Metabolic acidosis is a frequent but asymptomatic complication in
chronic kidney disease (CKD). In early stages of CKD
acidosis is limited to the renal tissue and progresses to reduced serum
bicarbonate levels. Reduced renal tissue pH and increased ammoniagenesis are the key mechanisms of the kidney to enhance
acid excretion to the urine. The expressed
protein patterns in the proximal tubular epithelial cells change remarkably, the proximal convoluted tubule develops
hypertrophy, and an intra-renal enhanced renin-angiotensin-system leads to interstitial
fibrosis. Since nephrons are numerically reduced in CKD each remaining functional unit has to progressively increase these mechanisms to keep up the equilibrium. The adverse effects of chronic
metabolic acidosis include aside from acceleration of progression of
kidney disease, the development or exacerbation of
bone disease, increased degradation of muscle with muscle wasting, enhanced protein degradation and
inflammation. Genome wide association studies demonstrated that tubular
acid-base transporters are involved in the development of arterial
hypertension. Several retrospective analyses have indicated that low serum
bicarbonate predicts death in cohorts with CKD and
cardiovascular disease. All studies confirmed a U-shaped association of mortality and serum
bicarbonate, indicating that both,
acidosis and
alkalosis are associated with increased mortality. Randomized controlled trials showed that base substitution, either by modification of the diet or by simply adding alkalizing agents, might halt the decline of kidney function in subjects with CKD. In 2012 a meta-analysis concluded that
alkali therapy might provide a long-term favorable effect on renal function in patients with CKD.