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.

Migrants with Mesoamerican nephropathy kidney failure (n=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 (n=63) and age/sex/place of origin–matched healthy participants (n=16). Survey results were extended to the bench; C57BL/6 mice (n=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; P=0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; P=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; P=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.

病因不明的慢性肾病（也称为中美洲肾病）的病因尚不清楚。我们调查了移民透析人群中美洲肾病的潜在病因。

通过排除已知的肾病病因，确定患有中美洲肾病肾衰竭的移民（ n = 52），并使用横断面调查与人口统计相似的其他原因肾衰竭患者（ n = 63）和年龄/性别/地点进行比较来源匹配的健康参与者（ n = 16）。调查结果延伸至替补席； C57BL/6 小鼠（ n = 73）每周接受 10-15 次腹腔注射百草枯（一种产生活性氧的除草剂）或媒介物。检查了肾功能、组织学和有机阳离子转运蛋白 2（百草枯的近端肾小管入口）和多药物和毒素挤出 1（挤出途径）的表达。对患有急性中美洲肾病的尼加拉瓜患者的肾脏活检进行上述转运蛋白染色，并与患有肾小管间质性肾炎和无中美洲肾病的患者进行比较。

中美洲肾病和肾衰竭患者都是年轻的农业工人，几乎全是男性；大多数来自墨西哥和萨尔瓦多；他们之前接触过农用化学品，包括百草枯（27%）。调整年龄/性别后，接触任何农用化学品或百草枯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； P = 0.002，比值比，12.25；95% 置信区间，1.51分别为 99.36； P = 0.02）。调整年龄/性别和其他协变量后，1 年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； P = 0.02）。与 16 名匹配的健康对照者相比，中美洲肾病肾衰竭与百草枯和农用化学品的暴露显着相关。百草枯治疗的雄性小鼠出现肾衰竭和肾小管间质性肾炎，与中美洲肾病一致。有机阳离子转运蛋白 2 的表达在男性肾脏中高于女性肾脏。百草枯处理增加了雄性肾脏中有机阳离子转运蛋白 2 的表达，并降低了多药和毒素排出 1 的表达；在尼加拉瓜中美洲肾病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有关，而小鼠长期接触百草枯（一种典型氧化剂）会诱发与中美洲肾病类似的肾衰竭。