ndocytosis. Background 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. Methods 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. Results 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-α 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. Conclusions 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 Vmax. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_07_31_ASN0000000000000420.mp3...

中文翻译：

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Uninephrectomy 术后富钾碱饮食、高血压和蛋白尿


粒细胞增多。背景 丢失或捐献肾脏与患高血压和白蛋白尿的风险有关。很少有研究涉及机制或干预措施。我们研究了富含 K+- 碱的饮食的潜在益处以及蛋白尿的机制。方法 雄性 Sprague Dawley 大鼠在肾切除术前饲喂 2% NaCl+0.95% KCl 饮食 （HNa-LK） 或 0.74% NaCl+3% K+-碱饮食 （HK-alk） 3 周，然后维持各自的饮食 12 周。在非肾切除术前后分析 BP （通过尾袖）、尿液、血液和肾蛋白。结果 在肾切除术前，HK-alk 喂养与 HNa-LK 喂养的大鼠表现出相似的血压和血浆 [K+]、[Na+]，但近端 （NHE3、碳酸氢钠协同转运蛋白 1、NaPi2） 和远端 （NCC、ENaC 和 pendrin） 转运蛋白丰度较高，这种模式促进了 K+ 和 HCO3− 的分泌。未肾单位切除术后，两种饮食的单肾单位 GFR 增加 50%，Li+ 清除率增加一倍;与 HNa-LK 相比，HK-alk 的血压增加较少，氨生成较低，近端小管转运蛋白的丰度保持较低，ENaC-α 下降，NCCp 增加，与 K+ 保守一致。非肾切除术后，与饮食无关，白蛋白尿增加了 8 倍，内吞受体的丰度降低（megalin 降低 44%，禁用同源物 2 降低 25%-35%），肾损伤分子-1 增加。结论 富含 K-碱的饮食通过抑制近端 Na+ 转运蛋白和增加 K+-碱分泌来减弱非肾切除术后高血压并促进酸清除。 此外，非肾单位切除术相关蛋白尿可能至少部分归因于单肾单位 GFR 升高伴 megalin 下调，从而降低了分数蛋白内吞作用和 Vmax。播客 本文包含 https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_07_31_ASN0000000000000420.mp3...