P2.I171: Urinary biomarkers in neonates born to mothers with preeclampsia

Background: Effects of preeclampsia (PE) on fetal renal development or function are unknown. We hypothesized that the circulating factors causing endothelial dysfunction and impaired renal function in mothers with PE adversely affect fetal kidneys.

Methods: All newborns with gestational age ≥32 weeks were eligible. Bag urine samples were stored at -70° C until assayed using commercially available ELISA kits for the following biomarkers: cystatin C, nephrin, kidney injury molecule – 1, and klotho. Urinary creatinine and protein contents were measured using standard techniques. Continuous variables were tested for normality and were analyzed using non-parametric statistics. Comparisons between the groups were made using t-tests or Wilcoxon Rank Sum Test. For categorical variables, Chi-square or Fisher’s exact analyses were used. A p value below 0.05 was considered significant.

Results: Sixty-eight mothers and their newborns with gestational age ≥32 weeks (34 study and 34 control) were enrolled. Sixteen mothers in the study group had severe features of PE. The mean weight and head circumference of infants in the two groups were similar but the infants in the study group had lower body length compared to the control group (46.4 ± 3.4 vs 48.6 ± 3.4 centimeters; p = 0.007). Urine protein and creatinine were significantly higher in study infants [protein 37.1 (14.4, 53.5) vs 20.3 (7.5, 30.0) mg/dl, p = 0.04; creatinine 63.4 (25.2, 96.6) vs 24.8 (19.8, 44.2) mg/dl, p = 0.008]. KIM-1 levels were below assay detection threshold in 13 (38%) study infants and 10 (29%) control infants (p =0.44). Urine protein, creatinine, cystatin C, and nephrin levels were above assay detection threshold in all 68 infants. Klotho levels were below assay detection threshold in 21 (62%) study infants and 10 (29%) control infants (p =0.007). Only those infants with a measurable urinary biomarker were included for comparisons of that urinary biomarker values between the two groups. Table 2 summarizes the results of urine analyses. There was no correlation between maternal urinary protein/creatinine ratio and levels of urinary biomarkers in their infants. The urinary protein, creatinine and nephrin concentrations had significant negative correlation with GA (p values 0.07, 0.0003 and 0.0008 respectively).

Conclusion: The results of our exploratory study demonstrate that exposure to PE in-utero results in altered renal function in the newborn. A significantly higher urinary protein and the observed trends in the levels of urinary nephrin and klotho in study infants are likely suggestive of glomerular immaturity and/or injury. Larger prospective studies with clinical follow up will help to explain the significance of these findings.