Adverse Effects of the Metabolic Acidosis of Chronic Kidney Disease

The kidney has the principal role in the maintenance of acid-base balance, and therefore, a fall in renal net acid excretion and positive H+ balance often leading to reduced serum [HCO3−] are observed in the course of CKD. This metabolic acidosis can be associated with muscle wasting, development or exacerbation of bone disease, hypoalbuminemia, increased inflammation, progression of CKD, protein malnutrition, alterations in insulin, leptin, and growth hormone, and increased mortality. Importantly, some of the adverse effects can be observed even in the absence of overt hypobicarbonatemia. Administration of base decreases muscle wasting, improves bone disease, restores responsiveness to insulin, slows progression of CKD, and possibly reduces mortality. Base is recommended when serum [HCO3−] is <22 mEq/L, but the target serum [HCO3−] remains unclear. Evidence that increments of serum [HCO3−] >26 mEq/L might be associated with worsening of cardiovascular disease adds complexity to treatment decisions. Further study of the mechanisms through which positive H+ balance in CKD contributes to its various adverse effects and the pathways involved in mediating the benefits and complications of base therapy is warranted.