ABSTRACT Aguascalientes, Mexico, has a high incidence and prevalence of advanced chronic kidney disease (CKD). CKD is especially frequent in young people ages 20–40 years in whom the cause of CKD was unknown, although kidney biopsies frequently showed focal segmental glomerulosclerosis (FSGS) and glomerulomegaly. Macias-Diaz et al. have now pursued this lead by screening teenagers in Calvillo, one of the hardest hit municipalities. They uncovered clinical, laboratory, kidney biopsy and exposure findings that define a new entity, Aguascalientes nephropathy, and are consistent with familial exposure to common environmental toxins, potentially consisting of pesticides. They hypothesize that prenatal exposure to these toxins may decrease nephron number. The young age of persons with FSGS would be consistent with a novel environmental toxin introduced more than 50 years ago but not present in the environment before. Key takeaways from this research are the need to screen teenagers for albuminuria, to provide kidney-protective strategies to patients identified as having CKD and for the research community to support Aguascalientes nephrologists and health authorities to unravel the cause and potential solutions for this CKD hotspot. In this regard, the screening approach and the cohort generated by Macias-Diaz et al. represent a giant step forward. The next steps should be to screen younger children for albuminuria and kidney size and to identify the putative toxins.