Onuigbo Macaulay A C, Onuigbo Nnonyelum T C
College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Ren Fail. 2008;30(4):363-71. doi: 10.1080/08860220801947363.
Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.
关于美国肾素-血管紧张素-醛固酮系统（RAAS）阻断策略使用的增加与终末期肾病（ESRD）流行加剧之间可能存在的联系，人们已提出担忧。大多数关于接受RAAS阻断治疗的肾动脉狭窄慢性肾脏病（CKD）患者出现加速肾衰竭的报告都是回顾性的。我们推测，因此这种综合征尚未得到充分理解，可能未被充分认识，需要进行前瞻性分析。作为一个更大队列的一部分，该队列中有100名接受RAAS阻断治疗的CKD患者，在同时服用血管紧张素转换酶（ACE）抑制剂和/或血管紧张素受体阻滞剂时出现肾衰竭恶化（血清肌酐较基线水平升高>25%），在2002年9月至2005年2月期间入组的26例患者（26%）存在血流动力学显著的肾动脉狭窄。停用RAAS阻断治疗，采用标准的肾脏病护理，并通过肾脏病饮食改良试验（MDRD）监测估算肾小球滤过率（eGFR）。他们包括26名白种人患者，男:女 = 10:16，年龄75.3±6.4（63 - 87）岁。平均随访时间为26.4±16.4（1 - 49）个月。入组前RAAS阻断治疗的持续时间为20.2±16.4（0.5 - 48）个月。与之前的报告相反，促发因素通常不存在（15/26），双侧肾脏患者中单侧肾动脉狭窄病变很常见（19/26），并且进展至终末期肾病很频繁（5/26）。五分之四的终末期肾病患者在5.5±4.1（1 - 11）个月后死亡。一名eGFR改善的患者在14个月后因转移性胃癌死亡。排除5例进展至终末期肾病的患者和2例早期失访的患者，在19例患者中，经过34.8±10.1（14 - 49）个月的随访，eGFR从27.8±9.5（11 - 47）升至36.7±16（14 - 68）ml/min/1.73m²体表面积（p = 0.014）。在这些接受或未接受肾动脉球囊扩张成形术（PTA）和支架置入术的患者中，停用RAAS阻断治疗数周至数月后，eGFR的这种改善很明显。然而，肾PTA/支架置入术在部分患者中进一步改善了eGFR。我们得出结论，老年肾狭窄CKD患者中与同时进行RAAS阻断治疗相关的肾衰竭/终末期肾病仍未得到充分理解且大多未被认识。双侧肾脏患者中的单侧病变、促发因素不存在以及尽管停用RAAS阻断治疗仍有高死亡率的进展至终末期肾病比之前认为的更常见。较低的基线eGFR（<35）可预测终末期肾病。我们的研究结果呼吁进行更大规模的前瞻性研究，特别是考虑到美国老龄人口中因RAAS阻断治疗导致医源性肾衰竭的担忧日益增加。美国老龄人口进一步增加了我们CKD患者群体中存在未被认识的肾动脉狭窄且其数量不断增加的可能性。
