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

Abstract

Hydrogen sulfide (H 2 S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-fourhour 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 logrank 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 AE 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.

Urinary Sulfate, Kidney Failure, and Death in CKD: The African American Study of Kidney Disease and Hypertension

“…The observation that urinary SO 4 and protein intake were strongly correlated yet only SO 4 was associated with risk of adverse clinical events suggests that SO 4 exerts its effects independently of protein intake. These findings are similar to those observed in kidney transplant recipients in whom higher urinary SO 4 was associated with lower mortality and graft failure (27,28). Similarly, individuals with diabetes and higher urinary SO 4 levels had lower risk of CKD progression (29,30).…”

“…Another possibility is that urinary SO 4 reflects total body sulfur abundance, and lower urinary sulfate excretion could signal a state of sulfur deficiency (28). Sulfur is a component of a variety of important molecules, including the sulfur-containing amino acids methionine and cysteine.…”