Chronic Kidney Diseases, MASLD
Conditions
Brief summary
Renal dysfunction is a frequent and clinically important complication in cirrhosis, and MASLD/NAFLD is associated with increased risk of incident CKD; however, finerenone has not been specifically studied in MASLD-cirrhosis populations despite proven cardiorenal benefits in diabetic CKD. This monocentric, open-label, randomized controlled trial at the Department of Hepatology, ILBS, New Delhi will enroll 160 adults (18-80 years) with MASLD/NAFLD cirrhosis, clinical grade I-II ascites, and stable eGFR ≥60 mL/min/1.73 m² (MDRD-6), with key exclusions including CTP class C, refractory ascites, significant coagulopathy, intrinsic kidney disease, recent major cardiovascular events, and other protocol-defined contraindications. Participants will receive standard medical treatment (dietary measures, diuretics as indicated, metabolic control, complication management, albumin/beta-blockers as needed) and will be randomized to finerenone (5 mg/day uptitrated to 10-20 mg/day) versus spironolactone (50 mg/day uptitrated to 100-200 mg/day). The primary endpoint is incident CKD at 6 months , defined as sustained eGFR \<60 mL/min/1.73 m² over 3 months. Secondary endpoints include MAKE/MACE/MALO at 6 months, drug-related adverse events (including hyperkalemia, hyponatremia, hypotension, hyperuricemia), AKI/AKD episodes, renal biomarkers (e.g., cystatin C, UPCR), ascites response, liver severity scores (MELD 3.0/MELD-Na/CTP), and metabolic/inflammatory/endothelial markers (e.g., HbA1c, HOMA-IR, hsCRP, vWF). Sample size (n=160; 80/arm) is powered to detect an absolute 20% reduction in CKD progression (35% to 15%) with 80% power and 5% alpha (10% dropout), with intention-to-treat analyses including Kaplan-Meier and Cox regression methods.
Interventions
OTHERStandard Medical Treatment
1. Salt restricted diet, high protein diet 2. Patient education 3. Use of loop diuretics as indicated and tolerated 4. Glycemic control in diabetic subjects- SGLT2 inhibitors/DPP4 inhibitors/ GLP-1 analog +/- insulin 5. Managing complications of liver disease 6. Albumin infusions as and when required as per physician's discretion. 7. Use of Beta blockers as indicated and tolerated.
DRUGFinerenone
finerenone 5 mg/day followed by 10 mg/day. Dose will be increased as necessary up to 20mg/day.
DRUGSpironolactone
Spironolactone 50mg/day followed by 100mg/day,Dose will be increased as necessary up to 200mg/day.
Sponsors
Institute of Liver and Biliary Sciences, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age \> 18 years \<80years 2. Patient of MASLD/ NAFLD cirrhosis with clinical ascites 3. Stable eGFR-(\>60 ml/min/1.73m2) calculated using MDRD-6 equation: eGFR (ml/min/1.73 m2) = 170 × (Scr)-0.999 × (Age)-0.176 × (0.762 if patient is female) × (1.180 if black) × (SUN)-0.170 × (Albumin)0.318
Exclusion criteria
1. Age \<18 years \>80 years 2. K/C/O systemic hypertension. 3. Coagulopathy- INR \>2.5 4. Post TIPS 5. CTP class C 6. Any intrinsic/structural kidney disease. 7. Refractory Ascites 8. Patient with HCC(outside MILAN criteria) or portal vein thrombosis 9. Pregnancy or Lactating mother 10. Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment 11. Patients with anuria, acute renal failure, or Addison's disease 12. Heart failure (NYHA II to IV) 13. History of hospitalization for hyperkalaemia or acute renal failure induced by previous aldosterone antagonist treatment 14. Ongoing drug or alcohol abuse 15. Uncontrolled type 2 DM ( HbA1C \> 9) 16. MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment 17. Coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\]) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomisation 18. Diagnosed Mixed ascites (additional etiology of ascites apart from portal hypertension) 19. Patients who are on spirinolactone with stable ascites in the past 12 weeks 20. Refusal to give consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of chronic kidney disease (CKD) in patients with MASLD/NAFLD related cirrhosis with clinical ascites at 6 months between both the groups, defined as: | 6 months | CKD diagnosis will be based on either of below criteria: 1. Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m² or 2. ≥30% decline in eGFR from baseline,assessed using the CKD-EPI equation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of hyperkalemia/hyponatremia/hypotension/hyperuricemia. | 6 months | — |
| Incidence of Acute Kidney Injury (AKI) - Number and proportion of participants developing Acute Kidney Injury - Based on KDIGO criteria (increase in serum creatinine ≥0.3 mg/dL in 48 hours or ≥1.5× baseline within 7 days) . | 6 months | — |
| Incidence of Acute Kidney Disease (AKD) - Number and proportion of participants developing Acute Kidney Disease (Kidney dysfunction lasting 7-90 days after AKI or de novo). | 6 months | — |
| Change in Model for End-Stage Liver Disease Sodium (MELD-Na) score- Mean change from baseline in MELD-Na score. | 6 months | MELD ranges from 6 to 40 |
| Change in Child-Turcotte-Pugh (CTP) score - Mean change from baseline in Child-Turcotte-Pugh score | 6 months | CTP ranges from 5 to 15 |
| Composite liver decompensation outcome- measured as % participants with ≥1 event, Includes: SBP, variceal bleed, hepatic encephalopathy. | 6 months | — |
Countries
India
Contacts
CONTACTDr Vakacherla Lohith, MD
CONTACTDr Rakhi Maiwall, DM
Outcome results
None listed