Figure 1

Pathogenesis of kidney disease progression due to chronic metabolic acidosis. Metabolic acidosis and/or a high dietary acid load may contribute to progressive kidney disease through multiple mechanisms, including increased ammonia generation per nephron leading to activation of the alternative complement pathway and increased endothelin-1 and aldosterone levels in the kidney. Each of these factors may cause tubule-interstitial injury leading to a decline in kidney function. Hyperaldosteronism could also accelerate glomerulosclerosis, although glomerular injury due to metabolic acidosis has not been reported in animal models.