Idiopathic calcium oxalate nephrolithiasis: a cellular disease.

Physico-chemical, metabolic and hormonal theories regarding the pathogenesis of calcium oxalate nephrolithiasis do not sufficiently explain many features of this disease. The recent findings of an abnormally faster oxalate self-exchange and higher phosphorylation of band 3 in erythrocytes of idiopathic calcium oxalate stone formers suggest the hypothesis that nephrolithiasis may be a cellular disease, characterized by a defect in the function of the anion-exchange. The cellular anomaly seems genetically controlled. Band 3 anion exchanger function seems to be biochemically regulated through modulation of band 3 phosphorylation, which depends on cyclic AMP- and phospholipid-sensitive Ca2+ independent protein kinases. In this light, a reduced glycosaminoglycan concentration in the erythrocyte membranes of stone formers might play a role, as these molecules exert a strong inhibitory effects on band 3 phosphorylation and anion transport in vitro and in vivo. An in vivo trial was performed in which stone formers were administered glycosaminoglycans orally. A reduction in oxalate excretion, and oxalate renal clearance, and a simultaneous correction of the abnormal RBC oxalate flux and band 3 phosphorylation were observed. These data suggest the existence of a link between the erythrocyte abnormality and oxalate transport by the kidney and gut.