Hyperkalemia Due to Nafamostat Mesylate

Abstract

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Regulation of prostasin by aldosterone in the kidney

“…We found that treatment of a mouse CCD cell line with aldosterone increased the secretion of prostasin protein into culture media and that aldosterone stimulated 22 Na uptake by increasing prostasin expression. We also found that increased aldosterone levels in rats markedly increased the urinary excretion of prostasin.…”

“…The activities of ENaC in M-1 cells were determined by measurement of amiloride-sensitive 22 Na uptake (16). Preliminary experiments determined that amiloride-sensitive uptake of 22 Na was linear for up to 15 minutes.…”

“…All assays were performed in duplicate. ENaC activity was determined as the difference between 22 Na uptake in the presence or absence of amiloride. The results were normalized for protein concentration and expressed as percentage of control.…”

“…Figure 3b shows that the addition of recombinant prostasin further increased the 22 Na uptake by 1.35-fold in control cells and by 1.56-fold in aldosterone-treated cells, suggesting that ENaC expressed on the apical membrane of M-1 cells are not fully activated by prostasin under basal conditions and that an aldosterone-induced increase in the prostasin abundance in the culture media has a definite role in the activation of ENaC. These results, taken together with the findings that aldosterone increases prostasin protein expression in M-1 cells, demonstrate that M-1 cells have aprotinin-sensitive Na uptake under basal conditions that is probably due to prostasin expression and that aldosterone substantially increases the prostasin-dependent Na uptake by increasing prostasin protein abundance.…”

Anti-tumor effect by inhibition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model

“…Also, high efficacy of nafamostat mesilate combined with gemcitabine for pancreatic cancer has been demonstrated in animal experiments (17) that applied to clinical trials (18). Nafamostat mesilate, which is a serine-protease inhibitor (19,20), is widely used for treatment of pancreatitis (21), disseminated intravascular coagulation (22), and anticoagulation in hemodialysis (23) in Japan, and has only minimal adverse effects such as hyperkalemia or hyponatremia (24)(25)(26).…”