CONTENTS
NEWS
The smallest and the best haematology
4
5
5
analyser in the world – and we’ve got it!
The most important industry fairs
Corlyte in the Cormay portfolio
DIAGNOSTICS IN WORLD
Usefulness of saliva analysis in monitoring
6–7
of dialysis and kidney function
DIAGNOSTICS IN PRACTISE
End products of nitrogen compound
metabolism – basic information.
8–11
Uric acid and its function in systemic disorders
FOCUS ON DIAGNOSTICS
Examples of renal diseases versus changes
in nitrogen metabolism products
12–13
CARE FOR YOUR HEALTH
14
Transplants – the priceless gift of life
STUDY
15
From case to case
Publisher: PZ Cormay SA
ul. Wiosenna 22
05-092 Łomianki
tel.: 22 751 79 10
faks: 22 751 79 11
e-mail: [email protected]
www.cormay.pl
2
Editorial staff: Chief editor
– Monika Dziachan – PZ Cormay SA
Editing and proofreading – Agape
Co-operation:
Dr n. med. Iwona Kozak-Michałowska
Whole truth in one drop
Preparation and production:
Agape. Agencja doradcza i wydawnicza
ul. Rękodzielnicza 11, 02-267 Warszawa
tel./faks: 22 886 62 26
e-mail: [email protected], www.agape.com.pl
Editors reserve the right to abridge
and edit published texts.
This issue was closed on 9th December 2010
CORMAY International Bulletin
EDITORIAL
Underestimated kidneys
e have just completed the latest issue of our
newsletter, which is devoted to underestimated
kidneys. Our diet includes proteins, various
salts and minerals. However, not all of them are necessary
for our bodies. Kidneys eliminate waste products, nitrogen
metabolites, and maintain the right amount of water in the
body. They also produce hormones and erythropoietin.
W
Kidneys are very effective organs and most of the
people can lead a normal life even when only 15% of renal function is maintained. Chronic renal insufficiency is
progressive and kidney function deteriorates irreversibly.
The symptoms, such as weakness, fatigue and sometimes
apathy or loss of appetite are non-specific. Patients often
ignore those symptoms, what leads to acute renal insufficiency. That is when the patient realises that a new kidney
is required. Such thought is very disturbing. However, one
must keep in mind that nowadays kidney transplant is the
best way to treat renal insufficiency. The success rate of
kidney transplant increases continuously. Twenty years ago
only 35% of transplanted kidneys retained their function
after one year from the operation. These days most of the
patients have a chance to maintain an active transplant for
many years. Thanks to the progress in immunosuppression
treatment and surgical techniques this number continues
to grow.
One must realise that kidney transplant is not the end
of the world. However, we should keep in mind that kidney
diseases are diagnosed in a late stage, because at the beginning the patient does not feel any pain.
I hope that this issue of our newsletter draws the attention of our readers to this problem. That problem may be
avoided thanks to education and preventive laboratory testing. Let’s promote a healthy lifestyle amongst the patients. Let’s not neglect the first alarming symptoms of urinary apparatus disorders.
Now let me leave you with this issue of “Your Laboratory”.
Tomasz Tuora
President of PZ CORMAY S.A.
President and CEO of Orphee S.A.
No. 3 (20), winter 2010
However, one must keep
in mind that nowadays kidney
transplant is the best way
to treat renal insufficiency.
The success rate of kidney
transplant increases
continuously
Whole truth in one drop
3
NEWS
An interview with Domingo Dominguez Chief Sales
Officer Orphée & Cormay SA.
The smallest and the best
haematology analyser in
the world – and we’ve got it!
Mythic 22 AL – what is that?
Domingo Dominguez: The new analyser belongs to our swiss family of hematology instruments called Mythic®. This time it is a 5-Diff
analyser with an autoloader.
Does the analyser work with barcode systems?
D.D.: Yes. The internal barcode reader enables automatic reading of patient data. It is also possible to connect an external barcode reader, e.g. for registration of STAT samples.
Does Mythic 22 Auto Loader use the optical method of measurement, like most ha ematology analysers?
D.D.: Yes. The analyser performs measurements by OCHF (Optical Cytometer Hydrofocus Free) optical technology. However, this
method cannot be compared with methods
employed by other similar analysers. The method of differentiation of five white cell populations is based on a unique and innovative
concept of active flow of a blood sample stream, surrounded by a static coat of diluent,
which limits its consumption. In addition, the
use of “OnlyOne” patent lysis reagent allows
measurement without the need for specific
eosynophil staining and an additional measurement track for basophils. Thanks to the
used technology, only three reagents and
only 20 μl l of whole blood are needed in order to perform the full CBC 5-Diff!
What about software?
D. D.: Our software is very special, as it registers all procedures – both maintenance and
operational. Our Clients are given a very useful
tool for monitoring performance and accuracy
of performed procedures. The software is very
intuitive and available in multiple languages.
Time for a brief summary
D.D.: The analyser meets the requirements
for analysers with full separation of white blood cells into five subpopulations. With the dimensions of 40 x 48 x 40 cm, it is the smallest analyser of this type in the world. It can be
placed anywhere in a laboratory. Colour LCD
touch screen, effective monitoring of reagent
consumption and all mentioned above make it
a member of the world class of 5-Diff haematology analysers with autoloader.
Thank you.
Only three reagents and very small
amount of blood sound encouraging.
D o e s t h e a u t o l o a de r h a v e
any special features?
D.D.: Special construction
of sample racks enables
loading in one run into
a Greiner type closed vacuum system and Sarstedt
type aspiration-vacuum
system. It is also possible
to add sample racks continuously while the autoloader is working. STAT
samples can be measured in an open system
without stopping
the measurements in progress. The loader holds 50
tubes (ten five-tube racks).
4
Interviewed by
Monika Dziachan
Whole truth in one drop
DOMINGO DOMINGUEZ – FACTS
Domingo Dominguez is a Spanish Citizen and
French resident. Just after graduate in Engineering
and Mechanics he started to work in ABX (1986) as
International Field Service Engineer and travelled
more than 200 days/year all around the world.
From 1989 to 1991 he moved to USA to be in charge of the US Technical Support and started to develop ABX Distributor Sales Network in Latin America.
In 1991, he came back to Montpellier and joined
the ABX Headquarter of the company to develop
the International Sales Department, and gradually climbed the scale to finally end up in 2002 at
the Head of the International Sales, Service & Training Department of Horiba ABX.
In 2002 he left ABX to create with former President and Engineers of ABX, Orphee in Geneva and
C2 Diagnostics in Montpellier. in 2010 Orphee has
been acquired by Cormay and he was appointed
Chief Sales Officer of the Cormay Group.
All over those 25 years of activity, Domingo Dominguez was mainly dedicated to International
Business Activity spending more than half of the
year travelling in every part of the world and exclusively in the IVD Market.
Domingo Dominguez enjoys very much his professional activity and believes that the most important to succeed in a professional career is when
you are doing something you like with people around you that share the same enthusiasm. Domingo Dominguez always privileges the direct contact with people when and where ever it is necessary. This is why he spends most of his time travelling and considers his job as a pleasant adventure
with many partners and friends all over the world.
