This pathway provides a novel insight into regulation of HIF-1 in ischemic kidney, characterized by co-existent hypoxia and inflammation. TOMINAGA NAOTO1, KIDA KEISUKE2, MATSUMOTO NAOKI3, AKASHI YOSHIHIRO J2, MIYAKE FUMIHIKO2, KIMURA KENJIRO1, SHIBAGAKI YUGO1 1Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine; 2Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine; 3Department of Pharmacology, St. Marianna University School of Medicine Introduction: Administration

of high-dose loop diuretics, such as furosemide,

to overcome diuretic resistance is sometimes inevitable during the treatment for severe congestive heart failure (CHF). Administration of diuretics at high dose, however, might cause a variety learn more Depsipeptide in vitro of complications including worsening renal function or metabolic/electrolyte disturbances, and a large-scale clinical study showed that this is also related to worsening prognosis. Co-administration of a novel vasopressin V2 receptor antagonist, tolvaptan, can lessen such adverse events by sparing the dose of loop diuretics; however, its safety in patients with significantly reduced renal function is not yet known. Methods: We co-administered tolvaptan 15 mg Non-specific serine/threonine protein kinase once daily orally for 7 days to 22 patients with CHF complicated by advanced chronic kidney disease (CKD) after administration of high dose of furosemide which was inadequate to control fluid overload. We classified these patients into three groups according to their estimated glomerular filtration rate (eGFR): CKD stages G3b, G4, and G5. Results: In the G3b group, serum sodium concentrations were significantly higher (P = 0.020) on day 8 (one day after the last dose) and, in the G5 group, serum potassium significantly increased (P = 0.037) compared to baseline values,

although these values stayed within reference range and did not seem clinically significant. Though serum urea nitrogen and serum creatinine concentrations rose significantly in the G4 group (P = 0.017 and P = 0.012, respectively), no patient in any group showed deterioration of renal function on day 2 and day 3. Significant change in serum uric acid was not observed in any group, and no significant change was observed in blood pressure or heart rate. Conclusion: We conclude that add-on tolvaptan to high-dose furosemide in patients with furosemide-resistant CHF complicated with advanced CKD was safe and was not associated with significant adverse events.