Mackinnon Bruce, Boulton-Jones Michael, McLaughlin Kevin
Renal Unit, Glasgow Royal Infirmary, Glasgow, UK and Foothills Hospital, Calgary, Alberta, Canada.
Nephrol Dial Transplant. 2003 Sep;18(9):1800-5. doi: 10.1093/ndt/gfg230.
Analgesic-associated nephropathy (AAN) is an important and preventable cause of chronic renal failure (CRF). Although its incidence is falling in some countries, others are witnessing an increase in the number of new cases.
The aim of this study was to evaluate the natural history of AAN, determine the correlates of the rate of decline in renal function and examine factors conferring an increased risk of death or dialysis in such patients. A prospective observational cohort study of all patients with AAN attending a single-centre was conducted.
Seventy-eight patients (25 male), with at least 24 months of follow-up for analysis, were diagnosed as having AAN over the 10-year period 1989-1999. During follow up, the mean (+/-SD) rate of change in estimated creatinine clearance (ECC) was -1.2 ml/min/year (+/-5.28). By multiple linear regression three variables were found to independently predict the rate of deterioration in ECC; continuing analgesic use (P < 0.001), degree of proteinuria at presentation (P = 0.002) and male sex (P = 0.03). A Cox's model revealed a 6-fold increase in the hazard of reaching the combined end-point of death or dialysis in those patients with AAN who continue to use analgesics. This was independent of the other two significant risk factors of pre-existing vascular disease (HR 3.93, 1.36-11.29) and ECC at presentation (HR 0.95, 0.91-0.98 per ml/min).
In patients with CRF due to AAN ongoing analgesic use, male gender and increasing proteinuria predict a more rapid decline in renal function. Patients who continue analgesics, those with pre-existing vascular disease and those with more advanced renal impairment at presentation, are at a significantly increased risk of reaching the combined end-point of death or end-stage renal failure requiring dialysis. The design of this study, however, leaves it open to the criticism that selection bias may account for some of its effects, and as with all work on AAN the possible confounding issue of reverse causality is difficult to dismiss.
镇痛剂相关性肾病（AAN）是慢性肾衰竭（CRF）的一个重要且可预防的病因。尽管在一些国家其发病率正在下降，但其他一些国家的新发病例数却在增加。
本研究的目的是评估AAN的自然病程，确定肾功能下降速率的相关因素，并研究此类患者死亡或透析风险增加的因素。对在单中心就诊的所有AAN患者进行了一项前瞻性观察队列研究。
在1989 - 1999年的10年期间，78例患者（25例男性）被诊断为AAN，且至少有24个月的随访数据用于分析。随访期间，估计肌酐清除率（ECC）的平均（±标准差）变化率为 -1.2 ml/min/年（±5.28）。通过多元线性回归发现，有三个变量可独立预测ECC的恶化速率；持续使用镇痛药（P < 0.001）、就诊时的蛋白尿程度（P = 0.002）和男性（P = 0.03）。Cox模型显示，继续使用镇痛药的AAN患者达到死亡或透析联合终点的风险增加了6倍。这独立于另外两个显著的危险因素，即既往存在血管疾病（风险比3.93，1.36 - 11.29）和就诊时的ECC（每ml/min风险比0.95，0.91 - 0.98）。
在因AAN导致CRF的患者中，持续使用镇痛药、男性以及蛋白尿增加预示着肾功能下降更快。继续使用镇痛药的患者、既往存在血管疾病的患者以及就诊时肾功能损害更严重的患者，达到死亡或需要透析的终末期肾衰竭联合终点的风险显著增加。然而，本研究的设计容易受到选择偏倚可能解释其部分效应的批评，并且与所有关于AAN的研究一样，反向因果关系这一可能的混杂问题难以消除。
