsyst: 151.6±5 mmHg, BPdiast: 86.2±3,1
mmHg, DN: 10.1±5.2 mo; mean±SEM). The most frequent histological findings
were on the whole of patients the membranous GN (MGN) (33.3%), the focal
segmental glomerulosclerosis (FSGS) (18%), the MGN with FSGS (7.7%), the
renal amyloidosis (AL) (7.7%) and the nodular glomerulosclerosis (7.7%). In
group A the most common findings were MGN (33%), FSGS (29%) and AL
(14.3%). In group B MGN (38.9%) and MGN with FSGS (16.7%) were the most
frequent causes of nephrosis. In group B the frequency of FSGS was 5%. The two
groups didn’t differ significantly in BP, BMI and DN. The only significant
difference was observed in the prevalence of FSGS and MGN. The appearance
of FSGS was significantly higher in group A, meanwhile MGN appeared in
higher proportion in group B. We didn’t find correlation between the cause of
nephrosis and the DN. Positive correlation can be observed between the age and
the cause of nephrotic syndrome (r=0.44, p<0.05). These findings indicate that
renal biopsy is the useful tool in elderly nephrotics in order to estimate the exact
dignosis concluding adequat therapy. Renal biopsy should never be omited on
grounds of age alone.
2001
A109
Abstracts
Clinical Nephrology: miscellaneous
EMAGEL® VS ALBUMIN IN THE TREATMENT OF
HYPOALBUMINEMIC PATIENTS WITH REFRACTORY
EDEMA
T Rampino, R Tiboldo, P Malvezzi, S Gilardi, A Ranghino, A
Massoglia, C Guidetti, M Maggio, A Dal Canton
Nephrology Dialysis and Transplant Unit, University and IRCCS
Policlinico San Matteo, Pavia, Italy
A low plasma albumin concentration and the ensuing low plasma
oncotic pressure play a pathogenic role in the development of
salt retention in patients with nephrotic syndrome (NS) and
cirrhosis (C). Therefore, in such patients, edema refractory to
salt restriction and diuretic treatment is currently treated with
i.v. albumin (Alb) infusion. To investigate whether Alb can be
substituted for less expensive plasma expander, we studied 27
hypoalbuminemic patients with NS (n 18) or C (n 9). 19 patients
received infusion of Alb plus diuretic (furosemide and/or
spironolactone and/or thiazide) (D) and 8 patients received
Emagel® (E) plus D. Age, sex, blood pressure (BP), plasma
urea, creatinine clearance, plasma Alb, proteinuria and diuretic
dose were comparable in the two groups. Diuresis, body weight
(BW), BP, biochemical tests of renal and liver function were
measured daily. At the end of the study weight loss (expressed
as *% of basal weight), time to reach the lowest BW (Tweight)
and total cost of the treatment were calculated. Linear regression analysis and Cox model were used for statistical analysis.
Neither of the treatments changed significantly BP, renal and
liver biochemical indices. *% BW and Tweight were not significantly different into two groups (average *% BW mean 6±4 in A
vs 7±4 in E, p<0.8) (Tweight median 7 day in A vs 5 day in E,
p<0.4). Tweight correlated with diuretic dose and diuresis
(p<0.001), but not with plasma expander type. The total cost
treatment was significantly higher in patients treated with A
than in patients treated with E (Euro 375.8±207.9 vs 77.3±60.7,
p<0.001). These results demonstrate that Emagel® can substitute albumin in the treatment of refractory edema in
hypoalbuminemic patients with a much more favorable cost/
benefit ratio.
