Letters
2522
argued that the reduction of proteinuria only reflected alterations of GFR (89 + 29 versus 78 + 28 ml/min, mean±SD,
P = n.s.). To objectify our findings a fractional protein clearance (proteinuria/creatinine clearance ratio) was calculated
which significantly decreased during the treatment period
(0.08+0.05 versus 0.05±0.04 mg/ml/min, /><0.04]. This
indicates that the amelioration of urinary protein excretion
was not directly related to changes of GFR. It could also be
argued that the decrease of proteinuria may be due to a
better diuretic-induced control of blood pressure or reduction
of extracellular fluid volume. However, in our patients we
found no correlation between the fall of proteinuria and
decline of blood pressure (R = 0.32, P = n.s.) or body weight
(R=0.09, P = n.s.). It is also unlikely that reduction of
proteinuria might be caused by a partial recovery of the
glomerular disease since renal disease had been controlled
for more than 1 year in the majority of patients and mainly
nephropathies with a low incidence of spontaneous recovery
were included. Furthermore we wish to state that no changes,
even in dosage, were made in the immunosuppressive drug
regime of kidney-graft recipients, that none of the other
patients received any immunosuppressive agents and that
angiotensin-converting-enzyme inhibitors were not administered. A possible antiproteinuric effect due to calciumchannel blockers is also unlikely because therapy was neither
initiated nor altered in dosage in pretreated patients.
Although we cannot offer an explanation for the observed
decrease of proteinuria, our data would confirm the findings
of a previous clinical study which showed that proteinuria
was reduced in 42% of nephrotic patients treated with
torasemide as monotherapy [2].
Division of Nephrology and Dialysis
Department of Medicine III
University of Vienna, 1090 Vienna
Austria
M. Franz
S. Banyai-Falger
O. Traindl
R. Klauser
J. Kovarik
E. Pohanka
1. Dunn CJ, Fitton A, Brogden RN. Torasemide. An update of its
pharmacological properties and therapeutic efficacy. Drugs 1995;
49: 121-142
2. Boecker WH, Kult J, Eberwein B.Efficacy and safety of torasemide (10-200 mg/day p.o.) in the treatment of edema in patients
with nephrotic syndrome. In. Puschett JB, ed. Diuretics IV:
Chemistry, Pharmacology and Clinical Applications. Elsevier,
1993; 51-54
Severe acute renal failure after administration of
contrast media in a patient treated with cisplatin
Sir
Cisplatin is an alkylating agent frequently used because of
its wide range of activity in the treatment of solid tumours.
Its main side-effect is nephrotoxicity; this toxicity is doselimiting with a cumulative action and can lead to irreversible
renal dysfunction [1]. Preventive measures are now well
known and consist mainly in expansion of the extracellular
fluid volume and suppression of concomitant therapy with
other nephrotoxins (especially aminoglycosides and nonsteroidal anti-inflammatory drugs) [2]. Very few data are
available on the association of cisplatin and iodinated radiocontrast agents.
We report here the case of a man. treated with parenteral
cisplatin for lung cancer, who developed a severe acute renal
failure after administration of radiocontrast agents despite
adequate preventive measures.
A 66-year-old man was admitted to our unit because of
oligoanuria, drowsiness, and dyspnoea. His history included
arterial hypertension, ischaemic cardiopathy with myocardial
infarction, and an episode of renal colic.
The exploration of left thoracic pain 2 months previously
led to diagnosis of a small-cell lung epithelioma. At the time
of diagnosis there were already metastases in the liver and
bone marrow.
Chemotherapy was started with cisplatin (70 mg/day for
2 days), cyclophosphamide, etoposide, and corticosteroids in
association with the administration of 2000 ml of 0.9% saline
per day. At the same time, two computerized tomographies
with intravenous injection of contrast media were performed
on day 1 and day 4 to complete metastatic evaluation. Serum
creatinine level before chemotherapy was 1.2 mg/dl and
calculated creatinine clearance 72 ml/min. From day 3, renal
function started to deteriorate and oligoanuria appeared.
Chemotherapy was stopped.
At his admission to our unit on day 7, blood pressure was
90/45 mmHg. Physical examination revealed drowsiness dyspnoea with left pleural effusion, and oligoanuria (250 ml/day)
despite intravenous administration of frusemide (250 mg/
day). Laboratory studies disclosed the following values:
serum urea nitrogen 2.6 g/1, creatinine 5.5 mg/dl, potassium
3.5 mmol/1, bicarbonate 37 mmol/1, calcium 1.81 mmol/1
with total protein 63 g/1, phosphorus 3.2 mmol/1 and haemoglobin 10.7 g/dl. Abdominal ultrasonographic study excluded
urinary obstruction.
An internal jugular catheter was inserted and the patient
was haemodialysed on the day following his admission.
Haemodialysis was continued (the patient was haemodialysed
6 times during his 19 days of hospitalization) until the
progressive amelioration of renal function and urine output.
When he was discharged, laboratory values were: serum urea
nitrogen 1.3 g/1 and creatinine 3.1 mg/dl. The patient died
one week later from acute respiratory deficiency.
Recently Oymak [3] reported the induction of an irreversible acute renal failure following intraperitoneal cisplatin
chemotherapy and contrast media injection in a woman
treated for ovarian cancer.
The pathophysiology of cisplatin's nephrotoxicity remains
unclear and disputed, but the main mechanism is a direct
tubular toxicity affecting the distal and collecting tubules in
human [4]. Transient renal ischaemia and direct renal tubular
toxicity have been suggested as possible mediators in the
development of contrast media nephrotoxicity [5]. Therefore
both cisplatin and contrast media may enhance the nephrotoxic potential of each other.
