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  • Review Article
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Drug stewardship in chronic kidney disease to achieve effective and safe medication use

Nature Reviews Nephrology (2024)Cite this article

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Abstract

People living with chronic kidney disease (CKD) often experience multimorbidity and require polypharmacy. Kidney dysfunction can also alter the pharmacokinetics and pharmacodynamics of medications, which can modify their risks and benefits; the extent of these changes is not well understood for all situations or medications. The principle of drug stewardship is aimed at maximizing medication safety and effectiveness in a population of patients through a variety of processes including medication reconciliation, medication selection, dose adjustment, monitoring for effectiveness and safety, and discontinuation (deprescribing) when no longer necessary. This Review is aimed at serving as a resource for achieving optimal drug stewardship for patients with CKD. We describe special considerations for medication use during pregnancy and lactation, during acute illness and in patients with cancer, as well as guidance for the responsible use of over-the-counter drugs, herbal remedies, supplements and sick-day rules. We also highlight inequities in medication access worldwide and suggest policies to improve access to quality and essential medications for all persons with CKD. Further strategies to promote drug stewardship include patient education and engagement, the use of digital health tools, shared decision-making and collaboration within interdisciplinary teams. Throughout, we position the person with CKD at the centre of all drug stewardship efforts.

Key points

  • Medication reconciliation and review is an essential first step in patient-centred drug stewardship.

  • Doses should be adjusted according to a patient’s glomerular filtration rate (GFR). Most pharmacokinetic information available is derived from creatinine-based equations, and for many medications, different creatinine-based equations to estimate GFR are interchangeable; however, use of equations that utilize both creatinine and cystatin C, or direct measurement of GFR, is advocated when the therapeutic range is narrow and precision is needed.

  • Drug choice should consider relative and absolute contraindications by GFR, and the increased nephrotoxicity of nephrotoxic medications to people with chronic kidney disease.

  • Acute illness and fluctuations in GFR should prompt frequent reassessment of GFR and medications; however, the implementation of routine sick-day rules has a substantial cost or opportunity cost, is not supported by evidence and may cause more harm than good.

  • For people with chronic kidney disease who might become pregnant, education around potential teratogens is important, but people should not be denied medication on the basis that they might become pregnant.

  • Culturally appropriate, multi-faceted educational and empowerment activities may include written instructional materials and digital technologies.

  • Health care workers and patients should collaborate to promote more equitable access to evidence-based medications within their countries and globally.

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Fig. 1: Suggested approach to GFR evaluation for drug dosing.
Fig. 2: A general approach to prescribing medications that may carry contraindications in people with CKD.
Fig. 3: Suggested steps of medication review and reconciliation.
Fig. 4: Impact of acute illness on medication management in CKD.

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Acknowledgements

R.K.H. has received funding from the National Institute on Aging of the National Institutes of Health (NIH) under Award Number K76AG059930. S.B.A. has received funding from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. L.A.I. reports funding from NIH, National Kidney Foundation. E.F.B has received funding from the National Institute of Allergy and Infectious Diseases of the NIH under Award Number K23AI14388 and the Agency for Healthcare Research and Quality. E.L.F. is supported by a Rubicon grant from the Netherlands Organization for Scientific Research. J.J.C. has received funding from the Swedish Research Council, the Swedish Heart and Lung Foundation and NIH 22-B0-00-1005839. We thank Laurie Tomlinson, London School of Hygiene and Tropical Medicine, UK, for her valuable contributions to the section on sick-day rules. Rasheeda Hall, Rümeyza Kazancıoğlu, Teerawat Thanachayanont, Germaine Wong, Dharsh Sabanayagam, Lesley A. Inker, Sofia B. Ahmed and Juan J. Carrero are work group members of the 2024 KDIGO guideline update on screening, detection and management of CKD. This review served to evaluate the evidence behind the drug stewardship chapter for those guidelines.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, and Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA

    Rasheeda K. Hall

  2. Division of Nephrology, Bezmiâlem Vakif University, Istanbul, Türkiye

    Rümeyza Kazancıoğlu

  3. Bhumirajanagarindra Kidney Institute Bangkok, Bangkok, Thailand

    Teerawat Thanachayanont

  4. Sydney School of Public Health, University of Sydney, Sydney, Australia

    Germaine Wong & Dharshana Sabanayagam

  5. University of Toronto, Toronto, Canada

    Marisa Battistella

  6. Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

    Sofia B. Ahmed

  7. Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, MA, USA

    Lesley A. Inker

  8. Department of Pharmacy, Mayo Clinic, Rochester, USA

    Erin F. Barreto

  9. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA

    Edouard L. Fu

  10. Department of Medicine and Health Research Methods, Evidence and Impact, McMaster University, Ontario, Canada

    Catherine M. Clase

  11. Medical Epidemiology and Biostatistics, Karolinska Institutet, and Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden

    Juan J. Carrero

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  1. Rasheeda K. Hall
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The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Juan J. Carrero.

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Competing interests

R.K. has received honoraria from Baxter. L.A.I. has received funding Omeros, Chinook Therapeutics, R3R and Travere Pharmaceuticals for research and contracts to Tufts Medical Center, and has consulted for Diamerix. E.F.B. has received funding from Numares, and has consulted for Wolters Kluwer. C.M.C. has received consultation, advisory board membership, honoraria or research funding from Sanofi, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim, Baxter and, through the Liv Academy, AstraZeneca. She is editor-in-chief of the Canadian Journal of Kidney Health and Disease. J.J.C. has received support from AstraZeneca, ViforPharma, Novonordisk, Astellas, MSD, GSK, Boehringer Ingelheim and Amgen, outside the scope of this work; he has also received lecture fees from Baxter, Fresenius Kabi, AstraZeneca, Astellas, GSK and Abbott, and has participated in advisory boards for AstraZeneca, Nestle and Bayer. The other authors do not declare any conflicts of interest.

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Nature Reviews Nephrology thanks Sunil Bhandari, who co-reviewed with Xenophon Kassianides, Marlies Ostermann and Menino Cotta, for their contribution to the peer review of this work.

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Hall, R.K., Kazancıoğlu, R., Thanachayanont, T. et al. Drug stewardship in chronic kidney disease to achieve effective and safe medication use. Nat Rev Nephrol (2024). https://doi.org/10.1038/s41581-024-00823-3

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