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Association between Glomerular Filtration Rate and Adverse Drug Reactions in Elderly Hospitalized Patients

The Role of the Estimating Equation

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Abstract

Background: 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.

Objective: 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.

Methods: 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/1.73m2) or eCCr (mL/min): ≥90, 60–89.9, 45–59.9, 30–44.9 or <30.

Results: 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 <45mL/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.

Conclusions: CKD-EPI-based estimates of eGFR outperformed MDRD-based estimates of eGFR and CG-based estimates of eCCr as a predictor of hADRs.

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Acknowledgements

The GIFA is partially supported by a grant (94000402) from the Italian National Research Council, Rome, Italy. The GIFA is a research group of the Italian Society of Gerontology and Geriatrics (SIGG: Società Italiana di Gerontologia e Geriatria) — the Italian Foundation for Research on Aging (FIRI-ONLUS: Fondazione Italiana per la Ricerca sull’Invecchiamento). A complete list of the GIFA investigators has been published previously.[10]

All authors declare that they have no conflict of interest to disclose.

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Authors and Affiliations

  1. Unit of Geriatric Pharmacoepidemiology, Italian National Research Centres on Aging (INRCA), Cosenza, Italy

    Andrea Corsonello

  2. Chair of Geriatrics, University Campus BioMedico, Rome, Italy

    Claudio Pedone & Raffaele Antonelli Incalzi

  3. Fondazione Alberto Sordi, Rome, Italy

    Claudio Pedone

  4. Scientific Direction, Italian National Research Centres on Aging (INRCA), Ancona, Italy

    Fabrizia Lattanzio

  5. Department of Gerontology, Geriatrics and Physiatry, Catholic University of Sacred Heart, Rome, Italy

    Graziano Onder

  6. San Raffaele Foundation, Cittadella della Carità, Taranto, Italy

    Raffaele Antonelli Incalzi

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Correspondence to Andrea Corsonello.

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Corsonello, A., Pedone, C., Lattanzio, F. et al. Association between Glomerular Filtration Rate and Adverse Drug Reactions in Elderly Hospitalized Patients. Drugs Aging 28, 379–390 (2011). https://doi.org/10.2165/11588280-000000000-00000

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