Adverse drug reactions commonly occur among patients with moderate to advanced chronic kidney disease (CKD), and these are often serious and may be preventable, according to findings from a French study published in the Clinical Journal of the American Society of Nephrology.
The study included 3033 patients with nondialysis CKD (median age 69 years; 65% men) with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort. Over 2 years, 536 patients experienced 751 adverse drug reactions, including 150 considered serious. The incidence rates of all and serious adverse events (AEs) were 14.4 and 2.7 per 100 person-years, respectively, Bénédicte Stengel, MD, PhD, of the Center for Epidemiology and Population Health in France, and colleagues reported.
Renal and urinary disorders were the most frequent AEs, particularly acute kidney injury (AKI), followed by gastrointestinal, musculoskeletal, and connective tissue disorders. Renal disorders and hemorrhages or bleeding accounted for two-thirds of serious reactions.
Clinicians prescribed a median 8 drugs to each patient, but 3 drug classes were responsible for a substantial proportion of all and serious AEs, including renin-angiotensin system (RAS) inhibitors, antithrombotic agents, and diuretics. Notably, antithrombotic agents (eg, vitamin K antagonists, heparin, platelet aggregation inhibitors, direct factor Xa inhibitors) caused 34% of serious adverse drug reactions. In two-thirds of cases overall, the drug was discontinued at least temporarily, whereas the drug dose was adjusted in 14% of cases.
Patients with an eGFR of less than 30 mL/min/1.73 m2 were 56% more likely to experience any AE events and 82% more likely to experience serious AEs compared with patients who had higher eGFR values. In addition, patients prescribed more than 10 drugs had a significant 1.6 and 2.1-fold greater risk of any and serious AEs, respectively, in adjusted analyses compared with patients prescribed fewer than 5 drugs. By comparison, patients with poor medication adherence had an approximately 1.4- and 1.6-fold greater risk of any and serious AEs, respectively, compared with those who had good medication adherence.
Thirteen percent of serious AEs were preventable and 19% potentially preventable, the report noted. A quarter of the preventable reactions were associated with patient self-medication. Patient education on proper drug use must be enhanced, according to the investigators.
“Our results highlight the major risk of specific pharmacological classes, particularly antithrombotic agents, which must be used cautiously in patients with CKD, especially at low eGFRs,” Dr Stengel’s team stated. “Greater awareness by the medical community of the importance of eGFR level in prescribing medications, increased involvement of pharmacists in systematically verifying eGFR for patient prescriptions, and enhanced patient education are key elements for preventing [adverse drug reactions] in this population at high risk.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Laville SM, Gras-Champel V, Moragny J, et al. Adverse drug reactions in patients with CKD. Clin J Am Soc Nephrol. doi: 10.2215/CJN.01030120