artigo dE rEvisão
bsbm cystatin c:
in transPlant Patients
a marker of renal function
brasíliamédica josé dE riBamar olivEira lima,1 tErEsa CristiNa alvEs FErrEira,2 maria iNês GomEs
dEolivEira3 E NataliNo salGado FilHo4
Assessment of renal function in patients submitted to kidney transplantation is of great importance in clinical prac-
tice, and the glomerular filtration rate is used as an indicator for this purpose. Measurement of serum creatinine is the
most widely used method for the estimation of gromerular filtration rate. However, the disadvantages of this method
are physiological and analytical influences (e.g., muscle mass, gender, certain antibiotics, bilirrubin, ketones) with the
assay and inadequate sensitivity for the early detection of small declines in gromerular filtration rate. Cystatin C is a
nonglycosylated low molecular weight (13 kDa) protein of the superfamily of cysteine proteinase inhibitors, which is
constantly produced by all nucleated cells. Due to its low molecular weight, cystatin C is freely filtered by the renal
glomeruli and then almost completely reabsorbed and metabolized in the proximal tubules without interference from
other low molecular weight proteins, thus permitting its use as a good marker of glomerular filtration. We present
here a review of studies published so far regarding the use of cystatin C as a promising marker for the assessment of
glomerular filtration in renal transplant patients.
Key words. Cystatin C; kidney transplantation; glomerular filtration; marker.
CistAtinA C: uM MARCAdOR de funçãO RenAl eM pACientes
A avaliação da função renal em pacientes submetidos a transplante renal é de grande importância na prática
clínica, sendo utilizada para esse fim como indicador a medida da taxa de filtração glomerular. A determinação da
creatinina sérica é o procedimento mais utilizado para essa avaliação, porém as desvantagens desse método são
as influências fisiológicas e analíticas, por exemplo, massa muscular, sexo, certos antibióticos, bilirrubinas, cetonas,
com o ensaio e inadequada sensibilidade para detecção precoce de pequenos declínios na taxa de filtração glomeru-
lar. A cistatina C é uma proteína não glicosilada de baixo peso molecular (13KDa), produzida constantemente em
todas as células nucleadas, pertencente à superfamília das proteínas inibidoras da cisteína proteinase. É livremente
filtrada pelos glomérulos renais devido ao seu baixo peso molecular, sendo a seguir quase totalmente reabsorvida
e metabolizada nos túbulos proximais, não sofrendo influência de outras proteínas de baixo peso molecular, o que
permite sua utilização como um bom marcador da filtração glomerular. Esta revisão aborda o uso da cistatina C como
marcador promissor de avaliação da filtração glomerular em pacientes transplantados renais, com base em estudos
até o momento realizados nesta população.
palavras-chave. Cistatina C; transplante renal; filtração glomerular; marcador.
introduction including chronic kidney disease. In this respect,
T he developed world is suffering from an epi-
demic of a broad spectrum of kidney diseases
which has only been begun to be understood.
