Defective H+ Secretion in Distal Renal Tubular Acidosis

While full-blown distal renal tubular acidosis (dRTA) is a clear cause of relentless kidney stone formation, nephrocalcinosis, and loss of kidney function, a forme fruste of the condition is incomplete dRTA which escapes the usual clinical detection. We have found that there are genetic variants of the B1 subunit of the V-ATPase and the anion exchanger AE-1, which results in incomplete dRTA in an autosomal dominant fashion. Based on the usual clinical parameters, these subjects with dRTA are indistinguishable from a regular calcium stone former.  We explore the molecular mechanisms of mutant B1 and AE1 alleles and their relationship to human incomplete dRTA using protein biochemistry and humans metabolic studies respectively.