Metabolic Acidosis of CKD: An Update

Jeffrey A. Kraut, MD; Nicolaos E. Madias, MD


Am J Kidney Dis. 2016;67(2):307-317. 

In This Article

Abstract and Introduction


The kidney has the principal role in the maintenance of acid-base balance. Therefore, a decrease in renal ammonium excretion and a positive acid balance often leading to a reduction in serum bicarbonate concentration are observed in the course of chronic kidney disease (CKD). The decrease in serum bicarbonate concentration is usually absent until glomerular filtration rate decreases to <20 to 25 mL/min/1.73 m2, although it can develop with lesser degrees of decreased kidney function. Non–anion gap acidosis, high–anion gap acidosis, or both can be found at all stages of CKD. The acidosis can be associated with muscle wasting, bone disease, hypoalbuminemia, inflammation, progression of CKD, and increased mortality. Administration of base may decrease muscle wasting, improve bone disease, and slow the progression of CKD. Base is suggested when serum bicarbonate concentration is <22 mEq/L, but the target serum bicarbonate concentration is unclear. Evidence that increments in serum bicarbonate concentration > 24 mEq/L might be associated with worsening of cardiovascular disease adds complexity to treatment decisions. Further study of the mechanisms through which metabolic acidosis contributes to the progression of CKD, as well as the pathways involved in mediating the benefits and complications of base therapy, is warranted.


The kidney maintains a stable serum bicarbonate concentration by reabsorbing the filtered bicarbonate and synthesizing sufficient bicarbonate to neutralize the net endogenous acid load.[1,2] Therefore, when kidney function is compromised, a primary reduction in serum bicarbonate concentration can develop. Previously termed uremic acidosis, this disorder is more appropriately called the metabolic acidosis of chronic kidney disease (CKD) because it is usually unaccompanied by signs or symptoms of uremia. In this review, we summarize current views on the mechanisms mediating the metabolic acidosis of CKD, its clinical and laboratory features, its adverse effects, and the benefits and complications of recommended therapy.