Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study

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 and explored modifying effects of vitamin C and heme iron intake. METHODS: Complete case analyses among private pesticide applicators and spouses. Water nitrate was estimated for public water supply (PWS) users from historical measurements and for private well users via random forest models; N=59,632. Dietary nitrate/nitrite from an NCI Diet History Questionnaire (1999–2003) was analyzed among 30,177 participants. Incident ESRD (to 2018) was ascertained via linkage to the U.S. Renal Data System. Adjusted hazard ratios (HRs) and 95% CIs were estimated for tertiles of exposure overall and within strata of vitamin C and heme iron. RESULTS: We identified 469 incident ESRD cases in the water analysis and 206 in the dietary analysis. Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but nitrate and nitrite from processed meats were positively associated with ESRD. Elevated ESRD risk with total dietary nitrite was observed only among participants with vitamin C intake below the median (T3 vs. T1 HR: 2.26, 95% CI: 1.05, 4.86) and among those with heme iron intake at or above the 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 overall and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. IMPACT STATEMENT: This study provides preliminary evidence that dietary nitrite and possibly dietary nitrate intake may contribute to ESRD risk.

Dazhe Chen, Christine G. Parks, Laura E. Beane Freeman, Jonathan N. Hofmann, Rashmi Sinha, Jessica M. Madrigal, Mary H. Ward, Dale P. Sandler