Onuigbo Macaulay A C, Onuigbo Nnonyelum T C
Mayo Clinic College of Medicine, Rochester, MN, USA.
Int Urol Nephrol. 2008;40(1):233-9. doi: 10.1007/s11255-007-9299-2. Epub 2008 Jan 15.
Notwithstanding proven renoprotection from RAAS blockade (AB) with ACE inhibitors and ARBs, and despite increasing utilization of AB in the US, we have continued to experience a CKD/ESRD epidemic. Given concerns for iatrogenic CKD/ESRD, we designed a prospective study to analyze the course of eGFR following withdrawal of AB in such patients.
Between September 2002 and February 2005, all consecutive CKD patients on AB presenting with >25% increase in baseline serum creatinine were enrolled. eGFR following withdrawal of AB was monitored. The main outcome measures were serum creatinine, MDRD eGFR, and UA/Cr.
100 Caucasians, M:F=52:48, mean age 71.5 years were enrolled. Mean follow up was 26 months. Sixteen patients progressed to ESRD, of whom seven died. In 74, eGFR improved from 23.9+/-9 (7-47) to 39.2+/-15.4 (17-89) ml/min/1.73 m(2) BSA, 26.5 (3-46) months after stopping AB (P=0.001). The majority of the cohort, 95 patients, had known risk factors: 26 with RAS, 12 hypovolemia, 11 sepsis, 10 NSAIDs/cox II inhibitor use/abuse, 7 CIN, 2 congestive heart failure, 2 obstructive uropathy, and 27 with other medical and surgical causes, including malignancies, postoperative states, and infections. In the 26 with RAS, 5 with higher baseline creatinine -2.1+/-0.6 versus 1.5+/-0.4 mg/dL, P=0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. The remaining five patients (one male and four females), mean age 68 (44-83) years, demonstrated sustained improved eGFR with discontinuation (four) or reduction (one) of RAAS blockade, despite normal renal arteries and the absence of known traditional risk factors. UA/Cr generally increased following withdrawal of AB.
Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study.
尽管已证实使用血管紧张素转化酶抑制剂（ACEI）和血管紧张素Ⅱ受体拮抗剂（ARB）阻断肾素-血管紧张素-醛固酮系统（RAAS）具有肾脏保护作用，且在美国使用这类药物的情况日益增多，但我们仍持续面临慢性肾脏病（CKD）/终末期肾病（ESRD）的流行。鉴于对医源性CKD/ESRD的担忧，我们设计了一项前瞻性研究，以分析此类患者停用RAAS阻断剂后估算肾小球滤过率（eGFR）的变化过程。
在2002年9月至2005年2月期间，纳入所有连续使用RAAS阻断剂且基线血清肌酐升高>25%的CKD患者。监测停用RAAS阻断剂后的eGFR。主要观察指标为血清肌酐、简化肾脏病膳食改良试验（MDRD）估算的肾小球滤过率以及尿酸/肌酐比值（UA/Cr）。
共纳入100名白种人，男性与女性比例为52:48，平均年龄71.5岁。平均随访时间为26个月。16例患者进展为ESRD，其中7例死亡。74例患者的eGFR从23.9±9（7 - 47）ml/min/1.73m²体表面积改善至39.2±15.4（17 - 89）ml/min/1.73m²体表面积，在停用RAAS阻断剂26.5（3 - 46）个月后出现改善（P = 0.001）。该队列中的大多数患者（95例）具有已知的危险因素：26例存在肾素-血管紧张素系统（RAS）异常、12例血容量不足、11例脓毒症、10例使用非甾体抗炎药/环氧化酶-2（COX-2）抑制剂/滥用此类药物、7例对比剂肾病（CIN）、2例充血性心力衰竭、2例梗阻性尿路病以及27例因其他内科和外科病因，包括恶性肿瘤、术后状态及感染。在26例存在RAS异常的患者中，5例基线肌酐水平较高（2.1±0.6对比1.5±0.4mg/dL，P = 0.013），进展为ESRD；5例ESRD患者中有4例在6.3个月后死亡。其余5例患者（1例男性和4例女性），平均年龄68（44 - 83）岁，尽管肾动脉正常且无已知传统危险因素，但停用（4例）或减少（1例）RAAS阻断剂后，eGFR持续改善。停用RAAS阻断剂后，UA/Cr通常升高。
在使用RAAS阻断剂的老年易感CKD患者中，氮质血症恶化情况往往（但并非总是）与已知的促发危险因素相关，目前仍未得到充分认识。停用RAAS阻断剂后，eGFR常常持续改善。执业医师应充分了解这些综合征。我们的观察结果需要进一步研究。
