Serum cystatin C as a reliable marker of changes in glomerular filtration rate in children with urinary tract malformations

PURPOSE: Cystatin C has been suggested as a simple method of estimating GFR more accurately than creatinine in children. We compared the diagnostic accuracy of cystatin C with serum creatinine and the Schwartz formula for estimating GFR in patients with UTMs. MATERIALS AND METHODS: We prospectively compared 72 patients with UTMs (20 days to 36 months old, 58 males and 14 females) with a group of 72 healthy controls (10 days to 48 months old, 53 males and 19 females). All patients underwent nuclear medicine clearance investigations with (99m)Tc DTPA. RESULTS: Serum concentration of cystatin C revealed a higher correlation with (99m)Tc DTPA (r = 0.62, p <0.001) than serum concentration of creatinine (r = 0.30, p <0.01) or Schwartz formula (r = 0.51, p <0.001). These results were more evident in patients with uropathy (19) with mild renal impairment. Agreement between methods was assessed using Bland Altman analysis. Mean differences between GFR calculated with (99m)Tc DTPA and cystatin C based GFR estimation or Schwartz formula were -2.6% +/- 46.7% and -73.4% +/- 53.6%, respectively. Diagnostic accuracy in identifying decreased GFR measured as AUC was always highest for cystatin C but hardly sufficient for the 3 variables. Cystatin C performed better in the 0 to 6-month-olds (0.70 +/- 0.08 for cystatin C, 0.58 +/- 0.07 for Schwartz estimate) and patients older than 12 months (0.82 +/- 0.09 for cystatin C, 0.65 +/- 0.11 for Schwartz estimate). CONCLUSIONS: Cystatin C proved to be a superior marker rate over serum creatinine in estimating glomerular filtration in children younger than 3 years with UTMs and mild renal impairment, thus, offering a more specific and practical measure for monitoring GFR.     

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C.

BACKGROUND: Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. METHODS: Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, beta2-microglobulin (beta2M), and [125I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. RESULTS: Cystatin C correlated best with GFR (r=0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and beta2M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and beta2M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For beta2M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 micromol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. CONCLUSION: Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and beta2M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.     

Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function.

BACKGROUND: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C was proposed as a new endogenous marker of GFR and in our study its diagnostic accuracy was compared with that of other markers of GFR. METHODS: In this study, 164 patients with CKD stages 2-3 (GFR 30-89 ml/min/1.73 m2), who had performed 51Cr-labelled ethylenediaminetetra-acetic acid clearance, were enrolled. In each patient, serum creatinine and serum cystatin C were determined. Creatinine clearance was calculated using the Cockcroft-Gault (C&G) and the modification of diet in renal disease (MDRD) formulas. RESULTS: The mean 51CrEDTA clearance was 57 ml/min/1.73 m2, the mean serum creatinine 149 micromol/l and the mean serum cystatin C 1.74 mg/l. We found significant correlation between 51CrEDTA clearance and serum creatinine (R = -0.666), serum cystatin C (R = -0.792), reciprocal of serum creatinine (R = 0.628), reciprocal of serum cystatin C (R = 0.753) and calculated creatinine clearance from the formulas C&G (R = 0.515) and MDRD formulas (R = 0.716). The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that serum cystatin C had a significantly higher diagnostic accuracy than serum creatinine (P = 0.04) and calculated creatinine clearance from the C&G formula (P < 0.0001), though only in female patients. No difference in diagnostic accuracy was found between serum cystatin C and creatinine clearance calculated from the MDRD formula. CONCLUSIONS: Our results indicate that serum cystatin C is a reliable marker of GFR in patients with mildly to moderately impaired kidney function and has a higher diagnostic accuracy than serum creatinine and calculated creatinine clearance from the C&G formula in female patients.     

