Metabolic acidosis and the progression of chronic kidney disease

Abstract

Metabolic acidosis is a common complication of chronic kidney disease. Accumulating evidence identifies acidosis not only as a consequence of, but as a contributor to, kidney disease progression. Several mechanistic pathways have been identified in this regard. The dietary acid load, even in the absence of overt acidosis, may have deleterious effects. Several small trials now suggest that the treatment of acidosis with oral alkali can slow the progression of kidney disease.

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.