Ruggenenti Piero, Perticucci Elena, Cravedi Paolo, Gambara Vincenzo, Costantini Marco, Sharma Sanjib Kumar, Perna Annalisa, Remuzzi Giuseppe
Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
J Am Soc Nephrol. 2008 Jun;19(6):1213-24. doi: 10.1681/ASN.2007090970. Epub 2008 Mar 19.
Heavy proteinuria is a major determinant of progression to ESRD for patients with chronic nephropathies and reducing proteinuria should be a key target for renoprotective therapy. In the Remission Clinic, we applied a multimodal intervention to target urinary proteins in 56 consecutive patients who had >3 g proteinuria/d despite angiotensin-converting enzyme inhibitor therapy. We compared the rate of GFR decline and incidence of ESRD in this cohort with 56 matched historical reference subjects who had received conventional therapy titrated to a target BP. During a median follow-up of 4 yr, the monthly rate of GFR decline was significantly lower in the Remission Clinic cohort (median -0.17 versus -0.56 ml/min per 1.73 m2; P < 0.0001), and ESRD events were significantly reduced (3.6 versus 30.4% reached ESRD). Follow-up BP, cholesterol, and proteinuria were lower in Remission Clinic patients than in reference subjects, such that disease remission or regression was achieved in up to 50% of patients who would have been otherwise expected to progress rapidly to ESRD on conventional therapy. Proteinuria reduction independently predicted a slower rate of GFR decline and ESRD incidence, but response to treatment differed depending on the underlying disease. Regarding safety, no patient was with drawn because of hyperkalemia. In summary, multidrug treatment titrated to urinary protein level can be safely and effectively applied to normalize proteinuria and to slow the loss of renal function significantly,especially among patients without type 2 diabetes and with otherwise rapidly progressing chronic nephropathies.
大量蛋白尿是慢性肾病患者进展至终末期肾病(ESRD)的主要决定因素,降低蛋白尿应成为肾脏保护治疗的关键目标。在缓解门诊,我们对56例尽管接受了血管紧张素转换酶抑制剂治疗但蛋白尿仍>3 g/天的连续患者应用了多模式干预措施来针对尿蛋白。我们将该队列中肾小球滤过率(GFR)下降率和ESRD发生率与56例匹配的接受传统治疗并将血压控制至目标值的历史对照受试者进行了比较。在中位随访4年期间,缓解门诊队列中GFR的每月下降率显著更低(中位数为-0.17 vs -0.56 ml/min per 1.73 m2;P < 0.0001),ESRD事件显著减少(达到ESRD的比例为3.6% vs 30.4%)。缓解门诊患者的随访血压、胆固醇和蛋白尿水平均低于对照受试者,以至于在原本预计会在传统治疗下迅速进展至ESRD的患者中,高达50%的患者实现了疾病缓解或病情逆转。蛋白尿减少独立预测了GFR下降速度减慢和ESRD发生率降低,但治疗反应因潜在疾病而异。在安全性方面,没有患者因高钾血症而退出治疗。总之,根据尿蛋白水平进行滴定的多药治疗可以安全有效地应用于使蛋白尿正常化并显著减缓肾功能丧失,尤其是在无2型糖尿病且原本慢性肾病进展迅速的患者中。