Ruilope Luis M, Segura Julian
Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain.
J Hypertens Suppl. 2006 May;24(3):S9-12. doi: 10.1097/01.hjh.0000229463.32480.a1.
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.
2型糖尿病（T2DM）常伴有高血压（BP）及多种心血管危险因素聚集，是终末期肾病最常见的病因。T2DM患者显性肾病的发展阶段包括：最初肾功能改变伴肾小球滤过率（GFR）升高，随后出现微量白蛋白尿、大量白蛋白尿或蛋白尿，即确诊为糖尿病肾病，最终进展为终末期肾病。需要早期干预以预防糖尿病肾病的发生，这需要有效控制不同的危险因素，尤其是高血压。在疾病的初始阶段，严格控制血压对于预防早期肾脏和血管损伤的发生至关重要。在T2DM患者中，充分控制血压尤为困难，大多数情况下需要联合治疗。百普乐，即培哚普利2mg与吲达帕胺0.625mg的固定复方制剂，与传统治疗策略相比，能显著降低血压；当需要进一步控制血压时，该复方制剂可加量至复代文。在一项针对T2DM患者进行的为期12个月的PRIME研究中，与依那普利单药治疗相比，培哚普利/吲达帕胺复方制剂除了能出色地控制血压外，还能显著降低尿白蛋白排泄量。在肾脏损伤更严重的阶段，必须考虑使用更高剂量的固定复方制剂。培哚普利/吲达帕胺肾脏保护作用的药理学基础是，该复方制剂在肥胖 Zucker 大鼠中可预防肾病及蛋白尿，且独立于血压控制。从肾病初始阶段就严格控制血压并抑制肾素-血管紧张素系统对于预防白蛋白尿是必不可少的。培哚普利/吲达帕胺固定复方制剂可极大地帮助临床医生实现上述目标，在肾病早期使用百普乐，晚期使用复代文。
