Serum cystatin C as an endogenous marker of renal function in patients with chronic kidney disease

The estimation of the glomerular filtration rate (GFR) is an essential part of the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C has been proposed as a new endogenous marker of GFR. Authors compared serum creatinine, creatinine clearance calculated from Cockcroft and Gault formula and serum cystatin C against (51)CrEDTA clearance in 252 patients with CKD and GFR <90 mL/min/1.73 m(2). Analysis of correlations and diagnostic accuracy (receiver operating characteristic curves) of different GFR markers indicate that serum cystatin C is a more reliable marker of GFR in patients with CKD than serum creatinine.     

Is cystatin C useful for the detection and the estimation of low glomerular filtration rate in heart transplant patients?

Although previously studied in patients with chronic kidney disease, there is less data for the use of cystatin C and cystatin C-based formulas in heart transplant recipients. The ability of creatinine and cystatin C to detect renal failure (glomerular filtration rate [GFR] below 60 mL/min/1.73 m(2)) in heart transplant patients has been compared. The accuracy and precision of a creatinine-based formula (Modification of Diet in Renal Disease [MDRD]) versus a cystatin C-based formula (Rule's formula) to estimate GFR have also been studied. GFR was measured using the (51)Cr-ethylenediamine tetraacetic acid tracer in 27 patients. There was no significant difference between GFR and the reciprocal of creatinine or cystatin C. Receiver operating characteristic curves for cystatin C and creatinine were similar. Both formulas were well correlated with the GFR. The bias of the cystatin C-based was significantly better than one of the MDRD formula, but the standard deviation appeared better for the MDRD formula (bias of +3.9 mL/min/1.73 m(2) versus +12 mL/min/1.73 m(2) and SD of 8.5 versus 11.6, respectively). Plasma cystatin C has no clear advantage over serum creatinine to detect renal failure in heart transplanted patients.     

Prediction of glomerular filtration rate in renal transplant recipients: cystatin C or Modification of Diet in Renal Disease equation?

BACKGROUND: To overcome disadvantages of serum creatinine two strategies have been suggested to identify patients with reduced glomerular filtration rate (GFR). On the one hand, the Modification of Diet in Renal Disease (MDRD) equation is now recommended to classify the stage of chronic kidney disease. On the other hand, cystatin C (Cys C) has been investigated in numerous studies, finding a higher sensitivity than creatinine in detecting diminished GFR. To date, no comparison of both strategies in patients after renal transplantation has been performed. METHODS: One hundred and five consecutive renal transplant recipients underwent (99m)Tc-DTPA-- clearance measurement. Simultaneously, MDRD estimates were calculated and Cys C serum levels were determined. ROC analyses were performed at different decision points from 20 to 70 mL/min/1.73 m(2). RESULTS: Although the area under the curve did not differ significantly between MDRD and Cys C within the tested GFR range, the AUC for Cys C tended to be higher when GFR exceeded 55 mL/min/1.73 m(2). A significantly higher diagnostic accuracy for Cys C compared with MDRD (p = 0.045 at 65 mL/min/1.73 m(2)) was found when investigating the subgroup of patients with well-functioning grafts (GFR>40 mL/min/1.73 m(2)). CONCLUSION: MDRD equation is equivalent to Cys C measurement in renal transplant recipients. As availability of MDRD is superior to Cys C, we recommend GFR estimation using the MDRD equation. Nevertheless, Cys C may serve as a confirmation test of high MDRD estimates in patients with well-functioning grafts because of superior accuracy in these patients.     

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell,Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.     

