Background End-stage renal failure of unknown origin (ESRD-UO) is a public health problem in Mexico and many regions of the world. The prevalence of ESRD-UO in Aguascalientes Mexico is one of the highest worldwide, particularly in adults between 20 and 40 years of age. Aim To screen adolescents for chronic kidney disease (CKD), identify risk factors, and histologically characterize adolescents with persistent albuminuria (pACR). Methodology This is a cross-sectional, observational, and comparative study of adolescents in whom serum creatinine and the albumin creatinine ratio (ACR) were determined when screening for CKD. A clinical evaluation and risk factor survey were conducted. Patients with an abnormal ACR (≥ 30 mg/gr) or a low glomerular filtration rate (GFR) (≤75 ml/min/1.73 m2) were reevaluated and a renal ultrasound was obtained (rUS). A kidney biopsy was performed in patients with pACR. Results Five-hundred and thirteen (513) students were included, 19 had pACR and 494 were controls. The prevalence of pACR was 3.7% (95%CI 2.1 – 5.3). Only one patient had a decreased GRF. None of the patients with pACR had anatomical abnormalities of the urinary tract by rUS. Patients with pACR had a decreased total renal volume in comparison with the control group (150 vs 195 ml/m2, p <0.01). Eighteen (18) kidney biopsies were performed, 72% had glomerulomegaly, and only one patient had mild fibrosis. Podocyte abnormalities were evident on electron microscopy: partial fusion (100%), microvillous degeneration (80%), and increased organelles (60%). Risk factors for pACR were: homestead proximity to maize crops, the use of pesticides at the father´s workplace, a family history of CKD, and blood pressure abnormalities. The body mass index and breastfeeding were protective factors. Conclusions The prevalence of pACR in adolescents in Aguascalientes is high, and histologic compromise is characterized by podocyte injury in the absence of fibrosis. The renal volume of pACR patients was decreased, suggesting oligonephronia. Exposure to environmental toxins such as pesticides, even prenatally, may be responsible for this pathological entity. Screening programs in adolescents by determining ACR are necessary in our milieu.