Acid/base balance is tightly regulated by kidney and lung. In kidney, proximal tubules and collecting ducts are the main sites of acid/base regulation. Proximal tubules reabsorb most of the bicarbonate filtered from glomeruli. On the other hand, a intercalated cells in collecting ducts secrete proton and reabsorb the regenerated bicarbonate. Carbonic anhydrase II (CAII) is located in the cytoplasm of both tubular cells, catalyzing the transformation between CO2 and HCO3 -. The main acid/base transporters in proximal tubules are the sodium-bicarbonate cotransporter (NBCe1) in the basolateral side and sodium-proton exchanger type 3 (NHE3) in the luminal side. Mutations in NBCe1 cause proximal renal tubular acidosis (pRTA) with ocular abnormalities and other extrarenal manifestations. In a intercalated cells, anion exchanger 1 (AE1) in the basolateral side and vacuolar type proton ATPase (V-ATPase) in the luminal side are the main transporters. Mutations in AE1 cause autosomal recessive distal renal tubular acidosis (dRTA) and/or autosomal dominant red blood cell dysmorphologies. Among multiple subunits of V-ATPase, mutations in a4 and B1 subunits cause autosomal recessive dRTA with or without impaired hearing. Mutations in CAII cause a mixed type RTA with osteopetrosis. Recent studies using genetically modified mice have significantly clarified the pathogenesis of RTA and associated extrarenal manifestations. Clinically, cases of secondary RTA due to systemic diseases such as multiple myeloma and Sjögren syndrome, or side effects of drugs are much more common than cases of hereditary RTA. In this chapter we will focus on the molecular mechanisms of RTA.
|Title of host publication||Advances in Medicine and Biology|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||16|
|ISBN (Print)||9781631174452, 9781631174445|
|Publication status||Published - 2014 Jan 1|
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