Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Transpl Int. 2020 Jul;33(7):752-761. doi: 10.1111/tri.13600. Epub 2020 Mar 23.
Hydrogen sulfide (H 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 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 ). 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 S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.
硫化氢（H2S）是由含硫氨基酸代谢产生的，据称是一种具有肾保护作用的化合物。24 小时尿硫酸盐排泄量（USE）可反映 H2S 的生物利用度。我们旨在研究在一个大型前瞻性肾移植受者（RTR）队列中，USE 与移植物失功的相关性。我们纳入了 704 例稳定的 RTR，这些患者至少在移植后 1 年接受了入组。我们应用对数秩检验和 Cox 回归分析来研究基线 24 小时尿液样本中 USE 与移植物失功的相关性。中位年龄为 55 [45-63] 岁（57%为男性），eGFR 为 45±19ml/min/1.73m2。中位 USE 为 17.1 [13.1-21.1]mmol/24h。在中位随访 5.3 [4.5-6.0] 年后，84 例 RTR 发生了移植物失功。在 USE 按性别分层的最低三分位组中，RTR 随访期间的移植物失功率高于中三分位和最高三分位组（分别为 18%、13%和 5%，对数秩检验 P<0.001）。在 Cox 回归分析中，USE 与移植物失功呈负相关[每增加 10mmol/24h 的 HR：0.37（0.24-0.55），P<0.001]。该相关性在调整了潜在混杂因素（包括年龄、性别、eGFR、蛋白尿、移植与基线之间的时间、BMI、吸烟和高敏 C 反应蛋白）后仍然独立存在[每增加 10mmol/24h 的 HR：0.51（0.31-0.82），P=0.01]。总之，这项研究表明，RTR 中 USE 与移植物失功呈显著负相关，表明 H2S 生物利用度较高是 RTR 移植物失功的一个新的、潜在可改变的因素。
