Familial Factors, Low Birth Weight, and Development of ESRD: A Nationwide Registry Study

Abstract

Background: Previous studies have demonstrated that low birth weight (LBW) is associated with higher risk for end-stage renal disease (ESRD). However, both LBW and ESRD cluster in families. The present study investigates whether familial factors explain the association between LBW and ESRD.

Study design: Retrospective registry-based cohort study.

Setting & participants: Since 1967, the Medical Birth Registry of Norway has recorded medical data for all births in the country. Sibling data are available through the Norwegian Population Registry. Since 1980, all patients with ESRD in Norway have been registered in the Norwegian Renal Registry. Individuals registered in the Medical Birth Registry with at least 1 registered sibling were included.

Predictor: LBW in the participant and/or LBW in at least 1 sibling.

Outcome: ESRD.

Results: Of 1,852,080 included individuals, 527 developed ESRD. Compared with individuals without LBW and with no siblings with LBW, individuals without LBW but with a sibling with LBW had an HR for ESRD of 1.20 (95% CI, 0.91-1.59), individuals with LBW but no siblings with LBW had an HR of 1.59 (95% CI, 1.18-2.14), and individuals with LBW and a sibling with LBW had an HR of 1.78 (95% CI, 1.26-2.53). Similar results were observed for individuals who were small for gestational age (SGA). Separate analyses for the association of age 18 to 42 years and noncongenital ESRD showed stronger associations for SGA than for LBW, and the associations were not statistically significant for age 18 to 42 years for LBW.

Limitations: Follow-up only until 42 years of age.

Conclusions: LBW and SGA are associated with higher risk for ESRD during the first 40 years of life, and the associations were not explained by familial factors. Our results support the hypothesis that impaired intrauterine nephron development may be a causal risk factor for progressive kidney disease.

Keywords: Low birth weight (LBW); early determinants of disease; end-stage renal disease (ESRD); genetic factors; index; intrauterine growth restriction; placental insufficiency; prenatal exposure delayed effects; sibling; small for gestational age (SGA).