1. Anomalous transmembrane anion transport has been observed in erythrocytes of patients with idiopathic calcium nephrolithiasis.
2. To verify whether cation transport is also abnormal, we investigated the frusemide-sensitive Na+ efflux from Na+-loaded erythrocytes and the natriuretic response to acute intravenous frusemide administration in calcium oxalate renal stone formers.
3. Frusemide administration induced a statistically significant smaller increase in the fractional excretion of Na+ in patients than in control subjects. Abnormal kinetic properties of erythrocyte Na+-K+-2Cl− co-transport were observed in approximately 60% of stone formers. The Km for Na+ of Na+-K+-2Cl− co-transport correlated with urinary Ca2+ excretion.
4. The abnormal kinetic properties of Na+-K+-2Cl− co-transport may be relevant for stone formation, hampering renal Ca2+ reabsorption in the distal nephron and determining critical physicochemical conditions for calcium/oxalate crystallization.