CysC-based Equations Research Articles

Comparison of risk prediction using the CKD-EPI equations and the MDRD study equation in patients with acutely decompensated heart failure

Purpose: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of the present study is to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with Acutely Decompensated Heart Failure (ADHF). Methods and results: 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated using the MDRD and CKD-EPI equations. The occurrence of mortality and HF hospitalization was recorded. Over the study period (median 365 days [interquartile range 238 to 370], 305 patients (58%) died or were rehospitalized for HF. Area under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 ml/min/1.73m2. After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (p<0.001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with a significant improvement in reclassification analyses (NRI = 10.8% and 12.5%, respectively). Conclusion: In patients with ADHF, CysC-based CKD-EPI equations were superior to MDRD Study equation for predicting mortality and/or HF hospitalization, and both improved clinical risk stratification.

Prevalence and determinants of chronic kidney disease in community-dwelling elderly by various estimating equations

BackgroundChronic kidney disease (CKD) represents a global public health problem. Few data exist in the elderly. The objective of the current study is to estimate the prevalence of CKD by means of various established and new equations and to identify the main determinants of CKD in elderly.MethodsThe ActiFE Ulm (Activity and Function in the Elderly in Ulm) study is a population-based cohort study in people of 65 years and older. Kidney function was assessed by means of estimated glomerular filtration rate (eGFR) based on two creatinine- (Cr-; MDRD, CKD-EPI) and one cystatin C - (CysC-) based method. The relationship between various potential risk factors and CKD was quantified using unconditional logistic regression.ResultsA total of 1471 subjects were in the final analysis (mean age 75.6 years, SD 6.56). Overall, prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was 34.3% by MDRD, 33.0% by CKD-EPI, and 14.6% by the CysC-based eGFR. All eGFRs showed statistically significant correlations with C-reactive protein, uric acid, as well as with lipid values. In multivariable analysis age was clearly related to prevalence of CKD and the risks were highest with the CysC-based equation. Females had a higher risk for CKD stages 3–5 with MDRD (OR 1.63; 95% CI: 1.23–2.16) whereas the OR was 1.23 (95% CI 0.92–1.65) with the CKD-Epi and OR = 0.89 (95% CI 0.58–1.34) with the CysC-based equation after multivariable adjustment. Although the cystatin C based definition of CKD resulted in a lower prevalence compared to the creatinine based ones, other measures of renal damage such as albuminuria were more prevalent in those defined by CysC-eGFR.ConclusionsPrevalence of CKD is very variable based on the used estimating equation. More work is needed to evaluate the various estimating equations especially in elderly before we are able to assess the practical consequences of the observed differences.

The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine-based equations

The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr- and CysC-based equations including the Chronic kidney disease (CKD)-EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft-Gault, Hoek, Larsson, and the CKD-EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty-five percent had a GFR < 60 ml/min/1.73 m(2) according to the IC. The Larsson, the Hoek and the CKD-EPI-CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr-based equations showed less bias than CysC-based formulas with a similar precision. All CysC-based equations were superior as compared with sCr-based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m(2).

Assessing Glomerular Filtration Rate in Hospitalized Patients

A specific method is required for estimating glomerular filtration rate GFR in hospitalized patients. Our objective was to validate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and four cystatin C (CysC)-based equations in this setting. This was an epidemiologic, cross-sectional study in a random sample of hospitalized patients (n = 3114). We studied the accuracy of the CKD-EPI and four CysC-based equations--based on (1) CysC alone or (2) adjusted by gender; (3) age, gender, and race; and (4) age, gender, race, and creatinine, respectively--compared with GFR measured by iohexol clearance (mGFR). Clinical, biochemical, and nutritional data were also collected. The CysC equation 3 significantly overestimated the GFR (bias of 7.4 ml/min per 1.73 m(2)). Most of the error in creatinine-based equations was attributable to calculated muscle mass, which depended on patient's nutritional status. In patients without malnutrition or reduced body surface area, the CKD-EPI equation adequately estimated GFR. Equations based on CysC gave more precise mGFR estimates when malnutrition, extensive reduction of body surface area, or loss of muscle mass were present (biases of 1 and 1.3 ml/min per 1.73 m(2) for equations 2 and 4, respectively, versus 5.9 ml/min per 1.73 m(2) for CKD-EPI). These results suggest that the use of equations based on CysC and gender, or CysC, age, gender, and race, is more appropriate in hospitalized patients to estimate GFR, since these equations are much less dependent on patient's nutritional status or muscle mass than the CKD-EPI equation.