MDRD Equations for Estimation of GFR in Renal Transplant Recipients

After renal transplantation monitoring and detection of slight-to-moderate changes in GFR is a prerequisite for an optimal patient management. Recently, several equations to estimate GFR were developed and verified in the MDRD study cohort. However, little is known about the application of the MDRD formulas in the setting of renal transplantation. We prospectively conducted a study of the GFR estimates of the Cockcroft and Gault (C&G), MDRD6-, MDRD7 and the abbreviated MDRD (aMDRD) with the true GFR as measured by (99m)Tc-DTPA clearance in 95 consecutive patients 6.5, 5.3-7.7 years (mean, 95% CI) after renal transplantation. On average the DTPA clearance was 37.4, 34.4-40.4 mL/min/1.73 m(2), which differed significantly from estimates of GFR by C&G (52.6, 48.3-56.9 mL/min/1.73 m(2)), MDRD7 (44.8, 40.7-49.0 mL/min/1.73 m(2)), MDRD6 (43.8, 39.9-47.7 mL/min/1.73 m(2)) and aMDRD (46.6, 42.4-50.9 mL/min/1.73 m(2)). Bias was lowest for MDRD6 (6.4 mL/min/1.73 m(2)) and highest for C&G (15.2 mL/min/1.73 m(2)). Precision was similar for MDRD7 and aMDRD (10.6 and 11.1 mL/min/1.73 m(2)) but significantly better for MDRD6 (8.6 mL/min/1.73 m(2); p < 0.035). Accuracy within 50% of real GFR was 55.8% for C&G, 83.2% for aMDRD, 87.4% for MDRD7 and 90.5% for MDRD6. MDRD equations perform significantly better than the commonly used C&G formula. Moreover, the MDRD6 equation provides the best diagnostic performance, and should therefore be preferred in renal transplant recipients.     

Cystatin C is not superior to creatinine-based models in estimating glomerular filtration rate in former kidney donors

BACKGROUND: The long-term renal consequences of kidney donation need to be accurately quantitated. Cystatin C is a freely filtered glycoprotein that may not have the limitations of creatinine as a measure of glomerular filtration rate (GFR). Whether cystatin C is superior to creatinine-based estimates of GFR in those who have donated a kidney in the past has not been tested. METHODS: We assessed the performance of seven cystatin C and two creatinine-based GFR prediction equations in 187 former kidney donors against iohexol GFR for measuring GFR. We calculated bias, precision, and relative accuracy of these models. RESULTS: The majority of former donors had a GFR >60 mL/min/1.73 m(2). All cystatin C models, except the Rule model, overestimated GFR (range 5.3-31.4 mL/min/1.73 m(2)). Among the cystatin C models, the Hoek and Rule formulas were least biased at 5.3 and -3.8 mL/min/1.73 m(2), most precise at 0.41, and were within 30% of iohexol GFR, 89.3 and 96% of the time, respectively. The Modification of Diet in Renal Disease (MDRD) formula underestimated GFR by 7.2 mL/min/1.73 m(2), was most precise (R(2)=0.47) and fell within 30% of measured GFR at the highest frequency of 96%. When all models were given a rank based on their performance in the bias, precision and accuracy domains, the MDRD model was clearly superior. CONCLUSION: The MDRD equation is superior to cystatin C-based equations for estimating GFR in former kidney donors. Creatinine measurement is cheaper and the MDRD GFR is given out by most laboratories and therefore it should be the preferred model in this population.     

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.     

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.     

An alternative formula to the Cockcroft-Gault and the modification of diet in renal diseases formulas in predicting GFR in individuals with type 1 diabetes

Chronic kidney disease is currently on the rise and not only leads to ESRD necessitating dialysis or transplantation but also increases cardiovascular disease risk. Measurement of the GFR, the gold standard for assessing kidney function, is expensive and cumbersome. Several prediction formulas that are based on serum creatinine are currently used to estimate the GFR, but none has been validated in a large cohort of individuals with diabetes. The performance of two commonly used formulas, the abbreviated Modification of Diet in Renal Disease (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine clearance, were examined against GFR measured by the renal clearance of iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT). The performance of these formulas was assessed by computing bias, precision, and accuracy. The DCCT participants had normal serum creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion than subjects in the original cohort Cockcroft Gault, which led to biased and highly variable estimates of GFR when these formulas were applied to the DCCT subjects. The MDRD substantially underestimated iothalamate GFR, whereas the Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2) and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall, only one third of the formula's estimates were within +/-10% of iothalamate GFR. By underestimating GFR, these formulas were likely to flag early declines in kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate and unbiased prediction of GFR from serum creatinine; percentage of estimate within 10% of measured GFR increased to 56%. A substantial variability in the estimates, however, remained.     

