Ethnic differences in renal water handling: a “thirsty” phenotype?

Abstract

Because African Americans (AA) tend to concentrate urine more than do Caucasians (CA) [Bankir, CJASN 2007] and to reabsorb Na more avidly, which could contribute to high blood pressure, 2 studies addressed ethnic differences in thick ascending limb (TAL) function. One, based on furosemide effects, concluded that TAL activity is greater in AA [Chan, Hypertension 2008]. Another showed that AA excrete a water load more slowly than CA, suggesting lesser TAL activity in AA [Sachdeva, Hypertension 2009]. This apparent contradiction actually reflects different functions of the medullary (M) and cortical (C) TAL subsegments (urine concentration and dilution, respectively) as illustrated by functional adaptations in mammals. Marine mammals, which never need to excrete solute‐free water, exhibit a proportionately much thinner cortex than other mammals [Beuchat, AJP 1996] suggesting low CTAL transport. In rats, chronic infusion of the V2 receptor agonist dDAVP resulted in large hypertrophy of MTAL and atrophy of CTAL [Bankir, Pflugers Arch. 1988]. Humans evolved in a hot, arid climate in which water conservation enhanced survival. Increased MTAL and decreased CTAL transport in AA have complementary effects, both favoring water conservation, which could be less critical for CA residing in cooler, wetter climates. Racial differences in TAL function could reflect adaptation by natural selection to local environments.