Comparison of high glomerular filtration rate thresholds for identifying hyperfiltration

Area of Science:

• Nephrology
• Renal Physiology
• Kidney Disease Research

Background:

• High glomerular filtration rate (GFR) is frequently utilized as a proxy for single-nephron hyperfiltration.
• The precise definition of high GFR that accurately represents the clinical and structural aspects of hyperfiltration requires clarification.

Purpose of the Study:

• To identify the definition of high GFR that best correlates with the clinical and structural characteristics of hyperfiltration.
• To evaluate different GFR measurement and estimation methods for their ability to identify hyperfiltration.

Main Methods:

• Living kidney donors were evaluated using measured GFR (mGFR) via iothalamate clearance and estimated GFR (eGFR) via the CKD-EPI equation.
• High GFR was defined using the 95th percentile, with both overall and age-specific thresholds, and GFR values were corrected or uncorrected for body surface area.
• Associations between high GFR definitions and clinical characteristics, kidney volume, and, in donors, biopsy findings (nephron number, glomerular volume) and single-nephron GFR were analyzed.

Main Results:

• The 95th percentile for corrected mGFR was 134 mL/min/1.73 m², and for eGFR was 118 mL/min/1.73 m².
• Age-based thresholds varied by GFR measurement method and correction status.
• High age-based uncorrected mGFR demonstrated the strongest associations with indicators of hyperfiltration, including higher single-nephron GFR, larger glomerular and kidney volumes, and increased urinary albumin, but also correlated with a higher nephron number.

Conclusions:

• High age-based uncorrected measured GFR (mGFR) most consistently reflects hyperfiltration.
• However, this definition has limitations in clinical utility as it does not differentiate between hyperfiltration and an increased number of nephrons.