Chronic Interstitial Nephritis in Agricultural Communities: Observational and Mechanistic Evidence Supporting the Role of Nephrotoxic Agrochemicals.

Chronic interstitial nephritis in agricultural communities (CINAC) is an epidemic of kidney disease affecting specific tropical and subtropical regions worldwide and is characterized by progressive chronic kidney disease (CKD) in the absence of traditional risk factors such as hypertension and diabetes. CINAC prevalence is higher among young, male agricultural workers, but also affects women, children, and non-agricultural workers in affected areas. Biopsies from patients with CINAC across regions commonly demonstrate tubular injury with lysosomal aggregates, tubulointerstitial inflammation and fibrosis, variable glomerular changes. Each endemic area holds environmental risk factors and patient/genetic milieus, resulting in uncertainty about the cause(s) of the disease. Currently, there is no specific treatment available for CINAC. We highlight survey findings of Houston-based migrant workers with CINAC, and draw similarities between kidney injury phenotype of CINAC patients and mice treated chronically with paraquat, an herbicide used worldwide. We propose potential pathways and mechanisms for kidney injury in CINAC patients, that may offer clues for potential therapies.