Efficacy of N-Acetylcysteine in Treatment of Overt Diabetic Nephropathy

Diabetic nephropathy has become the single most frequent cause of end-stage renal disease.

On a molecular level, at least five major pathways have been implicated in glucose-mediated vascular and renal damage and all of these could reflect a single hyperglycaemia-induced process of overproduction of reactive oxygen species.

Recent studies have shown that inflammation, and more specifically pro-inflammatory cytokines play a determinant role in the development of micro- vascular diabetic complications, most of the attention has been focused on the implications of TNF-α in the setting of diabetic nephropathy.

Glutathione is the most abundant low-molecular-weight thiol, and Glutathione/ glutathione disulfide is the major redox couple in animal cells.

N-acetylcysteine is effective precursors of cysteine for tissue Glutathione synthesis.

Not only does N-acetylcysteine exhibit antioxidant properties, but it may also counteract the glycation cascade through the inhibition of oxidation.

N-acetylcysteine can also reduce the apoptosis elicited by reactive oxygen species .

Indeed, N-acetylcysteine has been shown to inhibit reactive oxygen species induced mesangial apoptosis and to be able to protect cells from glucose-induced inhibition of proliferation.

• Diabetic Nephropathy
• Chronic Kidney Disease
• Diabetes Type 2

• Experimental: A, 1,III
  in this arm patients took 1200 mg N-acetylcysteine
  Intervention: Drug: N-acetylcysteine
• No Intervention: B,2, III

Inclusion Criteria:

• Diabetic patients with more than 500 mg protein in 24 hours urine protein sample
• Males and post-menopausal non-lactating and non-pregnant females.
• Age greater than or equal to 30 years of age.
• Serum creatinine less than 3.0 mg/dL (265 micromoles per liter)
• Willing and able to give informed consent

Exclusion Criteria:

• Type 1 (insulin-dependent; juvenile onset) diabetes
• Patients with known non-diabetic renal disease
• Renal allograft
• Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 months of study entry
• Cerebrovascular accident within 3 months of study entry
• New York Heart Association Functional Class III or IV
• Known allergies or intolerance to N-acetylcysteine
• Untreated urinary tract infection or other medical condition that may impact urine protein values.