Glomerular filtration rate estimated by cystatin C among different clinical presentations

Glomerular filtration rate (GFR) estimates from serum creatinine has not been generalizable across all populations. Cystatin C has been proposed as an alternative marker for estimating GFR. The objective of this study was to compare cystatin C with serum creatinine for estimating GFR among different clinical presentations. Cystatin C and serum creatinine levels were obtained from adult patients (n=460) during an evaluation that included a GFR measurement by iothalamate clearance. Medical records were abstracted for clinical presentation (healthy, native chronic kidney disease or transplant recipient) at the time of GFR measurement. GFR was modeled using the following variables: cystatin C (or serum creatinine), age, gender and clinical presentation. The relationship between cystatin C and GFR differed across clinical presentations. At the same cystatin C level, GFR was 19% higher in transplant recipients than in patients with native kidney disease (P<0.001). The association between cystatin C and GFR was stronger among native kidney disease patients than in healthy persons (P<0.001 for statistical interaction). Thus, a cystatin C equation was derived using only patients with native kidney disease (n=204). The correlation with GFR (r(2)=0.853) was slightly higher than a serum creatinine equation using the same sample (r(2)=0.827), the Modification of Diet in Renal Disease equation (r(2)=0.825) or the Cockcroft-Gault equation (r(2)=0.796). Averaged estimates between cystatin C and serum creatinine equations further improved correlation (r(2)=0.891). Cystatin C should not be interpreted as purely a marker of GFR. Other factors, possibly inflammation or immunosuppression therapy, affect cystatin C levels. While recognizing this limitation, cystatin C may improve GFR estimates in chronic kidney disease patients.     

Serum cystatin C--a superior marker of rapidly reduced glomerular filtration after uninephrectomy in kidney donors compared to creatinine

AIMS: Acute renal failure (ARF), defined by a rapid decrease of glomerular filtration rate (GFR), is associated with high mortality. Early and accurate detection of decreasing GFR is critical to prevent the progression of ARF and to potentially improve its outcome. Serum creatinine, the conventional GFR marker, has major limitations. We prospectively evaluated whether serum cystatin C detected a rapid GFR decrease earlier and more accurately than serum creatinine. METHODS: In ten patients undergoing nephrectomy for living related kidney transplantation, serum creatinine and cystatin C were determined daily. The decrease of GFR was quantitated preoperatively by creatinine clearance and MAG3 scintigraphy. The GFR decrease was defined by a 50-100% increase of cystatin C or creatinine from preoperative values. Ten patients without renal impairment served as controls. RESULTS: Initially, patients had a creatinine clearance of 105 +/- 14 ml/min/1.73 m2. Due to nephrectomy, patients lost 45 +/- 3% of their renal function. Serum cystatin C significantly increased already one, serum creatinine two days after nephrectomy. Cystatin C demonstrated an increase by 50-100% 1.4 +/- 0.9 days earlier than creatinine (p = 0.009). Serum cystatin C performed well detecting the GFR decrease with higher diagnostic values compared to creatinine. This was indicated by a sensitivity of 50, 70 and 80% of cystatin C to detect the GFR decrease on the three days following nephrectomy. CONCLUSIONS: Serum cystatin C detects rapid GFR decreases one to two days earlier than creatinine. Cystatin C is an early and accurate marker to detect rapid GFR decreases as in ARF.     

Serum cystatin C as an endogenous parameter of the renal function in patients with normal to moderately impaired kidney function

