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Recent advances in understanding renal ammonia metabolism and transport

Weiner, I. David; Verlander, Jill W.

Current Opinion in Nephrology and Hypertension: September 2016 - Volume 25 - Issue 5 - p 436–443
doi: 10.1097/MNH.0000000000000255

Purpose of review The purpose of this review is to provide a succinct description of the recent findings that advance our understanding of the fundamental renal process of ammonia metabolism and transport in conditions relevant to the clinician.

Recent findings Recent studies advance our understanding of renal ammonia metabolism. Mechanisms through which chronic kidney disease and altered dietary protein intake alter ammonia excretion have been identified. Lithium, although it can acutely cause distal renal tubular acidosis, was shown with long-term use to increase urinary ammonia excretion, and this appeared to be mediated, at least in part, by increased Rhcg expression. Gene deletion studies showed that the ammonia recycling enzyme, glutamine synthetase, has a critical role in normal-stimulated and acidosis-stimulated ammonia metabolism and that the proximal tubule basolateral bicarbonate transporter, NBCe1, is necessary for normal ammonia metabolism. Finally, our understanding of the molecular ammonia species, NH3 versus NH4+, transported by Rh glycoproteins continues to be advanced.

Summary Fundamental studies have been recently published that advance our understanding of the regulation of ammonia metabolism in clinically important circumstances, and our understanding of the mechanisms and regulation of proximal tubule ammonia generation, and the mechanisms through which Rh glycoproteins contribute to ammonia secretion.

aDivision of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine

bNephrology and Hypertension Section, North Florida/South Georgia Veterans Health System, Gainesville, Florida, USA

Correspondence to Dr I. David Weiner, MD, PO Box 100224, Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL 32610, USA. E-mail:

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