Association of Preterm Birth with Adverse Glomerular Disease Outcomes in Children and Adults

Background: While some studies of children with nephrotic syndrome have demonstrated worse outcomes in those born preterm compared with term, little data exists on associations of preterm birth with outcomes in adult-onset glomerular disease. Cardiovascular outcomes in those born preterm with glomerular disease are unknown. Methods: We performed a cross-sectional and longitudinal analysis of participants in the Cure Glomerulonephropathy (CureGN) cohort. Preterm (<37 weeks’ gestation) was compared to term (≥37 weeks’ gestation). A survival analysis and adjusted Cox proportional hazards model were used to examine a composite outcome of 40% decline in estimated glomerular filtration rate (eGFR) or progression to kidney failure. An adjusted logistic regression model was used to examine remission of proteinuria. Results: There were 2,205 term and 235 preterm participants. APOL1 risk alleles were more common in those born preterm. More pediatric than adult participants in CureGN were born preterm: 12.8% vs. 7.69% ( P <0.001). Adults born preterm as compared to term had a higher prevalence of Focal Segmental Glomerulosclerosis (FSGS) (35% vs. 25%, P =0.01) and APOL1 high-risk genotype (9.4% vs 4.2%, P =0.01). Participants born preterm had a shorter time interval to a 40% eGFR decline/kidney failure after biopsy ( P =0.001). In adjusted analysis, preterm participants were 28% more likely to develop 40% eGFR decline/kidney failure (Hazard Ratio: 1.28 [1.07, 1.54], P =0.008) and 38% less likely to attain complete remission of proteinuria (Odds Ratio: 0.62 [0.45, 0.87], P =0.006). There was no significant difference in cardiovascular events. Conclusions: Preterm birth was a risk factor for adverse outcomes in this heterogenous cohort of children and adults with glomerular disease. Adults born preterm were more likely to have an APOL1 high-risk genotype and FSGS. In analyses adjusted for FSGS and APOL1 risk status , there was less remission and faster progression of kidney disease in those born preterm.