Utility of endogenous creatinine clearance as a measure of renal function in
Authors Stephen Dunn, Zhonghua Qi, Erwin Bottinger, Metthew Breyer, Kumar Sharma
Submitted By Kumar Sharma on 8/5/2003
Status Published
Journal Kidney international
Year 2004
Date Published 5/1/2004
Volume : Pages 65 : 1959 - 1967
PubMed Reference 15086941
Background. The use of endogenous plasma creatinine levels and creatinine
clearance as a tool to evaluate renal function in mice has come under scrutiny
as prior studies have reported that the Jaffé alkaline picrate method grossly
overestimates true plasma creatinine in mice. As members of the NIDDK Animal
Models of Diabetic Complications Consortium (AMDCC), we evaluated the
performance and feasibility of an alternative HPLC-based method for standard
determination of plasma and creatinine clearance in mice. Our purpose was to
develop a simple method that provides a reliable, reproducible and sensitive
assay for small volumes (< 25 microliters) of mouse plasma.
Methods. We compared creatinine clearance measured by HPLC with the Jaffé
method and HPLC creatinine clearance with inulin clearance (FITC inulin in an
osmotic pump implanted in mouse) in C57BL/6J mice. Different groups of mice
underwent either 1 of 2 protocols; (Protocol A) dietary intervention with
normal, low salt + enalapril, or high salt. (Protocol B) induction of diabetes
using streptozotocin.
Results. (1) mean plasma creatinine levels were significantly lower (p< 0.0001)
by HPLC (0.128 ± 0.026 mg/dl) vs. Jaffé (0.4 ± 0.12 mg/dl) for mice on a normal
diet. Corresponding urine creatinine concentrations measured by HPLC and Jaffé
were similar. (2) Mean creatinine clearance by HPLC for mice on a normal diet
was 255 ± 68 µl/min/mouse. Low salt diet plus enalapril gave the lowest
creatinine clearance of 72.8 ± 24.2 while high salt yielded the highest at 369 ±
126 µl/min/mouse. (3) Diabetic mice (19-24 weeks of diabetes) exhibited
hyperfiltration as creatinine clearance was 524 ± 214 µl/min/mouse whereas
non-diabetic age/sex matched mice showed a mean creatinine clearance of 219 ± 50
µl/min/mouse. (3) Significant correlation was demonstrated for creatinine
clearance by HPLC vs. inulin clearance (R = 0.643; P < 0.001).
Conclusions. HPLC is highly accurate, much more sensitive and specific than
Jaffé for plasma creatinine measurements in mice. Creatinine clearance in mice
measured by HPLC reflects changes in renal function induced by diet and