Metabolic acidosis is a frequent complication in non-transplant
chronic kidney disease (CKD) and after
kidney transplantation. It occurs when net endogenous
acid production exceeds net
acid excretion. While nephron loss with reduced ammoniagenesis is the main cause of
acid retention in non-transplant CKD patients, additional pathophysiological mechanisms are likely inflicted in kidney transplant recipients. Functional tubular damage by
calcineurin inhibitors seems to play a key role causing
renal tubular acidosis. Notably, experimental and clinical studies over the past decades have provided evidence that
metabolic acidosis may not only be a consequence of CKD but also a driver of disease. In
metabolic acidosis, activation of hormonal systems and the
complement system resulting in
fibrosis have been described. Further studies of changes in renal metabolism will likely contribute to a deeper understanding of the pathophysiology of
metabolic acidosis in CKD. While
alkali supplementation in case of reduced serum bicarbonate < 22 mmol/l has been endorsed by CKD guidelines for many years to slow renal functional decline, among other considerations, beneficial effects and thresholds for treatment have lately been under intense debate. This review article discusses this topic in light of the most recent results of trials assessing the efficacy of dietary and pharmacological interventions in CKD and kidney transplant patients.