Agha Adnan, Bashir Kaukab, Anwar Eram
Medical Unit I, Jinnah Hospital, Lahore, Pakistan.
Nepal Med Coll J. 2007 Jun;9(2):79-83.
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.
2型糖尿病（T2DM）是一种全球性疾病，其引发的并发症糖尿病肾病是慢性肾衰竭的主要原因。微量白蛋白尿是糖尿病肾病的早期指标，也是心血管疾病发病的独立危险因素。数据表明，血管紧张素受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）等抗高血压药物可有效降低高血压T2DM患者的微量白蛋白尿，并延缓肾脏疾病的进展。但ARB对血压正常的T2DM患者预防微量白蛋白尿及后续肾病的作用尚未完全明确。为评估氯沙坦治疗血压正常的T2DM患者的抗微量白蛋白尿作用，开展了一项干预性二期临床试验。该研究在巴基斯坦拉合尔真纳医院糖尿病诊所进行，为期8个月。共评估了171例血压正常的T2DM合并微量白蛋白尿患者。在获得知情同意并进行基线24小时尿微量白蛋白定量后，选定患者开始服用氯沙坦50毫克/天，为期6个月。每月进行随访，监测血压、血糖控制情况、尿素/肌酐/钾水平以及氯沙坦治疗的任何不良反应。研究结束时重复进行定量微量白蛋白尿检测。171例患者中，149例（87.1%）的白蛋白尿显著减少，超过基线水平的30.0%，干预的最终结果变量（尿白蛋白，毫克/分升）显著降低（基线时平均为101.9±标准差21.7，治疗后为47.5±12.9），p<0.001，且副作用极小。氯沙坦的这些抗白蛋白尿作用在停药两个月后复查尿白蛋白时可见是可逆的。氯沙坦耐受性良好，在早期肾病的T2DM患者中显示出显著的抗蛋白尿作用，且与高血压无关，需要进一步开展长期大规模研究以证明其作为糖尿病肾病预防性治疗的有效性。
