Kidney Injury in Patients with CKD and Metabolic Acidosis

Results of retrospective analyses and single-center prospective studies have demonstrated an independent association between chronic metabolic acidosis and modifiable risk factors for progression of chronic kidney disease (CKD). In a special article in the Journal of the American Society of Nephrology, Donald E. Wesson, MD, FASN, and colleagues report on the mechanisms of kidney injury due to metabolic acidosis in patients with CKD [].

In patients with CKD, untreated metabolic acidosis commonly leads to an accelerated reduction in glomerular filtration rate. Mechanisms in reduction include adaptive responses that increase acid excretion, leading to a decline in kidney function.

Metabolic acidosis in patients with CKD stimulates production of intrakidney paracrine hormones, including angiotensin II, aldosterone, and entothelin-1 (ET-1). The hormones mediate the immediate benefit of increased kidney acid excretion; however, the chronic upregulation is associated with inflammation and fibrosis. CKD progression in the presence of chronic metabolic acidosis is also worsened by the stimulation of ammoniagenesis, increasing acid excretion but also leading to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage. Combined with these effects, acid accumulation in the kidney tissue also contributes to accelerated progression of CKD.

These adaptive responses are attenuated with treatment of chronic metabolic acidosis. Treatment also reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis and may result in slowing the progression of CKD in this patient population.