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利尿剂是否应该用于慢性肾病起始联合治疗降低心血管风险
[2012/2/2 13:27:32]
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  作者简介:
  George Bakris:美国芝加哥大学普利兹克医学院高血压疾病部教授,擅长于高血压诊断及降压治疗,尤其是复杂的、难治性高血压的治疗。肾病治疗亦是George Bakris教授的研究领域,尤其长于糖尿病相关性肾病的治疗。
  噻嗪类或噻嗪样利尿剂与肾素-血管紧张素系统(RAS)阻滞剂或钙离子拮抗剂用于减少普通人群的心血管事件。在慢性肾病中(CKD),尚无单独应用利尿剂对CKD进展的影响。在eGFR<45 ml/min/1.73m2的患者中,噻嗪类利尿剂无效且降压作用很弱,应首选袢利尿剂,如呋塞米和托拉塞米。但尚无检验袢利尿剂用于减慢肾病发展的试验。
  目前美国国家肾脏基金会肾脏疾病患者生存质量指南(The National Kidney Foundation Disease Outcomes Quality Initiative,K/DOQI)建议利尿剂应该联合RAS阻滞剂作为一线治疗用于晚期晚期蛋白尿性CKD的治疗。这是基于很多前瞻性试验(如卡托普利试验、RENAAL、IDNT)和对其他小型、短期试验进行回顾性分析得出的结论。然而,病情较轻的患者并不需要应用利尿剂。ACCOMPLISH肾病研究表明在没有蛋白尿的肾脏疾病中,RAS阻滞剂/CCB联合减缓肾病发展的效果优于RAS阻滞剂/利尿剂联合,且耐受性更好。此外,K/DOQI指南并没有对利尿剂在非蛋白尿患者中的应用作特别推荐。
  由于利尿剂会增加痛风、糖尿病和低血钾的风险,这些都需要增加其他药物以平衡风险,所以利尿剂应该作为非蛋白尿CKD患者的三线治疗选择。在周围性水肿患者中,噻嗪类利尿剂对那些不能遵循低盐饮食的患者具有很重要的作用。
  Thiazide or thiazide-like diuretics, given in combination with either a renin-angiotensin system (RAS) blocker or calcium antagonist, are known to reduce cardiovascular (CV) events in the general population. In CKD, diuretics, while known for lowering blood pressure (BP), have never been tested alone with regard to CKD progression. In patients with an estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2, thiazide diuretics are generally ineffective as diuretics and have minimal BP lowering, thus loop diuretics such as furosemide and torsemide should be preferred. Loop diuretics have never been tested with regard to slowing the progression of nephropathy.
  Current K/DOQI guidelines suggest that diuretics be included in combination with a RAS blocking agent as first line therapy in someone with advanced proteinuric CKD. This is based on many prospective studies, such as the Captopril trial, RENAAL and IDNT, as well as many retrospective analyses of other smaller, shorter-acting trials. However, while diuretics are needed in advanced kidney disease with proteinuria, less sick cohorts do not necessarily require diuretics. Data from the ACCOMPLISH renal study demonstrate that, in non-proteinuric kidney disease, a RAS blocker/CCB combination does better for slowing nephropathy progression and is better tolerated than a RAS/diuretic combination. Moreover, K/DOQI guidelines do not recommend a specific role for diuretics in non-proteinuric patients.
  Given that diuretics increase the risk of gout, diabetes and hypokalemia, all of which require additional therapy to circumvent, they should be reserved as third-line treatment in people with non-proteinuric CKD. In those with peripheral edema, thiazide diuretics have a role earlier in therapy especially in patients, who do not adhere to a low sodium diet.





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