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Background
Cystatin C is a novel serum marker of the glomerular filtration rate (GFR), a critical measure of normal kidney function. The FDA has approved Dade-Behring's automated immunoassay for this marker. Studies indicate that it is at least as good as serum creatinine for detecting renal dysfunction.
REFERENCE METHODS CHARACTERIZATION Reference intervals for serum cystatin C and serum creatinine in adults.
Erlandsen EJ, Randers E, Kristensen JH.
Department of Clinical Biochemistry, Viborg County Hospital, Denmark.
Clin Chem Lab Med 1998 Jun;36(6):393-7 Abstract quote
The aim of this study was to establish reference intervals for cerum cystatin C and serum creatinine in adults.
Blood samples were collected from 270 healthy blood donors (135 men and 135 women between 20 and 65 years old with 15 men and 15 women in each five-year-interval). Serum cystatin C was analyzed using an automated particle-enhanced immunoassay (DAKO Cystatin C PET kit) on the Cobas Mira S analyzer. Serum creatinine was analyzed using the Vitros Creatinine Slide, an enzymatic method on the Vitros 950 chemistry analyzer. The calculated reference intervals for serum cystatin C were 0.62-1.15 mg/l in women (median 0.84 mg/l, range 0.56-1.29 mg/l) and 0.51-1.25 mg/l in men (median 0.87 mg/l, range 0.42-1.39 mg/l). The Mann-Whithey U-test revealed no gender-related difference for cystatin C (p = 0.48).
A common reference interval in women and men was calculated to be 0.54-1.21 mg/l (median 0.85 mg/l, range 0.42-1.39 mg/l). The non-parametric reference interval for serum creatinine was 57-95 mumol/l in women (median 72 mumol/l, range 44-105 mumol/l) and 69-111 mumol/l in men (median 89 mumol/l, range 58-123 mumol/l).
Cystatin C in healthy women at term pregnancy and in their infant newborns: relationship between maternal and neonatal serum levels and reference values.
Cataldi L, Mussap M, Bertelli L, Ruzzante N, Fanos V, Plebani M.
Pediatric Department, School of Medicine, Catholic University of Roma, Italy.
Am J Perinatol 1999;16(6):287-95 Abstract quote
Human cystatin C, a basic low molecular mass protein with 120 amino acid residues, is freely filtered by the glomerulus and almost completely reabsorbed and catabolized by the proximal tubular cells. Cystatin C has been recently proposed as a new sensitive endogenous serum marker for the early assessment of changes in the glomerular filtration rate.
To define a reference basis for future clinical investigations in the perinatal period, we investigated the relationship between maternal and neonatal serum cystatin C in comparison with that of creatinine. We also defined reference values in healthy women at full-term pregnancy and in full-term newborns over the first 5 days of life.
Seventy-eight women with uncomplicated pregnancy, aged between 19 and 40 years, and their infant newborns (43 males, 35 females) were enrolled in the study. The gestational age ranged from 37 to 43 weeks, and the birth weight from 2.50 to 4.15 kg. Blood samples were taken from all the women immediately before delivery and from their newborns at birth, 72 and 96 h after birth. Maternal and neonatal renal function was evaluated by standards parameters and by calculating creatinine clearance. In all serum samples, we measured cystatin C, creatinine, and urea. At term gestation, serum cystatin C ranged from 0.64 to 2.30 mg/L. At birth, serum cystatin C values ranged from 1.17 to 3.06 mg/L, significantly decreasing after 3 and 5 days of life.
No correlation was found between maternal and neonatal serum cystatin C values (r = 0.09). As cystatin C serum levels in newborns are not significantly correlated with the respective maternal levels, neonatal serum cystatin C may originate almost exclusively in the neonate.
Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance.
Finney H, Newman DJ, Price CP.
Department of Clinical Biochemistry, St Bartholomew's and The Royal London School of Medicine and Dentistry, UK.
Ann Clin Biochem 2000 Jan;37 ( Pt 1):49-59 Abstract quote
Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range.
Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68-118 mumol/L, 58-120 ml/min/1.73 m2 and 0.51-0.98 mg/L, respectively. For women, the intervals were 68-98 mumol/L, 60-119 ml/min/1.73 m2 and 0.49-0.94 mg/L; for men, they were 78-123 mumol/L, 57-122 ml/min/1.73 m2 and 0.56-0.98 mg/L. This mean 95% reference interval for cystatin C in all donors under 50 years of age was 0.53-0.92 mg/L; for those over 50 years of age it was 0.58-1.02 mg/L. The small difference between make and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area.
Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.
Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.
Finney H, Newman DJ, Thakkar H, Fell JM, Price CP.
Department of Clinical Biochemistry, St Bartholomew's and The Royal London, School of Medicine and Dentistry, Turner Street, London E1 2AD, UK.
Arch Dis Child 2000 Jan;82(1):71-5 Abstract quote
AIM: To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine.
METHODS: Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaff?e methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36 weeks.
RESULTS: In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 micromol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex.
CONCLUSION: The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population
CLINICAL UTILITY CHARACTERIZATION Is serum cystatin C a sensitive marker of glomerular filtration rate (GFR)? A preliminary study on renal transplant patients.
Plebani M, Dall'Amico R, Mussap M, Montini G, Ruzzante N, Marsilio R, Giordano G, Zacchello G.
Department of Laboratory Medicine, Central Laboratory, Azienda Ospedaliera, Padova, Italy.
Ren Fail 1998 Mar;20(2):303-9 Abstract quote
Human cystatin C is a basic low molecular mass protein (13,359 Dalton) freely filtered through the glomerulus and almost completely re-absorbed and catabolized by proximal tubular cells.
We measured serum cystatin C in 38 kidney transplant patients (23 males, 15 females) aged between 6 and 32 years. To assess renal function, serum and urinary creatinine were also determined in all patients, and creatinine clearance was finally calculated. Cystatin C was determined by a particle-enhanced turbidimetric assay, and creatinine was measured by gas chromatography-mass spectrometry. To compare the diagnostic efficiency of cystatin C with that of creatinine, inulin clearance was performed on 12 renal transplant patients, and receiver operating characteristic (ROC) analysis was applied.
The results of this study demonstrate that serum cystatin C significantly increases in renal transplant patients with reduced creatinine clearance (< 70 mL/min per 1.73 m2) and that the diagnostic accuracy of serum cystatin C is better than of serum creatinine. Cystatin C may be utilized as a very marker of reduced GFR.
Changes in plasma cystatin C after renal transplantation and acute rejection in adults.
Le Bricon T, Thervet E, Benlakehal M, Bousquet B, Legendre C, Erlich D.
Laboratoire de Biochimie A, Service de Nephrologie et Transplantation Renale, and Laboratoire de Biochimie B, Hopital St-Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
Clin Chem 1999 Dec;45(12):2243-9 Abstract quote
BACKGROUND: Cystatin C has recently been proposed as an alternative marker of glomerular filtration rate. The diagnostic value of plasma cystatin C for the longitudinal assessment of kidney function after renal transplantation, however, has not been addressed.
METHODS: Renal function was evaluated in 30 adults receiving renal transplants (46 +/- 9 years, mean +/- SD) and in 56 healthy controls (38 +/- 10 years) using cystatin C. Plasma cystatin C was determined daily starting the day of surgery and for 3 weeks after surgery by an immunonephelometric assay.
RESULTS: Plasma concentration significantly decreased during the first week (-44% vs -29% for creatinine). Plasma cystatin C correlated with plasma creatinine (r = 0.741; P <0.0001) and the reciprocal of the creatinine clearance estimated by the Cockcroft-Gault formula (r = 0.882; P <0.001). In all three cases of acute renal impairment, the increase in plasma cystatin C values was more prominent than that of creatinine.
CONCLUSIONS: Plasma cystatin C is an alternative and accurate marker of allograft function in adult transplant patients. Increased sensitivity compared with creatinine for the detection of acute reduction in glomerular filtration rate allows in some cases a more rapid diagnosis of acute rejection or treatment nephrotoxicity.
Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate.
Filler G, Priem F, Vollmer I, Gellermann J, Jung K.
Department of Paediatric Nephrology, Charite Hospital, Humboldt University, Berlin, Germany.