CORMAY International Bulletin
NEWS
The most important
industry fairs
Over 4000 exhibitors, presented their offer in a 115000 m2 building
during Medica 2010 fairs in Dusseldorf. PZ CORMAY S.A. organised its
stand together with Orphee, the acquired company. We presented our
newest products, constructed with the use of the most advanced
technologies.
edica fairs are the largest, the most
important and the most renowned
M
medical fairs in the world. Every year producers of medical technology and equipment participate in order to confirm their
presence on the market and to meet their
suppliers and distributors. In her speech,
the German Chancellor Angela Merkel emphasised that Medica is a very impressive
event giving weight to the importance of
medical industry for the world economy.
This year, for the first time since the
acquisition of the Swiss company Orphee,
PZ CORMAY S.A. presented their products at shared stand. Both companies have 221 distributors in over 100 countries
together. As you may guess, the meetings
were endless. Almost 100 distributors visited our stand between 17th and 20th November.
“I am very pleased with the quality and
the outcome of the meetings. Mythic 22
haematology analyser with autoloader was
presented for the first time in the Western
Europe and it gained a lot of interest.
Even our direct competitors were very
impressed” – says Andrzej Kenik, Export
Manager PZ CORMAY S.A. & Orphee.
This year’s Medica gathered 137,200
people. 4400 exhibitors from 64 countries presented their products and services.
Arab Health
s usually in second part of January
Cormay was a part of biggest medical
A
exhibition in Middle East area- Arab Health.
Generally it was definitely successful
show showing the strength of two brands together0 Cormay and Orphee and confirming
the position of new group in the market
especially considering Arabic countries
Also this time we presented all Cormay products and also of course our Orphee analyzers- Mythic. It was the first presentation of
mythic 22 AL new model in these markets
and met a lot of interests from our current
and also new partners. Despite new analyzer
we made several meetings with our existing
partners and discussed possibilities and
threats connected with our business.
Some new possibilities appeared in Africa
and also in some new markets in Middle east.
No. 3 (20), winter 2010
Whole truth in one drop
5
DIAGNOSTICS IN WORLD
Usefulness of saliva analysis
for monitoring of dialysis
and renal function
Measurement of biological markers that demonstrate
distinguishable and regular changes from pre- to postdialysis
states can enable necessary monitoring of dialysis efficacy and
the level of renal function in patients with end-stage renal disease.
n their work Blicharz et al.1 suggest that
the measurement of biomarkers in saliva
may be an effective alternative method
for monitoring the effectiveness of haemodialysis. In particular, Blicharz et al. highlight
as markers of interest 2 small molecules present in saliva, nitrite and uric acid (UA).1
Monitoring of markers in saliva instead of serum is advantageous because saliva collection is a noninvasive, simple, and inexpensive approach with minimal infectious risk that
can be performed by the patient with no need for involvement from medical personnel.
Saliva can be tested at home, thus saving the
need for a visit to the clinic or hospital.
Markers for monitoring patients with
end-stage renal disease must fulfil 3 requirements: (a) the markers should properly reflect serum concentrations of toxins to be
dialyzed, (b) the correlation between the serum and saliva concentrations of the markers
should be as high as possible, and (c) the
concentrations of the markers in saliva should not be altered by intraoral conditions or
by processes associated with marker transport from serum into saliva.
Whole saliva is composed of components
that originate in the major and minor salivary glands as well as from nonsalivary glandular sources, and the composition of saliva
may vary under resting vs stimulated conditions2. More than 90% of saliva is secreted
by the major salivary glands, which include
the parotid, submandibular, and sublingual
glands, whereas only a small portion of saliva originates in minor salivary glands and intraoral sources such as oral mucosa or gingiva. Contribution to the saliva from gastrointestinal reflux is minute and of negligible
importance under normal conditions. Various components of saliva are either passively
diffused or actively transported directly from
the serum into the saliva through the oral
mucosa and/or gingiva. The composition of
I
6
such components in saliva may or may not
reflect their serum composition.3,4,5 The watery component and the electrolytes in saliva are derived from serum, but the various
immunoglobulins, enzymes, and proteins
may originate in the serum, the salivary
glands, or other intraoral and extraoral sites.
Analysis of saliva composition may be
used as a diagnostic tool for the localization
and assessment of various systemic diseases
(such as end-stage renal disease). Such analysis must be based on a broad understanding of the specific concentrations and origins of the various immunological and biochemical components of saliva.6,7 The composition of saliva is affected by 2 fundamental mechanisms:
1. THE
SOURCE OF SALIVA .
The salivary glands and oral saliva sources may be the primary sites in which the various components are formed, or they may
serve as sites through which various components are passively diffused or actively transported from the serum. The lack of a high
correlation between concentrations of a
component in saliva and in serum does not
necessarily disprove the serum origin of that
component but may simply reflect variability
in the diffusion process for the component.
When concentration correlations are high,
however, the source of the specific component in the saliva can be concluded to be serum.3,4,5
2. ORAL CAVITY MODULATION
OF SALIVA .
After secretion the composition of saliva
is altered by various processes that take place in the oral cavity.4 Saliva composition is
highly variable, much more so than serum
composition. Accordingly, the reader assessing the importance of the Blicharz et al.
study should not be surprised that not all of
Whole truth in one drop
the results obtained support the trends anticipated, i.e., not all measurements in all patients demonstrated significant decreases in
post- compared to predialysis saliva concentrations of nitrite and uric acid. Because of
the physiological variability of saliva composition, multiple measurements must be performed, a process that decreases SDs and
significantly improves the diagnostic sensitivity and specificity of such measurements. If
circumstances allow multiple saliva collections and analyses and these are inexpensive
and accurate, then the use of saliva for the
monitoring of dialysis efficacy can be recommended.
Important questions to be addressed in
regard to saliva monitoring are what molecules are the best biomarkers and what molecules best fulfil the 3 requirements previously specified. Of the few molecules Blicharz
et al. examined, UA and nitrite best fulfilled
these criteria. The authors point out that
measurement of pre- and posttreatment blood urea nitrogen is the gold standard test for
evaluating dialysis efficacy, but conflicting
observations have been reported regarding
the correlation of saliva urea with blood urea
nitrogen. Thus Blicharz et al. were seeking
alternative saliva markers that might prove
useful for non-invasive monitoring of dialysis
efficacy and renal function. We have previously reported on 2 molecules, blood urea nitrogen and potassium, whose measurement
can be valuable in assessing the general condition of almost every hospitalized patient.
We found these analytes to demonstrate very high correlation coefficients between serum and saliva: r = +0.85 and +0.50, respectively. Accordingly, monitoring of urea
nitrogen concentrations should certainly be
considered as part of routine saliva assessment in patients undergoing dialysis. We
recommend further analysis in much larger
cohorts of dialysis patients to investigate the
efficacy and feasibility of blood urea nitrogen
analysis performed according to the method
employed by Blicharz et al. The potential role of potassium and other small molecules
and ions that diffuse into the saliva from the
serum also should be evaluated. The 2 molecules suggested by Blicharz et al. seem to
at least provide a "proof of a concept" and
CORMAY International Bulletin
DIAGNOSTICS IN WORLD
In conclusion, although much more research is needed, the report by Blicharz et al.
provides early evidence of the usefulness of
saliva biomarkers, particularly for monitoring
dialysis. The use of saliva samples obtained
with simple, inexpensive, and user-friendly
test strips is a very attractive alternative to
the use of blood samples and may revolutionize care-monitoring strategies for dialysis
patients as well as for patients suffering from
other chronic diseases.
Rafael M. Nagler
Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, RamClinical Chemistry 54: 1415-1417, 2008; 10.1373/clinchem.2008.112136
(Clinical Chemistry. 2008; 54:1415-1417.)
© 2008 American Association for Clinical Chemistry, Inc.
bam Medical Center and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of
Technology, Haifa, Israel
Address correspondence to the author at:
Department of Oral and Maxillofacial Surgery
and Oral Biochemistry Laboratory, Rambam
Medical Center, Haifa, Israel.
Fax +972-46541295,
E-mail: [email protected]
may be suitable candidates for saliva monitoring to assess dialysis and renal function.
Both molecules are also involved in various
biological processes in the oral cavity and
are related to various oral pathologies such
as oral cancer and other oral pathologies related to free radicals.
Uric acid is considered the most important antioxidant molecule in saliva and contributes approximately 70% of the total antioxidant capacity of saliva. Correlations between concentrations of uric acid in saliva
and serum indicate that uric acid in saliva
originates in serum.6,8,9 UA may certainly be
recommended as a biomarker for assessing
dialysis because UA concentrations are profoundly decreased by dialysis.10,11,12 Saliva
nitrites are derived from the production and
metabolism of saliva nitrosamine derived
from the absorption of dietary nitrates
(NO3-) in the upper gastrointestinal tract
and their active concentration from the plasma into the saliva by the salivary glands.
This process occurs through an active transport system similar to that for iodide, thiocyanate, and perchlorate.13 In the oral cavity nitrates in saliva are turned into nitrites
(NO2-), which play an important role in carcinogenesis by reacting with amines and
No. 3 (20), winter 2010
amides to form the carcinogenic nitrosamines, thus initiating and promoting oral cancer.14,15 Oral cancer is the sixth most common human cancer, with an increasing incidence in younger people, a high morbidity
rate, and a 5-year mortality rate of about
50%. Free radicals such as reactive oxygen
and nitrogen species, which induce oxidative and nitrative stress, are principal inducers of oral cancer. Reactive nitrogen species in the form of the nitosamines NO3 and
NO2 and reactive oxygen species such as
superoxide radicals (O2-), hydroxyl radicals
(OH-), and hydrogen peroxide (H2O2) play
key roles in human cancer development
through base alterations and strand breaks
in DNA, damage to tumor suppressor genes, and enhanced expression of protooncogenes. Protein damage associated with
reactive oxygen species may also induce
mutations. UA is the major antioxidant molecule in saliva that reacts with and neutralizes reactive oxygen species in the oral cavity; therefore measurement of UA concentrations along with NO2-, as Blicharz et al.
suggest, is highly warranted, not only in patients with end-stage renal disease undergoing dialysis but also in patients with other
oncological and oxidative-related disorders.
Whole truth in one drop
References:
1. Blicharz TM, Rissin DM, Bowden M, Hayman RB, DiCesare C, Bhatia JS, et al.
Use of colorimetric test strips for monitoring the effect of hemodialysis on salivary
nitrite and uric acid in patients with end-stage renal disease: a proof of principle.
Clin. Chem. 2008; 54: 1473-1480.
2. Rudney JD, Kajander KC, Smith QT. Correlations between human salivary levels
of lysozome, lactoferrin, salivary peroxidase and secretory immunoglobulin A with
different stimulatory states and over time. Arch Oral Biol 1985; 30: 765-771.
3. Mandel ID. The role of saliva in maintaining oral homeostasis. J Am Dent Assoc
1989; 119: 298-304.
4. Nagler RM, Klein I, Zarzhevsky N, Drigues N, Reznick AZ. Characterization of
the differentiated profile of human saliva. Free Radic Biol Med 2002; 32: 268277.
5. Fox PC, van der Ven PF, Sonies BC, Weiffenbach JM, Baum BJ. Xerostomia:
evaluation of a symptom with increasing significance. J Am Dent Assoc 1985;
110: 519-525.
6. Nagler A, Ackerstein A, Or R, Naparstek E, Slavin S. Immunotherapy with
recombinant human interleukin-2 and recombinant interferon-alpha in lymphoma
patients post-autologous marrow or stem cell transplantation. Blood 1997; 89:
3951-3959.
7. Nagler A, Nagler RM, Ackerstein A, Levi S, Marmary Y. Major salivary gland
dysfunction in patients with hematological malignancies receiving interleukin-2based immunotherapy post-autologous blood stem cell transplantation [Abstract].
Bone Marrow Transplant 1997; 20: 575-580.
8. Moore S, Calder KAC, Miller NJ, Rice-Evans CA. Antioxidant activity of saliva and
periodontal disease. Free Radic Res 1994; 21: 417-425.
9. Kondakova I, Lissi EA, Pizarro M. Total reactive antioxidant potential in human
saliva of smokers and non-smokers. Biochem Mol. Biol. Int. 1999; 47: 911-920.
10. Meucci E, Littaru C, Deli G, Luciani G, Tazza L, Littarru GP. Antioxidant status
and dialysis: plasma and saliva antioxidant activity in patients with fluctuating
urate levels. Free Radic Res 1998; 29: 367-376.
11. Bibi G, Green Y, Nagler RM. Compositional and oxidative analysis in the saliva
and serum of pre-dialysis chronic-kidney-disease patients and end-stage-renalfailure patients on peritoneal dialysis. Ther. Apher. Dial. 2008; 12: 164-170.
12. Ben-Zvi I, Green Y, Nakhoul F, Kanter Y, Nagler RM. Effects of diabetes
mellitus, chronic renal failure and hemodialysis on serum and salivary antioxidant
status. Nephron Clin. Pract. 2007; 105: 114-120.
13. Tenovou J. The biochemistry of nitrates, nitrites, nitrosamines and other
potential carcinogens in human saliva. J Oral Pathol 1986; 15: 303-307.
14. Xia DS, Deng DJ, Wang SL. Destruction of parotid glands affects nitrate and
nitrite metabolism. J Dent Res 2003; 82: 101-105.
15. Stich HF, Rosin MP, Bryson L. The inhibitory effect of whole and deproteinized
saliva on mutagenicity and clastogenicity resulting from a model nitrosation
reaction. Mutat. Res. 1982; 97: 283-292.
7
DIAGNOSTICS IN PRACTISE
End product of
nitrogen compound
metabolism – basic
information.
Uric acid and its function
in systemic disorders
Nitrogen balance in the human body is subject to complex
regulation. Almost all hormones have direct or indirect effect
on protein and amino acid metabolism. Protein deamination,
intestinal bacteria and alimentary proteins are the primary
sources of nitrogen.
