Renal ammonia and bicarbonate production in chronic renal failure

A characteristic feature of chronic renal failure (CRF) is decreased urinary NH4+ excretion and an alteration in systemic acid-base balance. In normal humans, glutamine is an important precursor of urinary NH4+; however, in CRF, renal glutamine extraction is significantly decreased. This finding suggests that alternate sources for urinary NH4+ exist. In addition to being an important precursor of urinary NH4+, the metabolism of glutamine generates alpha-ketoglutarate, an important substrate for new renal HCO3- generation in the proximal tubule. A useful model of the metabolic derangements in human CRF is the subtotally nephrectomized rat. In this review, the ammoniagenic pathways in this model of CRF are characterized with an emphasis on the role of glutathione and gamma-glutamyltransferase. In addition, recent data are presented on the production and partitioning of NH4+ and HCO3- into blood and urine in normal rats and rats with CRF.