TUBERCULOSIS IN PATIENTS WITH CHRONIC RENAL FAILURE
J Peltier, J Stirnemann, B Viron, M Touam, F Martinez, C Jacquot, G Deray, J
Rossert
Assitance Publique-Hôpitaux de Paris, Paris, France
We performed a retrospective study of all patients (pts) with end stage renal
failure or with creatinine clearance below 20 mL/min who were treated for
tuberculosis (TB) in six departments of nephrology, between January 1995 and
December 1999. 40 pts were included. Their mean age was 60.4±2.4, the male/
female ratio was 26/14, and 60% of them were not from Western Europe. At the
time of diagnosis, 90% of pts complained of fatigue, weight loss or anorexia,
67% had fever, and CRP was above 30 mg/L in 77%. Only 5% of pts had pulmonary TB, while 23% had localized extrapulmonary TB (peritoneum: 2, lymph
nodes: 3, liver: 1, epididymis: 1, digestive tract: 1, pleura: 1), and 72% had
disseminated TB. TB was assertained by isolation of M. tuberculosis in 12 pts
(positive smear: 2) and by histological evidence of granuloma in 10 (lymph
node: 5, liver: 4, testis: 1, pleura: 1), while 20 were treated without bacteriological or histological evidence of TB. All 27 cultures of pleural or peritoneal fluids
were negative. Mortality rate was 37.5%, and it was directly related to TB in
20% of cases. All pts who died from TB died within two months after starting
chemotherapy. They were older than pts who did not die from TB (67.5±17
year-old versus 49.5±14, p<0.05), and had more often diffuse TB (75% versus
19%, p<0.005).
When compared with pts with positive mycobacterial cultures, pts with positive biopsies tended to be younger (mean age 56.5±4.4 versus 65.5±3.2), and
were more frequently immigrants (100% versus 50%, p<0.02). They had less
often pulmonary TB (25% versus 92%, p<0.005), while tuberculous lymphadenitis was more frequent (62.5% versus 16.5%, p<0.05). Finally, they tended to
have a better prognosis (TB-related mortality: 0% versus 33%).
When compared with pts with bacteriological or histological evidence of TB,
pts treated without definite proof of TB were more frequently on dialysis (95%
versus 70%, p<0.05). They had less often pulmonary TB (20% versus 70%, p<0.05)
and more serositis (19 versus 8, p<0.05). Mortality secondary to TB was similar in these 2 groups (20% in each group).
A110
COSTSANDSTANDARDISATIONOFURINALYSISINANEPHROLOGICAL
LABORATORY
Gai M, Mezza E, Bechis F, Iacuzzo C, Vischi M, Quaglia M, Cantaluppi V,
Burdese M, Jeantet A, Piccoli GB, Lanfranco G
Cattedra di Nefrologia, University of Torino – Italy
Urinalysis is fundamental in the general clinical practice and particularly in
the nephrological context. Aim of this study was to analyse the procedure used
in our laboratory with the goal of standardization of urinalysis in a
nephrological laboratory.
In the setting under study 20-40 urine samples are processed every day, 5-20
from the nephrology ward, 2-10 from the day hospital, 5-10 from the transplantation ward, 2-4 from other settings. Since a computerised registration occurs
(1992), 32500 urinalysis are recorded. Urinary sediment is processed by laboratory technicians and read either by a nephrologist or by a biologist. Sample
for urinary sediment is collected from the first-morning urine and examined
within 4 hours. The urine sample is tested with multireactive stripe AMES
MILES BAYER N-Multistick 10 SG. The sensitivity is high for albumin (threshold 250 mg/dL) but low for other proteins. A second method (Pyrogallol RedSDS) is emplojed to determine proteinuria (mg/dL) and proteinuria/
creatininuria ratio (mg/mg): the results are superimposable to the 24 hours
proteinuria. Afterwards, we centrifugate a urine sample of 10 mL for 10 minutes at 1500 RPM, then we collect from the residual volume, after resuspension,
a sample of 20 microliters for microscopic analysis. The slide is analysed by a
phase-contrast microscopy to better evidence the hyaline casts and the ghosterythrocytes: the first analysis is performed at lower zoom (100x) on an adequate number of fields (10-20), for a global qualitative assessment of the particles and a quantitative assessment of the casts. The second analysis is performed at higher zoom (400x) for a more accurate evaluation of the shape of
cellular elements and of the composition and size of casts.
The time expenditure is 10 minutes for the entire procedure; the most time consuming phase is urinary sediment analysis, requiring 6 minutes per slide by a
skilled operator. The National Healt Service pays 3.5 Euro per test covering
materials (1 Euro) and time of the operators (2.5 Euro).
COMPARISON BETWEEN TRADITIONAL ANALYSIS OF URINARY SEDIMENT AND AUTOMATED LECTURE BY UF-50 FLOW CYTOMETER
(SYSMEX)
Gai M, Mezza E, Cantaluppi V, Bechis F, Iacuzzo C, Quaglia M, Vischi M,
Burdese M, Jeantet A, Piccoli GB, Lanfranco G, Piccoli G
Cattedra di Nefrologia, University of Torino – Italy
Presently, the urinary sediment analysis is performed in at least two contexts:
screening test, quick and cheap, and sophisticated “small renal biopsy”, limited to a nephrological setting. Aim of this work was comparison between data
of urinary sediment lecture by using traditional microscopy and by using UF50 (SYSMEX) automated urinalysis.
