Academy of Diagnostics & Laboratory Medicine - Scientific Short
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Living kidney donation is a rare paradox in medicine, operating on a healthy person to benefit someone else, so ethical justification hinges on “minimal harm,” which in practice centers on rigorous, accurate assessment of the donor’s renal function. The glomerular filtration rate (GFR) assessment in donor evaluation is less a diagnostic snapshot than a prognostic gauge of a donor’s lifelong “renal runway” after nephrectomy. In routine care, while we lean heavily on estimated GFR (eGFR) because it’s fast and widely available, donor candidates are typically healthy and near-normal, where small variations can flip an eligibility decision. Add in biologic noise (muscle mass for creatinine, inflammation/thyroid/steroids for cystatin C), eGFR can appear precise yet lack the individual-level accuracy needed for an irreversible surgical decision.
This is not just a theoretical concern. The U.S. transplant regulator, the Organ Procurement and Transplantation Network (OPTN) does not permit donor verification using eGFR alone, and mandates measured GFR or creatinine clearance. Similarly, the KDIGO 2024 guidelines position eGFR as an initial screening tool that requires confirmatory testing and individualized assessment, particularly for candidates in the “gray zone” (60-89 mL/min/1.73 m2). Moving away from one-size-fits-all cutoffs, the guidelines also recommend age-informed thresholds and ESRD risk prediction models (such as the Grams models) to guide clinical decisions. Consistent with this, the British Transplantation Society guideline provides age-adapted reference tables, reflecting that the same GFR may be physiologic for an older donor but more concerning in a young donor.
In recent years, clinical practice has also shifted toward newer “updated” equations, most notably the 2021 CKD-EPIcr equation. OPTN has mandated the use of race-neutral eGFR equations to avoid race-based inflation that could falsely “normalize” kidney function in borderline transplant candidates and living donors. In parallel, the European Kidney Function Consortium has promoted full age-spectrum approaches (EKFC/FAS-family equations) to improve continuity of GFR assessment across age groups.
Against this backdrop, and the high stakes of donor selection, a practical question is: do contemporary eGFR equations classify donor eligibility reliably? Lahorewala and colleagues at Houston Methodist addressed this directly by benchmarking multiple eGFR equations against measured GFR (mGFR) in living donor candidates. Their results were clear: no eGFR equation was reliable for “ruling out” ineligible donors, but several were reasonably strong for identifying acceptable donors: 2021 CKD-EPIcr performed best overall, while 2021 CKD-EPIcr-cys performed best in Black donors. Across equations, the PPV for rejecting unacceptable donors (<60 mL/min/1.73 m2) was <35%, whereas the PPV for identifying acceptable donors (≥90 mL/min/1.73 m2) was >85%. A subsequent Mayo Clinic study echoed this finding. In addition, Lahorewala et al. also showed that among all tested equations, including CKD-EPI 2009, CKD-EPI 2021 and EKFC/FAS, using age/sex-specific thresholds improved donor eligibility classification.
Finally, OPTN policy itself is moving toward risk-based decision-making. The 2022 update no longer automatically excludes type 2 diabetes unless there is end-organ damage or unacceptable projected lifetime risk. This shift places a heavier burden on the accuracy of GFR: the more we individualize decisions, the more we must trust the numbers behind them. Ultimately, modern donor evaluation is not about finding reasons to say “no.” Instead, it aims to assess the risks of saying “yes” with sufficient accuracy to ensure “minimal harm, especially in the gray zone where eGFR alone is most likely to mislead.
