Bakris G L, Weir M R, DeQuattro V, McMahon F G
Rush University Hypertension Center, Rush Presbyterian/St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Kidney Int. 1998 Oct;54(4):1283-9. doi: 10.1046/j.1523-1755.1998.00083.x.
The degree of proteinuria in patients with diabetes correlates strongly with both an increase in progression of nephropathy as well as cardiovascular events. Moreover, post hoc analyses of recent clinical trials support the concept that reductions of blood pressure and proteinuria correlate with a slowed progression of nephropathy. Both angiotensin converting enzyme (ACE) inhibitors and the nondihydropyridine calcium antagonists, (non-DHPCAs) reduce both arterial pressure and proteinuria in those with diabetic nephropathy.
The present randomized, open label, parallel group designed study tests the hypothesis that, at similar levels of blood pressure, the combination of an ACE inhibitor, trandolapril (T) with the non-DHPCA, verapamil (V) produces a greater reduction in proteinuria over either agent alone at one year. Thirty-seven participants, mean age 59.6 +/- 5.8 years, with nephropathy (baseline creatinine 1.4 +/- 0.3 mg/dl and proteinuria of 1342 +/- 284 mg/dl) secondary to type 2 diabetes completed the study. Doses of drug were titrated in each group over eight weeks to achieve a goal blood pressure of < 140/90 mm Hg. All participants were counseled to ingest a sodium diet of < 120 mEq/day.
Proteinuria reduction from baseline was significantly greater in the T+V group compared to either T alone (-33 +/- 8%, T vs. -62 +/- 10%, T+V; P < 0.001) or V alone (-27 +/- 8%, V vs. -62 +/- 10%, T+V; P < 0.001). No significant differences in either glomerular filtration rate, arterial pressure, fasting blood glucose or urinary sodium excretion were noted at one year. The mean daily dose of the individual components of T+V (2.9 +/- 0.8 mg, T/219 +/- 21.1 mg V) was significantly lower than the dose of either T alone 5.5 +/- 1.1 mg/day (P < 0.01) or V alone 314.8 +/- 46.3 mg, given in two divided doses (P < 0.01).
These data support the concept that the combination of an ACE inhibitor with a non-DHPCA reduce proteinuria to a greater extent than either agent alone. This added antiproteinuric effect occurs at lower doses of each drug and is independent of further reductions in arterial pressure. These findings could have ramifications for slowing renal disease progression in patients with nephropathy from type 2 diabetes.
糖尿病患者的蛋白尿程度与肾病进展以及心血管事件的增加密切相关。此外，近期临床试验的事后分析支持这样的概念，即血压和蛋白尿的降低与肾病进展减缓相关。血管紧张素转换酶（ACE）抑制剂和非二氢吡啶类钙拮抗剂（非DHPCAs）均可降低糖尿病肾病患者的动脉血压和蛋白尿。
本项随机、开放标签、平行组设计的研究检验了以下假设：在相似的血压水平下，ACE抑制剂群多普利（T）与非DHPCA维拉帕米（V）联合使用，在一年时比单独使用任一药物能更大程度地降低蛋白尿。37名平均年龄为59.6±5.8岁、患有2型糖尿病继发肾病（基线肌酐1.4±0.3mg/dl，蛋白尿1342±284mg/dl）的参与者完成了该研究。每组在八周内滴定药物剂量，以实现血压目标<140/90mmHg。所有参与者均被告知摄入<120mEq/天的钠饮食。
与单独使用T（-33±8%，T组对比-62±10%，T+V组；P<0.001）或单独使用V（-27±8%，V组对比-62±10%，T+V组；P<0.001）相比，T+V组的蛋白尿从基线水平的降低幅度显著更大。一年时，肾小球滤过率、动脉血压、空腹血糖或尿钠排泄均未发现显著差异。T+V组各成分的平均每日剂量（2.9±0.8mg，T/219±21.1mg V）显著低于单独使用T的剂量5.5±1.1mg/天（P<0.01）或单独使用V的剂量314.8±46.3mg（分两次给药）（P<0.01）。
这些数据支持这样的概念，即ACE抑制剂与非DHPCA联合使用比单独使用任一药物能更大程度地降低蛋白尿。这种额外的抗蛋白尿作用在每种药物较低剂量时出现，且独立于动脉血压的进一步降低。这些发现可能对减缓2型糖尿病肾病患者的肾病进展产生影响。
