Creatinine - or cystatin C - based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60 mL/min/1.73 m2, in a population using these four equations. METHODS: CKD screening was performed in the Province of Liege, Belgium. On a voluntary basis, people aged over 50 years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60 mL/min/1.73 m2. RESULTS: The population screened consisted of 4189 people (47% were men, mean age 63 +/- 7y). Their mean serum creatinine and plasma cystatin C levels were 0.88 +/- 0.21 mg/dL and 0.85 +/- 0.17 mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations. CONCLUSIONS: Prevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference metho

Calibration and precision of serum creatinine and plasma cystatin C measurement: impact on the estimation of glomerular filtration rate

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to interassay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results (‘compensated Jaffe method’). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR[60 ml/ min/1.73 m2). Analytical limitations have led to the recommendation to give a grade ([60 ml/min/1.73 m2) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m2 (with MDRD) and 120 ml/min/1.73 m2 (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund– Malmo¨ (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated

The applicability of eGFR equations to different populations

The Cockcroft–Gault equation for estimating glomerular filtration rate has been learnt by every generation of medical students over the decades. Since the publication of the Modification of Diet in Renal Disease (MDRD) study equation in 1999, however, the supremacy of the Cockcroft–Gault equation has been relentlessly disputed. More recently, the Chronic Kidney Disease Epidemiology (CKD-EPI) consortium has proposed a group of novel equations for estimating glomerular filtration rate (GFR). The MDRD and CKD-EPI equations were developed following a rigorous process, are expressed in a way in which they can be used with standardized biomarkers of GFR (serum creatinine and/or serum cystatin C) and have been evaluated in different populations of patients. Today, the MDRD Study equation and the CKD-EPI equation based on serum creatinine level have supplanted the Cockcroft–Gault equation. In many regards, these equations are superior to the Cockcroft–Gault equation and are now specifically recommended by international guidelines. With their generalized use, however, it has become apparent that those equations are not infallible and that they fail to provide an accurate estimate of GFR in certain situations frequently encountered in clinical practice. After describing the processes that led to the development of the new GFR-estimating equations, this Review discusses the clinical situations in which the applicability of these equations is questioned