Clinical evaluation of valsartan and metoprolol tartrate in treatment of diabetic nephropathy with positive β1-adrenergic and anti-angiotensin II type 1 receptor antibody

Background  Studies have confirmed that angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitors (ACEI) in the treatment of diabetic nephropathy (DN) has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 (AT1) receptor antibody.

Methods  The epitopes of the second extracellular loop of β1 receptor (197-222) and AT1 receptor (165-191), were synthesized and used respectively to screen serum autoantibodies from patients with DN (n=371, group A), diabetes mellitus (DM) without renal failure (n=107, group B) and healthy blood donors (n=47, control, group C) by enzyme-linked immunosorbent assay (ELISA). Metoprolol tartrate 25–50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 mg, once a day, and nitrendipine 10–20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment.

Results  In DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls (all P <0.01). Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly (P <0.01) in DN patients with positive autoantibodies.

Conclusions  The findings suggest that these autoantibodies against β1 and AT1-receptor may play important roles in the pathogenesis of DN. Valsartan and metoprolol tartrate are effective and safe in the treatment of DN.