Pediatr Nephrol 1999 Aug;13(6):501-5 Abstract quote
Recently, the reciprocal of cystatin C (Cys-C), a non-glycosylated 13-kilodalton protein that is produced by all investigated nucleated cells, was found to correlate closely with glomerular filtration rate (GFR).
In order to determine the diagnostic validity in children for the detection of impaired GFR, venous blood samples from 381 children (aged 1.7-18 years) with various renal pathology referred for 51Cr-EDTA clearance investigations were obtained for measurement of Cys-C as well as beta2-microglobulin (beta2-MG) and serum creatinine. Two hundred and sixteen children with clearance values >90 ml/min per 1.73 m2 constituted a control group, with a normal GFR. In the control group, Cys-C values were normally distributed with a mean of 0.94+/-0.27 mg/l and an upper reference limit (97.5th percentile) of 1.47 mg/l. In all children, there was a positive correlation between 51Cr-EDTA clearance and the reciprocal of Cys-C (r=0.64, P<0.0001), beta2-MG (r=0.59, P<0.0001), creatinine (r=0.55, P<0.0001), and the height/creatinine ratio (r=0.73, Pz0.0001). Receiver-operating characteristics analysis showed that there were no significant differences between these three parameters for discriminating between patients with normal and reduced GFR, although there was a tendency towards the best diagnostic sensitivity of the GFR estimate according to the Schwartz formula.
We conclude that for the detection of mildly impaired GFR, a full clearance study cannot be replaced by measurement of serum Cys-C or beta2-MG concentrations.
Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy.
Stabuc B, Vrhovec L, Stabuc-Silih M, Cizej TE.
Institute of Oncology, Zaloska 2, 1000 Ljubljana, Slovenia. Faculty of Medicine, Vrazov trg 4, 1000 Ljubljana, Slovenia.
Clin Chem 2000 Feb;46(2):193-7 Abstract quote
BACKGROUND: Serum cystatin C, a cysteine protease inhibitor, has been suggested as a new marker of glomerular filtration rate (GFR). This study explored the possibility of replacing the creatinine clearance (CrCl) estimation of GFR with cystatin C in early detection of renal impairment in cancer patients on chemotherapy.
METHODS: Serum creatinine and cystatin C concentrations as well as 24-h CrCl were determined simultaneously in 72 cancer patients. Among them, 60 were treated with combined chemotherapy with cisplatin (CDDP). Creatinine was determined enzymatically with a spectrophotometric method. Serum cystatin C was determined by a particle-enhanced turbidimetric immunoassay.
RESULTS: Cystatin C and creatinine correlated significantly (P = 0.001) with CrCl. The correlation was significantly better for cystatin C than creatinine (r = 0.84 vs 0.74; P = 0.01). Stepwise regression analysis identified no differences for the correlations between cystatin C and CrCl in patients with or without metastases (r = 0.82 and 0.84, respectively) as well as before treatment and before the fourth cycle of chemotherapy (r = 0.70 and 0.75, respectively). A cystatin C cutoff concentration of 1.33 mg/L had 87% sensitivity and 100% specificity for detecting CrCl <78 mL/min. ROC analysis indicated that cystatin C was superior to serum creatinine for predicting CrCl <78 mL/min (P <0.04).
CONCLUSIONS: Serum cystatin C is superior to serum creatinine for detection of decreased CrCl and potentially for the estimation of GFR in cancer patients independent of the presence of metastases or chemotherapy.
Diagnostic value of serum cystatin C for evaluation of hepatorenal syndrome.
Demirtas S, Bozbas A, Akbay A, Yavuz Y, Karaca L.
Central Laboratory, Faculty of Medicine, Ankara University, Ibn-i Sina Hospital, Sihhiye, Ankara 06100, Turkey
Clin Chim Acta 2001 Sep 25;311(2):81-9 Abstract quote
BACKGROUND: The evaluation of renal function in patients with decompensated cirrhosis is important for prognosis, dosage assessment of potentially nephrotoxic drugs and recognition of changes in glomerular filtration rate (GFR) to decide paracentesis and diuretic therapy. Patients with many different disorders of hepatic function can present with various abnormalities of renal function in the absence of other known causes of renal failure which has been called hepatorenal syndrome (HRS). Some reports have pointed out that serum creatinine levels frequently failed to rise above normal levels even when glomerular filtration rate (GFR) is very low in cirrhotic patients with hepatorenal syndrome. The aim of this study was to determine if estimation of serum cystatin C could replace creatinine clearance in routine GFR determinations for patients with cirrhosis.
