Acid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosterone

Donald E. Wesson, Jan Simoni, Kristine Broglio, Simon Sheather

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

Dietary alkali slows GFR decline in humans with a moderately reduced glomerular filtration rate (GFR) despite the absence of metabolic acidosis. Similarly, dietary alkali slows GFR decline in animals with 2/3 nephrectomy (Nx), a chronic kidney disease (CKD) model without metabolic acidosis in which GFR decline is mediated by acid (H+) retention through endothelin (ET) and mineralocorticoid receptors. To gain insight as to whether this mechanism might mediate GFR decline in humans, we explored whether macroalbuminuric subjects with moderately reduced (CKD stage 2 = 60-90 ml/min; CKD 2) compared with normal estimated GFR (>90 ml/min; CKD 1), each without metabolic acidosis, have H+ retention that increases plasma levels of ET-1 and aldosterone. Baseline plasma ET and aldosterone concentrations were each higher in CKD 2 than CKD 1. Baseline dietary H+ and urine net acid excretion (NAE) were not different between groups, but an acute oral NaHCO3 bolus reduced urine NAE less (i.e., postbolus urine NAE was higher) in CKD 2 than CKD 1, consistent with greater H+ retention in CKD 2 subjects. Thirty days of oral NaHCO3 reduced H+ retention in CKD 2 but not CKD 1 subjects and reduced plasma ET and aldosterone in both groups but to levels that remained higher in CKD 2 for each. Subjects with CKD stage 2 eGFR and no metabolic acidosis nevertheless have H+ retention that increases plasma ET and aldosterone levels, factors that might mediate subsequent GFR decline and other untoward vascular effects.

Original languageEnglish
Pages (from-to)830-837
Number of pages8
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Acidosis
  • Bicarbonate
  • Chronic kidney disease
  • Diet

ASJC Scopus subject areas

  • Physiology
  • Urology

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