renal failure affects only a minority of the total
population with kidney disease, but is the most
The aging of the population is accompanied by a Chronic kidney disease is defined as the pres-
parallel increase in degenerative chronic diseases, ence of true kidney damage and/or a glomerular
Doutorando em Ciências da Saúde pela Universidade de Brasília. Correspondência. Serviço de Nefrologia. Hospital Universitário da Universidade Federal
do Maranhão. Rua Barão de Itapary, n.º 227, Centro. CEP: 65020-070, São Luís, MA, Brasil. Telefone: (98) 21091284. Fax (98) 2109-1194. Internet:
Doutoranda em Nefrologia pela Universidade Federal de Juiz de Fora
Mestranda em Ciências da Saúde pela Universidade Federal do Maranhão
Doutor em Nefrologia pela UNIFESP
Recebido em 20-2-2009. Aceito em 16-3-2009
46 Brasília Med 2009;46(1):46-53
CystatiN C iN traNsplaNt patiENts
filtration rate of 60 mL/min/1.73m2 or less for Various exogenous substances can also be used
at least 3 months, irrespective of the underlying to estimate glomerular filtration. The gold standard
cause of kidney damage.1,3 Estimation of glomeru- for the assessment of renal function is glomerular
lar filtration is an excellent method to assess renal filtration rate estimated from the renal clearance
function, and since a reduction in glomerular fil- of exogenous markers such as inulin or a labeled
tration rate precedes the occurrence of symptoms radioisotope (e.g., Cr-EDTA). Inulin, considered
related to renal failure. Thus, monitoring changes to be the gold standard, and Cr-EDTA are markers
in glomerular filtration permits to estimate the of glomerular filtration whose pharmacokinetic
rhythm of renal function loss. In addition, the clini- characteristics are close to ideal. However, several
cal application o f glomerular filtration estimation practical considerations have restricted the clinical
permits to predict the risks of complications of application of these markers, such as their intra-
chronic kidney disease, as well as adequate dose venous administration, assays that require com-
adjustment in the case of drugs excreted through plex reagents and/or equipment, and high costs.5
the kidneys by glomerular filtration.4 Therefore, these methods are only appropriate in
Renal function is generally evaluated by the highly specialized experimental studies or clinical
quantification of a glomerular marker that should trials since they are time consuming, expensive,
be eliminated or cleared from the organism by require special equipment, and have potentially
the mechanism of glomerular filtration. In routine significant side effects. Furthermore, both inulin
laboratory assessment, urea, serum creatine and and iothalamate contrast can cause severe compli-
creatinine clearance are used as the main mark- cations such as anaphylactic reactions.9
ers of renal function. Urea and creatinine are the Urea was the first endogenous substance used
most extensively used and studied endogenous for the assessment of renal function, whose con-
markers for the clinical assessment of glomerular centration was measured in serum. Urea is the
filtration. However, the production of these mark- main nitrogenated product of protein catabolism in
ers is influenced by a series of factors, such as humans, accounting for more than 75% of excreted
muscle mass and protein ingestion; in addition, non-protein nitrogen. The intense tubular process-
interferences with the creatinine assay have been ing of urea may lead this marker of renal function
reported.3,5,6 to underestimate glomerular filtration capacity.
Glomerular filtration cannot be directly esti- Urea presents few of the characteristics of an ideal
mated. However, if a substance presents a stable marker, with its production being variable and
plasma concentration, is freely filtered by the renal widely dependent on protein ingestion. Although
glomeruli, and is not secreted, reabsorbed, metabo- 25% of the urea produced is metabolized in the
lized or synthesized by the kidney, its filtered con- intestine, the resulting ammonia is reconverted
centration is equal to the amount excreted in urine. into urea. Thus, most urea is finally excreted by
An ideal endogenous marker of glomerular filtra- the kidneys. Due to its small molecular weight,
tion rate should have a constant production rate, urea is freely filtered by the glomeruli. However,
be eliminated from the circulation by glomerular urea can be reabsorbed and the amount of tubular
filtration only, be filtered freely by the glomeruli, resorption is variable.3,5,10
and should not be secreted or reabsorbed by the Although creatinine is the marker most frequently
distal or proximal renal tubules. Measurements of employed for the assessment of glomerular filtration,
creatinine clearance in 24-hour urine samples and its use is associated with a number of problems,
of serum creatinine have been the methods most particularly in children. The production of creatinine
widely used over the past years for the estimation is related to muscle mass. As a consequence, serum
of glomerular filtration; however, these methods creatinine levels may vary with growth irrespective
present practical limitations.7,8 of changes in glomerular filtration rate . In addi-
Brasília Med 2009;46(1):46-53 47
josé dE riBamar olivEira lima E Cols.
tion, tubular secretion of creatinine proportionally Serum cystatin C has recently been introduced
increases with decreasing glomerular filtration rate. as a new marker for the estimation of glomerular
Therefore, measurement of creatinine clearance may filtration rate and has shown a higher diagnostic
result in the overestimation of glomerular filtration value than serum creatinine in the detection of a
rate. The use of serum creatinine for the assessment reduced glomerular filtration rate.