METHODS: Serum cystatin C, creatinine clearance (Clcr), and 99mTc-DTPA clearance were determined in 26 patients with cirrhosis. According to Child-Pugh's classification, 21 patients were in group C and 5 were in Group B.
RESULTS: Pearson correlation analyses showed that correlation between serum cystatin C and 99mTc-DTPA clearance was r=-0.522, p=0.006, between serum creatinine and 99mTc-DTPA was r=-0.373, p=0.06. The results of our study demonstrated that neither serum creatinine nor creatinine clearance (Clcr) were good indicators of hepatorenal syndrome because the mean value for Clcr was found to be higher than Tc-DTPA clearance, and there was no correlation between these two parameters (r=0.059). Additionally, the mean value of serum creatinine was found to be within the normal range, whereas the mean DTPA clearance level was lower than normal range.
CONCLUSIONS: This finding could be explained by the fact that cirrhotic patients with poor nutrition may have decreased protein intake, low muscle mass and lack of converting capacity of creatine to creatinine. Thus, we suggest that serum cystatin C assay, which has good analytical performance, could replace or at least be added to creatinine measurement for GFR assessment in patients with cirrhosis.
Fetal serum concentrations of cystatin C and beta2-microglobulin as predictors of postnatal kidney function.
Bokenkamp A, Dieterich C, Dressler F, Muhlhaus K, Gembruch U, Bald R, Kirschstein M. Bonn
University Children's Hospital, Bonn, Germany.
Am J Obstet Gynecol 2001 Aug;185(2):468-75 Abstract quote
OBJECTIVES: Cystatin C and beta(2)-microglobulin are established serum markers of renal function in children and adults. In contrast to creatinine, diaplacental exchange is minimal. The aim of the study was to establish reference values in fetal serum and to test their efficiency in predicting postnatal kidney function.
STUDY DESIGN: This was a prospective noninterventional study measuring cystatin C and beta(2)-microglobulin by particle-enhanced immunoturbidimetry in excess serum from 129 cordocenteses performed in 84 fetuses. Reference intervals (mean +/- 1.96 SD) were calculated in a subgroup of 54 fetuses without evidence of kidney disease, and these reference values were evaluated in 75 sera from 55 fetuses.
RESULTS: Mean cystatin C was 1.66 +/- 0.202 mg/L (upper limit 2.06), and mean beta(2)-microglobulin was 4.25 +/- 0.734 mg/L. Unlike cystatin C, beta(2)-microglobulin decreased significantly with gestational age so that the upper reference limit was 7.19-0.052 x gestational age in weeks. beta(2)-Microglobulin had higher sensitivity (90.0% vs 63.6%) and cystatin C a higher specificity (91.8% vs. 85.5%) for the prediction of impaired renal function; diagnostic efficiency was equal (87.6% vs. 86.1%). Fetuses with impaired renal function at birth or who were aborted for renal malformations had higher cystatin C concentrations than those in a control group. beta(2)-Microglobulin was increased only in fetuses who were aborted.
CONCLUSION: Fetal serum cystatin C and beta(2)-microglobulin concentrations may be useful predictors of postnatal kidney function.
Assessment of renal function in renal transplant patients using cystatin C. A comparison to other renal function markers and estimates.
Risch L, Blumberg A, Huber AR.
Department of Laboratory Medicine, Kantonsspital Aarau, Switzerland.
Ren Fail 2001 May-Jul;23(3-4):439-48 Abstract quote
To date, little evidence is available to define the role of cystatin C in patients with renal transplants. Thus, to assess, whether cystatin C (CysC) provides better information on renal function than other markers, CysC, creatinine clearance (CrCl), serum creatinine (SCr), beta2-microglobulin (beta2-M), and 125I-Iothalamate clearance were determined in 30 patients.
