Community prescribing of potentially nephrotoxic drugs and risk of acute kidney injury requiring renal replacement therapy in critically ill adults: A national cohort study

Abstract

Background: Acute kidney injury demonstrates a high incidence in critically ill populations, with many requiring renal replacement therapy. Patients may be at increased risk of acute kidney injury if prescribed certain potentially nephrotoxic medications. We aimed to evaluate this association in ICU survivors.

Methods: Study design - secondary analysis of national cohort of ICU survivors to hospital discharge linked to Scottish healthcare datasets. Outcomes: primary - renal replacement therapy in ICU; secondary - early acute kidney injury (calculated using urine output and relative change from estimated baseline serum creatinine within first 24 h of ICU admission using modified-RIFLE criteria). Primary exposure: pre-admission community prescribing of at least one potential nephrotoxin: angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers, diuretics or nonsteroidal anti-inflammatory drugs. Statistical analyses: unadjusted associations - univariable logistic regression; confounder adjusted: multivariable logistic regression.

Results: During 2011-2013, 12,838 of 23,116 patients (55.5%) were prescribed at least one community prescription of at least one nephrotoxin; 1330 (5.8%) patients received renal replacement therapy; 3061 (15.7%) had acute kidney injury. Patients exposed to at least one examined nephrotoxin experienced higher incidence of renal replacement therapy (6.8% vs 4.5%; adjOR 1.46, 95%CI 1.24, 1.72, p < 0.001) and acute kidney injury (19.8% vs 10.9%; adjOR 1.61, 1.44, 1.80, p < 0.001). Increased risk of RRT was also found for angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers (adjOR 1.65, 1.40, 1.94), non-steroidal anti-inflammatory drugs (adjOR 1.12, 1.02, 1.44) and diuretics (adjOR 1.35, 1.14, 1.59).

Conclusions: Community prescribing of potential nephrotoxins increases the risk of renal replacement therapy/early acute kidney injury in ICU populations. Analyses were limited by the survivor dataset and potential residual confounding. Findings add consistency to previous research improving understanding of the harmful potential of these important medications and their timely cessation in acute illness.

Keywords: Renal replacement therapy; acute kidney injury; community prescribing; critical care; nephrotoxin.

Figure 1.

Patient flow diagram. Flow diagram describing reasons for exclusion from primary and secondary analyses. RRT: Renal replacement therapy.

Figure 2.

Forest plot of association between primary exposures (at least one potential nephrotoxin) and outcomes: unadjusted and adjusted results. Exposed drug class listed may be in combination with exposure to an additional class – for example, NSAIDs = Participants exposed to at least an NSAID +/− additional drug class. ACE-i: angiotensin-converting-enzyme inhibitor; AKI: early acute kidney injury occurring within 24 hours of ICU admission; ARB: angiotensin-II receptor blockers; NSAID: non-steroidal anti-inflammatory drug; OR: odds ratio; RRT: renal replacement therapy; 95% CI: 95% confidence interval.