Use of losartan in reducing microalbuminuria in normotensive patients with type-2 diabetes mellitus Adnan Agha, Kaukab Bashir and Eram Anwar Medical Unit I, Jinnah Hospital, Lahore, Pakistan Corresponding author: Dr. Adnan Agha, Medical Unit I, Jinnah Hospital, Lahore, Pakistan. e-mail: adnanagha@hotmail.com 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 of ARBs 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. 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. Keywords: Diabetes mellitus type 2, diabetic nephropathy, microalbuminuria, losartan, angiotensin receptor blocker. INTRODUCTION Type-2 diabetes mellitus (T2DM) is a worldwide pandemic and WHO predicts that the current figure of 170 million affected patients with diabetes will more than double to 370 million patients by the year 2030. 1 Pakistan is currently sixth in the list of countries with highest number of estimated cases of diabetes mellitus. 2 Approximately one third of patients with T2DM will develop diabetic nephropathy, which is one of the leading cause of chronic renal failure. 3 Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria >300 mg/dl or 200 mcg/min along with relentless decline in GFR and elevated blood pressure. The first sign of renal involvement in diabetic nephropathy is microalbuminuria i.e. 24-hour urinary albumin of 30- 300 mg/dl or urinary microalbumin excretion rate of 20-200 mcg/min, which can not be detected on routine methods of protein estimation. Gradually this progresses to proteinuria and overt nephropathy following which the GFR declines by 10-12 ml/min/year and hypertension ensues eventually leading to end stage renal disease (ESRD), 4 which has dismal survival rates even in the developed world. 5 Microalbuminuria is an early indicator of diabetic nephropathy and associated with increased risk of progressiveness of renal disease in T2DM. 6 Apart from that it is also an independent risk factor for vascular diseases as 40.0-50.0% patients of T2DM with microalbuminuria die from cardiovascular diseases. 7 The prevalence of microalbuminuria is 38.9% in Asian T2DM patients Microalbuminuria prevalence study cohort, 8 and 34.0% in Karachi, Pakistan 9 as compared 17.0-21.0% in overall western population based studies. 10 It is recommended that screening for microalbuminuria be done on an annual basis in patients with T2DM for early identification and intervention. 11 Therapeutic measures that reduce albuminuria/proteinuria also retard the progression of renal disease as shown in trials with T2DM patients with overt nephropathy where reduction in proteinuria >30.0% below baseline value is associated with better preservation of renal function. 12 These measures include achieving a target blood pressure of less than 130/80 and use of various pharmacological