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Renal Function Estimation

Glomerular filtration rate (GFR) is an indicator of global renal function. Normal values range from 120-130mL/min/1.73m2. It cannot be measured directly and the amount of nephron injury does not correlate to a proportional decrease in GFR (i.e. 10% loss of nephron function does not reduce GFR by 10%). Often many nephrons can be damaged before there is a measurable decrease in GFR.

Inulin clearance is the gold standard for measuring GFR. It is given exogenously followed by multiple timed urine and blood samples in order to accurately measure GFR. As such, it is not a useful test. Other exogenous markers such as radioisotopes or iohexol can be administered as well however each comes with inherent pitfalls.

Measuring endogenous markers of renal function are much more convenient. Creatinine, blood urea nitrogen, cystatin C, and many others have been examined. Serum creatinine is the most widely utilized. Its serum levels are inversely correlated to GFR. Though easily obtained, serum creatinine is not perfect. It is impacted by muscle mass, obesity, dietary intake, and changing volume of distribution. Serum creatinine is also slow to change when acute changes in renal function occur. Creatinine clearance, which requires 24-hour urine collection, overestimates GFR especially if GFR is low.

Multiple other equations have been developed to take into account different demographic data such as age, sex, and race. These include Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and CKD-EPI (CKD epidemiology collaboration). The CKD-EPI equation has been found to be more accurate at normal and mildly reduced GFR than MDRD. CKD-EPI was also found to show a lower prevalence of CKD and was better at predicting mortality risk.

The above equations based on creatinine become less accurate in certain ethnic groups, pregnant women, unusual body mass, morbid obesity, and amputees. Therefore, other compounds should be considered. Cystatin C is one of these other endogenous markers. The CKD-EPI equation can be adjusted to utilize cystatin C instead of creatinine.


  1. Levey AS, Stevens LA. Estimating GFR Using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation: More Accurate GFR Estimates, Lower CKD Prevalence estimates, and better risk predictions. Am J Kidney Dis. 2010; 55(4): 622. PubMed Link
  2. Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, Polkinghorne KR, Shankar A, Smith DH, Tonelli M, Warnock DG, Wen CP, Coresh J, Gansevoort RT, Hemmelgarn BR, Levey AS. Comparison of Risk Prediction Using the CKD-EPI Equation And the MDRD Study Equation for Estimated Glomerular Filtration Rate. JAMA. 2012; 307 (18):1941-1951. PubMed Link