Comparison of high glomerular filtration rate thresholds for identifying hyperfiltration

Background: High glomerular filtration rate (GFR) is often used as a surrogate for single-nephron hyperfiltration. Our objective was to determine the definition for high GFR that best reflects clinical and structural characteristics of hyperfiltration. Methods: We studied living kidney donors at the Mayo Clinic and Cleveland Clinic. Potential donors underwent evaluations that included measured GFR (mGFR) by iothalamate clearance and estimated GFR (eGFR) by the serum creatinine-based Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI) equation. High GFR was defined by the 95th percentile for each method (mGFR or eGFR) using either overall or age-specific thresholds. High mGFR was defined as both corrected and uncorrected for body surface area. The association of high GFR by each definition with clinical characteristics and radiologic findings (kidney volume) was assessed. In the subset that donated, the association of high GFR with kidney biopsy findings (nephron number and glomerular volume) and single-nephron GFR was assessed. Results: We studied 3317 potential donors, including 2125 actual donors. The overall 95th percentile for corrected mGFR was 134 mL/min/1.73 m2 and for eGFR was 118 mL/min/1.73 m2. The age-based threshold for uncorrected mGFR was 198 mL/min - 0.943×Age, for corrected mGFR it was 164 mL/min/1.73 m2 - 0.730×Age and for eGFR it was 146 mL/min/1.73 m2 - 0.813×Age. High age-based uncorrected mGFR had the strongest associations with higher single-nephron GFR, larger glomerular volume, larger kidney volume, male gender, higher body mass index and higher 24-h urine albumin, but also had the strongest association with high nephron number. A high age-height-gender-based uncorrected mGFR definition performed almost as well but had a weaker association with nephron number and did not associate with male gender. Conclusions: High age-based uncorrected mGFR showed the most consistent associations reflective of hyperfiltration. However, high age-based uncorrected mGFR has limited clinical utility because it does not distinguish between hyperfiltration and high nephron number.