300 urinary sediments were tested by UF-50 (SYSMEX) flow cytometer and
under phase-contrast microscopy (100x, 400x), on 10-20 fields. We compared
data for the following parameters: erythrocytes, leukocytes, casts, bacteria and
crystals. The statistical analysis was performed by SPSS. The comparison among
classes was made by using the χ2 test (Pearson) and K Cohen coefficient, to
assess concordance of results. Concordance was higher for erythrocytes and
leukocytes (84% and 88.6% respectively, p=0.000, K=0.66; p=0.000, K=0.72),
lower for bacteria (52.9% p=0.000, K= 0.23). As compared with traditional
readings, UF 50 performed better in the case of high number of erythrocytes or
leukocytes and bacteria. Crystals and casts were better detected by phase-contrast microscopy since UF-50 (SYSMEX) overestimated these elements (p=0.43,
K=0.04 and p=0.08, K=0.07). In particular for casts the UF-50 (SYSMEX) realizes a percentage of 40% of false positives, probably due to mucus interference.
In conclusion, combining the automated and traditional urinalysis, starting
with erythrocyte and leukocyte count by UF-50 (SYSMEX), with high sensitivity, but lower specificity, for formed elements, followed by traditional microscopy, more accurate in finding out morphological aspects and casts research,
maybe a time sparing policy allowing us not to loose the advantages of a morphological reading, limiting this time consuming procedure to cases selected
by the automated procedure.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
Clinical Nephrology: miscellaneous
TYPING OF PROTEINURIA BY IMMUNOFIXATION
Gai M, Bechis F, Iacuzzo C, Bergamo D, Quaglia M, Cantaluppi
V, Burdese M, Mezza E, Jeantet A, Piccoli GB, Lanfranco G.
Cattedra di Nefrologia, University of Torino – Italy
Anatomic and functional alterations of glomerular filter leads
to an increase of excretion of proteins with mw >67 kD. This
glomerular proteinuria can be further divided in two forms:
selective (presence of albumin and transferrin) or non-selective
(presence of proteins with mw >100 kD). By contrast, tubular
alterations leads to detection in urine samples of proteins with
mw<50 kD. In the so-called mixed types of proteinuria characterized by both glomerular and tubular damage, it is relevant to
search proteins with mw <23 because they are often associated
with a worse outcome towards chronic renal failure.
The aim of this study is the comparison of data obtained from
80 urine samples of different patients by using two analytical
methods: SDS-AGE Hydragel Proteinuria (SEBIA srl, Florence,
Italy) and plate immunofixation (CSI-Nefro, BIOCI, Turin, Italy).
In the SDS-AGE method proteins of different molecular weight
are separated by agarose gel-electrophoresis using SDS (sodium dodecyl-sulphate) as detergent. In the plate
immunofixation method proteins are detected by selective binding of specific polyclonal antibodies directed to Retinol Binding
Protein, transferrin, IgG and α2-macroglobulin.
In 71 on 80 cases analyzed (88.75%) the two different techniques showed similar results in evaluation of proteinuria due
to several nephropaties. In 9 cases (11.25%) both techniques
showed pathologic proteinuria, but only the immunofixation
assay allowed the specific detection of 4 cases of mixed noncomplete proteinuria and 5 cases of complete tubular proteinuria.
In conclusion our findings show that plate immunofixation assay offers a better evaluation of tubular proteinuria with a time
of incubation of 4 hours and with relative low costs (4 Euro)
compared to SDS-AGE method (8 Euro). Moreover this assay
can be simply established also in small laboratories and
Nephrologic Units.
Abstracts
TRACE ELEMENTS AND MARKERS OF OXIDATIVE STRESS
IN HEMODIALYSED PATIENTS (HD)
Varga Zs., Dombovári J*., Mátyus J., Kárpáti I., Seres I., Papp
L*., Kakuk Gy.
University of Debrecen, Ist Dept of Medicine, *Institute of Analytical Chemistry, Debrecen Hungary
HD therapy has been reported to interfere with the trace element
status in the body. Some of these trace elements are involved in
formation (Xanthine oxidase, XO) or in removal of oxygen-derived-radicals (superoxide dismutase, SOD).
