Which Methods for Determining Glomerular Filtration Rate Most Strongly Associate with Risk of Progression of Kidney Disease?

Abstract

Estimation of glomerular filtration rate (eGFR)3 by measurement of creatinine has become the mainstay approach to clinical assessment of kidney function. eGFR is used for screening for acute kidney injury, diagnosis and monitoring of chronic kidney disease (CKD), as an indication for initiation of hemodialysis, and for assessment of kidney function to determine whether patients can tolerate imaging contrast or whether certain nephrotoxic medicines are safe to administer. Measurement of creatinine and estimation of GFR has thus become one of the most widely used and useful tests in the modern clinical chemistry laboratory. Renal filtration rate and kidney function was originally measured by administering renally filtered (and not secreted) substances, such as inulin, and measuring their clearance in the urine compared to circulating concentrations (1). This approach, although accurate, has not been applicable for routine clinical use. In 1948, Jan Brod and Jonas Sirota proposed that renal filtration rate and function could be evaluated based upon urinary clearance of endogenous creatinine (2), allowing doctors to measure kidney function without having to administer inulin or other exogenous substances. Their original validation studies demonstrated that renal clearance of endogenous creatinine was approximately equal to that of exogenous inulin and that creatinine was primarily filtered by the glomerulus and not resorbed or actively secreted. Thus, measuring serum and urine creatinine allowed for a reasonable estimation of renal filtration rate. The only limitation of their method was that it required accurate measurement of urinary creatinine excretion through a 24-h timed collection of urine, lessening its practicability. In 1976, Cockcroft and Gault proposed that creatinine clearance could instead be estimated based …