Renal protection in diabetic patients: benefits of a first-line combination of perindopril-indapamide (Preterax).

Luis M Ruilope, Julian Segura
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Abstract

Type 2 diabetes mellitus (T2DM) is often accompanied by high blood pressure (BP) and the clustering of several cardiovascular risk factors, and is the most frequent cause of end-stage renal disease. The stages of development of overt nephropathy in T2DM patients range from an initial alteration in renal function with an increased GFR, followed by the development of microalbuminuria and macroalbuminuria or proteinuria, featuring an established diabetic nephropathy, which eventually progresses to end-stage renal disease. Early intervention is needed to prevent the development of diabetic nephropathy and requires effective control of the different risk factors, and in particular high BP. In the initial stages of the disease, strict BP control is crucial to prevent the development of initial renal and vascular damage. Adequate BP control is particularly difficult in T2DM patients and in most cases requires the use of combination therapy. Preterax, a fixed-dose combination of perindopril 2 mg and indapamide 0.625 mg, allows BP to be significantly reduced compared with conventional strategies; this combination can be uptitrated to BiPreterax when further BP control is needed. In the PREMIER study performed in T2DM over 12 months, the perindopril/indapamide combination brought about, in addition to excellent BP control, a significant reduction in urinary albumin excretion, compared with monotherapy with enalapril. In more advanced degrees of renal damage, higher doses of the fixed combination have to be considered. The pharmacological basis of the renoprotective effect of perindopril/indapamide is the demonstration that this combination prevented nephropathy as well as proteinuria in obese Zucker rats, independently of BP control. Strict BP control from the initial stages of nephropathy together with inhibition of the renin-angiotensin system is mandatory to prevent albuminuria. The fixed combination of perindopril/indapamide can greatly help clinicians in achieving the above goals, using Preterax in the early and BiPreterax in the late stages of nephropathy.

糖尿病患者的肾脏保护:perindopril-indapamide (Preterax)一线联合治疗的益处
2型糖尿病(T2DM)通常伴有高血压(BP)和几种心血管危险因素的聚集,是终末期肾脏疾病的最常见原因。T2DM患者显性肾病的发展阶段从最初的肾功能改变(GFR升高),随后发展为微量白蛋白尿和大量白蛋白尿或蛋白尿,以确定的糖尿病肾病为特征,最终发展为终末期肾病。预防糖尿病肾病的发展需要早期干预,需要有效控制不同的危险因素,特别是高血压。在疾病的初期,严格控制血压对于防止肾脏和血管损害的发展至关重要。在T2DM患者中,适当的血压控制尤其困难,在大多数情况下需要使用联合治疗。Preterax是一种perindopril 2 mg和indapamide 0.625 mg的固定剂量组合,与传统策略相比,可以显著降低BP;当需要进一步控制血压时,可以将该组合升级为BiPreterax。在为期12个月的T2DM PREMIER研究中,与依那普利单药治疗相比,培哚普利/吲达帕胺联合治疗除了能很好地控制血压外,还能显著减少尿白蛋白排泄。对于更严重程度的肾损害,必须考虑更高剂量的固定组合。培哚普利/吲达帕胺的肾保护作用的药理学基础是,该组合可以独立于血压控制,预防肥胖Zucker大鼠的肾病和蛋白尿。从肾病初期开始严格控制血压,同时抑制肾素-血管紧张素系统,是预防蛋白尿的必要措施。培哚普利/吲达帕胺的固定联合用药,在肾病早期使用Preterax,在肾病晚期使用BiPreterax,可以极大地帮助临床医生实现上述目标。
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