Optimalization of Nephroprotection Using N-Acetylcysteine

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.

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