BACKGROUND: Cystatin C is a proteinase inhibitor with a low molecular weight. The serum levels of cystatin C are mainly dependent on glomerular filtration rate (GFR) making cystatin C an endogenous parameter of GFR. The aim of the study was to elucidate the applicability of serum cystatin C as a parameter of GFR in patients with normal to moderately impaired kidney function and to estimate a reference interval for serum cystatin C. PATIENTS AND METHODS: Forty-six patients (25 males and 21 females) aged 22 to 83 years with various kidney diseases and 250 blood donors (164 males and 86 females) aged 19 to 64 years were included. Cystatin C was measured by an automated particle-enhanced nephelometric immunoassay, serum creatinine by an enzymatic and by Jaffé method, urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA clearance. RESULTS: Serum levels ofcystatin C and creatinine showed increments with decreasing values of 99mTc-DTPA clearance and a linear relationship was found between 99mTc-DTPA clearance and l/serum cystatin C, l/serum creatinine (enzymatic method), and creatinine clearance. Comparison of the non-parametric receiver-operating characteristic (ROC) plots for serum cystatin C (area under the curve (AUC) = 0.996; SE = 0.005), serum creatinine (enzymatic method) (AUC = 0.899; SE = 0.044), serum creatinine (Jaffé method) (AUC = 0.870; SE = 0.051), measured creatinine clearance (AUC = 0.959; SE = 0.025), and estimated creatinine clearance (0.950; SE = 0.029) revealed significant differences for serum cystatin C and serum creatinine (enzymatic and Jaffé method) (p values: 0.03 and 0.01). No significant differences were demonstrated between serum cystatin C and measured and estimated creatinine clearance (p value: 0.14 and 0.12). The non-parametric reference interval for serum cystatin C was calculated to be 0.51-1.02 mg/l (median: 0.79 mg/l; range: 0.33 - 1.07 mg/l). CONCLUSION: Serum cystatin C seems to be a better parameter of GFR than serum creatinine in adults with various types of kidney disease with normal to moderately impaired kidney function.     

Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients

BACKGROUND: Glomerular filtration rate (GFR) is the best overall index of renal function in health and disease. Inulin and 51Cr-EDTA plasma clearances are considered the gold standard methods for estimating GFR. Unfortunately, these methods require specialized technical personnel over a period of several hours and high costs. In clinical practice, serum creatinine is the most widely used index for the noninvasive assessment of GFR. Despite its specificity, serum creatinine demonstrates an inadequate sensitivity, particularly in the early stages of renal impairment. Recently, cystatin C, a low molecular mass plasma protein freely filtered through the glomerulus and almost completely reabsorbed and catabolized by tubular cells, has been proposed as a new and very sensitive serum marker of changes in GFR. This study was designed to test whether serum cystatin C can replace serum creatinine for the early assessment of nephropathy in patients with type 2 diabetes. METHODS: The study was performed on 52 Caucasian type 2 diabetic patients. Patients with an abnormal albumin excretion rate (AER) were carefully examined to rule out non-diabetic renal diseases by ultrasonography, urine bacteriology, microscopic urine analysis, and kidney biopsy. Serum creatinine, serum cystatin C, AER, serum lipids, and glycosylated hemoglobin (HbA1c) were measured. GFR was estimated by the plasma clearance of 51Cr-EDTA. In addition the Cockcroft and Gault formula (Cockcroft and Gault estimated GFR) was calculated. RESULTS: Cystatin C serum concentration progressively increased as GFR decreased. The overall relationship between the reciprocal cystatin C and GFR was significantly stronger (r = 0.84) than those between serum creatinine and GFR (r = 0.65) and between Cockcroft and Gault estimated GFR and GFR (r = 0.70). As GFR decreased from 120 to 20 mL/min/1.73 m2, cystatin C increased more significantly that serum creatinine, giving a stronger signal in comparison to that of creatinine over the range of the measured GFR. The maximum diagnostic accuracy of serum cystatin C (90%) was significantly better than those of serum creatinine (77%) and Cockcroft and Gault estimated GFR (85%) in discriminating between type 2 diabetic patients with normal GFR (>80 mL/min per 1.73 m2) and those with reduced GFR (<80 mL/min/1.73 m2). In particular, the cystatin C cut-off limit of 0.93 mg/L corresponded to a false-positive rate of 7.7% and to a false-negative rate of 1.9%; the serum creatinine cut-off limit of 87.5 micromol/L corresponded to a false-positive rate of 5.8% and to a false-negative rate of 17.0%. CONCLUSIONS: Cystatin C may be considered as an alternative and more accurate serum marker than serum creatinine or the Cockcroft and Gault estimated GFR in discriminating type 2 diabetic patients with reduced GFR from those with normal GFR.     

Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study

Research on early renal function decline in diabetes is hampered by lack of simple tools for detecting trends (particularly systematic decreases) in renal function over time when GFR is normal or elevated. This study sought to assess how well serum cystatin C meets that need. Thirty participants with type 2 diabetes in the Diabetic Renal Disease Study met these three eligibility criteria: GFR >20 ml/min per 1.73 m2 at baseline (based on cold iothalamate clearance), 4 yr of follow-up, and yearly measurements of iothalamate clearance and serum cystatin C. With the use of linear regression, each individual's trend in renal function over time, expressed as annual percentage change in iothalamate clearance, was determined. Serum cystatin C in mg/L was transformed to its reciprocal (100/cystatin C), and linear regression was used to determine each individual's trend over time, expressed as annual percentage change. In paired comparisons of 100/cystatin C with iothalamate clearance at each examination, the two measures were numerically similar. More important, the trends in 100/cystatin C and iothalamate clearance were strongly correlated (Spearman r = 0.77). All 20 participants with negative trends in iothalamate clearance (declining renal function) also had negative trends for 100/cystatin C. Results were discordant for only three participants. In contrast, the trends for three commonly used creatinine-based estimates of GFR compared poorly with trends in iothalamate clearance (Spearman r < 0.35). Serial measures of serum cystatin C accurately detect trends in renal function in patients with normal or elevated GFR and provide means for studying early renal function decline in diabetes.     

Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement

BACKGROUND: It is well known that serum creatinine may be used as a marker of renal function only if taking into account factors that influence creatinine production, such as age, gender, and weight. Serum cystatin C has been proposed as a potentially superior marker than serum creatinine, because serum cystatin C level is believed to be produced at a constant rate and not to be affected by such factors. However, there are limited data on factors that may influence serum cystatin C levels, and there are limited data comparing cystatin C-based estimates of renal function with creatinine-based estimates that adjust for such factors, especially in individuals with normal, or mildly reduced, renal function. METHODS: This was a cross-sectional study of 8058 inhabitants of the city of Groningen, The Netherlands, 28 to 75 years of age. Serum cystatin C and serum creatinine levels were measured, and creatinine clearance was determined from the average of two separate 24-hour urine collections. We performed multivariate analyses to identify factors independently associated with serum cystatin C levels after adjusting for creatinine clearance. Then, partial Spearman correlations were obtained after adjusting for factors that may influence serum cystatin C and creatinine levels. We also compared the goodness-of-fit (R(2)) of different multivariate linear regression models including serum cystatin C level and serum creatinine level for the outcome of creatinine clearance. RESULTS: Older age, male gender, greater weight, greater height, current cigarette smoking, and higher serum C-reactive protein (CRP) levels were independently associated with higher serum cystatin C levels after adjusting for creatinine clearance. After adjusting for age, weight, and gender, the partial Spearman correlations between creatinine and, respectively, serum cystatin C level and serum creatinine level were -0.29 (P < 0.001) and -0.42 (P < 0.001), respectively. The R(2) values for serum cystatin C level and serum creatinine level adjusted for age, weight, and gender were 0.38 and 0.42, respectively. The addition of cigarette smoking and serum CRP levels did not improve the R(2) value for the multivariate serum cystatin C-based model. CONCLUSION: Serum cystatin C appears to be influenced by factors other than renal function alone. In addition, we found no evidence that multivariate serum cystatin C-based estimates of renal function are superior to multivariate serum creatinine-based estimates.     

Association of cystatin C and estimated GFR with inflammatory biomarkers: the Heart and Soul Study.

