Drug-Induced Acute Kidney Injury: A Focus on Risk Assessment for Prevention

doi:10.1016/j.ccc.2015.06.005

Critical Care Clinics

Volume 31, Issue 4, October 2015, Pages 675-684

https://doi.org/10.1016/j.ccc.2015.06.005 Get rights and content

Section snippets

Key points

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Modifiable drug-specific exposures for nephrotoxicity are the duration of nephrotoxin treatment, cumulative or total daily dose of nephrotoxin, and pharmacokinetic and pharmacodynamic drug interactions.
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Acute kidney injury (AKI) detection strategies may mitigate further kidney injury, but they do little to prevent harm and have not used systematic creatinine surveillance for AKI in at-risk patients.
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The advent and wide dissemination of hospital-based electronic health records has led to automated

Epidemiology of drug-induced acute kidney injury

Critically ill patients receive twice the number of drugs as compared with non–critically ill patients, increasing the risk of developing significantly more adverse drug events, such as acute kidney injury (AKI).1, 2 Approximately 20% of the drugs prescribed in the intensive care unit (ICU) are considered nephrotoxic.³ Drugs are the third to fifth leading cause of AKI in this setting following sepsis and hypotension.4, 5, 6, 7 AKI occurs in 20% to 30% of critically ill patients, with drugs

Risk factors for drug-induced acute kidney injury

There are several susceptibilities and exposures that may contribute to AKI development as discussed in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.10, 21 Also a recent systematic review highlighted the risk factors for AKI in critically ill patients.⁹ The susceptibilities and exposures for AKI are listed in Table 1. Although these risks are for AKI, one assumes that they may apply to drug-induced AKI, although no specific comparison between risk factors of drug-induced AKI

Risk assessment for drug-induced acute kidney injury

Risk assessment for drug-induced AKI has predominantly been reactive in looking for AKI in patients who have been exposed to nephrotoxic medications. The advent and wide dissemination of hospital-based EHRs has led to automated AKI alerting systems, usually based on an increase in serum creatinine.³⁰ EHR-based safety tools include kidney injury triggers, such as the Institute for Healthcare Improvement’s Global Trigger Tool,³¹ a recent tool using Acute Kidney Injury Network definition,³² or

Prevention of drug-induced acute kidney injury

Prevention is the best approach to averting harm associated with nephrotoxins. This most efficient approach to evaluating risk factors, as mentioned in the risk-assessment section (earlier), will require either manual or electronic surveillance. Early detection of patients at risk for AKI requires clinicians to shift their approach away from waiting for an increase in serum creatinine, as this biomarker lags by 24 to 48 hours behind initial kidney injury.⁴⁷ Once high-risk patients are

Management of drug-induced acute kidney injury

One of the largest challenges in the management of drug-induced AKI is the identification of a drug-related cause. When trying to identify drug causes, we should review the patients’ entire medication list, including over-the-counter drugs and herbal products. An evaluation of suspected drugs includes consideration of the temporal sequence between the event and drug administration, objective evidence including drug concentrations when appropriate, prior knowledge of the event to support the

Future directions

Although the prevalence and impact of drug-induced AKI presents a serious health care burden, drug-induced AKI risk assessment remains generally relegated to broad demographic criteria; treatment consists of hydration and nephrotoxic medication avoidance. Recent efforts have commenced in 2 areas to personalize risk stratification and AKI detection: (1) assessment of genetic predisposition to specific nephrotoxic medications and (2) use of novel damage urinary biomarkers to identify AKI before

Summary

Drug-induced AKI is becoming recognized as a significant sequelae of care for hospitalized patients. Recent work to identify drug-induced AKI risk factors and develop systematic nephrotoxic medication exposure and AKI detection alerts and the association with the development of CKD has highlighted the enormous magnitude of the harm. It is hoped that current translational efforts to identify genetic polymorphisms that increase risk, or provide protection, to drug-induced AKI will allow us to

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