We determined some trace elements (Mn, Cu, Zn and Mo), enzyme activities (XO, SOD), and antioxidant status of HD patients (TBAR, glutathion, and Vitamin E levels in plasma and
O2- production by resting neutrophils) in case of 40 HD patients. They were divided to five subgroups: cardiovascular
(CAD), diabetes mellitus (DM-I), glomerulonephrosis (GN), TIN
and unknown origin (UO).
Mn
Cu
Zn
Mo
TBAR
O2XO
SOD
Glut
Vit E
Control
3.86±1.21
802±122
843±302
0.91±0.21
0.79±0.53
0.25±0.13
0.35±0.08
35.2±12.4
4.55±1.34
48.3±27
HD Mean
1.11±1.46*
1227±242*
1006±273
6.94±3.15*
1.09±0.39*
0.35±0.18
0.36±0.08
52±17*
1.73±0.33*
39.6±18.6*
CAD
0.44
1317
639
7.38
1.62
0.39
0.3
45.6
0.92
24.7
DM-I
0.86
1129
1064
4.55
0.92
0.27
0.41
59.8
0.98
51.0
GN
1.02
1217
707
7.3
1.32
0.25
0.33
65
1.25
32.8
TIN
1.11
1231 1239
943 1622
8.43
0.86
0.27
0.32
63.3
1.98
36.2
UO
2.11
7.04
0.72
0.29
0.33
51.6
2.02
26.2
*p<0.05.Bold numbers show the main differences in HD subgroups.
Positive correlation was found between concentrations of Mn
and Zn and SOD activity (0.77 and 0.35, respectively). In conclusion, trace element status of HD patients differs significantly
from that of controls and it show significant connection to XO
and SOD activity of plasma.
Research is granted by OTKA (T 22739).
PREVALENCE AND RISK FACTORS OF RENAL ARTERY STENOSIS IN PATIENTS UNDERGOING CARDIAC CATHETERIZATION FOR SUSPECTED
CORONARY ARTERY DISEASE
Weber-Mzell D, Kotanko P, Schumacher M, Klein W, Skrabal F
Krankenhaus der Barmherzigen Brüder, Graz, Austria, University Clinic
Internal Medicine, Department Clinical Cardiology, Graz, Austria
HYPERHOMOCYSTAEMIA (HHC) IN FOLIC ACID (FA) SUPPLEMENTED
HAEMODIALYSIS(HD)PATIENTSANDPOLYMORPHISMOFMETHYLENTETRAHYDROFOLATE REDUCTASE (MTHFR) ENZYME.
Kárpáti I, Balla J,Újhelyi L, Ben T, Mátyus J, Varga Zs, Muszbek L*, Kakuk G.
Ist Department of Medicine, *MKBPI, Health and Science Centre, University of
Debrecen, Hungary
The prevalence of significant renal artery stenosis (RAS) may be increased in
patients with clinical signs and symptoms of coronary artery disease (CAD).
The aims of this study were to determine the prevalence of RAS and associated
risk factors in an unselected cohort of patients undergoing cardiac catheterization for suspected CAD.
One hundred and seventy-seven eligible consecutive patients (62 females, 115
males) referred for cardiac catherization were studied. A serum creatinine
concentration > 2.0 mg/dl was an exclusion criterion. After left ventriculography, abdominal aortography was performed to screen for RAS. Significant
CAD and RAS were defined as a luminal narrowing of > 50%. Multivariate
logistic regression was used to define a set of variables predictive for RAS. The
diagnostic performance of clinical and catheterization-derived variables was
further tested by means of receiver operating characteristics (ROC) analysis.
In 110 patients (62%) significant CAD and in a total of 19 patients (11%) significant RAS were detected. In 2 subjects with significant RAS no CAD was found.
As compared to patients without RAS subjects with RAS were older (67+/-8 vs.
61+/-11 years, p=0.004), had higher systolic blood pressure (150+/-15 vs. 138+/
-20 mmHg; p=0.005) and a reduced creatinine clearance (61+/-16 vs. 80+/-22
ml/min). Stenosis of the LAD, CX and RCA were more frequent in patients with
significant RAS (p<0.002). The frequency of RAS increased with the number of
stenotic coronary vessels (Chi2=30.6, p<0.001, 4d.f.) and more stenotic coronary arteries were observed in the RAS group (3.8+/-1.2 vs. 2.3+/-1.3; p<0.001).
