Abstract: TH-PO0380
Renal-Protective Effects of Praliciguat in Preclinical Models of FSGS
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Zuk, Anna, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
Background
Focal segmental glomerulosclerosis (FSGS) is a podocytopathy characterized by progressive glomerular scarring. In the kidneys, the nitric oxide (NO) – soluble guanylate cyclase (sGC) – cyclic guanosine 3’,5’-monophosphate (cGMP) pathway protects podocytes from injury and loss. Praliciguat (PRALI) is a selective stimulator of sGC, that has been previously evaluated in phase 1 and 2 clinical trials across cardiometabolic and renal indications. By stabilizing the nitrosyl-heme complex of native/reduced sGC, PRALI amplifies endogenous NO-sGC-cGMP signaling to promote cell survival, and anti-inflammatory and anti-fibrotic effects. The objective of this study was to assess the renal-protective potential of PRALI in 2 preclinical animal models of FSGS.
Methods
PRALI was administered alone or with enalapril (ENAL) as background therapy in a mouse model of primary FSGS, and in a rat model of secondary FSGS. ENAL is an angiotensin-converting enzyme inhibitor. In the primary FSGS model, adriamycin was administered intravenously at 11.5 mg/kg to induce podocyte injury; PRALI was given orally (PO) twice a day at 3, 10, or 15 mg/kg; ENAL was given PO once a day at 30 mg/kg. In the secondary FSGS model, renal dysfunction was induced by 5/6 nephrectomy using a combination of arterial ligation induced–infarction and surgical resection; treatment was initiated 2 weeks after nephrectomy. PRALI was given in chow at 1.5, 3, or 10 mg/kg/day; ENAL was given in drinking water at 30 mg/kg/day. In both models, renal function and histopathology were assessed.
Results
PRALI monotherapy did not improve renal function or histopathology in either model. Rather, in both models, PRALI with ENAL as background therapy improved renal function relative to either monotherapy. In the primary FSGS model, PRALI on a background of ENAL significantly reduced glomerulosclerosis compared with PRALI monotherapy. In the secondary FSGS model, PRALI with ENAL treatment as background significantly decreased glomerulosclerosis compared with either agent alone, suggesting a synergistic effect on glomerular protection.
Conclusion
On a background of ENAL, PRALI improved renal function and reduced glomerulosclerosis in preclinical animal models of FSGS, supporting future clinical evaluation of PRALI in FSGS.
Funding
- Commercial Support – Akebia Therapeutics, Inc.