Iwona Kozak-Michałowska, MD
ost of amino acids in tissues is bound in protein. Free amino acids
in human tissue constitute only
0.5% of protein amino acids. Proteins in a
healthy individual amount to 160g/kg, out
of which amino acids are only 1g/kg. 1 –
1,5g of free amino acids (i.e. 1/50 of the
whole amount) enter the circulation. Over
50% of free amino acids are present in ske-
M
8
letal muscles. A portion of amino acids is
built into synthesised cellular proteins, another portion is catabolised and yet another
transported with blood to other tissues. Recycling of amino acids, i.e. inbuilding them
into proteins again in the same tissue in skeletal muscles is approximately 30% regardless of the condition of the body. The same
process in liver is approximately 60% in the
resorption state and 90% in the post-resorption state.
Whole truth in one drop
NITROGEN
BALANCE
Human body does not accumulate protein and amino acids and in the state of balance it does not accumulate nitrogen. Excess
of supplied proteins is decomposed and catabolysed. The nitrogen excretion is equal to
the amount of nitrogen supplied.
Catabolic metabolism of amino acids lead to production of ammonia. Small amounts of ammonia are formed as a result of
decomposition of purine and pyrimidine bases in all tissues. Ammonia has toxic properties and is produced mainly in skeletal muscles, intestines and kidneys, but also in the liver and other tissues. Its blood concentration is usually very low. Ammonia is bound
in a few different reactions. The most important of them all, taking place in all tissues, is
the reaction catalysed by glutamate synthetase. The liver is the only organ where the fiCORMAY International Bulletin
DIAGNOSTICS IN PRACTISE
nal ammonia detoxification occurs by inbuilding into urea molecules.
A healthy human body is in nitrogen balance, i.e. external loss of protein nitrogen
(mainly by amino acid catabolism) is balanced by the amount of nitrogen supplied.
Negative nitrogen balance happens when
daily protein consumption does not make
up for the loss of nitrogen (starvation, malnutrition, morbid conditions). Positive nitrogen balance is the result of accumulation
of protein in tissues and does not result
from excessive protein supply. It occurs in
the growth period, during pregnancy, lactation, in some hormonal disorders e.g.
excessive androgen secretion, in the adaptation period of intensive exercise, in the convalescence period and during supplementation of nitrogen loss e.g. after a period of
starvation.
NITROGEN
EXCRETION
The end products of nitrogen metabolism
are excreted mainly with urine. Daily excretion of all nitrogen metabolites in a healthy,
well-nourished person is equal to loss of approximately 16g of nitrogen. Urea constitutes approximately 85 % of nitrogen compounds in urine. Creatinine nitrogen and uric
acid nitrogen is the result of creatine and
nucleic acid metabolism. Apart from urea,
other protein related end-products of nitrogen metabolism constitute 8 – 10% of the
total nitrogen excretion. Of that ammonium
ions constitute 50% and various other metabolites make up the other half.
Nitrogen is also excreted in faeces and
through the skin. Faecal excretion amounts
to approximately 1 – 2 g/day and constitutes of unabsorbed alimentary nitrogen
compounds, endogenous compounds – bilirubin and stercobilin, exfoliated epithelial
cells and bacterial flora. Cutaneous loss
consists of exfoliated epithelial cells. Additional nitrogen loss occurs in bleeding e.g.
menstrual blood or bleeding in the gastrointestinal tract. Increased nitrogen excretion has been observed in vomiting, diarrhoea, serum fluid or pus exudation from
the wound surface, high temperature, infections, hyperthyroidism, hypercorticoidism and in diabetes.
EXCRETION
OF UREA
Urea is the primary end-product of amino acid nitrogen metabolism. With a healthy,
well-balanced diet containing approximately
90 g of protein per day, human body receives 14 – 16 g of nitrogen. Urea is synthesised in the liver in urea cycle metabolism. A
non-toxic water-soluble compound excreted
through the kidneys is produced as a result.
Urea is excreted mainly with urine. The
excretion depends on blood flow through
the kidneys, glomerular filtration and voluNo. 3 (20), winter 2010
me of the excreted urine. Approximately 40
– 60 % of urea is subject to reverse absorption in collective tubules. Approximately
10% of urea is excreted through the gastrointestinal tract (degraded by intestinal bacteria) or with sweat. Blood urea increases
due to the increase of alimentary protein
supply, increased catabolism (high temperature, starvation, extensive tissue damage,
loss of muscular mass, intestinal bleeding),
dehydration, renal diseases, hyperthyroidism and steroid and tetracycline treatment as they increase urea in the circulation. Blood urea decreases due to decreased alimentary protein supply, overhydration, decreased protein catabolism caused
by supply of anabolic steroids and liver diseases.
Serum urea can also be expressed by the
nitrogen, i.e. BUN (blood urea nitrogen).
Urea and BUN may be used interchangeably,
with the following conversion:
Urea (mg/dl) = BUN (mg/dl) x 2.14
BUN (mg/dl) = urea (mg/dl) x 0.46.
Urea is not the most effective indicator of
glomerular filtration rate (GFR). However, it
is useful for calculation of urea/creatinine index in mg/dl in serum, used for differential
diagnosis of acute renal failure. In prerenal
causes this index is >20 and in renal failure
<20.
CREATINE
AND CREATININE
Creatine is synthesised from amino acids
– primarily from arginine, glycine and methionine, in the liver, pancreas and kidneys.
Muscle creatine is reversibly phosphorylased
and dephosphorylased in reactions catalysed
by creatine kinase. A non-enzymatic, irreversible reaction of phosphocreatine dehydration to creatinine excreted with urine also occurs in the muscles. Traces of creatine
are physiologically excreted with urine, because it is almost totally resorbed in renal
tubules. Its concentration in serum and urine increases in advanced tumours, muscle
dystrophies, hyperthyroidism and in extensive surgery.
Creatinine, as creatine anhydride, is present in blood and urine and, apart from
urea, is one of the main nitrogen compounds. Daily creatinine excretion in urine in a
healthy person is fairly constant and depends
on the muscular mass (serum creatinine in
men is usually higher than in women), protein diet, and renal function. The amount of
excreted creatinine increases after exercise,
in high temperature, after extensive injury, in
acromegaly and gigantism. Decreased creatinine excretion occurs in patients with renal failure, after nephrotoxic drug treatment
and in intoxication with organic and inorganic compounds. Decrease of creatinine in
circulation occurs in starvation and corticosteroid treatment.
Whole truth in one drop
In normal renal function creatinine is almost totally filtered by glomeruli and is not
reabsorbed or excreted by glomerular cells.
It is therefore a good marker for evaluation
of renal filtration.
CALCULATION
OF RENAL CLEARANCE
In practice, renal clearance i.e. glomerular filtration rate is calculated. Compounds
used for renal clearance evaluation must meet the following criteria: freely permeate
through glomeruli, cannot be resorbed or
secreted in tubules, cannot be metabolised
in the kidneys, cannot be toxic or bind to serum proteins. Reference methods for GFR
calculation such as insulin clearance or methods based on various radioactive tracers
are too labour-consuming and expensive.
From a practical point of view the use of endogenous creatinine is very useful. Unfortunately this method is not very accurate with
the main disadvantage being frequent incompleteness of the 24h urine collection.
Another important issue is the evaluation of
estimated glomerular filtration rate (eGFR)
showing non-linear but close correlation
with the mass of functioning kidney interstitium.
