Low birth weight and risk of progressive kidney disease. Epidemiological and morphological studies

Background: Low Birth Weight (LBW) and Small for Gestation Age (SGA) are surrogate markers for fetal undernutrition and are associated with impaired nephron development in utero as suggested by the Brenner`s hypothesis. We investigated whether familial factors explain the association between LBW and ESRD, whether LBW and/or SGA predict progression to ESRD in IgAN patients and whether LBW and/or SGA is associated with altered glomerular size or density in young IgAN patients with preserved renal function. Methods: We linked medical birth data from the Medical Birth Registry of Norway (MBR), sibling data from the Norwegian Population Registry, ESRD data from the Norwegian Renal Registry (NRR) and kidney biopsy data from the Norwegian Kidney Biopsy Registry (NKBR). For Paper I and II, data were analysed in a retrospective cohort study design. Exposure variables for Paper I were LBW/ SGA in the participant and/or LBW/SGA in at least 1 sibling. For Paper II, exposure variables were LBW/ SGA among a cohort of IgAN patients. Outcome variable for Paper I and II was development of ESRD and data were analysed with cox regression statistics. For paper III we selected IgAN patients and control patients registered in the NKBR who had registered birth weight in the MBR and preserved renal function (i.e e GFR≥60 ml/min/1.73m2) at time of diagnosis. Differences in glomerular density and volume were investigated between subjects with or without LBW/SGA as well as between IgAN patients and controls. Results: In Paper I, we found that 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 hazard ratio (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 SGA. In Paper II we found that as compared to patients without LBW, patients with LBW had an increased risk of progression to ESRD with an HR of 2.0 (1.1-3.7) for the total cohort, 2.2 (1.1-4.4) for male and 1.3 (0.30- 5.8) for female). Similar results were observed for SGA but further analyses suggested that subjects with both LBW and SGA had the highest risk. In paper III we found that compared to IgAN patients without LBW or SGA, IgAN patients with LBW and/or SGA had larger glomerul