A new dimension to the Barker hypothesis: Low birthweight and susceptibility to renal disease

Background. There is an epidemic of renal failure among Aborigines in the Australia's Northern Territory. The incidence is more than 1000 per million, and is doubling every three to four years. We evaluated the relationship of birthweight to renal disease in adults in one high-risk community. Methods. We screened more than 80% of people in the community for renal disease, using the urine albumin/creatinine ratio (ACR, g/mol) as the marker, and reviewed records for birthweights. Results. Birthweights were available with increasing frequency for people born after 1956. In 317 adults aged 20 to 38 years at screening, the mean birthweight (SD) was 2.712 +/- 0.4 kg, and 35% had been low birthweight (LBW, less than 2.5 kg). Birthweight was positively correlated with body mass index (BMI), blood pressure, and diabetes rates, but was inversely correlated with ACR. The odds ratio for overt albuminuria in LEW persons compared with those of higher birthweights was 2.82 (CI, 1.26 to 6.31) after adjusting for other factors, and LEW contributed to an estimated 27% (CI, 3 to 45%) of the population-based prevalence of overt albuminuria. Multivariate models suggest that increasing BMI and blood pressure and decreasing birthweight act in concert to amplify the increases in ACR that accompany increasing age. Conclusions. LEW contributes to renal disease in this highrisk population. The association might be mediated through impaired nephrogenesis caused by intrauterine malnutrition. The renal disease epidemic in Aborigines may partly be the legacy of greatly improved survival of LEW babies over the last four decades. Disease rates should eventually plateau as birthweights continue to improve, if postnatal risk factors can also be contained.