PERINATAL EXPOSURE TO XENOBIOTICS AND KIDNEY VOLUME: A PROSPECTIVE COHORT STUDY

Mexico has one of the highest burdens of chronic kidney disease (CKD) worldwide. The state of Aguascalientes reports one of the highest prevalences globally, particularly among individuals aged 20–44 years (2632 pmp). In those under 40, more than 70% of CKD cases are of unknown etiology. The most frequent histological diagnosis in individuals aged 10–30 years is adaptive focal segmental glomerulosclerosis (FSGS). Based on these findings, screening studies were initiated in adolescents from this region. Renal biopsies from 143 adolescents revealed glomerulomegaly in 90%, incomplete podocyte foot process fusion without interstitial fibrosis, and a histological diagnosis of adaptive podocytopathy. Ultrasonographic studies in adolescents also demonstrated increased renal volume compared to non-albuminuric controls.
These findings suggest prenatal oligonephronia with compensatory renal hypertrophy during adolescence, evolving to adaptive podocytopathy and FSGS in adulthood—possibly explaining the high prevalence of CKD among young adults in the region.
This study aimed to describe the association between perinatal exposure to xenobiotics and renal volume at birth and at one year of age.

A prospective cohort study was conducted among pregnant women residing in Aguascalientes. Participants had no comorbidities except overweight or mild obesity. Samples were collected from maternal urine (MU), neonatal urine (NU), and amniotic fluid (AF). Between the fourth and fifth postnatal day, blood samples and renal ultrasounds were obtained. Follow-up evaluations, including renal ultrasound, were performed at one year of age. Renal volume was adjusted for body surface area (RV/BSA), and factors associated with values below the 5th percentile were analyzed. The change in RV/BSA (ΔRV/BSA) was calculated as the difference between the final and initial measurements. Multiple linear regression was used to assess factors associated with ΔRV/BSA.

A total of 394 women were enrolled; 95 were excluded due to missing neonatal samples or ultrasound, leaving 299 mother–infant pairs (mean maternal age 24.2 ± 5.1 years). Among neonates, 54.2% were male, with a mean birth weight of 3,266 ± 399 g. Factors associated with RV/BSA ≤5th percentile included female sex, maternal weight gain, glomerular filtration rate, methomyl detected in AF (OR 7.41; 95% CI 2.31–23.8), 2,4-dichlorophenoxyacetic acid (2,4-D) >10 ng/mL in AF (OR 4.99; 95% CI 1.58–15.7), in MU (OR 6.1; 95% CI 1.9–19.7), in NU (OR 5.1; 95% CI 1.10–26.2), fluoride in MU (OR 5.1; 95% CI 1.10–23.5), and fluoride in AF (OR 6.76; 95% CI 1.28–35.7). At one-year follow-up, 93 infants (mean age 12.8 months, 48.3% male) were reassessed. The median ΔRV/BSA was +6.5 mL/m² (IQR –16.1 to +24.8). Twenty-eight infants (30%) had perinatal exposure to at least one xenobiotic, which was associated with a smaller ΔRV/BSA (–6.6 vs +7.5, p=0.035) and a higher proportion with renal volume <10th percentile (21.4% vs 6.1%, p=0.029). The number of pesticides, fluoride exposure, and breastfeeding duration were significantly associated with ΔRV/BSA (Table 1).

VariableBeta (95%CI)p valuemultivariate Beta (95%CI)p value

Perinatal exposure to pesticides and fluoride was associated with smaller renal volume at birth and reduced renal growth during the first year of life.