Beneficial Effect of Amiloride on Progression of Chronic Kidney Disease

Phase 2

Recruiting

• Conditions: Chronic Kidney Disease(CKD); Proteinuria
• Interventions: Drug: amiloride; Drug: Placebo

• Registration Number: NCT06923709
• Lead Sponsor: Odense University Hospital

Brief Summary

This is a randomized, placebo-controlled, double-blinded crossover trial testing the effects of amiloride in patients with chronic kidney disease (CKD) and proteinuria.

In CKD with proteinuria, there is aberrant filtration of serine proteases and complement precursors into the tubular lumen. The interaction of these factors leads to proinflammatory complement activation, which may promote inflammation, opsonization, and formation of the membrane-attack complex, causing cell injury.

With the aim of preserving kidney function, reducing cardiovascular morbidity, and delaying renal replacement therapy in CKD, this study tests whether amiloride (10 mg/day) protects the filtration barrier, lowers albuminuria, and mitigates kidney inflammation through urokinase inhibition, independent of blood pressure effects.

Participants are randomized to receive amiloride (10 mg/day) or placebo for one week, with a 2-3-week washout period in between. Blood and urine samples are collected before and after each treatment period. Additionally, ECG, body composition measurements, blood pressure, and body weight are monitored.

The primary outcome measures are urinary C3a, soluble C5-9 (sTCC/MAC), and kidney injury biomarkers KIM-1 and NGAL. Secondary endpoints include the urinary albumin/creatinine ratio, protein/creatinine ratio, and blood pressure.

Detailed Description

Please refer to the protocol

Study Timeline

• Study Start: 2024-10-10
• Status Verified: 2025-04
• Study First Submitted: 2025-04-02
• Study First Submitted QC: 2025-04-10
• Last Update Submitted: 2025-04-10
• Study First Posted: 2025-04-11
• Last Update Posted: 2025-04-11
• Primary Completion: 2025-08-01
• Study Completion: 2025-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Amiloride	amiloride	Amiloride 5mg twice daily for 7 days followed by 2-3 weeks of washout and then placebo twice daily for 7 days
Placebo	Placebo	Placebo twice daily for 7 days followed by 2-3 weeks of washout and then Amilorid 5 mg twice daily for 7 days

Primary Outcome Measures

Name	Time	Method
Urine-C3a (ng/ml)	Measured before (day one) and after (day 8) each treatment period	Urine-C3a is measured in spot urine samples and expressed as u-C3a/creatinine (µg/g) to account for the dilution factor.
Urine C5-9-sTCC/MAC (U/ml)	Measured before (day one) and after (day 8) each treatment period	Membrane Attack Complex (MAC) of the complement system, specifically targeting the C5 to C9 proteins. u-C5-9 is measured in spot urine samples and expressed as u-C5-9/creatinine U/µmol to account for the dilution factor.
Kidney Injury Molecule-1 (KIM-1) pg/ml	Measured before (day one) and after (day 8) each treatment period	KIM-1 is a protein that serves as a biomarker used particularly in the context of kidney injury
Neutrophil Gelatinase-Associated Lipocalin (NGAL) (pg/mL)	Measured before and after each treatment period	NGAL is a protein associated with neutrophils used as a biomarker in the context of kidney injury.

Secondary Outcome Measures

Name	Time	Method
Urine albumin/creatinin ratio (mg/g)	Measured before (day one) and after (day 8) each treatment period	In spot urine samples, albumin and creatinin are measured
Urine protein/creatinin ratio	Measured before (day one) and after (day 8) each treatment period	In spot urine samples, albumin and creatinin are measured
Home blood pressure (mmHg)	Measured before (day one) and after (day 8) each treatment period	Home blood pressure are measured according to standard guidelines

Trial Locations

Locations (1)

Department of Nephrology, Odense University Hospital; 🇩🇰 Odense, Denmark