The Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
Center for Translational Research on Inflammatory Diseases, Houston, Texas.
Clin J Am Soc Nephrol. 2022 Sep;17(9):1293-1304. doi: 10.2215/CJN.16831221. Epub 2022 Aug 9.
The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Migrants with Mesoamerican nephropathy kidney failure (=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (=63) and age/sex/place of origin-matched healthy participants (=16). Survey results were extended to the bench; C57BL/6 mice (=73) received 10-15 weekly intraperitoneal injections of paraquat (a reactive oxygen species-generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy.
Patients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; =0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; =0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; =0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy.
Exposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.
不明原因的慢性肾脏病（又称中美洲肾病）的病因仍不清楚。我们在移民透析人群中研究了中美洲肾病的潜在病因。
设计、地点、参与者和测量方法：通过排除已知的肾脏疾病病因，确定了患有中美洲肾病肾衰竭的移民（=52 例），并使用横断面调查与其他病因（=63 例）和年龄/性别/原籍地匹配的健康参与者（=16 例）的肾衰竭患者进行比较。调查结果扩展到了实验室；C57BL/6 小鼠（=73 只）接受了 10-15 周的每周腹膜内注射百草枯（一种产生活性氧的除草剂）或载体。检查了肾功能、组织学以及有机阳离子转运蛋白-2（百草枯进入近端小管的入口）和多药和毒素外排 1（外排途径）的表达。对来自尼加拉瓜的急性中美洲肾病患者的肾脏活检进行了上述转运蛋白的染色，并与间质性肾炎患者和无中美洲肾病患者进行了比较。
患有中美洲肾病和肾衰竭的患者是年轻的农业工人，几乎全是男性；大多数来自墨西哥和萨尔瓦多；他们曾接触过农用化学品，包括百草枯（27%）。在调整年龄/性别后，接触任何农用化学品或百草枯均与中美洲肾病肾衰竭相关（比值比，4.86；95%置信区间，1.82 至 12.96；=0.002 和比值比，12.25；95%置信区间，1.51 至 99.36；=0.02）。调整年龄/性别和其他混杂因素后，1 年的农用化学品暴露与中美洲肾病肾衰竭相关（比值比，1.23；95%置信区间，1.04 至 1.44；=0.02）。与 16 名匹配的健康对照相比，中美洲肾病肾衰竭与接触百草枯和农用化学品明显相关。百草枯处理的雄性小鼠出现了与中美洲肾病一致的肾衰竭和间质性肾炎。雄性肾脏中有机阳离子转运蛋白-2 的表达高于雌性肾脏。百草枯处理增加了雄性肾脏中的有机阳离子转运蛋白-2 表达并降低了多药和毒素外排 1 的表达；在患有中美洲肾病的尼加拉瓜患者的肾脏中也观察到了类似的结果。
接触农用化学品与中美洲肾病相关，慢性接触百草枯（一种典型的氧化剂）可诱导类似于中美洲肾病的肾衰竭。