Serum cystatin C measured by a sol particle homogeneous immunoassay can accurately detect early impairment of renal function

BACKGROUND: A sol particle homogeneous immunoassay (SPIA) is a method to measure the serum cystatin C (cysC) level as a marker of the glomerular filtration rate (GFR). Recently, formulas to convert measured cysC to GFR have been developed. METHODS: A total of 154 patients (46 +/- 18 years old) who had undergone renal biopsy, sodium thiosulfate clearance (C thio) and 24-h creatinine clearance (24-hCcr) tests were subjects for the study. Their serum cysC levels were determined by SPIA. RESULTS: Multiple regression analysis revealed C (thio) and age as independent variables for serum creatinine concentration (Cr), while only C thio affected cysC. The equations using Cr or cysC showed significant correlation with C thio. Receiver-operating curve ROC analysis revealed that cysC and 24-hCcr shared comparable power to detect patients with GFR < 90 or 60 ml/min/1.73 m2 (AUC = 0.862 and 0.943 vs. AUC = 0.842 and 0.943, respectively), while Cr (AUC = 0.881) and MDRD2 (AUC = 0.888) showed slightly inferior ability to detect 60 ml/min/1.73 m2 than other parameters in the female population. The cut-off point of cysC and Cr obtained from the ROC analysis demonstrated strong power to detect patients with C thio < 90 ml/min/1.73 m2 or C thio < 60 ml/min/1.73 m2. According to CKD stages, the mean values of each equation were significantly different, like that demonstrated by 24-hCcr. CONCLUSION: SPIA could determine cysC levels that detected early renal impairment. The accuracy of cysC to detect early renal impairment may be superior to that of Cr in females, while it would be comparable to that of CG or MDRD when they are corrected by sex and age. Both cysC itself and cysC equations are effective to monitor the progress of renal impairment. The future standardization of cysC measurements and development of novel equation of cysC would contribute to the further improvement of GFR estimation in clinical practice.     

A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate.

BACKGROUND: In clinical practice, the glomerular filtration rate (GFR) is often estimated from plasma creatinine. Several studies have shown cystatin C (cys C) to be a better parameter for the diagnosis of impaired renal function. No data are available, however, on the performance of cys C in follow-up of patients, compared with creatinine. Also, comparisons of cys C with the Cockcroft and Gault (C&G) formula for estimation of GFR are few. METHODS: Plasma samples were obtained from 93 consecutive patients seen for GFR determination and from 30 patients with diabetes mellitus type 2, of whom 23 were investigated a second time after 2 years. GFR was determined with [125I]iothalamate. Plasma creatinine was determined enzymatically and the creatinine clearance calculated according to C&G. Cys C was measured with a particle-enhanced immunonephelometric method. RESULTS: GFR correlated with 1/cys C (r = 0.873) as well as with C&G (r = 0.876). The area under the curve (AUC) of the receiver operating curves (ROCs), a measure of diagnostic accuracy, for cys C (0.931) and C&G (0.938) were equal (P = 0.815) and both better than the creatinine AUC (0.848; P = 0.006). Bland and Altman analysis showed that the simple formula GFR = -4.32 + 80.35 x 1/cys C, derived from our data, gave more accurate (P < 0.0001) and more precise (P = 0.024) GFR estimates than obtained with the C&G formula. The day-to-day variation (biological +analytical) for cys C was small (3.1%, SD 2.51%) in diabetic patients. In the follow-up study in diabetic patients, cys C was the parameter which had the best correlation (r = 0.66) with changes in GFR. CONCLUSIONS: Cys C shows a high correlation with GFR. With a very simple formula, cys C gives a good estimate of GFR, more accurate and precise than C&G. Because biological variation is low, cys C gives also a good assessment of GFR changes during follow-up. Cys C is the preferred endogenous parameter for GFR.     

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     

Estimating the glomerular filtration rate using serum cystatin C levels in patients with spinal cord injuries

Study design:Prospective cohort study.Objectives:To investigate the relationship between (51)chromium-ethylene-diamine-tetra-acetate ((51)Cr-EDTA) clearance, serum cystatin C (CysC), serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR(MDRD), MDRD stands for modification of diet in renal disease) based on the serum creatinine in patients with complete or incomplete spinal cord injury (SCI) and to develop and evaluate a GFR-estimating equation using serum CysC.Settings:Spinal Cord Injury Unit, Viborg Regional Hospital, Viborg, Denmark.Methods:Ninety-eight men and 47 women with SCI were included in the study. Serum CysC levels were measured by an automated particle-enhanced nephelometric immunoassay, serum and urine creatinine levels were measured by an enzymatic method traceable to the IDMS creatinine reference method, and (51)Cr-EDTA clearance was measured by a multiple plasma sample method.Results:The area under the curves (AUCs) in the non-parametric receiver operating characteristics (ROC) plots for serum CysC were compared with serum creatinine and to eGFR(MDRD) and revealed a significant difference (P-value<0.05) for all SCI patients. There was no significant difference between the AUC for serum CysC compared with the AUC for creatinine clearance. GFR (ml?min(-1) per 1.73?m(2)) can be calculated from serum CysC values (mg?l(-1)) using the equation eGFR(CysC)=212·exp(0.914·CysC). The model accurately predicted the GFR of 88% of patients within ±30% of the measured GFR, and it was able to predict the GFR of 50% of patients within ±10% of the measured GFR.Conclusion:In patients with SCI, GFR can be estimated independent of age, sex and muscle mass by a newly developed equation based on a single serum CysC value.     