BACKGROUND: Cystatin C is a marker of kidney function that may also be associated with inflammation. In this study, we compared the relative strengths of association of cystatin C and estimated glomerular filtration rate (eGFR) with inflammatory biomarkers. METHODS: We measured serum cystatin C and creatinine in 990 outpatients with coronary artery disease enrolled in the Heart and Soul Study. GFR was estimated (eGFR) by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. We compared the associations of serum cystatin C and eGFR with C-reactive protein (CRP) and fibrinogen, after adjustment for 24 h creatinine clearance. RESULTS: Cystatin C concentrations had moderate correlations with CRP (r=0.15, P<0.001) and fibrinogen (r=0.26, P<0.0001); eGFR had similar correlations with CRP (r=-0.17, P=0.01) and fibrinogen (r=-0.25, P<0.001) among persons with eGFR60 ml/min (r=0.04, P=0.32; r=-0.03, P=0.38). Quartiles of cystatin C were strongly and directly associated with CRP (P=0.02) and fibrinogen (P<0.007) after multivariate adjustment. However, these associations disappeared after adjustment for creatinine clearance (P=0.26 and 0.23, respectively). CONCLUSIONS: Cystatin C concentrations have moderate associations with CRP and fibrinogen that are not independent of creatinine clearance. Although a gold standard of kidney function is lacking, this analysis suggests that cystatin C captures an association of mildly impaired kidney function with increased inflammation.     

Clinical assessment of serum cystatin C as a marker of glomerular filtration rate in patients with various renal diseases

Background. Recent reports have raised questions about the validity of estimating glomerular function and changes in glomerular function from measurements of serum creatinine. To evaluate the clinical usefulness of serum creatinine levels in terms of estimation of glomerular filtration rate (GFR), we determined serum cystatin C levels in 152 patients with various renal diseases and compared them with serum creatinine levels. Methods. Serum cystatin C levels were measured by particle-enhanced immunonephelometry. Two-h creatinine clearance (Ccr) was used as an indicator of GFR. Results. There was a significant positive correlation between serum cystatin C and creatinine levels (r = 0.941) in patients with various renal diseases. Serum cystatin C and creatinine were inversely correlated to Ccr. The overall correlation between serum cystatin C and Ccr was slightly stronger than that between serum creatinine and Ccr. In the patient group with a critical Ccr level (Ccr, 60–80 ml/min per 1.48 m²), the correlation between the reciprocal serum cystatin C levels and Ccr (r = 0.441) was significantly stronger (P < 0.01) than that between the reciprocal serum creatinine levels and Ccr (r = 0.212). A mild reduction of Ccr was detected more easily by serum cystatin C than by serum creatinine, as the clinical sensitivity and specificity of serum cystatin C were superior to that of serum creatinine. Conclusions. The cystatin C assay by particle-enhanced immunonephelometry was found to be a sensitive, fully automated, and rapid method. Serum cystatin C appears to be a promising marker of GFR in patients with impaired renal function. Its diagnostic potential was slightly superior to that of serum creatinine in adults with various renal diseases. Received: October 7, 1998 / Accepted: November 4, 1999     

Cystatin C: efficacy as screening test for reduced glomerular filtration rate

Serum cystatin C, a cysteine proteinase inhibitor, has been proposed as a marker of glomerular filtration rate (GFR). Serum cystatin C, serum creatinine and creatinine clearance were measured in 226 patients with various nephropathies, covering the entire range of renal function, to evaluate the efficacy of cystatin C as a screening test to detect reduced creatinine clearance in comparison to creatinine. Subgroups of 53 patients with glomerular and 26 patients with tubular impairment were compared to assess whether cystatin C performed differently in either glomerular or tubular impairment. Cystatin C detected reduced creatinine clearance with higher sensitivity (97 vs. 83%), and higher negative predictive value (96 vs. 87%) compared to creatinine. In parallel, 95% sensitivity of cystatin C as derived from receiver-operating characteristic plot was significantly higher (p < 0.05). In the subgroups with glomerular or tubular impairment, cystatin C and creatinine did not significantly differ with regard to efficacy. Serum cystatin C is as efficacious as serum creatinine to detect reduced GFR as measured by creatinine clearance. The efficacy of cystatin C as a screening test may even be superior compared to creatinine. In addition, the efficacy of cystatin C is independent of either glomerular or tubular impairment.     

Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes

AIM: To evaluate plasma cystatin C as a marker of the glomerular filtration rate in patients with type 2 diabetes and their age and sex-matched controls. MATERIALS AND METHODS: Forty-seven patients with one decade of type 2 diabetes and 51 non-diabetic control subjects were studied. Plasma cystatin C was measured by particle-enhanced turbidimetric immunoassay in a new application for the Hitachi 704 analyzer. For comparison, plasma creatinine and creatinine clearance were measured. The plasma clearance of 51Cr-EDTA by the single injection method was utilized as reference. RESULTS: In patients with type 2 diabetes the correlation coefficient between plasma cystatin C and the plasma clearance of 51Cr-EDTA was 0.774 (Spearman's coefficient) and that between plasma creatinine and the plasma clearance of 51Cr-EDTA was 0.556 (p = 0.001 for the difference). The correlation between creatinine clearance and the plasma clearance of 51Cr-EDTA was 0.411. In receiver operating characteristic (ROC) curve analysis the diagnostic accuracy of plasma cystatin C was significantly better than that of plasma creatinine (p = 0.047) or creatinine clearance (p = 0.001). The best diagnostic efficiency (98%) for cystatin C was obtained when the cut-off limit was set at 1.32 mg/l. In the control group the correlation coefficients were: between cystatin C and the plasma clearance of 51Cr-EDTA 0.627, between creatinine and the plasma clearance of 51Cr-EDTA 0.466 and between creatinine clearance and the plasma clearance of 51Cr-EDTA 0.416. The area under the ROC plot curve of cystatin C was also greatest in the control group, but the diagnostic accuracy of cystatin C was marginally better than that of either plasma creatinine (p = 0.05) or creatinine clearance (p = 0.08). Among the control subjects various non-renal causes may have interfered with cystatin C concentrations reducing the correlations. CONCLUSIONS: Cystatin C measurement is a more sensitive and specific test for GFR in patients with type 2 diabetes than plasma creatinine or its clearance, when GFR is normal or only slightly reduced. If an elevated cystatin C concentration is found, non-renal factors have to be excluded. The turbidimetric application described here can easily be applied for most clinical chemistry analyzers and is therefore useful in daily clinical practice.     

Evaluation of measured and calculated creatinine clearances as glomerular filtration markers in different stages of liver cirrhosis.

BACKGROUND: Discrepant results have been published regarding the suitability of creatinine clearance (C(Cr)) as a measure of glomerular filtration rate (GFR) in cirrhotic patients with normal renal function. SUBJECTS AND METHODS: In this study we evaluated the accuracy and precision of measured and calculated C(Cr) as indexes of GFR by comparing their values to those of inulin clearance (C(In)) in 10 healthy subjects and 20 patients with either Child's class A or Child's class C liver cirrhosis. RESULTS: The accuracy and precision of GFR estimates obtained by measuring C(Cr) were good in all three study groups. The mean values of the C(Cr)/C(In) ratio were 1.05, 1.03 and 1.04, respectively, and the corresponding coefficients of variations were 2.9, 2.9 and 3.8%. A close correlation between C(Cr) and C(In) was also found in each study group (r = 0.98, 0.99 and 0.97, respectively, with p < 0.001 in each case). C(Cr) calculated from serum creatinine by means of the Cockcroft-Gault formula (predicted GFR) proved to be a suitable measure of GFR in normal subjects and patients with Child's class A cirrhosis: the predicted-to-true GFR ratios were 0.93 and 0.94, respectively, CV was 12% in both cases. Moreover, a significant correlation between predicted and true GFR was observed in both groups (r = 0.73, p < 0.02 and r = 0.69, p < 0.025, respectively). On the contrary, in Child's class C cirrhotics, calculated C(Cr) significantly overestimated GFR (predicted-to-true GFR ratio 1.23, CV 20%) and no significant correlation was found between predicted and true GFR (r = 0.58, p > 0.05). CONCLUSION: In conclusion, this study shows that measured C(Cr) is a reliable index of GFR in cirrhotic patients, irrespective of the degree of liver dysfunction. Calculated C(Cr) is still an adequate marker of GFR in patients with compensated liver cirrhosis, whereas it overestimates GFR in patients with decompensated cirrhosis. A lower muscle mass, a reduced ability to convert creatine to creatinine, and the presence of ascites are most likely responsible for the overestimation of GFR by the Cockcroft-Gault formula in the latter patients.     