One of the most useful ways of establishing to what extent the kidney function is
impaired is an indirect evaluation of GFR on
the basis of measured serum creatinine,
the patient’s age and body mass. Normal
creatinine clearance is approximately 100
ml/min/1.73m2 and it decreases with age.
Usually the following formulas are used:
Cockroft-Gault formula:
eGFR = [(140 – age) x body mass] /
[serum creatinine (mg/dl) x 72].
For women the result is multiplied
by 0.85 as well as simplified version of the
MDRD formula:
eGFR = 186 x [serum creatinine (mg/dl)]
-1.154 x [age]-0.203 x [0.742 for women]
x [1.212 for the black race]
or the full MDRD formula, which requires additional measurement of serum urea
nitrogen and albumins:
eGFR = 170 x [albumin]0.318 x [creatini ne]-0.999 x [age]-0.176 x [BUN]-0.170 x
[0.762 for women] x [1.18 for the black
race]
The best known formula which was frequently used in the past was based on measurement of serum creatinine, creatinine in
urine from 24h urine and daily volume of
urine:
eGFR = [serum creatinine (mg/dl)] /
[serum creatinine (mg/dl) x daily urine
volume]
This formula had its limitations. In the
written form it allowed the clearance calculation in a, so called, standard adult, i.e. with
normal body mass and height amounting to
1.73 m2 of body surface. In all other cases
9
DIAGNOSTICS IN PRACTISE
correction of the body surface had to be implemented. It concerned children, adolescents, emaciated, overweight, short or very
tall people. Furthermore the calculated value
depended on the correctness of the 24-hour urine collection.
Amongst various formulas for GFR calculation, Schwartz formula used for children
and adolescents is also worth mentioning:
GFR ml/min/1.73 m2 = k x height [cm] /
[creatinine (mg/dl)]
Where:
k = 0.33 – 0.45 for infants; 0.55 for
children 2 – 12 years old and for adolescent
girls; 0.70 for adolescent boys.
It must be taken into consideration that
all these formulas are designed for screening
tests, aiming at detection of chronic renal diseases. Any deviations from normal values
should be investigated further.
Uric acid is excreted from the body primarily through kidneys (approximately 70%)
and to some extent through skin and gastrointestinal tract (up to 30%). According to
four-phase transport model in the kidneys, a
very large portion (over 90%) of the uric
acid is filtrated in glomeruli, in the proximal
tubule almost 100 % is reabsorbed and
then excreted into the distal tube in the
amount of approximately 50% of the filtered
load. In the next stage post-secretory reabsorption of up to 80% of secreted uric acid
takes place.
Increased excretion of uric acid often leads to urolithiasis. Urine pH is an important
factor for urinary calculi formation. Lowering
of pH values causes decreased uric acid solubility – this property is also important
when detecting tubular transport disorders.
Increased excretion of uric acid and urinary
calculi formation, as well as in gout, may be
Increased blood uric acid is often associated
with excessive weight, lipid disorders, diabetes
and hypertension
URIC
ACID
Uric acid is the end-product of the metabolism of purine, whose derivative are
nitrogen bases included in the nucleic
acids. Xanthine produced from hypoxanthine is its direct precursor. Both reactions
occur in the presence of xanthine oxidase.
Uric acid formed in such reaction is poorly soluble in body fluids. In the presence of
uricase (urate oxidase) uric acid is converted into allantoin – a compound which has
higher water solubility and is easily excreted with urine. Unfortunately humans,
most of primates and some animals e.g.
dalmatians, have a congenital metabolic
block consisting in the lack of uricase activity and purine breakdown ending at the
stage of uric acid.
Approximately 250 – 750 mg of uric
acid per day is produced in the human body
and in order to maintain homeostasis, such
load of urates must be excreted.
Purines which are the source of uric acid
are obtained from nutrition and from decomposition of decaying cells. The body also has its own way of de novo synthesis of
purines, which are used to complement the
pool of high-energy adenosine triphosphate
and guanine triphosphate nucleotides (ATP
and GTP). If the daily production of uric acid
exceeds 250 – 750 mg and the kidneys are
not able to excrete the produced amount,
hyperuricemia (increase of serum uric acid)
occurs.
10
due to diet rich in purine or to medical treatment. Urinary calculi formation may also
be caused by excessive urine acidity or concentration with limited fluid availability even
during normal excretion of uric acid.
Increased level of blood uric acid is often
associated with excessive weight, lipid disorders, diabetes and hypertension.
HYPERURICEMIA
It is estimated than only 10 – 15 % of hyperuricemia cases are the result of excessive
uric acid production in the body. In over 90%
of the cases hyperuricemia is caused by impaired renal excretion. Blood uric acid may
increase in renal failure, gout, conditions
with excessive cell decay or increased nucleic acid metabolism and catabolism occurring
in tumours (increase even up to 50 mg/dl),
leucemias, myeloproliferative syndrome, psoriasis, anaemia, anticancer drugs (up to 20
mg/dl), specific genetic defects e.g. deficiency of hypoxanthine-guanine phosphoribosyltransferase (Lesch-Nyhan syndrome), lead
poisoning or alcohol poisoning. Hyperuricemia may be caused by diuretics, such as thiazides. Aspirin and other salicylates affect uric
acid in various ways. Low concentration of
aspirin (when taken sporadically) may cause
an increase of uric acid concentration. High
doses of aspirin (prescribed in rheumatoid
arthritis) cause decrease of uric acid levels.
The decrease is also observed in some liver
diseases and cancers.
Whole truth in one drop
Increased blood uric acid is often associated with excessive weight, lipid disorders,
diabetes and hypertension. It has been noted over a hundred years ago that patients
suffering from the above conditions are at an
increased risk of death due to cardiovascular
diseases. It has been observed that many patients with hypertension have a family history of gout. In the past fifty years clinical and
epidemiological research confirmed the relationship between hyperuricemia and myocardial infarction, stroke, all cardiovascular
events in the general population, and – most
of all – hypertension. In prospective research
conducted on a large population within Framingham Study, it has been proven that serum uric acid is an independent prognostic
for development of hypertension. According
to various authors the frequency of hyperuricemia in hypertension is 3 to 54 percent,.
The most probable hypothesis assumes that
hyperuricemia in hypertension is due to hemodynamic disorders of the renal function,
which lead to decreased blood flow through
kidneys and cause disorders of tubular transport of the uric acid.
Increase in serum uric acid contributes to
atherosclerotic changes in blood vessels
through higher platelet aggregation and influences the endothelial cells through modification of their function. Serum uric acid is
a sensitive marker of subclinical inflammation process within the blood vessel walls.
This process is always concurrent with atherosclerotic plaque formation. Proinflammatory action of uric acid is closely connected
with influence on smooth muscle cells and
stimulation of mononuclear cells to produce
proinflammatory cytokines such as interleukin 1b, interleukin 6 and tumour necrosis
factor TNF-alpha.
GOUT
High uric acid is connected with gout,
defined as arthritis caused by sodium urate
crystallisation in the synovial fluid followed
by crystal phagocytosis and with formation
of crystal deposits in tissues. The cause of
uric acid crystallisation is not known. Gout
caused by a metabolic error leading to overproduction of the uric acid is referred to as
primary gout. Genetic conditioning is also
considered to be one of the risk factors. Lately it has been proven that uric acid concentration and excretion is mainly modulated by genetic polymorphism of SLC2A9
protein.