In subjects with > 2 coronary artery lesions ROC analysis demonstrated a sensitivity of 0.842 and a specificity of 0.766 for the diagnosis of RAS. The groups
with or without RAS did not differ with respect to gender, lipids, proteinuria,
fasting blood glucose and glycosylated hemoglobin (HbA1c).
RAS is prevalent in a significant proportion of patients undergoing cardiac
catheteriszation for suspected CAD. Patients with > 2 diseased coronary arteries, a reduced creatinine clearance and an elevated systolic blood pressure
should be screened for the presence of RAS by abdominal aortography after left
ventriculography.
It is known that hyperhomocysteinaemia (HHC) is an independent risk factor
of atherosclerosis. In HD patients the frequency of HHC is much greater than in
the normal populations. The aims of our examination were to determine the
frequency of HHC and polymorphism of MTHFR in our HD patients being on
folic acid supplementation, and to compare the total homocystein (tHCy) levels
to concentrations of folic acid and Vitamin B12 in plasma, and to MTHFR
alleles. 120 HD patients were involved in the study.
It was found that in our HD patients who are under continuous folic acid supplementation the mean level of HCy were 16.8±7.2 uM, of FA was 24.2±22.6 ug/L,
and of B12 was 887±594 ng/L. The HHC (HCy>20 uM) was only found in 22.3
% of all patients. Interestingly, a closed negative connection between levels of
HCy, FA and B12 vitamin were observed in spite of the supplementation. When
HCy was<15 uM (53.4 % of total), the FA was 29.2±24.7 ug/L and the B12 was
1151±785 ng/L, when the HCy was >30 uM (9.7 % of total) the FA was 10.4±12.1
ug/L, and B12 was 326±107 ng/L In HD patients the frequency of the homozygous form of MTHFR (T/T) was the same then in the normal population (13 %
vs. 12%). However, in patients with HHC (HCy> 30 uM) the frequency of homozygous form of MTHFR was about 30 %. The HCy levels and MTHFR polymorphism showed closed connection: in wild type group(C/C) the HCy was
14±7 uM, in heterozygous group (C/T) HCy was 17.2±6.2 uM, and in homozygous group (T/T) HCy was 21±19 uM.
In conclusion, the long-term folic acid supplementation decreased the mean
level of HCy, the frequency of HHC in HD patients. However, in folic acid resistant group HCy was elevated, and at the same time low levels of FA and B12
were observed.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
A111
Abstracts
Clinical Nephrology: miscellaneous
NONSELECTIVE BETA-ADRENERGIC BLOCKADE AUGMENTS FASTING HYPERKALEMIA IN HEMODIALYSIS
PATIENTS
M Nowicki, J Miszczak-Kuban
Department of Nephrology and Dialysis, “Polish Mother’s Memorial Hospital” Research Institute, Lodz, Poland
Fasting hyperkalemia in patients with end-stage renal failure is
a well documented phenomenon. The increase of serum potassium during fasting may be dependent on the decreased insulin
secretion but possibly also on changes in the sympathetic activity.
Twelve anuric, long-term (6.4±2.7 years; mean±SD) hemodialysis patients underwent three periods of 18-hour fasting (from 6
p.m. to 12 a.m.). At the beginning of each fasting period a single
dose of a nonselective β-blocker nadolol (80 mg) or β1-selective
blocker betaxolol (20 mg) or placebo were given in a random
order and in a blinded fashion. The wash-out period was 7 days.
The mean decrease of blood pressure was similar after nadolol
and betaxolol (18±10 vs 18±11 mmHg) as was a decrease in
heart rate (20±3 and 19±7, respectively). Serum potassium was
not different before each of the fasting periods. The increase of
serum potassium during fasting was highly significant in each
case. The mean increase of serum potassium was 1,2±0.4 mmol/
l after nadolol, 1,0±0.4 after betaxolol and 0.6±0.6 after placebo.
This effect was significantly larger after nadolol than after placebo (p=0.01) but such relation was not significant with respect
to betaxolol (p=0.4). Serum insulin as well as glucose decreased
significantly and to the similar extend during each fasting period. Plasma aldosterone was unchanged.