Correlation and ROC curves were obtained and characteristics like sensitivity and specificity were calculated. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation for CysC and SCr measurements were compared in 85 renal transplant patients. CysC correlated best with GFR, whereas SCr, CrCl and beta2-M all had lower correlation coefficients. CysC was superior to SCr, even when renal function equations of were used. The diagnostic accuracy of CysC was significantly better than SCr. but did not differ significantly from CrCl and beta2-M. Together, our data show that in patients with renal transplants, CysC has a similar diagnostic value as CrCl. However, it is superior to determinations of SCr. The intraindividual variation of CysC is significantly greater than that of SCr. This might be due to better ability of CysC to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment.
In conclusion, CysC allows for easy and accurate assessment of renal function (GFR) in steady state renal transplant patients and is clearly superior to the commonly used serum creatinine.
Cystatin C is not more sensitive than creatinine for detecting early renal impairment in patients with diabetes.
Oddoze C, Morange S, Portugal H, Berland Y, Dussol B.
Laboratoire Central and Centre d'Investigation Clinique, Hopital Sainte Marguerite.
Am J Kidney Dis 2001 Aug;38(2):310-6 Abstract quote
This study evaluated serum cystatin C as a potential new marker of glomerular filtration rate (GFR) in 49 patients who had steady-state diabetes with early renal impairment.
We determined the correlation between GFR measured by chromium 51-labeled EDTA and levels of serum cystatin C, serum creatinine, serum beta(2)-microglobulin, endogenous creatinine clearance, and Cockcroft formula. Sensitivity and specificity for the diagnosis of renal failure, defined as a GFR less than either 80 or 60 mL/min/1.73 m(2), were calculated by receiver operating characteristic (ROC) curves for creatinine, cystatin C, and beta(2)-microglobulin. Finally, we compared mean values of these three serum parameters in patients grouped according to GFR using the two definitions of renal failure.
Correlation coefficients with GFR were -0.77 for serum creatinine level, -0.65 for serum cystatin C level, -0.71 for serum beta(2)-microglobulin level, +0.56 for endogenous creatinine clearance, and +0.69 for Cockcroft formula (all P < 0.001). With a cutoff value of 60 mL/min/1.73 m(2), areas under the ROC curve were 0.972 for beta(2)-microglobulin, 0.925 for cystatin C, and 0.916 for creatinine levels. With a cutoff value of 80 mL/min/1.73 m(2), these were 0.838 for beta(2)-microglobulin, 0.780 for cystatin C, and 0.905 for creatinine levels (P = not significant between parameters). These results were not altered after the exclusion of patients (n = 8) with a serum creatinine level greater than 1.41 mg/dL. When patients were classified into three groups according to GFR (group 1, >80 mL/min/1.73 m(2); group 2, 60 to 80 mL/min/1.73 m(2); group 3, <60 mL/min/1.73 m(2)), mean values of serum parameters in the three groups were statistically different (P < 0.0001) except between groups 1 and 2 for cystatin C and beta(2)-microglobulin. With patients classified into two groups (GFR > or < 80 mL/min/1.73 m(2)), mean values for each parameter were statistically different (P < 0.001).
Sensitivity, specificity, and positive and negative predictive values for serum creatinine and serum cystatin C levels were very close for both definitions of renal failure. Serum cystatin C is not better than serum creatinine or serum beta(2)-microglobulin levels for estimating GFR in patients with steady-state diabetes using ROC curves or other validation tests.
Cystatin C is an independent predictor of fasting and post-methionine load total homocysteine concentrations among stable renal transplant recipients.
Aras O, Tsai MY, Hanson NQ, Bailey R, Rao G, Hunninghake DB.
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455-0392, USA.
Clin Chem 2001;47(7):1263-8 Abstract quote
BACKGROUND: An increased prevalence of hyperhomocysteinemia with an increased incidence of cardiovascular disease events has been reported among stable renal transplant recipients (RTRs). Preliminary studies in a small number of these individuals have shown that serum creatinine and cystatin C, both markers of kidney function and glomerular filtration rate, are independent determinants of fasting tHcy concentrations; however, determinants of tHcy concentrations after a methionine load have not been studied.
METHODS: We determined the prevalence of both fasting and 4-h post-methionine load (PML) tHcy concentrations in 78 stable RTRs and compared the role of cystatin C with the role of serum creatinine as determinants of fasting and PML tHcy.
