Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.

中文翻译：

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代谢性酸中毒引起的慢性肾脏病肾脏损伤的机制。

回顾性分析和单中心前瞻性研究确定慢性代谢性酸中毒是CKD进展的独立且可改变的危险因素。在患有CKD的患者中，未经治疗的慢性代谢性酸中毒通常会导致GFR加速下降。造成这种减少的机制包括增加酸排泄但导致肾功能下降的适应性反应。CKD中的代谢性酸中毒会刺激肾脏内旁分泌激素（包括血管紧张素II，醛固酮和内皮素-1（ET-1））的产生，它们介导增加肾酸排泄的直接好处，但它们的慢性上调会促进炎症和纤维化。慢性代谢性酸中毒还会刺激氨生成，增加酸的排泄，但也会导致氨诱导的补体激活和C3和C5b-9的沉积，从而可能引起肾小管间质损害，进而使疾病恶化。这些作用以及肾脏组织中的酸积累共同促进了肾脏疾病的进展。慢性代谢性酸中毒的治疗减弱了这些适应性反应。降低血管紧张素II，醛固酮和ET-1的水平；减少氨气生成；并减少炎症和纤维化，可能导致CKD进程减慢。慢性代谢性酸中毒的治疗减弱了这些适应性反应。降低血管紧张素II，醛固酮和ET-1的水平；减少氨气生成；并减少炎症和纤维化，可能导致CKD进程减慢。慢性代谢性酸中毒的治疗减弱了这些适应性反应。降低血管紧张素II，醛固酮和ET-1的水平；减少氨气生成；并减少炎症和纤维化，可能导致CKD进程减慢。