Is cystatin C a better marker than creatinine for evaluating residual renal function in patients on continuous ambulatory peritoneal dialysis?

Current clinical assessments of residual renal function (RRF) for continuous ambulatory peritoneal dialysis (CAPD) patients usually require 24 h of urine collection, which is sometimes difficult for patients and contributes to random errors. Objective. Our study aims to investigate whether serum cystatin C (CysC) can serve as a better marker of RRF than serum creatinine (Cr) in CAPD and to develop a formula to estimate RRF with CysC levels. One hundred and sixty CAPD patients from a single dialysis unit were randomly divided into modeling (n(1) = 120) and validation (n(2) = 40) groups. RRF was assessed as the average of the renal clearances of urea and creatinine. We then derived RRF formulas based on the CysC and Cr levels from the modeling group and validated them by comparison with a published CysC-based equation and Modification of Diet in Renal Disease formula. CysC levels were inversely related to RRF, Kt/V(urea) and total weekly Ccr but were unrelated to age, gender, body mass index, diabetes or peritoneal clearance. The RRF formulas derived from CysC and Cr were (sinh(ln(6.736-0.566 CysC)))(2) and (sinh(ln(6.097-0.265 Cr)))(2), respectively. When applied to the validation group, the estimated RRF based on CysC (2.8 ± 1.2 mL/min/1.73 m(2)) was similar to that of on Cr (2.8 ± 1.3 mL/min/1.73 m(2)) and the measured RRF (2.9 ± 1.7 mL/min/1.73 m(2)). The CysC formula showed a small bias, with the best 30 and 50% accuracy and had a larger area under the curve and higher sensitivity and specificity when compared to the Cr formula and other formulas. Serum CysC may be a good marker for the estimation of RRF in CAPD patients. The derived CysC formula may be used to reliably estimate RRF in CAPD patients without the need for collection of 24 h urine.

A new serum cystatin C-based equation for assessing glomerular filtration rate in liver transplantation

Cystatin C (CysC) has been identified to be an alternative marker of glomerular filtration rate (GFR), but no CysC-based equation has been developed for patients receiving liver transplantation. Serum CysC and (99m)Tc-DTPA clearance (true GFR) were measured simultaneously on post-transplant days 1, 4 and 7. A new equation was constructed based on an observation group of 30 patients and its predictive ability was compared with three other CysC-based equations (Hoek, Filler and Larsson) based on a validation group of 30 patients. The new equation for calculating GFR was defined as 19.12+96.21x(1/CysC) and the derived GFR was estimated at 97.4+/-30.2 mL/min/1.73 m(2) and was close to the true GFR (96.8+/-32.8 mL/min/1.73 m(2)). Estimates of GFR by Hoek, Filler and Larsson formulas (61.4+/-25.4, 73.8+/-31.9 and 61.3+/-29.6mL/min/1.73 m(2), respectively) differed significantly from the true GFR. Correlation between the true GFR and all formulas showed no significant difference. Bias was neglectable for the new equation (mean difference: 0.6 mL/min/1.73 m(2)) but remarkable for the other three equations (mean difference: -22.9 to -35.4 mL/min/1.73 m(2)). Accuracy within 10%, 30% and 50% of the true GFR for the new equation (30.0%, 76.7% and 93.3%) was significantly higher than those of the other three equations (p<0.001 for all). A new serum CysC-based equation was established in this study and it was shown to be accurate in estimating GFR after liver transplantation, compared to the formulas of Hoek, Filler and Larsson.