RESULTS: Of the 78 RTRs, 21 (26.9%) had fasting and PML tHcy within the respective reference intervals, and 57 (73.1%) had increased plasma tHcy. Of these 57 RTRs, 22 had fasting hyperhomocysteinemia, 9 had PML hyperhomocysteinemia, and 26 had combined hyperhomocysteinemia (both fasting and PML). Unadjusted Pearson correlations showed that fasting plasma tHcy correlated with both cystatin C (r = 0.564; P <0.001) and creatinine (r = 0.519; P <0.001) and that increases in PML tHcy modestly correlated with cystatin (r = 0.205; P = 0.072), but not creatinine (r = 0.057; P = 0.624). General linear regression modeling with stepwise analysis of covariance showed that both cystatin C (partial R = 0.554; P <0.001) and creatinine (partial R = 0.535; P <0.001) were independent predictors of fasting tHcy, but of the two, only cystatin C (partial R = 0.242; P = 0.035) was an independent predictor of increased PML tHcy.
CONCLUSIONS: Clinically stable RTRs have an excess prevalence of moderate hyperhomocysteinemia, and additional cases can be detected by methionine loading. Both creatinine and cystatin C are independent predictors of fasting tHcy in these individuals; however, only cystatin C is a determinant of tHcy concentration after a methionine load, probably because cystatin C is a more sensitive marker of glomerular filtration rate than serum creatinine.
INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS CHARACTERIZATION Biological variation of cystatin C: implications for the assessment of glomerular filtration rate.
Keevil BG, Kilpatrick ES, Nichols SP, Maylor PW.
Department of Clinical Biochemistry, University Hospital of South Manchester, Wythenshawe Hospital, UK.
Clin Chem 1998 Jul;44(7):1535-9 Abstract quote
To assess the inherent potential for detecting mild to moderate reductions in glomerular filtration rate, this study determined the biological variability of serum cystatin C and creatinine in 12 healthy subjects.
After accounting for analytical variation, interindividual variance accounted for 93% and intraindividual variance accounted for 7% of serum creatinine biological variation. As such, to lie outside the assay reference interval, some subjects must exceed 13 SD from their usual mean value, whereas in others, a change of only 2 SD would be sufficient. For cystatin C, interindividual variation explained 25% and intraindividual variance explained 75% of biological variability. Therefore, the upper limit of the population reference interval for cystatin C is seldom more than 3-4 SD from the mean value of any healthy individual. The critical difference for sequential values significant at P < or = 0.05 was calculated as 37% for serum cystatin C and 14% for serum creatinine.
We conclude that cystatin C is potentially a better marker for detecting impaired renal function than serum creatinine, but serum creatinine is probably still the better marker for detecting temporal changes of renal function in individuals with established renal disease.
Elevation of serum cystatin C concentrations in patients with chronic liver disease.
Takeuchi M, Fukuda Y, Nakano I, Katano Y, Hayakawa T.
Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Eur J Gastroenterol Hepatol 2001 Aug;13(8):951-5 Abstract quote
OBJECTIVE: We examined serum cystatin C concentrations in patients to explore the possible clinical application of cystatin C as a marker of disease severity in cases of chronic liver diseases.
METHODS: Serum cystatin C concentrations were determined by an enzyme-linked immunosorbent assay kit in 103 patients with various chronic liver diseases and compared with concentrations in healthy control volunteers.
RESULTS: The mean cystatin C concentration was 0.68 +/- 0.03 mg/l in chronic hepatitis patients, 1.13 +/- 0.09 mg/l in liver cirrhosis patients and 1.16 +/- 0.10 mg/l in hepatocellular carcinoma patients, all significantly higher than concentrations in the control volunteers (P < 0.0001). Significant correlations were observed between cystatin C concentrations and total bilirubin levels, albumin levels, platelet levels, type IV collagen levels and hyaluronic acid levels. Serum cystatin C concentrations correlated well with histological stages despite the lack of correlation with histological grades.
CONCLUSION: Our results show that serum cystatin C increases with the progression of chronic liver disease and that it is a potential marker for liver fibrosis.