Nonselective β-adrenergic blockade increases the hyperkalemic
effect of fasting in hemodialysis patients.
TREATMENT OF ATYPICAL RECURRENT HAEMOLYTIC
URAEMIC SYNDROME (HUS) - 17-YEARS EXPERIENCE.
T. Šuláková, H. Ptoszková, B. Blazek, L. Mrhacová, J. Pták, J.
Slaný
Dept. of Paediatrics, University Hospital Ostrava, Czech Rep.
The authors refer to 4 cases of atypical HUS with a recurrent or
relapsing course of disease. The patients are 3 boys and 1 girl
from one Moravian region aged of 13, 21, 22 and 23 years. The
periods of the follow-up observations are 11, 12, 15 and 17
years (mean 13.75 years). The patients had the first episode of
illness at the age of 10 months, 4, 6 and 10 years, respectively.
They had 4, 7, 8 and 15 attacks of the disease (mean 8.5 attacks
for 1 patient). Prodromal features were nonspecific including
vomiting, stomach pain, infection of upper respiratory tract
and, in 1 patient, diarrhoea. Severe haemolytic anaemia and
trombocytopenia preceded the first episode of HUS in 3 children. Serum complement levels were normal in all patients. The
signs of central nervous system involvement appeared temporarily in 2 patients. Renal biopsy was performed in 1 patient
with the histological finding of vascular trombotic
microangiopathy. All patients were treated symptomatically,
with corticosteroids and fresh frozen plasma (FFP), but the effect of the therapy was only transitive. From 1994 to 1999 plasma
exchange (PE) therapy was included in the therapeutic schedule
(6, 8, 16 and 38 PE, mean 17 PE per 1 patient). Therapeutic PE
always led to normalisation of haematological and biochemical
parameters. After PE 3 patients had relapses of illness 6, 14 and
49 months after PE therapy, respectively.
CONCLUSION: Fresh frozen plasma therapy has only temporarily improved the clinical situation in our patients with atypical recurrent HUS. Plasma exchange therapy was associated
with the significantly prolonged remission period, but did not
prevent further relapses of the disease. GFR of our patients
remains in normal range after plasma exchange.
A112
FUMONOSIN (FB1) AND SPHINGANINE/SPHINGOSINE RATIO AMONG
OTHER PARAMETERS AS POTENTIAL PATHOGENIC RISK FACTORS OF
NEUROLOGIC DEFICITS IN EGYPTIAN CHILDREN AND ADULT RENAL
PATIENTS
MG Saadi, FI Fadel*, EM Abdalla#, NA Hassan+ and SM Ibrahim
The departments of internal medicine and nephrology, pediatric nephrology*,
ophthalmology+; Cairo University ; and mycotoxicology laboratory: National
Research Institute# ; Egypt.
Neurologic deficits are common problems in renal patients with or without
impaired kidney functions. Various pathogenic factors were blamed for these
deficits. FB1 an occasional neurotoxic mycotoxin was shown to be responsible
for neurologic disturbances in horses, by disturbing the sphingolipid metabolism. It was detected as a contaminant among several food stuffs in Egypt, but
was not studied as a risk factor in humans. In this study visual evoked response
(VER) was used as an indicator of neurologic dysfunction in 40 CRF patients on
regular dialysis treatment ( 20 children and 20 adults ), 40 patients with different glomerulopathies (GN) having normal or impaired kidney functions (20
children and 20 adults) and 10 healthy controls. They were investigated for the
serum FB1, sphinganine, sphingosine, calcium, phosphorus, parathyroid hormone (PTH), aluminium (Al), urea, creatinine, blood gases and hemoglobin
percent. FB1 associated with an elevation of the sphinganine/sphingosine ratio
was encountered in 12/40 CRF patients and 12/40 GN patients and none of the
controls. Of the GN 9/40 had delayed VER, and 3 of these 9 had positive FB1.
Of the CRF 13/40 had delayed VER This delay was detected in 8/12 cases with
positive FB1, and in 10/19 cases with more than double the high normal PTH
and in13/34 with Al more than 20 ug/dl. Al was the sole of these risk factors
in 2/13 with delayed VER, but neither high PTH nor positive FB1 was encountered solely in any of these cases. VER showed no correlation with the serum
creatinine, Hb% and pH. There was no statistical difference between the results
of these risk factors among the children and adults of each group.
