Clinical trial NCT00572663: Optimalization of Nephroprotection Using N-Acetylcysteine
Official title: The Effect of N-Acetylcysteine on Proteinuria and Markers of Tubular Injury in Non-Diabetic Patientswith Chronic Kidney Disease-Placebo Controlled, Randomized,Open, Cross-Over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Proteinuria
Keywords: Proteinuria
Antioxidant
N-acetylcysteine
Lead sponsor: Medical University of Gdansk
Sponsor class: OTHER
First posted: 2007-12-13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is find whether the addition of N-acetylcysteine (antioxidant) to dual renin-angiotensin-aldosterone system blockade involving angiotensin converting enzyme inhibitor and AT-1 angiotensin II receptor blocker leads to the reduction of proteinuria, main prognostic marker of chronic kidney disease progression.

Detailed description: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney diseases (CKD), and inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) may retard CKD progression. Dual pharmacological blockade of the RAAS with ACEI and ARB is recommended as a standard renoprotective management at least in patients with nondiabetic proteinuric CKD. However, neither ACEI nor ARB, even in high doses or in concomitant usage, abrogate the progression of CKD completely. Innovative approaches are needed to keep patients with CKD off dialysis. Additional antioxidant (N-acetylcysteine) may prove to be such beneficial therapeutic concept. To shed more light on this issue, we performed a randomised open controlled study to evaluate the influence of triple N-acetylcysteine and RAAS therapy on surrogate markers of kidney injury, i.e. proteinuria, markers of tubular involvement and kidney fibrosis.

Eligibility criteria: Inclusion Criteria:

* Chronic kidney disease
* Stable proteinuria above 300 mg/24 hours (no variations above 25% in the last 6 months)
* Normal or slightly impaired stable renal function defined as serum creatinine level below 1.7 mg/dl (eGFR \> 45 ml/min)

Exclusion Criteria:

* Nephrotic syndrome
* Steroids or other immunosuppressive treatment minimum during six months before the study
* Diabetes mellitus
* Potassium serum level \> 5.1 mEq/L
* Albumin serum level \< 2.0mg/dL
* Creatinine serum level \>2 mg/dl
* Current diagnosis of heart failure New York Heart Association (NYHA) Class II-IV
* Clinically significant valvular heart disease or second or third degree heart block without a pacemaker
* History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic cerebral attack
* History of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention
* History of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years
* Pregnant or nursing women
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.
* History of alcohol abuse
* NSAID abuse (more than 2 doses per week)
* Known or suspected contraindications to the study medications, including history of allergy to ACE inhibitors, AT-1 receptor blockers and N-acetylcysteine

Primary outcomes:
measure: Investigate the antiproteinuric effect of adding antioxidant, N-acetylcysteine to the combination therapy with angiotensin converting enzyme inhibitor and AT-1 receptor blocker in maximal recommended doses.
Secondary outcomes:
measure: Investigate the effect of the study intervention on urine excretion of N-acetyl-β-D-glucosaminidase, alfa1-microglobulin and amino-terminal propeptide of type III procollagen
Other outcomes:
Locations:
Study officials:
affiliation: Department of Nephrology Transplantology and Internal Medicine. Medical University of Gdansk
name: Boleslaw Rutkowski, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: