Runcaciguat, a novel soluble guanylate cyclase activator, shows renoprotection in hypertensive, diabetic, and metabolic preclinical models of chronic kidney disease

• DOI: 10.1007/s00210-021-02149-4
• Publication Date: 2021-09-22T05:02:30Z
• Authors: Agnès Bénardeau; Antje Kahnert; Tibor Schomber; Jutta Meyer; Mira Pavkovic; Axel Kretschmer; Bettina Lawrenz; Elke Hartmann; Ilka Mathar; Joerg Hueser; Jan R. Kraehling; Frank Eitner; Michael G. Hahn; Johannes-Peter St...; Peter Sandner
• Keywords: Cyclic guanosine monophosphate; Soluble guanylyl cyclase

Abstract Chronic kidney diseaQueryse (CKD) is associated with oxidative stress which can interrupt the nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling and decrease cyclic guanosine monophosphate (cGMP) production. Low cGMP concentrations cause damage progression of CKD. The novel sGC activator runcaciguat targets oxidized heme-free form sGC, restoring production under stress. purpose this study to investigate if could provide an effective treatment for Runcaciguat was used not only in rat CKD models different etiologies comorbidities, namely hypertensive rats, renin transgenic (RenTG) rat, angiotensin-supplemented (ANG-SD) but also rats diabetic metabolic CKD, Zucker fatty (ZDF) rat. duration 2 42 weeks applied orally doses from 1 10 mg/kg/bid. In these models, significantly reduced proteinuria (urinary protein creatinine ratio; uPCR). These effects were significant at did or moderately systemic blood pressure. Moreover, decreased injury biomarkers attenuated morphological damages. RenTG improved survival rates markers heart injury. data demonstrate that exhibits cardio-renal protection reduce pressure as well models. data, therefore, suggest runcaciguat, its specific mode action, represents efficient approach CV diseases. Graphical abstract