Background

Nitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD).

Objectives

We investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation.

Methods

We performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993−1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999−2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake.

Results

We identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C <median (T3 vs. T1 HR: 2.26, 95%CI: 1.05, 4.86) and with heme iron ≥median (T3 vs. T1 HR: 1.73, 95%CI: 0.89, 3.39).

Significance

ESRD incidence was associated with dietary nitrate/nitrite from processed meat among all study participants and with total dietary nitrite among participants with lower vitamin C or higher heme iron intake.

Impact statement

There are few well-established environmental risk factors for end-stage renal disease (ESRD), a worldwide public health challenge. Ingestion of nitrate and nitrite, which may lead to endogenous formation of carcinogenic N-nitroso compounds, has been linked to some cancers and chronic diseases. We investigated these exposures in relation to ESRD in an agricultural cohort. ESRD incidence was associated with dietary nitrate/nitrite from processed meat and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. This study provides preliminary evidence that points to dietary nitrite and possibly dietary nitrate intake as a potential contributor to ESRD.

中文翻译：

---

农业健康研究中持证农药施用者及其配偶摄入硝酸盐和亚硝酸盐与终末期肾病

背景

硝酸盐和亚硝酸盐的摄入与肾癌有关，可能是通过内源性形成致癌的N-亚硝基化合物。这些暴露也可能导致终末期肾病 (ESRD)。

目标

我们在农业健康研究中调查了饮用水硝酸盐和膳食硝酸盐和亚硝酸盐摄入量（总量和按食物类型）与 ESRD 事件的关联。我们还探讨了维生素 C 和血红素铁摄入量的改变作用，这可能会影响内源性亚硝化。

方法

我们对私人农药施用者及其配偶进行了完整的案例分析。我们获得了入组时（1993−1997 年）主要饮用水源为公共供水（PWS）或私人水井的参与者的水硝酸盐估计值（N  = 59,632）。平均硝酸盐浓度是根据 PWS 用户的历史数据计算的，并根据私人井用户的随机森林模型预测的。膳食硝酸盐和亚硝酸盐的分析仅限于在随访期间（1999−2003 年）完成 NCI 饮食史调查问卷的 30,177 名参与者。通过与美国肾脏数据系统的链接确定了 2018 年的终末期肾病事件。我们估计了暴露三分位数 (T) 与 ESRD 总体关联的调整后风险比 (HR) 和 95% CI，并探讨了维生素 C 和血红素铁摄入量分层的影响。

结果

我们确定了 469 例 ESRD 病例（其中 206 例用于饮食分析）。水硝酸盐和总膳食硝酸盐/亚硝酸盐与终末期肾病（ESRD）无关，但终末期肾病（ESRD）的增加与加工肉类中的硝酸盐和亚硝酸盐有关。我们发现，仅在维生素 C < 中位数（T3 与 T1 HR：2.26，95% CI：1.05，4.86）和血红素铁≥中位数（T3 与 T1 HR：1.73，95%）的参与者中，亚硝酸盐与 ESRD 之间存在明显关联。 CI：0.89，3.39）。

意义

在所有研究参与者中，终末期肾病的发生率与加工肉类中的膳食硝酸盐/亚硝酸盐有关，在维生素 C 摄入量较低或血红素铁摄入量较高的参与者中，ESRD 发病率与膳食亚硝酸盐总量有关。

影响报告

终末期肾病（ESRD）是一项全球性的公共卫生挑战，目前几乎没有明确的环境危险因素。摄入硝酸盐和亚硝酸盐可能会导致内源性形成致癌的N-亚硝基化合物，与一些癌症和慢性疾病有关。我们在农业队列中调查了这些与 ESRD 相关的暴露。ESRD 的发生率与加工肉类中的膳食硝酸盐/亚硝酸盐以及维生素 C 较低或血红素铁摄入量较高的亚组中的总膳食亚硝酸盐有关。这项研究提供了初步证据，表明膳食亚硝酸盐和可能的膳食硝酸盐摄入量是导致 ESRD 的潜在因素。