Iohexol Plasma Clearance in Animal Models: The Clear Choice for Measuring Early Renal Dysfunctio

Abstract

Glomerular filtration rate is a measure of the kidney’s ability to filter blood. In animal models of early kidney failure, there is no routine method to accurately measure GFR. The expensive gold standard of GFR measurement is exogenous inulin clearance. The commonly used method, endogenous plasma creatinine concentration, is unreliable and insensitive, especially at normal levels of renal function. This study investigates the utility of iohexol, an inexpensive radio-contrast agent as a promising exogenous marker for plasma clearance kidney function evaluation in rats. Early stages of progressive kidney failure were induced with a 0.25% adenine diet in male Sprague Dawley rats (N=8) over 5 weeks. Both plasma clearance of iohexol and inulin and creatinine concentration were evaluated following weekly venous injections and blood sampling. Plasma iohexol clearance and plasma inulin clearance strongly correlate (R2=0.95). However, plasma creatinine concentration correlated weakly with iohexol(R2=0.53) and inulin(R2=0.58). Iohexol plasma clearance accurately measures changes in kidney function, especially in in comparison to creatinine analysis. The data demonstrates creatinine is an inappropriate marker for renal function in early adenine-induced CKD rat models. Ongoing analysis of this data suggests refinement of the protocol will yield a simple method for routine measure of kidney function in murine lab animals. This tool will facilitate advancement in kidney disease onset and allow for more accurate interpretation of kidney function in the various animal models.