Background: Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a 'multihit' model of albuminuria in young adults in one remote Aboriginal community.
Methods: Urinary albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years and evaluated in the context of birthweights, a history of 'remote' poststreptococcal glomerulonephritis (PSGN; ≥5 years earlier) and current body mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of subjects and 22.8% had a remote history of PSGN.
Results: ACR levels rose with age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25% of males and 45% of females). In multivariate models, birthweight (inversely), remote PSGN and current BMI were all independent predictors of ACR levels. The effects of birthweight and PSGN and their combination were expressed through amplification of ACR levels in relation to age and around the group median BMI of 20.8 kg/m2. In people with BMI <20.8 (57.8% of all males and 40.3% of the females), LBW and PSGN alone had minimal effects on ACR, but in combination they strikingly amplified ACR in relation to age. Those with BMI ≥20.8 (which included 42.2% of the males and 59.7% of the females) had higher ACR levels, and both LBW and a PSGN history, separately and in combination, were associated with striking further amplification of ACR in the context of age.
Conclusion: Much of the great excess of disease in this population is explained by high rates of the early life risk factors, LBW and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.