Comparison between creatinine and cystatin C-based GFR equations in renal transplantation

Estimation of glomerular filtration rate (GFR) from serum creatinine (Scr) or cystatin C (Cys C) exhibit variable performances. We compared the performances of 14 Scr and 9 Cys C estimated GFR equations using inulin clearance (Clin) as the reference test in 103 stable renal transplant populations. Bias, precision, receiving operation characteristics (ROC), accuracy within 30% ranges from the reference method and agreements of each test were compared. Mean Clin was 46.4+/-20.9 ml/min/1.73 m2. Scr and Cys C levels correlated well with each other (r=0.83, P<0.0001) and with Clin (r=-0.57 and -0.53, P<0.001, respectively). ROC analysis demonstrated no superiority of Cys C over Scr. Gats equation achieved the highest accuracy of 70% in patients with GFR>or=60 ml/min/1.73 m2. In patients with GFR>or=60 ml/min/1.73 m2, the Nankivell equation demonstrated the highest accuracy of 73.91%. Cys C-based equations were not depicted to be thoroughly accurate. Bias, precision and agreement were otherwise similar in all GFR tests. Scr-based equations did not appear to be inferior to Cys C-based equations as a means to estimate GFR in renal transplant patients.

Derivation and Validation of Cystatin C–Based Prediction Equations for GFR in Children

Cystatin C (CysC) may be a better marker of glomerular filtration rate (GFR) than serum creatinine (SCr) level. Few studies derived CysC-based GFR prediction equations for children. Objectives of this study are to: (1) derive CysC-based GFR prediction equations for children, and (2) compare these equations with published formulae. Patients younger than 18 years undergoing iothalamate GFR (IoGFR) testing were studied prospectively. Data collected were age, sex, CysC level, SCr level, IoGFR, height, weight, and diagnosis. By using linear regression, 2 equations were derived and compared with 3 previously published formulae by using Bland-Altman analysis and diagnostic characteristics. Local coefficients were derived for comparison formulae. There were 111 GFR tests from 103 patients (age, 12.7 +/- 4.7 years; IoGFR, 73.6 +/- 35.7 mL/min/1.73 m(2) [1.23 +/- 0.60 mL/s/1.73 m(2)]; 60% male; and 25% post-renal transplantation). The 2 equations derived were the CysEq (including CysC level) and the CysCrEq (including CysC and SCr levels). Overall, the 2 new equations had bias and precision similar to previously published formulae when local coefficients were used. However, in patients with a renal transplant or spina bifida, the 2 new equations were less biased and more precise. All CysC-based equations performed better than the Schwartz formula. This study provides 2 CysC-based GFR prediction equations that are accurate, precise, and sensitive for detecting abnormal GFRs. Three previously published CysC GFR prediction equations have been validated for the first time. Prediction equations based on CysC level are likely to provide more accurate estimates of GFR than SCr-based equations.

Cystatin C-based calculation of glomerular filtration rate in kidney transplant recipients

Cystatin C (Cys C) has been shown to be an alternative marker of renal function. However, estimation of the glomerular filtration rate (GFR) based on Cys C has received little attention. Recently, several Cys C-based equations were developed in different patient cohorts. To date, the benefit of a Cys C-based GFR calculation in patients after renal transplantation (RTx) remains to be elucidated. We compared the diagnostic accuracy of three Cys C-based formulae (Larsson, Hoek, Filler which used an immunonephelometric method) with the results of the Modification of Diet in Renal Disease (MDRD) formula. GFR was measured by means of technetium-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) clearance in 108 consecutive patients after RTx. Correlation coefficients of all calculated GFR estimates with the true GFR were high but did not differ significantly from one another (0.83-0.87). The MDRD and Filler equations overestimated GFR significantly, whereas the Larsson equation significantly underestimated GFR. Bias of the Hoek formula was negligible. Precision of the Hoek (8.9 ml/min/1.73 m(2)) and Larsson equations (9.6 ml/min/1.73 m(2)) were significantly better than MDRD equations (11.4 ml/min/1.73 m(2); P< or =0.035 each). Accuracy within 30% of real GFR was 67.0 and 65.1% for the MDRD and Filler formulae, and 77.1% for the Larsson and Hoek formulae, respectively. Accuracy within 50% of true GFR for the Hoek formula (97.2%) was better than for the MDRD equations (85.3%). Cys C-based formulae may provide a better diagnostic performance than creatinine-based equations in GFR calculation after RTx.

