Tolins J P, Hostetter M K, Hostetter T H
J Clin Invest. 1987 May;79(5):1447-58. doi: 10.1172/JCI112973.
Chronic potassium deficiency results in progressive tubulointerstitial injury, associated with augmented renal ammoniagenesis. We investigated the role of elevated renal ammonia levels and the interaction of ammonia with the complement system in this injury. Potassium deficiency was induced in rats by feeding a low potassium diet. Experimental animals received 150 mM NaHCO3 or equimolar NaCl, as drinking water. After 3 wk, NaHCO3 supplemented rats demonstrated decreased ammonia production, less renal hypertrophy, less histologic evidence of injury, and less proteinuria. In in vitro studies on normal cortical tubular fragments, the addition of ammonia to serum in concentrations comparable to renal cortical levels in potassium-deficient animals significantly increased tubular deposition of C3 as quantitated by a radiolabeled antibody binding technique. Thus, alkali supplementation reduced chronic tubulointerstitial disease in a rat model of hypokalemic nephropathy. We propose that increased cortical ammonia levels contribute to hypokalemic nephropathy through ammonia-mediated activation of the alternative complement pathway.
慢性钾缺乏会导致进行性肾小管间质损伤，并伴有肾脏氨生成增加。我们研究了肾脏氨水平升高的作用以及氨与补体系统在这种损伤中的相互作用。通过喂食低钾饮食在大鼠中诱发钾缺乏。实验动物饮用150 mM NaHCO₃或等摩尔的NaCl作为饮用水。3周后，补充NaHCO₃的大鼠氨生成减少，肾脏肥大减轻，损伤的组织学证据减少，蛋白尿也减少。在对正常皮质肾小管片段的体外研究中，以与低钾动物肾脏皮质水平相当的浓度向血清中添加氨，通过放射性标记抗体结合技术定量显示，显著增加了C3在肾小管的沉积。因此，碱补充减少了低钾性肾病大鼠模型中的慢性肾小管间质疾病。我们提出，皮质氨水平升高通过氨介导的替代补体途径激活而导致低钾性肾病。
