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The renin–angiotensin system from conception to old age: the good, the bad and the ugly
Author(s) -
Lumbers Eugenie R,
Pringle Kirsty G,
Wang Yu,
Gibson Karen J
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12098
Subject(s) - nephron , diabetes mellitus , medicine , disease , incidence (geometry) , renin–angiotensin system , kidney disease , end stage renal disease , failure to thrive , low birth weight , kidney , endocrinology , physiology , pregnancy , biology , genetics , physics , blood pressure , optics
Summary The renin–angiotensin system ( RAS ) plays a critical role in placentation and nephrogenesis. Failure to thrive during intrauterine life, possibly related to placental dysfunction and impaired expression of the renal RAS , as well as prematurity, results in smaller kidneys at birth and reduced nephron number. The remaining nephrons are therefore hyperfiltering from birth. Hyperfiltration, infections and Type 2 diabetes cause glomerular and tubular fibrosis, leading to further reductions in nephron number. The intrarenal RAS plays a key role in promoting tubulointerstitial fibrosis. Low birth weight and a high incidence of preterm birth program Indigenous children for early onset renal disease in adult life. Indigenous Australians have 404 000 fewer nephrons than non‐Indigenous Australians. This, coupled with the high incidence of infectious diseases (particularly acute post‐streptococcal glomerulonephritis) and the increasing prevalence of Type 2 diabetes, explains why end‐stage renal disease is of epidemic proportions in Indigenous Australians. The existence of RAS gene polymorphisms and inflammatory cytokines may further potentiate susceptibility to renal disease in Indigenous Australians.