Estimation of glomerular filtration rates after orthotopic liver transplantation: Evaluation of cystatin C–based equations

Early detection of renal dysfunction in patients after orthotopic liver transplantation is important. Creatinine-based equations to estimate glomerular filtration rate (GFR) were found to be less accurate in liver transplant recipients than in their original populations. Since cystatin C (CysC) is independent from muscle mass and hepatic biosynthesis, we evaluated the diagnostic accuracy of 3 CysC-based equations (Larson, Hoek, and Filler formulae) that are based on the same CysC method as that of our center in comparison to the abbreviated creatinine-based modification of diet in renal disease (MDRD) formula in 59 liver transplant recipients. "True GFR" was measured by 99mTc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) clearance. Neither correlation with the GFR (correlation coefficients: 0.594-0.640) nor precision (root mean square error: 15.7-18.17 mL/min/1.73 m(2)) differed significantly between the tested formulae. The biases of the Hoek and Larsson formulae were significantly smaller than those of the MDRD and Filler equations (-0.1 and -2.3 vs. 10.1 and 7.9 mL/min/1.73 m(2), respectively; P </= 0.0023). Mean estimates of MDRD (61.9 +/- 21.4 mL/min/1.73 m(2)) and Filler (61.2 +/- 22.1 mL/min/1.73 m(2)) differed significantly from the measured GFR (52.3 +/- 17.5 mL/min/1.73 m(2); P < 0.005), whereas Larsson and Hoek did not (49.5 +/- 20.2 and 51.4 +/- 17.9 mL/min/1.73 m(2), respectively). Accuracy within 30% and 50% of the true GFR was best for the Hoek (76.3% and 93.2%) formula, albeit not significantly different from MDRD (64.4% and 83.1%). Taken together, these data show the best overall performance for GFR estimates derived from the Hoek equation with respect to bias, precision, and accuracy.

Calculation of glomerular filtration rate based on Cystatin C in cirrhotic patients

Plasma creatinine and creatinine clearance are of limited value for the estimation of renal function in cirrhotics. In these patients, cystatin C (Cys C) has been proposed as an alternative marker of glomerular filtration rate (GFR) and Cys C-based equations for calculation of GFR have been developed in non-cirrhotic patient cohorts. We retrospectively analyzed correlation, bias, precision and accuracy of two Cys C-based formulae (Larsson and Hoek) for GFR estimation in comparison with two creatinine-based equations (Cockroft & Gault and MDRD). The Cys C was determined by an immunonephelometric method. The GFR was measured by means of inulin clearance in 44 consecutive patients with liver cirrhosis. On average, inulin clearance was 28.3 (95% CI: 29.2-41.3 ml/min/1.73 m2). Creatinine as well as Cys C-based equations overestimated the true GFR by 105-154%. However, Cys C-based equations showed significantly lower bias and higher precision than the creatinine-based formulae. Correlation and accuracy tended to be better with the Hoek and Larsson equation than with the Cockroft & Gault or MDRD formulae. Hoek and Larsson equations showed a similar diagnostic performance in all statistical procedures. Our data suggest a significant improvement of GFR estimation in liver cirrhotics by means of the Cys C-based Hoek and Larsson formulae. However, all estimates remain a crude approximation of true GFR and thus cannot replace gold standard methods.