Inserm, Centre for research in Epidemiology and Population Health, U1018, Villejuif, France.
Nephrol Dial Transplant. 2011 Sep;26(9):2852-9. doi: 10.1093/ndt/gfq827. Epub 2011 Feb 3.
Glomerular filtration rate (GFR) decline with age increases the risk of inappropriate dosing of drugs. We investigated the determinants and the mortality associated with the use of drugs that are contraindicated or require dose adjustment according to kidney function among the community-dwelling elderly.
The Three-City population-based study included 8701 participants ≥65 years from 1999 to 2001. Exposure to the risk of inappropriate drug dosage was defined as reported use of either a contraindicated drug or one requiring dose adjustment according to the individual baseline glomerular filtration rate estimated (eGFR) with the Modification of Diet in Renal disease study equation. Six-year mortality was analysed using Cox models adjusted for several sociodemographic, biologic and clinical risk factors.
The overall percentage of exposure to the risk of inappropriate drug use was 13.3% (contraindication, 0.8%): it was 52.5% (4.5%) in those with an eGFR of 30-59 and 96% (48%) in those <30 mL/min/1.73 m(2). Antihypertensive agents, fibrates and psycholeptics accounted for most of the drugs with dosing recommendations and antidiabetic agents and antihistamines for those contraindicated. Individuals at risk were more likely to be men, older, and under treatment for hypertension or hypercholesterolemia. Exposure to either risk was independently related to higher all-cause mortality (hazard ratio 1.4, 95% confidence interval 1.0-1.9) in participants with eGFR <60 mL/min/1.73 m(2).
Contraindicated drug prescription was uncommon but >10% of the population took drugs requiring renal dosing adjustments. Regular monitoring of eGFR may prevent excess mortality associated with inappropriate drug prescription in the elderly.
肾小球滤过率（GFR）随年龄下降会增加药物剂量不当的风险。我们研究了社区居住的老年人中，根据肾功能选择禁忌或需要剂量调整的药物使用与死亡率之间的相关性。
该研究为三城市人群基础研究，纳入了 1999 年至 2001 年间≥65 岁的 8701 名参与者。风险药物剂量不当的暴露定义为报告使用禁忌药物或需要根据个体基线肾小球滤过率（用肾脏病饮食改良试验方程估算）调整剂量的药物。使用 Cox 模型调整了几个社会人口统计学、生物学和临床危险因素后，分析了 6 年死亡率。
总体风险药物剂量不当的暴露率为 13.3%（禁忌，0.8%）：eGFR 为 30-59 的患者中，这一比例为 52.5%（4.5%），eGFR<30 mL/min/1.73 m2 的患者中，这一比例为 96%（48%）。降压药、贝特类和精神类药物是大多数有剂量建议的药物，而抗糖尿病药和抗组胺药是禁忌药物。有风险的患者更可能是男性、年龄较大、正在接受高血压或高胆固醇治疗。在 eGFR<60 mL/min/1.73 m2 的患者中，风险暴露与全因死亡率升高独立相关（危险比 1.4，95%置信区间 1.0-1.9）。
禁忌药物处方不常见，但有>10%的人群使用需要肾脏剂量调整的药物。定期监测肾小球滤过率可能会预防老年人中与药物剂量不当相关的过度死亡率。
