Elsevier

Clinical Biochemistry

Volume 40, Issues 3–4, February 2007, Pages 153-161
Clinical Biochemistry

Review
How to estimate GFR-serum creatinine, serum cystatin C or equations?

https://doi.org/10.1016/j.clinbiochem.2006.10.014Get rights and content

Abstract

Plasma or serum creatinine is the most commonly used diagnostic marker for the estimation of glomerular filtration rate (GFR) in clinical routine. Due to substantial pre-analytical and analytical interferences and limitations, creatinine cannot be considered accurate. Besides, the diagnostic sensitivity to detect moderate GFR reduction is insufficient. Equations to estimate GFR based on serum creatinine have been introduced, which included anthropometric data to compensate for the limitations of creatinine. Most validated and applied are the MDRD and the Cockcroft–Gault equation for adults, and the Schwartz equation for children. These equations can be calculated at the bedside or issued by the laboratory and provide accurate GFR estimates from 20 to 60 mL/min/1.73 m2 with good accuracy but moderate to poor bias and precision. Further limiting is the lack of creatinine reference methods and of calibration material. Lately, the low molecular weight protein cystatin C was introduced as a GFR estimate superior to creatinine. In particular, serum cystatin C is sensitive to detect mild GFR reduction between 60 and 90 mL/min/1.73 m2. However, no reference method and no uniform calibration material exist for cystatin C either. Further limitations are the effect of thyroid dysfunction, of high glucocorticoid doses and potentially the presence of cardiovascular diseases on cystatin C levels. To evade these obstacles and to further improve GFR estimation, cystatin C-based equations have been proposed, which seem to be superior to creatinine-based ones. However, this issue requires further evaluation. We propose a panel of GFR markers to facilitate the detection of reduced GFR at various stages and in different populations; this however needs to be extended and refined in the near future. In principle, clinicians should be aware of the limitations of and cautioned not to overrate estimated GFR by single markers or calculated by equations and should not entirely rely on GFR estimates to make precise clinical decisions.

Introduction

Chronic kidney disease (CKD) and end-stage renal disease in particular are major health problems worldwide with dramatically rising incidence and prevalence. The population with end-stage renal disease in the USA increased from approximately 200,000 in 1991 to 380,000 in 2000, and it has recently been predicted to almost double to 710,000 by 2015 [1]. Patients with diabetes and hypertension are particularly affected by this negative development. However, most patients with CKD are only identified or adequately treated with significant delay, which is critical to stop progression of CKD to end-stage renal disease and to lower the enormous cardiovascular co-morbidity associated with CKD. This development has raised great concern and has led to the first global definition and classification of CKD in 2004 by the independent international Kidney Disease Improving Global Outcome organisation (KDIGO) [2]. KDIGO recommended two laboratory tests for an earlier detection of CKD: estimation of glomerular filtration rate, as this is the best estimate of functioning renal mass (eGFR), using the simplified equation derived from the Modification of Diet in Renal Disease Study (MDRD), and determination of proteinuria, preferably microalbuminuria, corrected for urine creatinine. The recommendations have been accepted almost worldwide in the nephrological community. The widespread use of eGFR in particular is an important step forward, but it necessarily represents a simplification. This review will present an overview over the potential and limitations of the most common endogenous GFR markers and estimations of GFR presently used in clinical practice.

Section snippets

Creatinine

An ideal endogenous marker of glomerular filtration rate (GFR) should be produced at a constant rate and be eliminated exclusively by glomerular filtration [3]. Under such conditions, its steady state serum concentration reflects GFR. The urinary clearance of inulin is generally regarded the gold standard to measure GFR [4]. As this method requires continuous intravenous infusion and multiple, timed urine collections, and inulin measurement is expensive and not routinely available, it has

Acknowledgments

Conflict of interest: A.B. received honoraria from Dade Behring, Marburg, Germany, and DAKO, Glostrup, Denmark; S. H. and W. H. received honoraria from Dade Behring, Marburg, Germany.

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