Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease

Abstract

Background: We sought to comprehensively describe drug-related components associated with acute kidney injury (AKI) in patients with chronic kidney disease (CKD), describing the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the 1-year incidences of the recurrence of drug-related AKI, kidney failure, and death.

Methods: CKD-REIN is a French national prospective cohort of 3033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 ml/min/1.73 m²). AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital reports, medical records, and patient interviews. Expert nephrologists used the KDIGO criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs).

Results: Over a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3033 study participants. The drug-related component associated with AKI accounted for 236 cases, and 28% were judged to be preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. A history of cardiovascular events, diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥5 drugs taken daily were associated with a greater risk of drug-related AKI. Full recovery was not attained in 64 (27%) of the 236 cases of drug-related AKI. The 1-year cumulative incidences of recurrence of drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI.

Conclusions: Drug-related AKI is prevalent among patients with CKD. Even though a substantial proportion of these events were classified as stage 1, our findings point to a poor prognosis.

Keywords: acute kidney injury; adverse drug reaction; chronic kidney disease; drugs; pharmacoepidemiology.

Figure 1:

AKI flowchart.

Figure 2:

Stage of AKI, according to the medication component.

Figure 3:

Medications primarily implicated in drug-related acute kidney injuries, by setting of occurrence.

Figure 4:

Diagram of drug associations implicated in drug-related AKI. A10, drugs used in diabetes; A12, mineral supplements; B01, antithrombotic agents; B03, antianemic preparations; C01, cardiac therapy; C02, antihypertensives; C03, diuretics; C07, beta blocking agents; C08, calcium channel blockers; C09, agents acting on the renin-angiotensin system; C10, lipid modifying agents; J01, antibacterials for systemic use; J05, antivirals for systemic use; L01, antineoplastic agents; L04, immunosuppressants; M01, anti-inflammatory and antirheumatic products; M02, topical products for joint and muscular pain; M04, antigout preparations; N02, analgesics; N03, antiepileptics; N05, psycholeptics; V08, contrast media. Note: Associations of therapeutic classes are shown for drug-related acute kidney injuries for which at least two drugs were implicated (n = 132). The wider the link between two therapeutic classes, the more frequently the association is found to be involved in drug-induced AKI. The combination of two drugs from the same therapeutic class may have contributed to drug-related AKI (e.g. diuretics, C03). RASis and diuretics, two diuretics, and diuretics and antibiotics were the three most frequent associations.

Figure 5:

Cumulative incidence rates of various events after a first drug-related AKI, by setting of occurrence. (a) Cumulative incidence rates of various events after a first drug-related AKI. (b) After a first community-acquired drug-related AKI. (c) After a first hospital-acquired drug-related AKI.