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 as a marker of early changes of renal function in Fabry nephropathy

BACKGROUND: A sensitive, feasible and reproducible marker for renal function is necessary to evaluate the clinical efficacy of enzyme replacement therapy (ERT) in Fabry nephropathy. Serum creatinine has some limitations and cystatin C has been proposed, in other nephropathies, as a useful marker of renal function. The use of cystatin C as a marker of glomerular filtration rate (GFR) was investigated in Fabry patients receiving ERT. METHODS: Renal function was evaluated with serum creatinine, serum cystatin C and estimated GFR (through Modification of Diet in Renal Disease [MDRD], Cockcroft-Gault [C&G] and Hoek formulae) in 21 Fabry patients receiving ERT with agalsidase alfa for 3 years and in 13 Fabry patients receiving agalsidase alfa for 4 years. RESULTS: During years of ERT while serum creatinine remained stable, cystatin C values showed a significant, increasing trend right from the first year of ERT. CONCLUSIONS: In Fabry disease, cystatin C is a sensitive and reliable marker of renal function, and it should be taken into account when evaluating GFR trends during ERT.     

Characteristics of population with normal serum creatinine impaired renal function and: the validation of a MDRD formula in a healthy general population

BACKGROUND AND AIMS: Glomerular filtration rate (GFR) provides the most accurate estimation of renal function. This study investigated the clinical characteristics of patients with impaired renal function having a normal serum creatinine level. We also validated whether the new Modification of Diet in Renal Disease (MDRD) formula can be applied in a healthy general population. MATERIAL AND METHODS: A total 393 participants who had serum creatinine concentration below 132.6 micromol/L without underlying diseases were randomly selected on an address basis in Ansan City. According to the level of GFR, they were divided into 3 groups and we analyzed their clinical characteristics. In 75 subjects, who were randomly selected 25 cases in each group based on GFR estimated by Cockcroft-Gault (C-G) formula, true GFR was measured using the 99mTc-DTPA renal clearance method. RESULTS: A total 393 (male: 106, female: 287) participants were as follows: GFR < 60 ml/min/1.73 m2; 4% (n = 25); 60 < or = GFR < 90 ml/min/1.73 m2; 26.2% (n = 103); GFR > or = 90 ml/min/1.73 m2; 67.4% (n = 265). In the group of decreased GFR, the mean age was older (67.4+/-10.7 vs. 48.7+/-12.8 vs. 39.4+/-8.2 years, p < 0.001), the gender was male (90.33+/-28.77 vs. 110.55+/-31.64, p < 0.001), and amount of proteinuria more increased (0.61 (0.56) vs. 0.33 (0.34) vs. 0.38 (0.33) gm/day, p = 0.007). The accuracy and precision of each formula were assessed by the difference in GFR measured by the 99mTc-DTPA renal clearance method--estimated GFR by each formula (deltaGFR), and the coefficient of determination (r2) of different predictive equations. The results were as follows: deltaGFR = -14.78+/-46.03, r2 = 0.79 (24-hour urinary creatinine clearance), deltaGFR=-16.79+/-57.32, r2 = 0.66 (100/serum creatinine), deltaGFR = 9.54+/-39.18, r2 = 0.87 (C-G formula), deltaGFR = -12.30+/-54.31, r2 = 0.66 (AASK formula), deltaGFR = 8.70+/-37.62, r2 = 0.79 (MDRD formula). Multiple linear regression analysis and logistic regression analysis showed that age, serum creatinine, total cholesterol and 24-hour urinary protein excretion were independently related to GFR and associated with a significant increase in the risk of decrement of GFR. CONCLUSIONS: From these results, a more accurate assessment of renal function should be required in a population characterized by older age, male gender and more proteinuria. The MDRD study formula and Cockcroft-Gault formula have greater accuracy and precision with true GFR, and this equation can be applied in subjects with healthy general population.     

