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 [doi.org/10.1068/ASN.2019070677].

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.