In conclusion, we suggest that radiographic procedures
with intravascular contrast material should be delayed for at
least 2 weeks in patients receiving chemotherapy with
cisplatin.
Service de Nephrologie
Groupe Hospitalier Pitie-Salpetriere
Paris
France
N. Raynal-Raschilas
G. Deray
C. Bagnis
C.Jacobs
1. Hannedouche T, Godin M, Fillastre JP. Complications renales
de la chimiotherapie anticancereuse. Path Biol 1986: 34: 1113
2. KJeinknecht D. Insuffisances renales aigue's provoquees par des
medicaments ou des produits de contraste. Rev Prat 1995;
45(13): 1633
3. Oymak O. Contrast media induced irreversible acute renal failure
in a patient treated with intraperitoneal cisplatin. Clin Nephrol
1995: 44(2): 135
4. Fillastre JP, Viotte G, Morin JP. Moulin B. Nephrotoxicity of
antitumoral agents. Adv Xephrol 1988: 17: 175
2523
Letters
5. Deray G. Baumelou A. Martinez F, Brillet G, Jacobs C. Renal
vasoconstriction after low and high osmolar contrast agents in
ischemic and non ischemic canine kidney. Clin Nephrol 1991;
36: 93
Correlation of whole blood activated partial
thromboplastin time and plasma activated partial
thromboplastin time in haemodialysis patients
Sir,
Heparinization during haemodialysis remains a challenging
problem. Under-anticoagulation may result in the clotting
of vascular access sites and in the extracorporeal circuit.
Over-heparinization exposes the patient to risks of prolonged
bleeding, aggravating the bleeding tendency common in
uraemic patients.
I
120
r
i
i
i
\
HO 160 1B0 ZOO 220 240 260 280 300
WBAPPT (seconds)
One of the major barriers for the optimal dosing of heparin
lies with the difficulty of monitoring the adequacy of anticoagulation during a 3-4 h haemodialysis session. The routine
plasma activated partial thromboplastin time (aPPT) for
monitoring heparin is not useful in this setting as the turnaround time for the test is too long.
Other monitoring tests which have been used include the
whole blood coagulation test (Lee-White test) [1] and ACT
(activated clotting time) [2], The automated ACT system
resolves the problems of a manual test (Lee-White)
and gives more reproducible results. The Endpoint
Microcoagulation Analyzer (International Technidyne
Corporation, Edison, New Jersey) is an automated system
which measures the whole blood activated partial thromboplastin time (WBAPPT). It is a portable, rapid, bedside
coagulation test which requires only a small blood sample
size (15 ui). Good in vitro correlation (r = 0.86) between the
WBAPPT as determined by the endpoint and plasma aPPT
has been established using heparinized blood from healthy
donors [3]. However, validation of this correlation in
haemodialysis patients has not been reported.
We studied the correlation between the WBAPPT and
plasma aPPT using heparinized blood from five patients
during haemodialysis. Blood was collected at 0, 0.5, 1,2 and
3 h after the start of haemodialysis for monitoring of heparin
therapy. An aliquot of the blood sample was used for
measurement of WBAPPT using the endpoint and the
remainder sent for plasma aPPT determination. The average
blood flow rates were 400-500 ml/min with corresponding
dialysate flow rates of 800 ml/min. Hollow fibre dialysers
were used (Terumo 175 or the Altin 170).
Figure 1 demonstrates 21 sets of data obtained from the
five haemodialysis patients. There was good linear correlation
between WBAPPT and plasma aPPT ratio (r2 = 0.62). The
endpoint has been used to evaluate the ability of a heparin
dosing protocol to maintain WBAPPTs within a desired
ranged [4].
In summary, there is good in vivo correlation between
plasma aPPT and WBAPPT in haemodialysis patients using
the endpoint. It provides an alternative tool which is useful
for monitoring heparin therapy during haemodialysis.
Albany College of Pharmacy,
C. L. Low
and Albany Medical College,
G. Eisele
Albany,
G. R. Bailie
New York, USA
1. Swartz RD. Anticoagulation in patients on hemodialysis. In:
Nissensson N, Fine R, Gentile D, eds. Clinical Dialysis, 2nd edn.
Appleton and Lange, East Norwalk, CT, 1990
2. Caruana RJ, Keep D. Anticoagulation. In: Daugirdas JT, Ing
TS, eds. Handbook of Dialysis, 2nd edn. Little. Brown and Co.,
Boston, MA, 1994: Ch 7, 121
3. Edison Institute, Edison, New Jersey. Endpoint—Operator's
Manual.
4. Low CL, Bailie GR, Morgan S, Eisele G. Effect of a sliding scale
protocol for heparin on the ability to maintain whole blood
activated partial thromboplastin times within a desired range in
hemodialysis patients. Clin Nephrol 1996; 45: 120-124
1
Transcatheter intravascular embolotherapy of renal
arteriovenous fistula—method of choice
1-
0
r
120
HO
160
i
1B0
i
ZOO 220
i
i
240
260
280
300
KBAPPT (seconds)
Fig. 1. Linear correlation between plasma aPPT and WBAPPT.
Sir,
The occurrence of an arteriovenous (AV) fistula in native
kidneys is still a well-recognized complication of percutaneous biopsy, with an incidence of up to 16% [1,2]. A
13-year-old, previously healthy boy experienced a severe
Henoch-Schonlein purpura with life-threatening gastrointes-