Alkaff Firas F, Kremer Daan, Thaunat Olivier, Berger Stefan P, van den Born Jacob, Genovese Federica, Karsdal Morten A, Bakker Stephan J L, Rasmussen Daniel G K, Tepel Martin
Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Division of Pharmacology and Therapy, Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia.
Transplant Direct. 2024 Feb 21;10(3):e1591. doi: 10.1097/TXD.0000000000001591. eCollection 2024 Mar.
Kidney fibrosis is a suggested cause of kidney failure and premature mortality. Because collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether urinary endotrophin, a collagen type VI fragment, is associated with graft failure and mortality among kidney transplant recipients (KTR).
In this prospective cohort study, KTR with a functioning graft ≥1-y posttransplantation were recruited; 24-h urinary endotrophin excretion was measured using an ELISA method. Multivariate Cox regression analyses were performed.
A total of 621 KTR (mean age 53 y old, 43% female) at a median of 5.2 y posttransplantation were included. Median 24-h urinary endotrophin excretion was 5.6 (3.1-13.6) µg/24h. During a median follow-up of 7.5 y, 87 KTR (14%) developed graft failure and 185 KTR (30%) died; 24-h urinary endotrophin excretion was associated with increased risk of graft failure (hazard ratio [95% confidence interva] per doubling = 1.24 [1.08-1.42]) and all-cause mortality (hazard ratio [95% confidence intervals] per doubling = 1.14 [1.03-1.25]) independent of potential confounders including plasma endotrophin concentration. Twenty-four-hour urinary protein excretion was a significant effect modifier for the association with mortality (P = 0.002). Twenty-four-hour urinary endotrophin excretion was only significantly associated with mortality in KTR with low levels of proteinuria.
Urinary endotrophin is independently associated with an increased risk of graft failure in all KTR and mortality only in KTR with low levels of proteinuria. Further studies with different KTR populations are needed to confirm these findings.
肾纤维化被认为是肾衰竭和过早死亡的原因。由于VI型胶原蛋白与肾纤维化密切相关，我们旨在评估尿内营养蛋白（一种VI型胶原蛋白片段）是否与肾移植受者（KTR）的移植失败和死亡率相关。
在这项前瞻性队列研究中，招募了移植后有功能移植物≥1年的KTR；采用ELISA法测量24小时尿内营养蛋白排泄量。进行多变量Cox回归分析。
共纳入621例KTR（中位年龄53岁，43%为女性），移植后中位时间为5.2年。24小时尿内营养蛋白排泄量中位数为5.6（3.1 - 13.6）μg/24小时。在中位随访7.5年期间，87例KTR（14%）发生移植失败，185例KTR（30%）死亡；24小时尿内营养蛋白排泄量与移植失败风险增加相关（每增加一倍的风险比[95%置信区间]=1.24[1.08 - 1.42]），与全因死亡率相关（每增加一倍的风险比[95%置信区间]=1.14[1.03 - 1.25]），且独立于包括血浆内营养蛋白浓度在内的潜在混杂因素。24小时尿蛋白排泄量是与死亡率相关性的显著效应修饰因素（P = 0.002）。24小时尿内营养蛋白排泄量仅在蛋白尿水平低的KTR中与死亡率显著相关。
尿内营养蛋白与所有KTR移植失败风险增加独立相关，且仅与蛋白尿水平低的KTR死亡率相关。需要对不同的KTR人群进行进一步研究以证实这些发现。