Increase of nucleic acid turnover in the
body (e.g. in proliferative diseases), disorders of uric acid excretion through kidneys
or increase in reabsorption is referred to as
secondary gout.
Gout occurs more often in men than in
women. It usually affects well-nourished,
well-built men who are over 40 years of
Biuletyn Informacyjny PZ CORMAY
DIAGNOSTICS IN PRACTISE
Lately it has been proven that uric acid
concentration and excretion is mainly
modulated by genetic polymorphism
of SLC2A9 protein
age. In women the onset usually occurs
over the age of 65 and at that age the prevalence rate is equal in both male and
female. In the early stages patients experience gout attacks. Chronic inflammatory
changes and organ symptoms occur as the
disease progresses. Patients suffering from
gout should limit the consumption or avoid purine-rich foods such as giblets (e.g. liver, kidneys), stock soup, meat, sardines,
some seafood, yeast, mushrooms and some
vegetables such as spinach, asparagus, beans and peas. Alcohol, especially beer,
must also be eliminated. Both chronic and
single doses of ethanol cause the increase
of blood uric acid as a result of its decreased excretion.
No. 3 (20), winter 2010
Gout is a chronic condition. The basic
detection criteria are:
• increased blood uric acid; during a gout
episode it may even be over 20 mg/dl,
but it may also remain normal,
• recurring episodes of acute arthritis with
remission periods lasting even a few
years,
• presence of urate deposits or sodium
urate crystals in joints, synovial fluid and
tissues; synovial fluid analysis for detection of urate crystals is considered to be
the golden standard confirming the clinical diagnosis; synovial fluid has inflammatory properties, and it is recommended
to perform synovial fluid culture due to
concurrent bacterial infections,
Whole truth in one drop
• renal complications with symptoms of interstitial tubular damage, changes within
kidney vessels, disorders of glomerular
function
• formation of urate deposits in the urinary
tract (urate urolithiasis).
In the past few years occurrence of
gout has become more frequent. This phenomenon is mainly due to ageing of the
population, whose members suffer from a
range of chronic diseases such as type 2
diabetes, hypertension, chronic circulatory
diseases, chronic renal diseases, excess
weight.
References
1. S. Angielski, J. Rogulski: Biochemia kliniczna. PZWL 1991
2. J. Naskalski: Ocena wielkości GFR w oparciu o stężenie kreatyniny i wzory
korygujące. Badanie i Diagnoza, 2008, 14, 68-71
3. M. Nowicki: Metody wykrywania i oceny postępu przewlekłej choroby nerek.
Choroby Serca i Naczyń, 2007, 4, 137-141
4. M. Majdan, O. Borys: Dna i schorzenia towarzyszące podwyższonemu stężeniu
kwasu moczowego Annal Acad Med. Stetinensis, 2010, 56, Suppl. 1, 34-39
5. K. Kostka-Jeziorny, A. Tykowski: Wpływ terapii hipotensyjnej na stężenie kwasu
moczowego. Arter Hypertens, 2007, 11, 151-163
6. P. Samborski, P. Bogdański, D. Pupek-Musialik: Nowe spojrzenie na kwas
moczowy u chorych z zespołem metabolicznym – fakty i kontrowersje.
Endokrynologia, Otyłość i Zaburzenia Przemiany Materii, 2008, 4, 86-94
7. K. Chiżyński, M. Różycka: Czy hiperurykemia jest czynnikiem ryzyka chorób
układu krążenia? Wiadomości Lekarskie, 2006, 59, 364-367
11
FOCUS ON DIAGNOSTICS
Examples of renal diseases
versus changes in nitrogen
metabolism products
Changes in the concentration of nitrogen metabolism
products occur in many renal diseases. In this article
the author discusses two examples – chronic kidney
disease and acute renal failure.
Iwona Kozak-Michałowska, MD
CHRONIC
KIDNEY DISEASE
The term „chronic kidney disease” (CKI)
was introduced in 2002 in the National Kidney Foundation guidelines (NKF K/DOQI). It
is a broader term than previously used
“chronic kidney failure”, as it also covers
changes observed in the initial stage of the
disease such as proteinuria or microalbuminuria which occur chronically for at least
three months without kidney damage (normal filtration rate). The following further four stages of the disease are covered by both
definitions:
• second stage – latent failure – damage of
up to 50% of functioning renal interstitium, slight impairment of urine concentration capacity, normal urea, creatinine
12
often reaching the high end of the normal
range, possible hypertension
• third stage – balanced failure – damage
to 50 – 75% of renal interstitium, evident
impairment of urine concentration capacity (isosthenuria), polyuria (risk of dehydration), anaemia, increased serum urea,
creatinine and uric acid concentration,
hypertension
• fourth stage – imbalanced failure - damage to over 75% of renal interstitium,
changes in blood and urine parameters,
oliguria, characteristic clinical symptoms
• fifth stage – end-stage failure – the condition requiring renal replacement therapy.
Measurement of serum creatinine and
evaluation of glomerular filtration rate is crucial in chronic kidney disease diagnosis.
GFR is the basis for classification of chronic kidney disease
Stage
1
2
3
4
5
Opis
Normal or increased GFR
Slight impairment of GFR (latent, early CKI)
Moderate impairment of GFR (balanced, moderate CKI)
Significant impairment of GFR (imbalanced, advanced CKI)
End-stage kidney disease
Whole truth in one drop
GFR (ml/min/1.73 m2)
g90
60–89
30–59
15–29
<15 or dialysis
CORMAY International Bulletin
FOCUS ON DIAGNOSTICS
Even a slight increase in creatinine concentration requires further diagnostics. According to the estimations, 4 million patients in
Poland might be suffering from CKI; 15,000
from end-stage kidney disease and the number of patients requiring dialysis rises by 10
% every year. The alarming data calls for discussions regarding stricter standards enabling early detection of the condition. This
will allow retardation of progress or even reversing the effects of the disease. Recommendation of preventive yearly measurement
of serum creatinine in all adults might be a
good solution. Creatinine concentration increases in proportion to the progression of
the disease. In the second stage it is usually
at the level of 1.2 – 2 mg/dl, in the third stage 1.5 – 4.0 mg/dl, and in the fourth and fifth stage over 5 mg/dl.
GFR calculation based on serum creatinine requires age, sex and body mass corrections. Therefore, the most useful method of evaluation of glomerular filtration is
agreed to be the intermediate evaluation
taking into account all these parameters.
Cockroft Gault formula and MDRD described in the previous article have the most
practical use.
Serum urea is determined by a number
of factors. It depends on renal perfusion,
volume of excreted urine, intensity of metabolic processes, daily alimentary protein
supply and glomerular filtration. When the
two first factors remain unchanged, increase
of urea concentration may occur only when
GFR is significantly decreased. Furthermore, the level of urea depends on various postrenal factors, medications (tetracyclines,
glycocorticosteroides), it increases in dehydration and high temperature. For these reasons urea is not considered to be a sensitive index for evaluation of renal function,
especially in detection of early stages of kidney failure.
