Specific Drugs Yield More Adverse Reactions for Chronic Kidney Disease Patients

Solene M. Laville

There is currently very little known about the burden of adverse drug reactions in patients with chronic kidney disease (CKD).

A team, led by Solène M. Laville, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors linked to adverse drug reactions in patients with CKD.

In the Chronic Kidney Disease-Renal Epidemiology and Information Network cohort, the investigators examined 3033 outpatients with chronic kidney disease, 65% of which were men.

Each patient had an eGFR<60 ml/min per 1.73 m², with follow-up for 2 years.

The team identified adverse drug reactions from hospitalization reports, medical records, and participant interviews. The reactions were also assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology.

The median age of the patient population was 69 years old, while 55% of the individuals had an eGFR≥30 ml/min per 1.73 m², and 45% had eGFR<30 ml/min per 1.73 m².

Each individual was prescribed a median of 8 drugs and over the course of 2 years, 536 patients had a 751 adverse drug reactions, There were also 150 adverse reactions in 125 participants were classified as serious for rates of 14.4 (95% CI, 12.6-16.5) and 2.7 (95% CI, 1.7-4.3) per 100 person years, respectively.

Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable and 16 caused death, directly or indirectly.

The most adverse drug reactions were imputed by renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%). However, antithrombotic agents caused 34% of serious adverse drug reactions in the study and was discontinued in 71% of cases, at least temporarily.

Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR<30 compared to patients with an eGFR of ≥30 ml/min per 1.73 m² (1.8; 95% CI, 1.3-2.6), in those prescribed more than 10 drugs compared to less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4).

“Adverse drug reactions are common and sometimes serious in patients with CKD,” the authors wrote. “Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions.”

Recently, investigators tried to test whether vitamin k supplements could decrease cardiovascular events for CKD patients.

Each patient was randomly assigned to receive either 400 μg oral vitamin K2 (n = 80) or a matching placebo (n = 79) once daily for a year.

Ultimately, the researchers did not find differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function.

The study, “Adverse Drug Reactions in Patients with CKD,” was published online in the Clinical Journal of the American Society of Nephrology.