Serum cystatin C as an index of renal function in kidney transplant patients

Management of renal transplant patients requires periodic measurement of renal function, which is usually assessed by measuring the glomerular filtration rate (GFR). The most commonly used marker for GFR is serum creatinine, although muscle wasting and tubular secretion may lead to overestimation of the actual GFR. Serum concentrations of the low-molecular-weight proteins, cystatin C and beta(2)-microglobulin (B(2)M), may afford useful markers to determine a reduced GFR. We investigated whether these molecules provide reliable indicators of renal function in 75 renal transplant patients. Cystatin C and B(2)M correlated significantly with creatinine (r =.648, P <.05 and r =.578, P <.05, respectively). Inverse serum creatinine was superior to inverse cystatin C and inverse B(2)M when renal function equations were used (r =.95, P <.05, according to MDRD; r =.87, P <.05, according to Cockroft-Gault). Receiver operating characteristic (ROC) analysis was performed to quantitate the accuracy of the different markers to detect reduced GFR using a cutoff value of 70 mL/min. No significant difference between the areas under the ROC curves comparing cystatin C and B(2)M was observed; however, serum creatinine demonstrated a significantly greater value than cystatin C (.981 vs.724, P =.001). We conclude that serum creatinine is a more efficacious marker than serum cystatin C to assess renal function.     

Cystatin C-based equations in renal transplantation: moving toward a better glomerular filtration rate prediction?

Creatinine-based glomerular filtration rate (GFR) estimators perform poorly in renal transplant recipients. Cystatin C might be a better alternative to serum creatinine in assessing renal graft function. We compared several cystatin C-based equations with the modification diet renal disease (MDRD) equation in 120 adult renal transplant recipients for whom the GFR was measured by the gold standard inulin clearance. Mean inulin-measured GFR was 52.6 mL/min/1.73 m (range, 13-119). The Hoek, Rule, Le Bricon, and Filler cystatin C-based formulas showed significantly better performances (accuracy 30% of 82%, 81%, 78%, and 71%), than the MDRD equation (58%, Mac Nemar test, P<0.01). Sensitivity to detect a GFR below 60 mL/min/1.73 m was significantly higher for the Hoek and the Rule equations (0.95, 95% CI 0.91-1) than for the MDRD equation (0.76, 95% CI 0.67-0.85). These data confirm that cystatin C as a GFR marker offers significant advantages over creatinine in renal transplantation.     

Comparison of serum cystatin C and creatinine levels in determining glomerular filtration rate in children with stage I to III chronic renal disease

Abstract

Background: Pediatric studies are relatively scarce on the superiority of cystatin C over creatinine in estimation of glomerular filtration rate (GFR). This study measured cystatin C and serum creatinine levels, and compared GFR estimated from these two parameters in patients with chronic renal disease. Methods: This prospective, observational, controlled study included 166 patients aged 1–18 years diagnosed with stage I to III chronic renal disease, and 29 age- and sex-matched control subjects. In all patients, GFR was estimated via creatinine clearance, Schwartz formula, Zappitelli 1 and Zappitelli 2 formula and the results were compared using Bland–Altman analysis. Results: Patients and controls did not differ with regard to height, body weight, BMI, serum creatinine and serum cystatin levels, and Schwartz formula-based GFR (p?>?0.05). There was a significant relationship between creatinine and cystatin C levels. However, although creatinine levels showed a significant association with age, height, and BMI, cystatin C levels showed no such association. ROC analysis showed that cystatin C performed better than creatinine in detecting low GFR. Conclusion: Cystatin C is a more sensitive and feasible indicator than creatinine for the diagnosis of stage I to III chronic renal disease.     