ACUTE
RENAL FAILURE
Acute renal failure (ARF) is the condition
of sudden deterioration of kidney function
leading to increase of nitrogen compound
concentration (urea, creatinine, uric acid
and others) in body fluids and to water-electrolyte imbalance. The three distinguished
forms of the disease are: acute prerenal, renal and postrenal failure.
Acute prerenal failure is usually the result
of:
• hypovolemia (severe diarrhoea, extensive
burns, wounds and injuries),
• dehydration (insufficient fluid supply),
• endogenous fluid movement (intestinal
obstruction, peritonitis, acute pancreatitis),
• internal and external haemorrhages,
• vasomotor disorders (shock, septicemia,
end-stage cirrhosis),
No. 3 (20), winter 2010
• acute circulatory failure (myocardial infarction),
• hypercalcemia (multiple myeloma, sarcoidosis, hypoparathyroidism).
Decrease of blood pressure results in renal ischemia. After treatment of the cause of
acute renal ischemia the decreased GFR quickly and fully reaches the normal levels.
Interstitial failure is caused by inflammatory and non-inflammatory conditions leading to renal failure – acute glomeruli diseases and interstitial nephritis or diseases of
renal vessels – thrombosis, polyarteritis no-
to obtain a sample) is decreased. Dialysis
treatment is recommended when urea exceeds 200 mg/dl and creatinine is over 9.0
mg/dl.
In the polyuria stage (lasting for 7 to 10
days) 3 to 5 litres of urine are excreted daily. GFR increases, however glomerular function is still impaired. In this stage serum urea
and creatinine concentration is still increased, but slowly returning to normal levels.
Concentration of these parameters returns
to normal only in the recovery stage and
usually takes 4 to 6 weeks.
RIFLE classification
Category
Risk
Damage
Failure
Serum creatinine
Diuresis ml/kg/h
1.5-fold increase
2-fold increase
3-fold increase or concentration over 4.0 mg/dl,
with sudden increase by 0.5 mg/dl
dosa, septic or cardiogenic shock, poisoning, burns, dehydration, hypothermia.
Acute postrenal failure is caused by urinary tract obstruction due to e.g. pressure
from an existing tumour (uterine cancer), deposits in nephrolithiasis, blood clots, urethral obstruction (bladder cancer, prostate
overgrowth or prostate cancer), post-surgery complications (ureteral transection).
A widely accept citerion for ARF detection is a sudden (less than 4 weeks) increase
in plasma creatinine exceeding 3.5 mg/dl or
an 0.5 mg/dl increase within hours or days
and a decrease of creatinine clearance of approximately 50%.
RIFLE (risk, injury, failure, loss, end-stage renal disease) classification based on the
dynamics of the increase of serum creatinine
and on hourly diuresis rate has been proposed as a standardisation tool for ARF.
Four stages can be observed in interstitial
ARF: initial, oliguria, polyuria and recovery.
During the fist stage the laboratory parameters of the renal failure may remain unchanged, with prevailing symptoms of the underlying disease. In the oliguria stage usually lasting 7 to 14 days (however this period may
take up to six weeks) dialysis is often required as a life-saving treatment. This stage is
very hazardous with the risk of death reaching 70%. Due to impaired urine excretion, even anuria, and GFR decrease, compounds which in normal circumstances are
excreted through kidneys, deposit in the circulation. The concentration of creatinine,
uric acid and urea increases. Increase of
urea is connected not only with impaired
excretion but also with increased catabolism
of proteins mainly from skeletal muscles,
caused by increasing metabolic acidosis (disorders in excretion of H+ ions). Urea and
creatinine concentration in urine (if possible
Whole truth in one drop
< 0.5 for 6 hours
< 0.5 for 12 hours
< 0.3 for 24 hours or anuria for
24 hours
Laboratory testing, including urea and
creatinine, is important for differentiation
between prerenal and renal ARF. The increase rate of serum urea and creatinine depends on the severity of kidney damage and
on the formation rate of these substances,
which is significantly increased in catabolic
states. In order to evaluate the ARF dynamics it is important to monitor the changes
in these parameters on a daily basis. The
urea concentration of 200 mg/dl is the differentiating value. Values above indicate
prerenal causes and values below point to
renal causes of ARF.
The following indicators are also used:
• serum urea/serum creatinine
• urine urea/serum urea
values above 20 indicate prerenal ARF
and values below – renal causes
• urine creatinine/serum creatinine
values above 40 – prerenal causes, values below 20 – renal causes.
ARF occurs in various clinical conditions. It must be considered in all patients
admitted with unclear acute symptoms.
The prognosis depends on the underlying
disease, the age and possible complications. Current mortality rate due to ARF is
40 – 70%. Before the dialysis treatment
was introduced the mortality rate was over
90%.
References
1. M. Nowicki: Metody wykrywania i oceny postępu przewlekłej choroby nerek.
Choroby Serca i Naczyń, 2007, 4, 137-141
2. I. Kozak-Michałowska: Cystatyna C – wskaźnik funkcji nerek. Twoje Laboratorium, 2009, 2, 9-11
3. M. Klocek: Kliniczne implikacje łagodnej niewydolności nerek. Badanie i Diagnoza, 2008, 14, 65-68
4. A. Bętkowska-Prokop, E. Janusz-Grzybowska: Ostra niewydolność nerek. Badanie i Diagnoza, 2001, 7, 17-20
5. M. Luciak: Przewlekła niewydolność nerek. PZWL 2002
6. Z. Hruby: Nefrologia praktyczna. PZWL 2001
7. A. Szczeklik, P. Gajewski: Choroby wewnętrzne. Medycyna Praktyczna 2009
13
CARE FOR YOUR HEALTH
Transplants – the priceless gift of life
In many cases organ or tissue transplantation is the ultimate
life-saving solution. Therefore it is very important to raise the
social awareness of this type of treatment and its benefits.
Tadeusz Baranowski
rgan donors” is a humorous or
even contemptuous term used by
passers-by to describe fast-riding
motorcyclists. This is quite accurate, as the
road accident victims whose lives cannot be
saved, but who are brought to hospital in a
sufficient condition, can become organ donors. On the other hand the term “organ
donor” is wrong and harmful because it
should not be used in a derogatory way since the act of donation is the ultimate sacrifice and the most precious gift that can be
given to another person.
O
THE BEGINNINGS OF KIDNEY
TRANSPLANTOLOGY
Transplantology is a relatively new area
of medicine. The first successful kidney
transplant was performed in 1954 in Boston. In 1990 an American surgeon Joseph
Murray who conducted the surgery was
awarded the Nobel Prize in medicine.
This new treatment method was introduced in Poland a few years later. In 1965
in Wroc³aw a renowned surgeon Wiktor
Boss conducted the first kidney transplant
operation from a deceased donor. Unfortunately the surgery failed. The first successful kidney transplant collected from a deceased donor was performed one year later in
Warsaw by Jan Nielubowicz and Tadeusz
Or³owski. Two years later in 1968, Wiktor
Boss succeeded in transplanting a kidney
from a live donor. It was the first successful
surgery of this type in Poland.
SOCIAL
AND LEGAL ISSUES
Insufficient number of donors is the ongoing problem in transplantology. Usually
the blame is laid on low social awareness.
