Abstract
Endogenous markers of kidney function are insensitive to early declines in glomerular filtration rate (GFR) and in rodent models, validated, practical alternatives are unavailable. In this study, we determined GFR by modeling the plasma clearance of two compounds, iohexol and inulin, and compared the findings to common endogenous markers. All plasma clearance methods of both iohexol and inulin detected a decline in renal function weeks prior to any increase in endogenous marker. Iohexol plasma clearance and inulin plasma clearance had a very high agreement and minimal bias when using 12‐sample models. However, only iohexol could be accurately simplified to a two‐sample, one‐compartment estimation strategy. Following an IV injection of low‐dose iohexol and two timed blood samples at 30 and 90 min, one can accurately approximate a complex 12‐sample strategy of plasma clearance. This method is simple enough to use in routine, longitudinal analysis of larger cohort animal studies.
Highlights
The delayed rise in plasma creatinine or urea is well known to result in an underestimation of declines in kidney function, at early stages (Morgan et al 1978; Levey 1990; Katayama et al 2011)
Plasma clearance (PC) of an exogenous substance to estimate glomerular filtration rate (GFR) is much simpler than urinary clearance and is more accurate than endogenous biomarkers (BrøchnerMortensen 1985)
Following a single injection of exogenous markers, plasma clearance can be determined from the decline in plasma concentration over time and the dose (D) injected (PC = D/AUC)
Summary
The delayed rise in plasma creatinine or urea is well known to result in an underestimation of declines in kidney function, at early stages (Morgan et al 1978; Levey 1990; Katayama et al 2011) Despite their limitations, endogenous biomarkers of kidney function, such as creatinine and urea, are widely used to evaluate kidney function in experimental models. The gold standard methodology for measuring glomerular filtration rate (GFR), both in humans and in animal models, is the urinary clearance of inulin (Levey 1990; Shobeiri et al.2013) This method is rarely used clinically (White et al 2008; Eknoyan et al 2012) and experimentally, likely due to the technical difficulty, cost, or feasibility of use in repeated measures.
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