Sotomayor Camilo G, Groothof Dion, Vodegel Joppe J, Eisenga Michele F, Knobbe Tim J, IJmker Jan, Lammerts Rosa G M, de Borst Martin H, Berger Stefan P, Nolte Ilja M, Rodrigo Ramón, Slart Riemer H J A, Navis Gerjan J, Touw Daan J, Bakker Stephan J L
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Kidney Int. 2021 May;99(5):1213-1224. doi: 10.1016/j.kint.2020.08.027. Epub 2020 Sep 14.
The kidney is one of the most sensitive organs to cadmium-induced toxicity, particularly in conditions of long-term oxidative stress. We hypothesized that, in kidney transplant recipients, nephrotoxic exposure to cadmium represents an overlooked hazard for optimal graft function. To test this, we performed a prospective cohort study and included 672 outpatient kidney transplant recipients with a functioning graft of beyond one year. The median plasma cadmium was 58 ng/L. During a median 4.9 years of follow-up, 78 kidney transplant recipients developed graft failure with a significantly different distribution across tertiles of plasma cadmium (13, 26, and 39 events, respectively). Plasma cadmium was associated with an increased risk of graft failure (hazard ratio 1.96, 95% confidence interval 1.56‒2.47 per log ng/L). Similarly, a dose-response relationship was observed over increasing tertiles of plasma cadmium, after adjustments for potential confounders (donor, recipient, transplant and lifestyle characteristics), robust in both competing risk and sensitivity analyses. These findings were also consistent for kidney function decline (graft failure or doubling of serum creatinine). Thus, plasma cadmium is independently associated with an increased risk of long-term kidney graft failure and decline in kidney function. Further studies are needed to investigate whether exposure to cadmium represents an otherwise overlooked modifiable risk factor for adverse long-term graft outcomes in different populations.
肾脏是对镉诱导的毒性最敏感的器官之一，尤其是在长期氧化应激的情况下。我们假设，在肾移植受者中，镉的肾毒性暴露是影响移植肾功能最佳状态的一个被忽视的危险因素。为了验证这一点，我们进行了一项前瞻性队列研究，纳入了672名移植肾功能正常超过一年的门诊肾移植受者。血浆镉的中位数为58 ng/L。在中位随访4.9年期间，78名肾移植受者出现移植失败，且血浆镉三分位数组间的分布有显著差异（分别为13、26和39例事件）。血浆镉与移植失败风险增加相关（每log ng/L的风险比为1.96，95%置信区间为1.56至2.47）。同样，在对潜在混杂因素（供体、受体、移植和生活方式特征）进行调整后，随着血浆镉三分位数的增加观察到剂量反应关系，在竞争风险分析和敏感性分析中均稳健。这些发现对于肾功能下降（移植失败或血清肌酐翻倍）也一致。因此，血浆镉与长期肾移植失败风险增加和肾功能下降独立相关。需要进一步研究以调查镉暴露是否是不同人群中长期移植不良结局的一个原本被忽视的可改变风险因素。
