Serious Adverse Drug Reactions Frequent in Nondialysis CKD

Patients with moderate to advanced nondialysis-dependent chronic kidney disease (CKD) have increased risks of serious adverse drug reactions (ADRs), especially as kidney function declines, regardless of older age and polypharmacy.

In the nationally representative French CKD-REIN (Chronic Kidney Disease-Renal Epidemiology and Information Network) prospective study, 360 of 3033 patients (11.9%) seen by outpatient nephrologists experienced 488 serious ADRs over a median 4.7 years. Kidney and urinary disorders and hemorrhage accounted for 70% of serious ADRs, Sophie Liabeuf, PharmD, PhD, of CHU Amiens-Picardie, in Amiens, France, and colleagues reported in the American Journal of Kidney Diseases. These ADRs occurred at a significantly higher rate among patients with a baseline estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m² than among patients with higher eGFR. Each 1 mL/min/1.73m² decrease in baseline eGFR was significantly associated with a 2.2% increased risk of AKI and an 8% increased risk of bleeding.

A subsequent AKI episode occurred in 14% of patients and subsequent bleeding in 13%. Yet serious ADRs were reported by patients in only 8% of cases, Dr Liabeuf’s team reported, highlighting the need for greater patient education and awareness of signs and symptoms affiliated with an ADR, such as vomiting or diarrhea.

ADRs By Drug Class

Antithrombotic agents (36.3%) and renin-angiotensin system (RAS) inhibitors (15.8%) accounted for a substantial proportion of serious ADRs, followed by diuretics (12.9%) and systemic antibacterials (5.5%). Contrast agents, analgesics, diabetes drugs, gout medications, antineoplastic agents, immunosuppressants, and other cardiovascular drugs each accounted for less than 5% of serious ADRs. Approximately half of serious ADRs involved 1 drug, and half involved 2-3 drugs. Drug discontinuation occurred in 80% of serious ADR cases.

Drug-related AKI was frequently due to concomitant use of multiple diuretics, a diuretic plus RAS inhibitors, or nonsteroidal anti-inflammatory drugs (NSAIDs) plus a RAS inhibitor or a diuretic. Drug-related bleeding were frequently due to use of an oral anticoagulant plus an antiplatelet agent or an oral anticoagulant plus a selective serotonin reuptake inhibitor.

Serious ADRs associated with antithrombotics occurred at a significantly higher rate in patients with an eGFR less than 30 mL/min/1.73m². According to the investigators, “the risk-benefit ratio for antiplatelet agents and anticoagulants must be systematically reassessed when kidney function deteriorates in patients with CKD.”

In 46% of serious ADRs, the implicated drug had been taken by the patient for more than 1 year. In 15% and 22% of serious ADRs, the implicated drug had been taken for at least 1 month or 1 week before the reaction, respectively. In 4% and 7%, the drug had been introduced on the same day or within 7 days of the ADR, respectively.

Hospitalization and Death

Th vast majority of serious ADRs (95.7%) involved hospitalization, according to Dr Liabeuf and colleagues. Nearly a third of the serious ADRs (including 38% of the drug-induced AKIs) occurred during hospitalization. Death or a life-threatening event occurred in 11% of cases. The number of fatal events would be substantial at the population level, according to the investigators.

Preventability

More than 27% of the 488 serious ADRs were preventable or potentially preventable, Dr Liabeuf’s team pointed out. Most commonly, prescriptions did not comply with the FDA-approved label, such as a contraindication or an inappropriately high dose given kidney function. Patients themselves caused 22 preventable cases of serious ADRs because of medication errors, self-medication (eg, NSAIDs), and self-induced drug intoxication.

“Given the elevated risk of ADRs (and especially AKI) in a CKD setting, patient education about nonrecommended drugs needs to be improved,” according to Dr Liabeuf’s team.

Disclosure: CKD-REIN is supported by numerous pharmaceutical companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Renal and Urology News