of glomerular filtration is limited because this vari-
able is affected by glomerular filtration-independent history of cystatin c
factors such as age, gender, race, body surface area, Cystatin C was discovered in 1961 as gamma-
diet, drugs, and differences in laboratory methods, as trace in an electrophoretic band of cerebrospinal
well as 24-hour urine collection due to sampling er- fluid and was also identified in urine in the same
rors and daily variations in creatinine excretion.7,5,11,12 year. The first immunoassay for the quantification
Therefore, the National Kidney Foundation (NKF) of cystatin C was developed by Lofberg and Grubb
has published guidelines for laboratories recom- in 1979. This assay was a lengthy competitive im-
mending the information of glomerular filtration munoradiometric assay with a detection limit of
rate based on serum creatinine, age, gender and race, 30 µg/L, which was more than sufficient to detect
and eliminating the use of 24-hour urine collection cystatin C in serum of healthy subjects and to per-
for the estimation of glomerular filtration rate. Ac- mit studies of cystatin C reference values. In 1985,
cording to the NKF, the measurement of creatinine the strong inverse correlation of serum cystatin C
alone is not the most accurate method to estimate with glomerular function was demonstrated for
the degree of renal function and equations taking the first time.3,17,18
into account factors other than serum creatinine are
Serum creatinine is commonly used as a marker Cystatin C is a member of the superfamily of
of glomerular filtration. However, it does not pre- cysteine protease inhibitors and is considered to
cisely reflect glomerular filtration, especially in be the most important physiological inhibitor of
renal transplant recipients. In addition, physical endogenous cysteine proteases. Cystatin C is a low
activity, muscle mass, protein passage and tubular molecular weight (13 kDa) protein constantly pro-
secretion influence the concentration of serum duced by nucleated cells, which is freely filtered by
creatinine. Similarly, the Cockcroft-Gault formula the glomeruli and reabsorbed and catabolized, but
based on creatinine does not resolve this disadvan- not secreted, by renal tubules. In the presence of
tage and, therefore, alternative approaches have normal renal function, tubular resorption and ca-
been tested to increase the accuracy of glomerular tabolism of cystatin C are almost complete and the
filtration rate estimation. Recently, the so-called protein is only detected in small amounts in urine.
modification of diet in renal disease (MDRD) In healthy subjects, urinary cystatin C measured
population study has established a formula based on by radial immunodiffusion is less than 0.30 mg/L.
four parameters, which was found to be an excellent Increased urinary cystatin C levels were noted
equation for the estimation of glomerular filtration especially in renal disorders such as tubular dam-
rate. Therefore, the National Kidney Foundation age associated with Chinese herbs, HIV-induced
has proposed this equation for the classification of nephropathy and acute interstitial nephritis. Cys-
chronic kidney disease .14 However, these equations tatin C does not suffer interference from other low
were mainly developed and tested in chronic kid- molecular weight proteins such as retinol-binding
ney disease patients under conservative treatment, protein and beta(2)-microglobulin, which are also
with few studies determining the validity of these used for the assessment of glomerular filtration
equations in other groups of patients such as renal capacity during severe malnutrition and inflam-
transplant recipients.15,16 matory and infectious processes.3,8,19-22
48 Brasília Med 2009;46(1):46-53
CystatiN C iN traNsplaNt patiENts
methods for the measurement of cystatin c particle-enhanced turbidimetric immunoassay,
Although the first studies regarding cystatin but there is still no consensus. Comparisons be-
C date back to 1985, an adequate technique for tween the results of different studies are difficult
the automatic measurement of cystatin C was because of the use of different analytical methods,
only introduced in 1994 after various attempts at calibration, antisera and variations in patient age.
