Renal tubular acidosis: developments in our understanding of the molecular basis.
Renal tubular acidosis is a metabolic acidosis due to impaired acid excretion by the kidney. Hyperchloraemic acidosis with a normal anion gap and normal (or near normal) glomerular filtration rate, and in the absence of diarrhoea, defines this disorder. However, systemic acidosis is not always evident and renal tubular acidosis can present with hypokalaemia, medullary nephrocalcinosis and recurrent calcium phosphate stone disease, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. Renal dysfunction in renal tubular acidosis is not always confined to acid excretion and can be part of a more generalised renal tubule defect, as in the renal Fanconi syndrome. Isolated renal tubular acidosis is more usually acquired, due to drugs, autoimmune disease, post-obstructive uropathy or any cause of medullary nephrocalcinosis. Less commonly, it is inherited and may be associated with deafness, osteopetrosis or ocular abnormalities. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. In vitro functional studies of these mutant proteins in cell expression systems have helped to elucidate the molecular mechanisms underlying renal tubular acidosis, which ultimately may lead to new therapeutic options in what is still treatment only by giving an oral alkali.
Laing
Christopher M
CM
Centre for Nephrology, Royal Free and University College Medical School, London NW3, UK.
Toye
Ashley M
AM
Capasso
Giovambattista
G
Unwin
Robert J
RJ
D000141:Acidosis, Renal Tubular / Q000145:classification / Q000235:genetics / Q000503:physiopathology*; D000328:Adult; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000502:physiology; D024402:Carbonic Anhydrase II / Q000502:physiology; D002648:Child; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D006180:Proton-Translocating ATPases / Q000502:physiology
D001457:Anion Exchange Protein 1, Erythrocyte; D006180:Proton-Translocating ATPases; D024402:Carbonic Anhydrase II