Clinical trial NCT03170336: A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein
Official title: The Effect and Safety of Amiloride in Decreasing Proteinuria for Patients With Chronic Kidney Disease in a Prospective , Crossover, Open-label Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Kidney Diseases
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2017-05-31
Enrollment: 40
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.Then the patients will discontinue amiloride or hydrochlorothiazide for a washout for 4 weeks, but continue with ACEI(angiotensin-converting enzyme inhibitor ) or ARB. After that patients will cross over to receive another medication for another 8 weeks.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The remission of proteinuria
timeFrame: after treatment for 12 weeks
Secondary outcomes:
measure: estimated Glomerular Filtration Rate
timeFrame: after treatment for 12 weeks
measure: creatinine
timeFrame: after treatment for 12 weeks
measure: hyperkalemia
timeFrame: at 12 weeks after treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nephrology Dept,Guangdong General Hospital
state: Guangdong
Study officials:
References: