Metabolic acidosis: new insights from mouse models

Abstract

Purpose of review 

Metabolic acidosis is a severe disturbance of extracellular pH homeostasis that can be caused both by inborn or acquired defects in renal acid excretion or metabolic acid production. Chronic metabolic acidosis causes osteomalacia with nephrocalcinosis and urolithiasis. In the setting of end-stage renal disease, metabolic acidosis is often associated with increased peripheral insulin resistance, and represents an additional independent morbidity risk factor. This review summarizes recent insight, gained primarily from mouse models, into the mechanisms whereby the kidney regulates and adapts acid excretion.

Recent findings 

Human genetics and various mouse models have shed new light on mechanisms that contribute to the kidney's ability to excrete acid and adapt appropriately to metabolism. Progress in four specific areas will be highlighted: mechanisms contributing to the synthesis and excretion of ammonia; insights into adaptive processes during acidosis; mechanisms by which the kidney may sense acidosis; and the pathophysiology of acquired and inborn errors of renal acid handling.

Summary 

Genetic mouse models and various messenger RNA and proteome profiling and screening technologies demonstrate the importance of various acid-base transporting proteins and a metabolic and regulatory network that contributes to the kidney's ability to maintain the systemic acid-base balance.