We can conclude that long duration of Al intoxication is an actual risk factor
responsible for neurologic deficit in the CRF group, which may be aggravated
by a high PTH an/or a positive FB1.
SELECTIVITY INDEX (SI), URINARY RETINOL BINDING
PROTEIN (RBP) AND SERUM TGF-beta AS PREDICTORS OF
STEROID RESPONSIVENESS IN PEDIATRIC NEPHROTIC
SYNDROME (NS)
R El-Baroudy, FI Fadel, AM Hagras, SM El-Gohary*, SM
Mekhemer*, NM Abdel-Wahed, NA El-Marakby and MG Saadi#
The departments of pediatrics, clinical pathology* and internal
medicine and nephrology#, Cairo University, Egypt.
Response to treatment of NS in children can be determined by
pathologic diagnosis. Several other non-invasive tests have been
tried to predict steroid responsiveness.
In this work leakage of different proteins from the glomerular
basement membrane denoted by SI using immunoglobulin G
and transferrin ratio, and in association with tubular dysfunction denoted by urinary RBP, as well as TGF-beta as a marker of
cytokine mediation of the inflammatory reaction were tested in
40 children with NS as well as 10 healthy normal children. The
patients were 28 steroid responsive (group I) and 12 steroid
resistant (group II) NS.
SI showed 100 % specificity and 43 % sensitivity in detecting
steroid responsiveness where 43 % of gp I had SI < 0.18 (range
0.05 – 0.43), and all patients of gp II had SI > 0.18 (range 0.18 –
0.93). Meanwhile urinary RBP was < 1.20 mg/L in gp I and >
2.54 mg/L in gp II, with no overlap indicating more predictivity.
Furthermore TGF-beta was significantly higher than controls in
both groups p < 0.001, and lower in gp I (93.84 + 9.09 g/mmol)
than gp II (126.33 + 13.26 g/mmol) p < 0.001. Values > 105 g/
mmol are suggestive of steroid resistance.
These studied parameters may be used to expect response to
treatment and indicate early biopsy for pathologic diagnosis
and combined immunosuppresive regimens in those suspected
to be steroid resistant.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
Clinical Nephrology: miscellaneous
Abstracts
LONGITUDINAL ANALYSIS OF QUALITY OF LIFE (QOL) IN PATIENS WITH
CHRONIC RENAL FAILURE (CRF).
F. Baiardi1, R. Cocchi2, A. Sturani2, A. Fabbri2, E. Degli Esposti3, G. Emiliani2,
G. Valpiani1, M. Fusaroli 2.
1
CliCon Health, Economics and Outcome Research, Ravenna, Italy, 2Nephrology
and Dialysis Department, Ravenna Health Service, 3Outcome research Unit,
Asl, Ravenna, Italy
THE EFFECT OF AMLODIPIN AND DOXAZOSIN ON INSULIN RESISTANCE IN CHRONIC RENAL FAILURE
A. Yildiz1, M. Hursit1, S.M. Kayacan 1, A.V. Celik1, H. Yazici1, K.
Karsidag2, E. Ark1
Istanbul School of Medicine, Dept. of Internal Medicine, Div. of
Nephrology1 and Diabetology2, Istanbul, Turkey
Information on the longitudinal measurements of QoL in patients with CRF is
lacking. Therefore, we performed a longitudinal study aiming to evaluate the
impact of CRF and its treatment methods on QoL of patients undergoing conservative treatment (CT), hemodialysis (HD), peritoneal dialysis (PD) and transplantation (TP) of the province of Ravenna.
The QoL assessment was measured by means of SF-36. The questionnaire was
administrated by periodic personal interviews to all patients with CRF on
dialysis, with renal transplatation and on conservative therapy in care of the
Renal Unit of the Ravenna Hospital (Italy) since September 1997 to April 2000.
The physical and the mental components of the eight scales of the SF-36 were
combined into a physical (PCS) and a mental (MCS) component summary score.
Data were performed using a multivariate analysis of variance (Generalised
Linear Model for repeated measurements) with the SPSS-Windows version
10.0 (SPSS Inc., Chicago, USA).
225 patients performed at least two questionnaires during the study period
(mean time elapsing between the two administrations: 17.32±6.57 months), 28
were on CT, 119 on HD, 17 on PD, 30 on TP and 31 switched treatment between
the first and the second administration.