GFR prediction using the MDRD and Cockcroft and Gault equations in patients with end-stage renal disease.

BACKGROUND: Although prediction equations are recommended to determine GFR and creatinine clearance (CrCl), neither the MDRD equations nor the Cockcroft and Gault formula have been validated for the low levels of GFR present in end-stage renal disease (ESRD). The accuracy of the MDRD equations and the Cockcroft and Gault formula in predicting GFR and CrCl, respectively, was examined in patients with ESRD and its relationship to the basal GFR and two markers of malnutrition, urinary creatinine and body fat determined. METHODS: Inulin clearance (C(in)) was measured in 26 non-diabetic patients with ESRD and the 24 h CrCl determined. GFR was predicted using three equations derived from the MDRD study population containing four to six variables. Both CrCl and GFR were predicted from the Cockcroft and Gault formula. Estimates of bias and precision were obtained and Bland and Altman analysis performed. Body fat was measured by DEXA scan. RESULTS: The predicted GFR (MDRD) was 10% lower than C(in) (8.83+/-0.71 ml/min/1.73 m2) with all three MDRD equations, showing a similar degree of precision and bias. C(in) gave a negative correlation with the difference between the predicted GFR (MDRD) and the measured GFR. The predicted GFR (MDRD) underestimated GFR when C(in) >8 ml/min/1.73 m2 but overestimated GFR when C(in) <8 ml/min/1.73 m2. The Cockcroft and Gault formula overestimated CrCl by 14% and overestimated C(in) by 35%. C(in) gave a negative correlation with the difference between the predicted GFR (Cockcroft and Gault) and measured GFR, overestimating GFR when C(in) <13 ml/min/1.73 m2. The overestimation of GFR by the MDRD equation was not associated with urinary creatinine excretion. However, both Cockcroft and Gault and the MDRD predictions showed a positive, but weak, correlation with body fat. CONCLUSION: The MDRD equations were more accurate in predicting the group mean GFR in patients with ESRD than the Cockcroft and Gault formula. However, the predicted GFR using either formula was related to the basal GFR and percentage body fat.     

A Comparison of GFR estimating formulae based upon s-cystatin C and s-creatinine and a combination of the two.

BACKGROUND: Current recommendations (KDIGO and NKF-K/DOQI) are that patients with chronic kidney diseases (CKD) should be classified in stages 1-5 based on GFR. A serum creatinine-based prediction equation (abbreviated MDRD formula) can be used to estimate GFR (eGFR). Cystatin C has been proposed as an alternative filtration marker to creatinine. We present validation of currently used formulae for eGFR based upon s-creatinine and s-cystatin C and we compare two different methods for the determination of cystatin C. METHODS: S-cystatin C and s-creatinine were measured in 644 patients referred for determination of GFR by plasma clearance of iohexol during the period 1 June 2004 to 31 December 2005. S-cystatin C was determined by turbidimetry using two different reagents (DAKO A/S and Gentian A/S). The 644 patients were divided into two groups. Group 1 was used to calculate own eGFR-formulae based on s-cystatin C (Orebro-cyst). Group 2 was used to validate the formulae. Three creatinine-based equations (Cockcroft-Gault, MDRD and Jelliffe) and seven cystatin C-based (Larsson, Hoek, Filler, leBricon, Grubb and Orebro-cyst DAKO, Gentian) were evaluated. Evaluation was done according to the recommendations by K/DOQI. RESULTS: In the test sample (group 2) mean GFR (iohexol clearance) was 50.4 ml/min/1.73 m(2) (range 12-150)-mean s-cystatin C (DAKO AS) was 1.63 mg/l and mean s-cystatin C (Gentian AS) 1.92 mg/l. The s-cystatin C concentrations obtained by the Gentian method were approximately 10% lower than the DAKO method within the normal GFR range but were approximately 40% higher within the low GFR range. Bias for the creatinine-based equations was in the range -0.9 to 5.9 ml/min/1.73 m(2) and for the cystatin C-based equations in range -2.4 to 7.9 ml/min/ 1.73 m(2). Accuracy within 30% ranged from 68.6 to 80.4% and 54.0 to 82.9%, respectively. By combining both, an accuracy within 30% for 87.0% could be reached (MDRD/cystatin C by Gentian). Overall the patients were correctly classified for the different stages of CKD in 62.1-64.0% for the creatinine-based equations, 61.5-72.0% for the cystatin C-based equations and 70.2-73.9% for the combination. CONCLUSION: Estimating GFR using formulae based on s-creatinine or s-cystatin C alone was equally accurate according to the NKF K/DOQI guidelines. A formula that combines both provided a greater accuracy. If Cystatin C, which is clearly more expensive, is used, the choice of the cystatin C determination method and an adjusted prediction equation is essential. Use of the IDMS-traceable MDRD seems to yield the best cost-benefit ratio for routine practice.     

Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation.

BACKGROUND: Based on the data derived from the Modification of Diet in Renal Disease (MDRD) study, a new equation was developed for the estimation of glomerular filtration rate (GFR). This equation, which takes into account body weight, age, sex, serum creatinine, race, serum urea, and serum albumin, provided a more accurate estimation of GFR in patients with renal insufficiency. However, this prediction equation has not been validated in subjects with normal or supra-normal GFR. METHODS: In a cross-sectional study, we measured GFR by inulin clearance in 46 healthy controls and 46 non-complicated type 1 diabetic patients. In this study population, GFR was predicted by measured creatinine clearance, the Cockcroft-Gault formula, and the MDRD equation. RESULTS: In the healthy subjects, mean GFR (+/-SD) was 107+/-11 as compared to 122+/-18 ml/min per 1.73 m(2) in the diabetic patients. This difference in GFR was reflected by a lower serum creatinine (76+/-8 vs 71+/-8 micro mol/l) in the diabetic patients. In the healthy controls, median absolute differences (and the 50th-75th-90th percentile of percentage absolute differences) between predicted and measured GFR were 5.2 ml/min per 1.73 m(2) (4.9-9.8-18.5%) for creatinine clearance, 9.0 ml/min per 1.73 m(2) (8.6-14.3-24.6%) for the Cockcroft-Gault formula, and 10.7 ml/min per 1.73 m(2) (10.9-16.3-25.5%) for the MDRD equation. In the diabetic patients, these differences were 8.3 ml/min per 1.73 m(2) (7.6-9.3-13.0%) for creatinine clearance; 11.8 ml/min per 1.73 m(2) (10.1-16.0-22.5%) for the Cockcroft-Gault formula, and 18.8 ml/min per 1.73 m(2) (16.0-24.2-31.9%) for the MDRD equation. CONCLUSIONS: In subjects with a normal or increased GFR, the new MDRD-prediction equation of GFR is less accurate than creatinine clearance or the Cockcroft-Gault formula, and offers no advantage.     

Evaluation of creatinine-based estimates of glomerular filtration rate in a large cohort of living kidney donors

BACKGROUND: Accurate determination of kidney function is critical in the evaluation of living kidney donors and higher donor glomerular filtration rate (GFR) is associated with better allograft outcomes. However, among transplant centers donor kidney function evaluation varies widely. METHODS: The performance of creatinine clearance (CrCl), Modification of Diet in Renal Disease (MDRD), the re-expressed MDRD equations with standardized creatinine, and the Cockcroft-Gault (CG) formula as compared with (125)I-iothalamate GFR (iGFR) was analyzed in 423 donors. All methods of GFR measurement were then evaluated for their association with graft function at 1 year. RESULTS: The MDRD and re-expressed MDRD equations underestimated iGFR whereas CG showed minimal bias (median difference=-11.0, -16.3, and -0.5 mL/min/1.73 m(2), respectively). CrCl overestimated iGFR (10 mL/min/1.73 m(2)). The MDRD, re-expressed MDRD, and CG formulas were more accurate (88%, 86%, and 88% of estimates within 30% of iGFR, respectively) than CrCl (80% within 30% of iGFR). Interestingly, low bias and high accuracy were achieved by averaging the MDRD estimation with the CrCl result; both methods available to the clinician in most transplant centers. We also showed that predonation GFR as measured by isotopic renal clearance or any of the creatinine-based estimation formulas may be associated with allograft function at 1 year, whereas the widely used CrCl was not. CONCLUSIONS: Variable performance was seen among different GFR estimations, with CrCl being the poorest. Recent recommendations to use the MDRD equation with standardized serum creatinine did not improve its performance. However, recognizing the limited availability of GFR laboratories, these methods are still clinically useful if used with caution and understanding their limitations.