Jaber Bertrand L, Madias Nicolaos E
Department of Medicine, Tufts University School of Medicine, Caritas St. Elizabeth's Medical Center, Boston, Mass 02135, USA.
Am J Med. 2005 Dec;118(12):1323-30. doi: 10.1016/j.amjmed.2005.02.032.
Chronic kidney disease constitutes a highly prevalent health problem worldwide. Left untreated, it progresses inexorably to greater levels of severity at variable rates. The morbid impact of chronic kidney disease is heightened by its role as risk factor for cardiovascular disease. In the past two decades, considerable gains have been realized in retarding progression of chronic kidney disease by emphasizing blood pressure control and blockade of the renin-angiotensin system. Notwithstanding, the therapeutic goal of preventing or arresting chronic kidney disease progression remains unfulfilled. Currently attainable rates of decrease in glomerular filtration rate remain at 2 to 8 mL/min/y depending on the underlying disease. It is now believed that to achieve optimal therapeutic targets (proteinuria of <500 mg/day and decrease in glomerular filtration rate of 1 mL/min/y, the average age-related decline) we must introduce novel strategies and a multifaceted approach to treatment that interrupts multiple mechanisms of progression. To this end, and wherever relevant, new approaches to cause-specific treatment must be applied, such as targeted immunosuppression, intensive glycemic control, gene therapy, and enzyme replacement therapy. Furthermore, in all chronic kidney disease, we must interfere more effectively with the multitude of common mechanisms of progression. Established or putative, such approaches include aggressive blood pressure control; advanced renin-angiotensin system blockade; cytokine modulation and antifibrotic therapy; aldosterone blockade; endothelin blockade, nitric oxide modulation and vasopeptidase inhibition; antioxidant therapy; statin therapy; glycosaminoglycan therapy; anemia therapy; dietary restrictions; lifestyle changes; and pharmacogenomic profiling. Such a concerted, multifaceted approach to management might indeed prevent or arrest progression of chronic kidney disease, or even achieve regression of chronic kidney disease.
慢性肾脏病是全球普遍存在的严重健康问题。若不治疗,病情会以不同速率不可避免地进展至更严重程度。慢性肾脏病作为心血管疾病的危险因素,其致病影响更为突出。在过去二十年中,通过强调血压控制和肾素 - 血管紧张素系统阻断,在延缓慢性肾脏病进展方面取得了显著成效。尽管如此,预防或阻止慢性肾脏病进展的治疗目标仍未实现。目前,根据基础疾病不同,肾小球滤过率的下降速率仍维持在每年2至8毫升/分钟。现在人们认为,要实现最佳治疗目标(蛋白尿<500毫克/天,肾小球滤过率下降1毫升/分钟/年,即与年龄相关的平均下降速率),我们必须引入新策略和多方面的治疗方法,以阻断多种进展机制。为此,在相关情况下,必须采用针对特定病因的新治疗方法,如靶向免疫抑制、强化血糖控制、基因治疗和酶替代治疗。此外,对于所有慢性肾脏病,我们必须更有效地干预多种常见的进展机制。既定的或推测的此类方法包括积极控制血压;强化肾素 - 血管紧张素系统阻断;细胞因子调节和抗纤维化治疗;醛固酮阻断;内皮素阻断、一氧化氮调节和血管肽酶抑制;抗氧化治疗;他汀类药物治疗;糖胺聚糖治疗;贫血治疗;饮食限制;生活方式改变;以及药物基因组分析。这种协调一致、多方面的管理方法确实可能预防或阻止慢性肾脏病的进展,甚至实现慢性肾脏病的逆转。