Potassium-Alkali-Enriched Diet, Hypertension, and Proteinuria following Uninephrectomy.

Abstract

A K-alkali–enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing Na⁺ reabsorption. Uninephrectomy-associated proteinuria could be attributed to elevated single-nephron GFR and downregulation of megalin, which reduced fractional protein endocytosis. Losing or donating a kidney is associated with risks of developing hypertension and albuminuria. Few studies address mechanisms or interventions. We investigate the potential benefits of a K⁺- alkali–enriched diet and the mechanisms underlying proteinuria. Male Sprague Dawley rats were fed either a 2% NaCl+0.95% KCl diet (HNa-LK) or a 0.74% NaCl+3% K⁺-alkali diet (HK-alk) for 3 weeks before uninephrectomy and then maintained on respective diets for 12 weeks. BP (by tail-cuff), urine, blood, and kidney proteins were analyzed before and after uninephrectomy. Before uninephrectomy, HK-alk–fed versus HNa-LK–fed rats exhibited similar BPs and plasma [K⁺], [Na⁺], but lower proximal (NHE3, sodium bicarbonate cotransporter 1, NaPi2) and higher distal (NCC, ENaC, and pendrin) transporter abundance, a pattern facilitating K⁺ and HCO₃⁻ secretion. After uninephrectomy, single-nephron GFR increased 50% and Li⁺ clearance doubled with both diets; in HK-alk versus HNa-LK, the increase in BP was less and ammoniagenesis was lower, abundance of proximal tubule transporters remained lower, ENaC-<i>α</i> fell, and NCCp increased, consistent with K⁺ conservation. After uninephrectomy, independent of diet, albuminuria increased eight-fold and abundance of endocytic receptors was reduced (megalin by 44%, disabled homolog 2 by 25%–35%) and kidney injury molecule-1 was increased. The K-alkali–enriched diet blunted post-uninephrectomy hypertension and facilitated acid clearance by suppressing proximal Na⁺ transporters and increasing K⁺-alkali secretion. Furthermore, uninephrectomy-associated proteinuria could be attributed, at least in part, to elevated single-nephron GFR coupled with downregulation of megalin, which reduced fractional protein endocytosis and V_max. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_07_31_ASN0000000000000420.mp3