The balance of the evidence on acid-base homeostasis and progression of chronic kidney disease

Abstract

Normalization of acid-base homeostasis in chronic kidney disease (CKD) holds promise for mitigating disease progression, but whether efforts should focus on patients with low serum bicarbonate or high dietary acid load is unknown. Vallet et al. report that low urinary ammonia excretion independently associates with increased progression in moderate CKD. Whether this finding implicates differences in endogenous acid production or the ability to excrete an acid load in the pathogenesis of progression requires further study.

Figure. Framework for interpreting relationship between urine ammonia and CKD progression

Panel A depicts the pre-existing working hypothesis, whereby high dietary acid load coupled with impaired tubular function result in metabolic acidosis and CKD progression (Blue arrows). In this framework, interventions that reduce acid load via dietary changes or alkali supplements may slow CKD progression via changes in acid base status. Red dashed arrows represent an alternative hypothesis whereby high acid load may promote CKD progression by increasing renal ammoniagenesis and stimulating renin-angiotensin-aldosterone system (RAAS) activation even in the absence of metabolic acidosis. Panel B depicts an alternative framework for interpreting the study in this issue of Kidney International that reports a relationship between low, as opposed to high, urinary ammonia excretion with CKD progression. Low urinary ammonia excretion may be a powerful marker of tubular function that is at least partially independent of GFR and associated independently with outcomes (Dashed purple arrows). Lower urinary ammonia may indicate a proclivity toward development of metabolic acidosis, but the “appropriateness” of the urinary ammonia can only be fully understood relative to the acid-base status and the acid load.