The Association Between Metabolic Acidosis and the Progression of Chronic Kidney Disease: A Review of the Evidence

Abstract

Introduction: Chronic Kidney Disease (CKD) is a progressive condition for which identifying modifiable risk factors is a key therapeutic goal. Metabolic acidosis, a common complication of CKD, was historically viewed as a consequence of renal failure rather than a contributor to its progression.

Literature Review: A review of the pivotal scientific and clinical literature reveals a paradigm shift in this understanding. Large, prospective observational studies provided strong and consistent evidence that a lower serum bicarbonate concentration is an independent predictor of a more rapid decline in glomerular filtration rate (GFR) and an increased risk of progression to end-stage renal disease. The biological plausibility for this association was established through experimental research that identified several mechanisms of acidosis-induced renal injury, including the activation of the complement system and the increased production of pro-fibrotic mediators such as endothelin-1 within the kidney. Furthermore, a landmark randomized controlled trial provided the first direct clinical evidence that correcting metabolic acidosis with oral alkali supplementation could significantly slow the rate of GFR decline in patients with CKD.

Conclusion: The body of evidence reviewed establishes chronic metabolic acidosis as an important, independent, and modifiable risk factor for the progression of CKD. This research has provided a new therapeutic target and a strong evidence-based rationale for the routine monitoring and treatment of even mild metabolic acidosis to preserve kidney function.