standardization. This assay was the result of the One advantage of the Dako particle-enhanced
simultaneous development of two immunofluo- turbidimetric immunoassay is that the assay can be
rescence techniques using latex particles (PETIA, performed with any automated spectrophotometer
particle-enhanced turbidimetric immunoassay). or clinical analyzer, whereas particle-enhanced
These two assays, which used the same anti- nephelometric immunoassay was only developed
body and calibrator but different particles, yielded for analyzers from the same manufacturer. There
extremely concordant results. This assay was is agreement between various authors that refer-
soon followed by the development of a particle- ence values can be the same for men and women,
enhanced nephelometric immunoassay (PENIA) although some investigators have described higher
using the Behring nephelometric systems. reference values for males.3,8
particle-enhanced nephelometric immunoassay A differentiation between ages has been sug-
and immunofluorescence techniques using latex gested, but there is still no consensus for a cut-off
particles provided the basis for four commercially (50 or 65 years) since cystatin C concentration in-
available techniques for the determination of creases with age, whereas glomerular filtration de-
cystatin C.8,22 creases in parallel. Previous studies have reported
Most clinical assessments are performed using that renal volume decreases from 20 to 30% in the
these two automated immunonephelometric and fourth decade of life to 40% in the eighth decade.3
immunoturbidimetric assays, which are both very Galteau et al proposed a low reference range (0.63
rapid and sensitive and can and should be included to 1.03 mg/L) for subjects older than 60 years.
in the routine of clinical laboratories that attend Finney et al, studying 398 subjects ranging in age
all types of patients, especially children. Cystatin from 65 to 101 years, suggested markedly higher
C can be measured in small volumes (25 µL) of reference limits (0.93 to 2.68 mg/L) for the group
either serum or plasma. This test does not suffer aged 60 to 79 years, and a range of 1.07 to 3.35
interference from the yellow pigment found in sera mg/L for the group aged 80 years.24
of highly jaundiced patients. However, cystatin C
is influenced by intense lipemia and hemolysis.22 cystatin c concentration and renal function
particle-enhanced nephelometric immunoassay is in transPlant Patients
performed with the Siemens BN II nephelometer, In renal transplant patients, early detection
which requires 80 µL of a plasma sample. The du- of impaired kidney function is critical so that
ration of the assay is six minutes and the intra- and efforts to prevent further deterioration of graft
interassay coefficients of variation are 1.8 and 1.1%, function or rejection can be instituted. Because
respectively.3 In a meta-analysis, Dharnidharka et serum creatinine has a smaller intra-individual
al23 found that the immunonephelometric assay is variability than cystatin C, it is postulated that
superior to the turbidimetric assay for the analysis serum creatinine will more reliably detect small
of cystatin C, with the observation of higher cor- changes in glomerular filtration rate and therefore
relation coefficients in studies using the immunon- will be better able to identify those at risk of acute
ephelometric assay (14 studies) compared to other transplant rejection.25
techniques (21 studies). From their preliminary study of renal transplant
Particle-enhanced nephelometric immunoas- patients, Le Bricon et al. however found that cysta-
say produces slightly lower reference values than tin C was more sensitive than serum creatinine for
Brasília Med 2009;46(1):46-53 49
josé dE riBamar olivEira lima E Cols.
detecting decreases in glomerular filtration rate and ing immediate post-transplant complications than
delayed graft function, with the potential for more serum creatinine. However, the authors pointed
timely intervention.26 Follow-up studies have found out the small number of patients included, with
glomerular filtration rate over-estimation of 30% further studies being necessary to confirm whether
and 40% by plasma creatinine and 24-hour creati- cystatin C levels predict graft complications and
nine clearance respectively. Even though cystatin C their relationship with other factors.
underestimated glomerular filtration rate by 14% it The study by Akbas et al 30 evaluated 75
was still more sensitive in detecting impaired renal stable renal transplant patients with a mean age
function ( glomerular filtration rate cut-off <80 mL/ of 34 ± 10.23 years. Serum cystatin C, beta(2)-
min/1.73 m2) than serum creatinine and creatinine microglobulin and creatinine concentrations were
clearance, with no false-negative results.27 determined in individual blood samples and crea-
Krieser et al11 studied 19 pediatric renal trans- tinine clearance was measured in 24-hour urine
plant recipients (15 boys and 4 girls) ranging in age samples. Cystatin C and beta(2)-microglobulin
from 8.35 to 19.06 years ( median of 13.52 years) were significantly correlated with creatinine (r =
over a period of 18 months. 99mTc-DPTA glom- 0.648, P < 0.05 and r = 0.578, P < 0.05, respec-
erular filtration rate measurement were simultane- tively). Inverse creatinine was superior to cystatin
ously compared with measurements of cystatin C C and beta(2)-microglobulin when renal function
and serum creatinine. The correlation coefficients equations were used (r = 0.95, P < 0.05, according
for the relationship of creatinine to 99mTc-DPTA to modification of diet in renal disease; r = 0.87, P
glomerular filtration rate and of cystatin C to = 0.05, according to Cockcroft-Gault). The authors
99mTc-DPTA glomerular filtration rate were 0.64 concluded that serum creatinine is a more effective
and 0.58, respectively. The authors concluded that marker than serum cystatin C for the assessment
there was no significant difference between serum of renal function. Koçak et al31 evaluated the im-
cystatin C and serum creatinine and that, due to the pact of cystatin C, creatinine, C-reactive protein
higher cost of cystatin C measurement compared and amyloid A as markers of the degree of renal
to creatinine, the former offers no advantage in function on the third and seventh day after trans-
the monitoring of renal function in pediatric renal plantation in 35 renal transplant recipients (21 men
transplant recipients. Visvardis et al28 evaluated and 14 women). Serum cystatin C and creatinine
18 transplant patients ranging in age from 31 levels on the third and seventh post-transplant days
to 67 years with stable renal function in the 6th were lower than pretransplant values (P ≤ 0.001).
postoperative month and without changes in the However, no significant differences in cystatin C
immunosuppressor regimen. Cystatin C, creatinine or creatinine levels were observed between the
and glomerular filtration estimated by creatinine third and seventh day after transplantation. The
clearance, the Cockcroft-Gault formula and the creatinine/cystatin C ratio was reduced on the
MDRD equation were measured. Cystatin C was third day of the post-transplant period and contin-
significantly correlated with creatinine clearance ued to decline on the seventh day. This ratio was
(r = -0.768), Cockcroft-Gault (r = 0.854), serum high in only one patient who presented an acute
creatinine (r = 0.629) and modification of diet in rejection episode. The study showed that cystatin
renal disease (r = 0.604). According to Leach et C was superior to creatinine on the third day of
al29 who studied 21 renal transplant recipients the post-transplant period. However, no apparent
(16 men and 5 women) ranging in age from 21 difference in cystatin C distribution was observed
to 71 years (mean of 51 years) over a period of 5 at the end of the first week, with a sensitivity of
years, serum cystatin C is a promising marker of 0.489 estimated by a nonparametric curve.
glomerular filtration rate during renal transplant In a cohort study, Christensson et al20 evalu-
follow-up, with this marker more rapidly detect- ated the diagnostic accuracy of serum cystatin C
50 Brasília Med 2009;46(1):46-53
CystatiN C iN traNsplaNt patiENts
measurements compared to enzymatic creatinine C was correlated with plasma creatinine (r = 0.741,
measurements as serum markers of glomerular P < 0.001) and the reciprocal of creatinine clear-
filtration rate (established from iohexol clearance) ance estimated by the Cockcroft-Gault formula (r
in 125 stable renal transplant patients and patients = 0.882, P < 0.001). In all three cases of acute renal
in the early postoperative phase with stable graft failure, the increase in plasma cystatin C levels
function. Serum cystatin C showed a significantly was more prominent than creatinemia, with the
closer correlation with iohexol clearance (r = 0.89 authors concluding that cystatin C is an alternative
or 79% covariance) than serum creatinine (r = 0.81 and an accurate marker of graft function in renal
or 66% covariance) (P = 0.033). transplant recipients which is more sensitive than
White et al32 estimated glomerular filtration creatinine in the detection of acute reduction in
rate in 117 adult renal transplant recipients. Glom- glomerular filtration rate.
erular filtration rate was measured by 99mTc- To overcome the disadvantages of serum creati-
DTPA and the bias, precision and accuracy of nine, two strategies have been proposed to identify
each equation were determined. Mean 99TmTc patients with reduced glomerular filtration rate.