Determination of serum cystatin C: biological variation and reference values.
Galteau MM, Guyon M, Gueguen R, Siest G.
Laboratoire de Biologie Clinique, Centre de Medecine Preventive, Vandoeuvre-Les-Nancy, France.
Clin Chem Lab Med 2001 Sep;39(9):850-7 Abstract quote
Human cystatin C is a low molecular weight protein which has been proposed as a better marker of glomerular filtration rate than creatinine. To be able to interpret results obtained in different patient populations it is necessary to define cystatin C reference values.
We measured serum concentration of cystatin C in 1223 subjects using a particle-enhanced nephelometric assay. Subjects were aged 4 to 79 years and were selected among apparently healthy individuals who came to the Centre for Preventive Medicine in Vandoeuvre-Les-Nancy, France. We observed a Gaussian distribution of cystatin C concentration in serum. We did not find any effect of age or gender in children, hormonal status in women (puberty, menopause, oral contraceptives or hormone replacement therapy) or alcohol intake. Cystatin C concentration was slightly lower in female than in male adults below the age of 60 years. Cystatin C levels significantly increased above the age of 60 in both males and females, probably due to physiological aging of renal function. No other significant differences were observed between males and females.
Using multiple regression analysis, moderate correlations were observed between body mass index and cystatin C, and between smoking and cystatin C, but these were not biologically significant. According to the literature, only methylprednisolone and cyclosporin A increased and decreased cystatin C levels, respectively. The reference values for cystatin C obtained in a carefully selected population were 0.75+/-0.089 mg/l for children aged 4-19 years, 0.74+/-0.100 mg/l for males and 0.65+/-0.085 mg/l for females (aged 20-59 years), and 0.83+/-0.103 mg/l for older individuals (> or =60 years).
Serum cystatin C-immunoglobulin high-molecular-weight complexes in kidney and liver transplant patients.
Hermida J, Romero R, Tutor JC.
Laboratorio Central y Servicio de Nefrologia, Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Kidney Int 2001 Oct;60(4):1561-4 Abstract quote
BACKGROUND: It has been suggested recently that the glomerular filtration rate (GFR) in renal transplant patients is underestimated by serum cystatin C due to an impaired filtration of complexed cystatin C with immunoglobulins. Consequently, serum cystatin C may not be a reliable marker of GFR in these patients. Our study was designed to determine whether this supposition is correct.
METHODS: In 87 serum samples from patients with various kidney diseases, 182 samples from renal transplant patients, and 72 samples from liver transplant patients, the concentrations of cystatin C and creatinine were determined, as well as the residual concentration of cystatin C after precipitation of macromolecules with polyethylene glycol (PEG; 6000 molecular weight).
RESULTS: The residual concentration of serum cystatin C after precipitation with PEG in all cases was much higher (70 to 100%) than that expected in the case of the existence of cystatin C-immunoglobulin complexes. In the kidney and liver transplant patients, there was no significant correlation between the residual concentration of cystatin C and the postoperative time (r = -0.098).
CONCLUSIONS: The results suggest that in renal or liver transplant patients there is no formation of high molecular weight serum cystatin C-immunoglobulin complexes, regardless of the post-transplant period.
Serum cystatin C in patients with myeloma.
Finney H, Williams AH, Price CP.
Department of Clinical Biochemistry, The Royal London Hospital, Barts and The London NHS Trust, Whitechapel, E1 1BB, London, UK.
Clin Chim Acta 2001 Jul 5;309(1):1-6 Abstract quote
BACKGROUND: Cystatin C is a low molecular weight protein thought to be synthesised by all nucleated cells and freely filtered by the kidney. It has been proposed as a marker for GFR; however, it has been suggested that there may be limitations to its use, because it may be over-expressed in some tumour cells and the abnormal tissue growth may also lead to an increased circulating level.
METHODS: We investigated the serum cystatin C levels in 60 patients with myeloma, comparing results with those for serum creatinine, beta(2)-microglobulin and the paraprotein concentration. Results: We found no correlation between cystatin C and the paraprotein concentration in these patients.
CONCLUSION: These results suggest that disease burden does not correlate to the circulating level of cystatin C in patients with myeloma.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
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