Mechanisms of hyperkalemia caused by nafamostat mesilate.

1. Nafamostat mesilate (NM) is a novel serine-protease inhibitor used for the treatment of acute pancreatitis and disseminated intravascular coagulation. Recently, NM has been reported to cause hyperkalemia due to reduced urinary excretion of potassium (K). 2. This review briefly summarizes the roles of the cortical collecting duct (CCD) in the renal K excretion. 3. In vitro microperfusion technique was applied to examine whether NM, and its two metabolites, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol, directly act on the CCD. 4. It was demonstrated that these compounds act mainly on the apical membrane of the collecting duct cell in the CCD and inhibit the amiloride-sensitive sodium (Na) conductance, resulting in an inhibition of K secretion. PGBA had the most potent action. 5. This direct action of these two metabolites, rather than NM, could contribute to the NM-induced hyperkalemia.