Navis G, de Zeeuw D
Department of Nephrology, State University Groningen, The Netherlands.
J Hum Hypertens. 1996 Oct;10(10):669-73.
Proteinuria may be involved in the final common pathway of progressive renal function loss. If so, intervention treatment that reduces proteinuria might prevent or retard long-term renal function loss. In renal patients and in experimental renal disease the severity of proteinuria is associated with the rate of long-term renal function loss. Several large trials on the prevention of long-term renal function loss by antihypertensive treatment with ACE inhibitors (ACEi), were recently completed in diabetic and in non-diabetic renal disease. In those studies long-term renal function loss could indeed be retarded by ACEi; these ACEi regimens were associated with a more effective reduction of proteinuria than control regimens. In studies with a single treatment regimen (drug treatment or a protein restricted diet) a more effective reduction of proteinuria is associated with a more favourable long-term course of renal function as well. As reduction of proteinuria is mostly associated with a lower blood pressure (BP) the respective contributions of the fall in BP and in proteinuria are hard to dissect. Remarkably, however, the efficacy of the reduction of proteinuria (but not of BP) at onset of antihypertensive treatment is predictive of long-term renal outcome. Albeit consistent with a causal role of proteinuria reduction in renoprotection these data cannot distinguish between proteinuria as a marker or a mediator of renal damage. In view of the consistent association of antiproteinuric efficacy with long-term renal outcome we suggest that it would be worthwhile to attempt to improve long-term renoprotection by a strategy aimed at enhancing antiproteinuric efficacy. This approach is feasible as antiproteinuric efficacy of ACEi can be enhanced in several ways, ie, by dietary sodium and protein restriction and by adding a diuretic or indomethacin. Such a strategy would require that titration for adequate BP control is followed by titration for a maximal antiproteinuric effect. If this treatment strategy would improve long-term renal outcome, it would not only be a step forward in the clinical treatment of chronic renal failure, but it would also provide compelling evidence for a causal role of proteinuria in the progression of renal disease.
蛋白尿可能参与了肾功能进行性丧失的最终共同途径。如果是这样，降低蛋白尿的干预性治疗可能会预防或延缓长期肾功能丧失。在肾病患者和实验性肾脏疾病中，蛋白尿的严重程度与长期肾功能丧失的速率相关。最近在糖尿病和非糖尿病肾病患者中完成了几项关于使用血管紧张素转换酶抑制剂（ACEi）进行抗高血压治疗以预防长期肾功能丧失的大型试验。在这些研究中，ACEi确实可以延缓长期肾功能丧失；与对照方案相比，这些ACEi方案能更有效地降低蛋白尿。在采用单一治疗方案（药物治疗或蛋白质限制饮食）的研究中，更有效地降低蛋白尿也与更有利的肾功能长期病程相关。由于蛋白尿的减少大多与血压降低相关，因此血压下降和蛋白尿减少各自的作用难以区分。然而，值得注意的是，抗高血压治疗开始时蛋白尿减少（而非血压降低）的疗效可预测长期肾脏结局。尽管这些数据与降低蛋白尿在肾脏保护中的因果作用一致，但无法区分蛋白尿是肾脏损伤的标志物还是介质。鉴于抗蛋白尿疗效与长期肾脏结局之间的一致关联，我们认为尝试通过旨在提高抗蛋白尿疗效的策略来改善长期肾脏保护是值得的。这种方法是可行的，因为ACEi的抗蛋白尿疗效可以通过几种方式提高，即通过饮食中钠和蛋白质的限制以及添加利尿剂或吲哚美辛。这样的策略需要在滴定以实现充分的血压控制之后，再滴定以达到最大的抗蛋白尿效果。如果这种治疗策略能改善长期肾脏结局，这不仅将是慢性肾衰竭临床治疗的一大进步，还将为蛋白尿在肾脏疾病进展中的因果作用提供有力证据。
