A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein (ANTI-UPRO)

The Effect and Safety of Amiloride in Decreasing Proteinuria for Patients With Chronic Kidney Disease in a Prospective , Crossover, Open-label Study.

Nowadays, the prevalence of chronic kidney disease (CKD) in China is about 10.8%,and nearly 120 million people suffer from CKD, which has become a serious public health problem in China. Study confirmed that proteinuria is an independent risk factor for the continuous deterioration of glomerular filtration rate (GFR) in patients with CKD. So it is of great significance to explore the strategy of reducing proteinuria.

According to our previous study, Amiloride can inhibit the expression of uPAR in podocytes and reduce proteinuria, This clinical trial aims to evaluate the effect and safety of Amiloride in decreasing proteinuria for patients with Chronic Kidney Disease.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: Amiloride; Drug: Hydrochlorothiazide

Detailed Description

Amiloride is a Na+ channel blocker and has been used as a diuretic. It mainly inhibits the exchange of Na+-K+ and Na+-H+ in the distal tubule and collecting duct of the kidney, thus increasing the excretion of Na+ and water, reducing the excretion of K+ and H+. Recent studies have found a significant increase in urine uPA in patients with massive proteinuria.Urine uPA concentration were positively correlated with urinary protein and decreased with remission of proteinuria. In children and adults with nephrotic syndrome,as well as rat with proteinuria induced by puromycin amino-nucleoside, amiloride can inhibit uPA concentration in urine, which may be one of the mechanisms of amiloride in reducing proteinuria.

This study is a prospective , crossover, open-Label study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least four weeks prior to the study. The baseline data would be recorded. Patients enrolled will receive either amiloride or hydrochlorothiazide first for 8 weeks.Hydrochlorothiazide, a similar diuretic as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then the patients will discontinue amiloride or hydrochlorothiazide for a washout for 4 weeks, but continue with the ACE inhibitor or ARB. After that patients will cross over to receive another medication for another 8 weeks. We aim to evaluate the effect and safety of Amiloride in decreasing proteinuria for patients with chronic kidney disease.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nephrology Dept,Guangdong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients at the age of more than 14 years old with chronic kidney disease
• Good compliance of treatment
• PCR≥500mg/g.cr ，more than double confirmed
• Patients who written informed consent

Exclusion Criteria:

• less than 14 years of age
• eGFR≤30ml/min.1.73m2；
• poor compliance of treatment
• Previously intolerant or allergic to hydrochlorothiazide
• Patients with history of gout within six months
• Patients with active infection
• Patients with severe cardiopulmonary disease and dysfunction of central nervous system
• history of malignancy
• life expectancy is less than 1 years
• women who are pregnant,lactating and lack of contraception.
• enrolled in other clinical trials within 3 months
• patients who have used immunosuppressive agents or corticosteroids recently or in the past 12 weeks.
• patients without informed consent written or who enable or unwilling to comply with protocol approved by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: amiloride; Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks	Drug: Amiloride; Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks.
Active Comparator: hydrochlorothiazide; hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.	Drug: Hydrochlorothiazide; hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The remission of proteinuria	after treatment for 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
estimated Glomerular Filtration Rate	time to a 50% reduction in baseline estimated Glomerular filtration rate (according to CKD-EPI) and to doubling of baseline creatinine	after treatment for 12 weeks
creatinine	time to doubling of baseline creatinine	after treatment for 12 weeks
hyperkalemia	The ratio of hyperkalemia occurred at 12 weeks after treatment.	at 12 weeks after treatment

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): September 18, 2020
• Last Update Submitted That Met QC Criteria: September 16, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Diuretics, Potassium Sparing; Sodium Chloride Symporter Inhibitors; Acid Sensing Ion Channel Blockers; Epithelial Sodium Channel Blockers; Hydrochlorothiazide; Amiloride
• Other Study ID Numbers: GGH2016422H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No