The donorship can be divided into two
groups: from live and from deceased donors. One can become a live donor for the
next of kin, an adopted person, the spouse
or for another person in the event of special
personal circumstances (this must be approved by the district court having jurisdiction
over the donor’s place of residence).
In order to become a donor one must
have unrestricted capacity to perform acts
in law and must express their free will to
become a donor in writing before the do-
14
ctor. The potential donor is informed of
possible risks associated with the procedure and is thoroughly examined. The donation procedure concerns only organs and
tissues which may be taken from a living
person, such as kidneys or bone marrow.
TRANSPLANTS IN
AND ABROAD
POLAND
A survey conducted in Poland in 2007
for CBOS showed that transplantation medicine is broadly supported by the public.
However, people are more comfortable
with the transplant from a deceased person
and find it difficult to accept the idea of
a transplant from a live donor. The decision
of organ donation from a deceased person
is not always supported – in 2004 Poltransplant received 696 alerts of organs availa-
Kidney transplant conditions
•compatibility of donor’s and recipient’s main
blood types
•negative result of cross matching between
donor’s lymphocytes and recipient’s serum
•good clinical condition of the potential recipient
The person whose tissue type matches the donor’s
tissue type most closely becomes the recipient.
Waiting time is another important factor – priority is
given to those who have been waiting longer.
ble from deceased donors; 124 of them
were not followed out of which 64 was due
to family refusal. The number of persons
awaiting transplant in Poland is the most
pressing issue. In 2009, 2604 persons required a kidney, pancreas and liver transplant and in only 23 cases the organs were
collected from a living donor.
According to Poltransplant data, kidneys
are the most often transplanted organs in Poland. In 2010 kidney transplants constituted
almost 75 percent of all transplantation
surgeries (the organs transplanted in Poland are liver, pancreas, heart and lungs).
Last year the numbers were as follows:
almost 1000 transplants from deceased
donors (25% increase compared with
2009), 50 transplants from a living family member (117% increase) and 20
kidney-pancreas transplants. Poltransplant emphasised that last year showed
a record number of kidney transplants
from a living family member.
Studies published in 2010 in ”Clinical
Journal of the American Society of Nephrology” showed that approximately 500 thousand patients in the US suffer from kidney
failure and 48% of those are over 60 years
old. The scientists emphasise the fact that
these patients have a greater chance of
a transplant from a live or a deceased donor and that they die less often before receiving the required organ. Almost 45% of
kidney transplants in the world come from
live donors, but in Poland it is only 1.5% of
all kidney transplants performed in adult
patients. In Poland only 2500 operations
of that type were carried out in the period
from January 2007 until March 2010, while in the US that number reached almost 50,000 (20 times more than in Poland) in a two-year period. The best pancreas transplant results are achieved during
the concurrent kidney transplant. There
were 62 surgeries of this type in Poland in
the above mentioned period, while in the
US that number was 40 times larger. In the
US almost 20,000 liver transplants were
carried out, while in Poland there were less
than 700. According to available data, almost 3500 transplants were carried out in
Poland in the above period, while in the US
the number reached almost 84,000 which
is 24 times more (and the US data does
not include 2010).
We still need to change the attitude of
the patients and potential donors. Media
can play a great role in educating the public
and debunking the myths.
CORMAY International Bulletin
STUDY
Clinical
Every reader can become involved in this
section. We are willing to publish any interesting
and non-standard cases you may have
encountered.
We hope that the published cases will become
a useful educational tool for mastering your
diagnostic skills.
case study
Clinical Case section aims at broadening,
refreshing and consolidating your knowledge.
A 49-year-old male with renal disease in the 5th
stage of glomerulonephritis, admitted to hospital
with the temperature of up to 39°C, sore throat,
resting dyspnea and generalised pruritus.
In 1996–2000 the patient received renal
replacement therapy. In 2000 he received a kidney
transplant. In 2007 the patient was again qualified
for renal replacement therapy with haemodialysis
due to nephropathy of the transplanted kidney.
During the course of examination upon admission
small petechial haemorrhages, heart rhythm
disorders and blood pressure of 170/100 mm/Hg
were observed.
Some of the laboratory test results
Test
Leucocytes
Erythrocytes
Haemoglobin
Platelets
Urea
Creatinine
Potassium
CRP
INR
1st day
3rd day
5th day
1.49 x 10 /μl
0.56 x 10 /μl
0.18 x 10 /μl
3.19 x 10 /μl
10.0 g/dl
68 x 103/μl
196.5 mg/dl
10.1 mg/dl
6.1 mmol/l
176 mg/l
–
2.97 x 10 /μl
9.3 g/dl
38 x 103/μl
–
8.9 mg/dl
–
211 mg/l
1.58
2.90 x 10 /μl
9.2 g/dl
9.0 x 103/μl
–
9.4 mg/dl
6.5 mmol/l
281 mg/l
1.63
3
6
3
6
3
6
7th day
0.14 x 103/μl
2.28 x 106/μl
7.1 g/dl
16.0 x 103/μl
–
6.7 mg/dl
6.1 mmol/l
292 mg/l
2.32
On the 6th day of hospitalisation liver enzymes and amylase activity testing was performed, with the following results:
• AST – 234 U/l (N: 0 – 38);
• ALT – 193 U/l (N: 0 – 40);
• GTP – 97 U/l (N: 0 – 66));
• Amylase – 110 U/l (N: 0 – 80).
On the 4th day of hospitalisation, at the doctor’s request, the family delivered all medicines recently taken by the patient. They included methotrexate which has never
been prescribed before. It appeared that the drug was being taken by mistake, as the patient was certain that it was metohexal – a beta blocker that he had been
taking for some time.
Despite treatment, the patient died on the 7th day of hospitalisation due to circulatory and respiratory failure.
Diagnosis:
Methotrexate poisoning in an end-stage renal failure patient.
Discussion:
Chronic renal disease is a condition requiring special care when prescribing medicines. Methotrexate overdose was the reason of the patient’s death. It is a cytotoxic
drug used mainly in cancer therapy as well as in immunosuppression therapy in rheumatoid arthritis and psoriasis. Due to high cytotoxicity, its serum concentration
must be constantly monitored.
Methotrexate is absorbed in the gastrointestinal tract; it binds to proteins in serum, mainly to albumins. It is excreted primarily by the kidneys. Large doses of cytostatic
drugs may cause precipitation in the kidneys which leads to renal failure. Its neurotoxic action intensifies with the increased doses. In patients with chronic renal
disease its biological half-life extends depending on the degree of kidney damage and reduction of its clearance is adequate to worsening of the renal function.
Additionally, damage to bone marrow was observed as a result of accumulation of the drug. As a result of agranulocytosis a severe systemic infection occurred, which
was the main mode of dying.
Acknowledgments:
Thank you to Zbigniew Zbróg, MD, the head of Nephrology Department WSS im. M. Kopernika in Łódź for providing clinical data and a publication „Zatrucie
metotreksatem” A. Fater-Dębska, J. Kurzawa, B. Kaczmarek, A. Szuflet, Z. Zbróg; Acta Clinica et Morphologica, 2009, 12, 37–40.
No. 3 (20), winter 2010
Whole truth in one drop
15
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