The type of treatment, Hb and serum creatinine levels did not influence significantly QoL score. A significant, negative correlation was found between age
and PCS and MCS scores (p<0.001 for both). Diabetes influenced negatively the
PCS score (p<0.05).
A general, significant worsening was observed for both PCS (p<0.001) and
MCS (p<0.05) scales at the second relevation step. In particular, after adjustement
for case mix (mean age and Hb level, comorbidity), HD patients showed the
heaviest deterioration both for PCS and MCS (p<0.05).
Contrary to the results of other studies, where the physical score tended to
decrease over time while the mental score tended to remain stable, our patients
exhibited a deterioration in the overall QoL (both physical and mental).
Insulin resistance (IR) in chronic renal failure (CRF) is well-known.
The beneficial effects of doxazosin (D) on IR have been reported
in patients with essential hypertension. In this randomized-controlled study, we aimed to compare the effect of D and amlodipin
(A) on IR in patients with CRF. Fifteen patients with CRF (M/F:
5/10, mean age: 46±13 years) and 9 controls (M/F:3/6, mean
age: 35±8 years) were included. Patients and controls had no
family history of diabetes mellitus. Homeostasis Model Assessment (HOMA) was calculated as a marker of IR. Patients were
grouped randomly to D (n:8;2-4mg/day) and A (n:7;5-10mg/
day) arms. Baseline biochemical analysis (fasting serum glucose, BUN, creatinin, uric acid, cholesterol and cholesterol subgroups) and parameters related with insulin metabolism (insulin, C-peptid, HOMA) were similar between A and D groups.
There was no difference in age, gender and body mass index
among study groups. The follow-up time was 12 week.
Patients with CRF has higher HOMA (1.83±0.55 vs 1.00±0.36,
p=0.001), fasting insulin (8.06±1.98 vs 4.46±1.31 IU/l, p<0.001)
and serum triglyceride levels (197±136 vs 112±67 mg/dl,
p=0.04) as compared to control. Serum HDL-cholesterol levels
was significantly lower in patients with CRF than controls (40±10
vs 57±14 mg/dl, p=0.02). HOMA significantly decrease after D
(1.91±0.45 vs 1.41±0.21, p=0.02), however no difference was
found after A. Also, fasting insulin levels were decreased after
12-week D therapy from 8.17±1.22 vs 6.58±0.84 IU/l, p=0.02),
but not change was seen after A. Lipid parameters did not
significantly change during study period in two groups. No
adverse effect was observed during the 12-week period in study
groups.
In conclusion, D has an effect on IR in patients with CRF, whereas
A has no effect. This may be advantage in the treatment of
hypertension of this group of patients for preventing some longterm complication of IR.
FIRST RESULTS OF INTERACTIVE COMPUTER ASSISTED
TEACHING IN NEPHROLOGY.
Burdese M, Quaglia M, Bergamo D, Garofletti Y, Martino B,
Mezza E, Jeantet A, Segoloni GP, Piccoli GB.
Chair of Nephrology, University of Torino - Italy
The new European organization of the Medical School and the
increased number of lessons lead to a revision of our teaching
approach. A pilot program of computer assisted interactive
teaching in Nephrology was stared in the University of Torino,
Italy. Teaching of Nephrology occurs during the 4th year of Medical School and consists of 21 hours of formal lessons, in 10
hours/student of interactive lessons in small groups (20-30)
and in optional lessons, courses and seminars. Computer assisted teaching with televoters was performed during interactive teaching (100 hours) and in 6/11 optional seminars or courses
(20 hours). Time required for preparing the computerized interface (slide show, clinical cases, questions and answers for the
televoters) ranged from 8 to 10,5 hours for each subject. Student
opinions, gathered by an anonymous questionnaire (103 students: 24.2% males, 75.8% females, mean age 22,3 years), were
positive: the average score was 8.24/10, range 6/10-10/10.
62% of the students suggest to extend this experience to selected
University courses, 38% to all the courses. The mean advantages were the check of knowledge in real time (86%) and the
anonymous participation to the discussion (61%); no drawback was reported by 65%, time for answering was too short for
29%. In conclusion: student satisfaction and time savings for
the teachers, together with the advantages of an easy updating
of the lessons are the grounds for further extending computer
assisted teaching in Nephrology and in other fields of Internal
Medicine.
Nephrology Dialysis Transplantation
Vol. 16 n.6
2001
A113