Evaluation of cystatin C with iohexol clearance in cardiac surgery

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery. Methods: Twenty‐one patients scheduled for elective coronary artery bypass grafting were prospectively enrolled in the study. Before surgery and on the second post‐operative day, an iohexol clearance was performed. Plasma cystatin C, plasma creatinine and plasma C‐reactive protein were determined before surgery and on the first, second, third and fifth post‐operative day. Estimated creatinine and cystatin C clearances were determined. Results: Post‐operative cystatin C and 1/cystatin C correlated strongly to iohexol clearance (r=?0.90 and 0.86) and so did creatinine and 1/creatinine (r=?0.83 and 0.78). Estimated creatinine clearance differed from iohexol clearance (P<0.01), whereas estimated cystatin C clearance did not differ from iohexol clearance (P=0.81). No correlation was found between C‐reactive protein and cystatin C. Conclusion: This study indicates that clearance estimations based on cystatin C are more accurate compared with estimations based on creatinine in determining GFR in cardiac surgery. Cystatin C has, in this study population, a stronger correlation to iohexol clearance than creatinine.     

Cystatin C as a marker for glomerular filtration rate in pediatric patients

Cystatin C is a non-glycated 13-kilodalton basic protein produced by all nucleated cells. The low molecular mass and the basic nature of cystatin C, in combination with its stable production rate, suggest that the glomerular filtration rate (GFR) is the major determinant of cystatin C concentration in the peripheral circulation. Recently published studies have shown that cystatin C correlates more strongly than creatinine with GFR measured using the ⁵¹Cr-EDTA clearance. The aim of this study was to evaluate serum cystatin C as a marker for GFR in children. GFR was determined on medical indications using the ⁵¹Cr-EDTA technique in pediatric patients (2–16 years) in our renal unit. Simultaneously their cystatin C and creatinine concentrations were also measured. Of our 52 patients, 19 had a reduced renal function (<GFR 89 ml/min per 1.73 m²) based on the ⁵¹Cr-EDTA clearance. The correlation of cystatin C with the isotopic measurement of GFR tended to be stronger (r=0.89, P=0.073) than that of creatinine (r=0.80). Receiver operating characteristic analysis showed that the diagnostic accuracy of cystatin C was better (P=0.037) than that of creatinine in discriminating between subjects with normal renal function and those with reduced GFR. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine. Hence, cystatin C seems to be an attractive alternative for the estimation of GFR in children. Received: 13 May 1998 / Revised: 22 September 1998 / Accepted: 22 October 1998     

Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults.

BACKGROUND: Cystatin C, a marker of renal function, has been shown to be an independent predictor of cardiovascular disease (CVD) in older adults, but few data are available in middle-aged adults. Moreover, no study has compared cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged adults, and it is not known whether cystatin C is related to an early stage of atherosclerosis. METHODS: We evaluated the relationships between serum creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all divided into tertiles), microalbuminuria and carotid atherosclerosis in a population-based random sample of 523 adults aged 35-64 years from the Seychelles (Indian Ocean). GFR was estimated using the modification of diet in renal disease (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound. RESULTS: The mean age of the study sample was 52 years, and 55% were women. Carotid IMT was higher in participants with microalbuminuria (802 vs 732 microm, P<0.001) and was inversely associated with GFR tertiles (from 728 to 809 microm, P for trend=0.002). IMT was not associated with cystatin C or creatinine (P for trend=0.10 and 0.16, respectively). In multivariate analyses adjusted for cardiovascular risk factors, the association between microalbuminuria and IMT remained (P=0.047), while the association between GFR and IMT disappeared (P for trend=0.33). CONCLUSIONS: Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis beyond traditional cardiovascular risk factors among middle-aged adults. Cystatin C does not have a stronger relationship with carotid atherosclerosis in middle-aged adults than creatinine.