using four equations (Filler, Le Bricon, Larson, On the one hand, the modification of diet in renal
and Hoek) that are based on serum cystatin C disease equation is now recommended for the clas-
concentration and seven equations that are based sification of the stage of chronic kidney disease
on serum creatinine -DTPA glomerular filtration and, on the other, cystatin C has been investigated
rate was 58 ± 23 mL/min/1.73m2. The Filler and in numerous studies and has shown a higher sensi-
Le Bricon equations based on cystatin C presented tivity than creatinine in the detection of a reduction
the smallest varia- tion (1.7 and 3.8 mL/min/1.73 in glomerular filtration rate. Poge et al21 compared
m2, respectively) and the highest precision (11.4 the two strategies in patients after transplantation. A
and 11.8 mL/min/1.73 m2) and accuracy (87 and total of 105 consecutive renal transplant recipients
89% in 30% of glomerular filtration rate measure- were submitted to Tc99m-DTPA clearance mea-
ments). The cystatin C-based equations continued surement. Simultaneously, modification of diet in
to be accurate even when glomerular filtration rate renal disease estimates were calculated and serum
was >60 ml/min/1.73 m2. The creatinine-based cystatin C levels were determined. The linear re-
equations were not as accurate, with only 53 to gression curve was analyzed at different decision
80% of estimates in 30% of glomerular filtration points from 20 to 70 ml/min/1.73 m2. The study
rate measurements. The authors concluded that concluded that the modification of diet in renal
cystatin C-based equations are more accurate in disease equation is equivalent to cystatin C mea-
predicting glomerular filtration rate in renal trans- surement in renal transplant recipients. Since the
plant recipients than traditional creatinine-based feasibility of modification of diet in renal disease
equations and that further studies are necessary is superior to that of cystatin C, the authors recom-
to determine whether cystatin C-based estimates mended the use of the modification of diet in renal
of glomerular filtration rate will be sufficiently disease equation for the estimation of glomerular
accurate to monitor long-term graft function. filtration rate. However, cystatin C may serve as
Le Bricon et al26 evaluated renal function in a confirmation test of overestimated modification
30 adult renal transplant recipients and 56 healthy of diet in renal disease in patients with good graft
controls using cystatin C. Cystatin C was deter- function because of its superior accuracy in these
mined daily starting on the day of surgery and for patients. Zahran et al12 compared the performance
3 weeks after surgery by an immunonephelometric of serum cystatin C and cystatin C-based glom-
assay. The results showed that plasma cystatin erular filtration rate versus serum creatinine and
concentration was significantly reduced during the creatinine-based glomerular filtration rate between
first week (-44% vs -29% for creatinine). Cystatin 14 studies on renal transplant patients, with 70% of
Brasília Med 2009;46(1):46-53 51
josé dE riBamar olivEira lima E Cols.
the studies showing superiority of cystatin C over 8. Newman DJ. Cistatina C como marcador de la veloci-
dad de filtración glomerular. Acta Bioquim Clín Latinoam.
serum creatinine. 2003;37:63-70.
9. Roos JF, Doust J, Tett SE, Kirkpatrick CM. Diagnostic
final comment accuracy of cystatin C compared to serum creatinine for
Most studies analyzed in this review showed that the estimation of renal dysfunction in adults and children. A
serum quantification of cystatin C is a satisfactory meta-analysis. Clin Biochem. 2007;40:383-91.
and promising method for the evaluation of renal 10. Riella MC, Pecoits-Filho R. Insuficiência renal crônica:
function in renal transplant patients, especially during fisiopatologia da uremia. In: Miguel Riella (ed). Princípios
de nefrologia e distúrbios hidroeletrolíticos. 4.ª ed. Rio de
the immediate post-transplant period. Cystatin C was Janeiro: Guanabara-Koogan; 2003. p.661-90.
found to be superior when compared to serum creati-
11. Krieser D, Rosenberg AR, Kainer G, Naidoo D. The re-
nine, presenting a higher sensitivity in the detection lationship between serum creatinine, serum cystatin C and
of an acute reduction in glomerular filtration and glomerular filtration rate in pediatric renal transplant recipi-
ents: a pilot study. Pediatr Transplant. 2002;6:392-5.
thus permitting the early identification of alterations
in graft function. In addition, cystatin C is a useful 12. Gantzer ML. Cystatin C: analysis and utility in monitoring
tool for the detection of eventual immunological GFR. Lab Medicine. 2003;34.
and non-immunological processes in the transplant 13. National Kidney Foundation. K/DOQI. Clinical practice
population. However, controlled prospective studies guidelines for chronic kidney disease: evaluation, classifica-
tion, and stratification. Am J Kidney Dis. 2002;39(2 Suppl
involving a larger number of renal transplant patients 1):S1-266.
are necessary to confirm this indication.
