Paradoxical Association of Predonation Urine Protein with Kidney Function in Living Kidney Donors without Obesity

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Background: Clinical significance of pre-donation proteinuria in living kidney donors (LKD) is unknown. We aim to examine the association between pre-donation urinary protein:creatinine ratio (UPCR) and the risk of kidney function decline in LKD. Methods: A retrospective cohort study using OPTN/SRTR included adult LKD undergoing donation between 6/1972 and 9/2022. The association between pre-donation UPCR and time-to-event of ≥35% decline in post-donation eGFR from pre-donation eGFR was examined by multiple Cox regression. Results: Of 174,311 adult LKD, the mean±SD age was 41±12 years and 60% were female. Mean pre-donation UPCR was 2.12 ±9.23 mg/g of Cr and UPCR at immediate post-donation, 6-, 12-, and 24-months post-donation were 1.23±6.54, 1.44±8.26, 1.72±9.26, and 1.37±7.96 mg/g of Cr, respectively. The median (IQR) pre-donation eGFR was 91 (75, 111) mL/min/1.73 m2. Median eGFR at immediate post-donation, 6-, 12-, and 24-months post-donation were 50 (40, 62), 54 (44, 67), 55 (45, 68), and 57 (47, 70) mL/min/1.73 m2, respectively. Out of 38,780 LKD with post-donation eGFR data at 6, 12, or 24 months, 31,054 LKD had the event of ≥35% decline in post-donation eGFR from pre-donation eGFR with a median time to follow-up of 6.77 months (IQR 5.93, 12.67). The incidence rate of the event was 0.08 person-months. After adjusting for age, race/ethnicity, U.S. citizenship, education level, history of pre-donation BMI, hypertension, diabetes, and pre-donation SBP and DBP, every 1 mg/g of Cr increase in pre-donation UPCR was associated with a 0.8% lower risk for the event (HR 0.992, 95%CI 0.985, 0.998). Obesity status was an effect measured modifier with a decreased risk of a decline in eGFR ≥35% observed in LKD with pre-donation normal weight and overweight, but not obesity (HRnormal weight 0.988, 95%CI 0.977, 0.999; HRoverweight 0.989, 95%CI 0.978, 0.999; and HRobesity 1.003, 95%CI 0.991, 1.014). Conclusion: Pre-donation UPCR is inversely associated with the risk for a significant decline in post-donation eGFR in LKD with normal weight and overweight. Relatively less glomerular hyperfiltration in non-obese LKD may contribute to a reno-protective effect regardless of the degree of pre-donation proteinuria.

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