ABSTRACT
Type-2 diabetes mellitus (T2DM) is a global disease and its resultant complication, diabetic nephropathy, is a leading cause of chronic renal failure. Microalbuminuria is an early indicator of diabetic nephropathy and is also an independent risk factor for cardiovascular morbidity. Data have shown that anti-hypertensives like Angiotensin receptor blockers (ARB), and Angiotensin converting enzyme inhibitors (ACEI) reduce microalbuminuria and retards the progression of renal disease effectively in hypertensive T2DM patients. But the effects ofARBs on preventing microalbuminuria and ensuing nephropathy in normotensive patients with T2DM is yet to be fully established. To assess the anti-microalbuminuric effects of losartan therapy in normotensive T2DM patients. Interventional Phase Two Clinical Trial was done. Study was done at Diabetic Clinic, Jinnah Hospital Lahore, Pakistan over 8 months. A total of 171 normotensive patients with T2DM and microalbuminuria were evaluated. After informed consent and baseline 24-hour urinary microalbuminuria quantification the selected patients were started on losartan 50 mg/day for a six-month period. Monthly follow-ups were done to monitor the blood pressure, glycemic control, urea/creatinine/potassium levels and any untoward effects of losartan therapy. Quantitative microalbuminuria was repeated at the end of study. Out of the 171 patients, 149 (87.1%) had significant albuminuria reduction >30.0% of their baseline and the variable of final outcome of intervention (urinary albumin in mg/dl) was significantly reduced (Mean 101.9 +/- SD 21.7 baseline and 47.5 +/- 12.9 post therapy) with p<0.001 and with minimal side-effects. These anti-albuminuric effects of losartan were reversible as seen on rechecking the urinary albumin two months after discontinuation of treatment. Losartan was well tolerated and demonstrated significant anti-proteinuric effects in patients with T2DM with early nephropathy independent of hypertension, warranting further long-term large-scale studies to prove its usefulness as preventive therapy for diabetic nephropathy.