Background: Isotopic glomerular filtration rate (iGFR) measurement is comparable to the inulin method. In this study, we compared urinary and plasma iGFR methodologies in patients with diabetic nephropathy. Methods: A total of 147 patients from 3 sites in the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at baseline, 18 and 36 months. Results: The mean (with standard deviation) plasma iGFR of 60.7 (24.9) ml/min/1.73 m2 compared to urinary iGFR of 52.0 (28.0) ml/min/1.73 m2 was statistically significant (p value <0.001). Although plasma and urinary iGFRs were highly related (R2 = 0.86), plasma iGFR increasingly overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional analyses, the two measures of iGFR were weakly related (R2 = 0.32) in regard to patients' change over 18 months of follow-up. Conclusion: Plasma iGFR may not be a suitable method for accurately measuring GFR in patients with advancing degrees of chronic kidney disease from diabetic nephropathy.

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