14. Pöge U, Gerhardt T, Stoffel-Wagner B, Palmedo H, Klehr
H, Sauerbruch T, Woitas RP. Prediction of glomerular filtra-
thanks to tion rate in renal transplant recipients: cystatin C or modi-
fication of diet in renal disease equation? Clin Transplant.
Dr. Luis Alberto Simeoni, professor at the Uni- 2006;20:200-5.
versity of Brasilia, for reviewing the manuscript.
15. Gaspari F, Ferrari S, Stucchi N, Centemeri E, Carrara
F, Pellegrino M, Gherardi G, Gotti E, Segoloni G, Salvadori
M, Rigotti P, Valente U, Donati D, Sandrini S, Sparacino V,
references Remuzzi G, Perico N; MY.S.S. Study Investigators. Per-
formance of different prediction equations for estimating
1. Shilipak MG. Cystatin C as a marker of glomerular filtration renal function in kidney transplantation. Am J Transplant.
rate in chronic kidney disease: influence of body composition. 2004;4:1826-35.
Nat Clin Pract Nephrol. 2007;3:188-9.
16. Estrada-Zambrano A, Biosca-Adzet C, Bayés-Genís
2. Arias IM, Pobes A, Baños M. Cistatina C. Nuevo marcador B, Doladé-Botias M, Lauzurica-Valdemoros R, Romero-
de función renal. Nefrologia. 2005;25:217-20. González R. Evaluation of the equations to estimate the
glomerular filtration rate in kidney transplant recipients.
3. Prates AB, Amaral FB, Vacaro MZ, Camargo JL, Silveir Transplant Proc. 2007;39:2210-3.
SP. Avaliação da filtração glomerular através da medida da
cistatina C sérica. J Bras Nefrol. 2007;29:48-55. 17. Laterza OF, Price CP, Scott MG. Cystatin C: an improved
estimator of glomerular filtration rate? Clin Chem. 2002;48:5
4. Hojs R, Antolinc B, Gorenjak M, Puklavec L. Serum cystatin 699-707.
C – A new marker of glomerular filtration rate. Zdrav Vestn.
2004;73:171-5. 18. Finney H, Newman DJ, Gruber W, Merle P, Price CP.
Initial evaluation of cystatin C measurement by particle-
5. Martins TR, Fadel-Picheth CM, Alcântara VM, Scartezini enhanced immunonephelometry on the Behring neph-
M, Picheth G. Cistatina C: um novo marcador para filtração elometer systems (BNA, BN II). Clin Chem. 1997;43(6 Pt
glomerular comparada ao clearance de creatinina e à crea- 1):1016-22.
tinina sérica. Rev Bras Anal Clin. 2003;35:207-13.
19. Herget-Rosenthal S, Feldkamp T, Volbracht L, Kribben A.
6. Risch L, Blumberg A, Huber A. Rapid and accurate as- Measurement of urinary cystatin C by particle-enhanced neph-
sessment of glomerular filtration rate in patients with renal elometric immunoassay: precision, interferences, stability and
transplants using serum cystatin C. Nephrol Dial Transplant. reference range. Ann Clin Biochem. 2004;41(Pt 2):111-8.
20. Christensson A, Ekberg J, Grubb A, Ekberg H, Lindström
7. Pecoits-Filho R. Diagnóstico de doença renal crônica: ava- V, Lilja H. Serum cystatin C is a more sensitive and more
liação da função renal. J Bras Nefrol. 2004;26(Supl. 1):4-5. accurate marker of glomerular filtration rate than enzymatic
52 Brasília Med 2009;46(1):46-53
CystatiN C iN traNsplaNt patiENts
measurements of creatinine in renal transplantation. Nephron perior to 24-h creatinine clearance and plasma creatinine for
Physiol. 2003;94:19-27. estimation of glomerular filtration rate 3 months after kidney
transplantation. Clin Chem. 2000;46(8 Pt 1):1206-7.
