Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

Hydrogen sulfide (H(2)S), produced from metabolism of dietary sulfur‐containing amino acids, is allegedly a renoprotective compound. Twenty‐four‐hour urinary sulfate excretion (USE) may reflect H(2)S bioavailability. We aimed to investigate the association of USE with graft failure in a large prospective cohort of renal transplant recipients (RTR). We included 704 stable RTR, recruited at least 1 year after transplantation. We applied log‐rank testing and Cox regression analyses to study association of USE, measured from baseline 24 h urine samples, with graft failure. Median age was 55 [45–63] years (57% male, eGFR was 45 ± 19 ml/min/1.73 m(2)). Median USE was 17.1 [13.1–21.1] mmol/24 h. Over median follow‐up of 5.3 [4.5–6.0] years, 84 RTR experienced graft failure. RTR in the lowest sex‐specific tertile of USE experienced a higher rate of graft failure during follow‐up than RTR in the middle and highest sex‐specific tertiles (18%, 13%, and 5%, respectively, log‐rank P < 0.001). In Cox regression analyses, USE was inversely associated with graft failure [HR per 10 mmol/24 h: 0.37 (0.24–0.55), P < 0.001]. The association remained independent of adjustment for potential confounders, including age, sex, eGFR, proteinuria, time between transplantation and baseline, BMI, smoking, and high sensitivity C‐reactive protein [HR per 10 mmol/24 h: 0.51 (0.31–0.82), P = 0.01]. In conclusion, this study demonstrates a significant inverse association of USE with graft failure in RTR, suggesting high H(2)S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.