Unit of Geriatric Pharmacoepidemiology, Italian National Research Centres on Aging (INRCA), Cosenza, Italy.
Drugs Aging. 2011 May 1;28(5):379-90. doi: 10.2165/11588280-000000000-00000.
Reduced renal function increases the risk of adverse drug reactions (ADRs) to hydrosoluble drugs (hADRs). However, the ability of different equations to calculate estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCCr) and thereby predict the risk of developing hADRs has not previously been compared.
The aim of this study was to investigate which of three different equations for estimating renal function (Cockcroft-Gault [CG], Modification of Diet in Renal Disease [MDRD] and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) was the most effective at predicting incident hADRs.
This multicentre study had an observational design and included 81 acute-care general (internal) or geriatric medicine wards in academic hospitals throughout Italy. Our series consisted of 10,442 hospitalized patients with a mean ± SD age of 70.2 ± 14.9 years enrolled in the GIFA study. The main outcome measures were incident ADRs during hospital stay. Data on these were collected and classified as hADRs or ADRs to liposoluble drugs (lADRs). Patients were grouped according to their eGFR (mL/min/1.73 m²) or eCCr (mL/min): ≥90, 60-89.9, 45-59.9, 30-44.9 or <30.
The multivariable adjusted risk of hADRs progressively increased with decreasing eGFR as determined by estimates of mL/min/1.73 m² calculated using CKD-EPI (60-89.9: hazard ratio [HR]=1.07 [95% CI 0.70, 1.72]; 45-59.9: HR=1.62 [95% CI 1.0, 2.69]; 30-44.9: HR=2.13 [95% CI 1.24, 3.64]; <30: HR=2.30 [95% CI 1.28, 4.14]) and, to a lesser extent, MDRD (60-89.9: HR=1.15 [95% CI 0.75, 1.76]; 45-59.9: HR=1.73 [95% CI 1.09, 2.73]; 30-44.9: HR=2.14 [95% CI 1.30, 3.53]; <30: HR=1.99 [95% CI 1.11, 3.57]) equations. The risk of hADRs also increased with lower eCCr, but only at CG eCCr <45 mL/min (30-44.9: HR=1.61 [95% CI 0.96, 2.77]; <30: HR=1.76 [95% CI 1.0, 3.18]). Neither eGFR nor eCCr were associated with lADRs.
CKD-EPI-based estimates of eGFR outperformed MDRD-based estimates of eGFR and CG-based estimates of eCCr as a predictor of hADRs.
肾功能下降会增加水溶性药物不良反应（ADRs）的风险（hADRs）。然而，不同的方程计算估计肾小球滤过率（eGFR）或估计肌酐清除率（eCCr）并预测发生 hADRs 的风险的能力尚未进行比较。
本研究旨在比较三种不同的肾功能估计方程（ Cockcroft-Gault [CG]、肾脏病饮食改良试验 [MDRD]和慢性肾脏病流行病学合作研究 [CKD-EPI]）预测 hADRs 发生的效果。
这是一项多中心观察性研究，包括意大利多所学术医院的 81 个急性普通（内科）或老年医学病房。我们的系列包括 10442 名住院患者，平均年龄为 70.2 ± 14.9 岁，参加了 GIFA 研究。主要观察指标为住院期间发生的不良反应。收集并分类为 hADRs 或脂溶性药物不良反应（lADRs）。根据 eGFR（mL/min/1.73 m²）或 eCCr（mL/min）将患者分组：≥90、60-89.9、45-59.9、30-44.9 或 <30。
使用 CKD-EPI 估计的 mL/min/1.73 m² 计算的 eGFR 逐渐降低，hADRs 的多变量调整风险也随之增加（60-89.9：风险比 [HR]=1.07 [95% CI 0.70, 1.72]；45-59.9：HR=1.62 [95% CI 1.0, 2.69]；30-44.9：HR=2.13 [95% CI 1.24, 3.64]；<30：HR=2.30 [95% CI 1.28, 4.14]），而使用 MDRD 估计的 eGFR 风险也略有增加（60-89.9：HR=1.15 [95% CI 0.75, 1.76]；45-59.9：HR=1.73 [95% CI 1.09, 2.73]；30-44.9：HR=2.14 [95% CI 1.30, 3.53]；<30：HR=1.99 [95% CI 1.11, 3.57]）。eCCr 降低也与 hADRs 风险增加相关，但仅在 CG eCCr <45 mL/min 时（30-44.9：HR=1.61 [95% CI 0.96, 2.77]；<30：HR=1.76 [95% CI 1.0, 3.18]）。eGFR 和 eCCr 均与 lADRs 无关。
与 MDRD 估计的 eGFR 相比，基于 CKD-EPI 的 eGFR 估计和基于 CG 的 eCCr 估计更能预测 hADRs。
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