21. Zahran A, El-Husseini A, Shoker, A. Can cystatin C
replace creatinine to estimate glomerular filtration rate? A 28. Visvardis G, Griveas I, Zilidou R, Papadopoulou D, Mitso-
literature review. Am J Nephrol. 2007;27:197-205. poulos E, Kiriklidou P, Manou E, Ginikopoulou E, Meimaridou
D, Pavitlou A, Sakellariou G. Glomerular filtration rate estima-
22. Okay TS. Cistatina C: um novo marcador de função renal tion in renal transplant patients based on serum cystatin-C
em crianças. Rev Assoc Med Bras. 2002;48:93-117. levels: comparison with other markers of glomerular filtration
rate. Transplant Proc. 2004;36:1757-9.
23. Dharnidharka VR, Know C, Stevens G. Serum cystatin C
is superior to serum creatinine as a marker of kidney function: 29. Leach TD, Kitiyakara C, Price CP, Stevens JM, Newman
a meta-analysis. Am J Kidney Dis. 2002;40:221-6. DJ. Prognostic significance of serum cystatin C concentra-
tions in renal transplant recipients: 5-year follow-up. Trans-
24. Wasén E, Suominen P, Isoaho R, Mattila K, Virtanen plant Proc 2002;34:1152-8.
A, Kivelä SL, Irjala K. Serum cystatin C as a marker of
kidney dysfunction in an elderly population. Clin Chem. 30. Akbas SH, Yavuz A, Tuncer M, Ruhi C. Gurkan A, Cetin-
2002;48:1138-40. kaya R, Demirbas A, Gultekin M, Akaydin M, Ersoy F. Serum
cystatin C as an index of renal function in kidney transplant
25. Chew JS, Saleem M, Florkowski CM, George PM. Cys- patients. Transplant Proc. 2004;36:99-101.
tatin C – a paradigm of evidence based laboratory medicine.
Clin Biochem Rev. 2008;29;47-62. 31. Koçak H, Oner-Iyidogän Y, Gürdol F, Koçak T, Nane I,
Genc S. Cystatin-C and creatinine as indices of glomerular
26. Le Bricon TL, Thervet E, Benlakehal M, Bousquet B, filtration rate in the immediate follow-up of renal transplant
Legendre C, Erlich D. Changes in plasma cystatin C after patients. Clin Exp Med. 2005;5:14-9.
renal transplantation and acute rejection in adults. Clin Chem.
1999;45:2243-9. 32. White C, Akbari A, Hussain N, Dinh L, Filler G, Lepage N,
Knoll GA. Estimating glomerular filtration rate in kidney trans-
27. Le Bricon TL, Thervet E, Froissart M, Benlakehal M, plantation: a comparison between serum creatinine and cys-
Bousquet B, Legendre C, Erlich D. Plasma cystatin C is su- tatin C-based methods. J Am Soc Nephrol. 2005;16:3763-70.
Termo usado como reforço de expressão, mas é cientificamente errôneo. Amiúde, “inúmeros” tem sido usado em
referência a elementos contáveis. Os números são infinitos. Logo, qualquer quantidade é numerável. É contestável citar,
portanto, num relato formal, que “o paciente sofreu inúmeras operações” ou que “podem ocorrer inúmeras complicações” e
ditos semelhantes. Podemos substituir termos como inúmeros, um sem-número e inumeráveis por numerosos, copiosos,
muitos, vários, grande número, elevado ou alto número de. Há elementos incontáveis (mas não inumeráveis), como
estrelas, grãos de areia no mar, folhas nas florestas.
Fonte: Bacelar S, Galvão CC, Alves E, Tubino P. Expressões médicas – Glossário de dúvidas e dificuldades da linguagem médica. Brasília:
brasíliamédica Stilo Gráfica; 2008.
Brasília Med 2009;46(1):46-53 53