TY - JOUR
T1 - Urinary sulfate excretion and risk of late graft failure in renal transplant recipients - a prospective cohort study
AU - Said, Mohammad Yusof
AU - Post, Adrian
AU - Minovic, Isidor
AU - Londen, van, Marco
AU - van Goor, Harry
AU - Postmus, Douwe
AU - Heiner Fokkema, M.R.
AU - Berg ,van den, Else
AU - Pasch, Andreas
AU - Navis, Gerjan
AU - Bakker, Stephan
N1 - © 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.
PY - 2020/7
Y1 - 2020/7
N2 - Hydrogen sulfide (H2S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-four-hour urinary sulfate excretion (USE) may reflect H2S 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 m2). 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 H2S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.
AB - Hydrogen sulfide (H2S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-four-hour urinary sulfate excretion (USE) may reflect H2S 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 m2). 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 H2S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.
KW - chronic graft failure
KW - hydrogen sulfide
KW - protein intake
KW - renal transplantation
KW - ISCHEMIA-REPERFUSION INJURY
KW - HYDROGEN-SULFIDE
KW - BLOOD-PRESSURE
KW - SURVIVAL
KW - NUTRITION
KW - CATECHOLAMINES
KW - ASSOCIATION
KW - PROGRESSION
KW - MORTALITY
KW - PROTEIN
U2 - 10.1111/tri.13600
DO - 10.1111/tri.13600
M3 - Article
C2 - 32112582
VL - 33
SP - 752
EP - 761
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 7
ER -