Drug-Induced AKI in the ICU: are we missing preventable risks?

In critically ill patients, drug therapy and kidney function are closely interconnected. Some drugs may contribute to the onset or progression of acute kidney injury (AKI), while the development of AKI may make the dose or dosing interval of ongoing treatments no longer appropriate.

Because AKI is often multifactorial, the presence of a potentially nephrotoxic drug in a patient’s treatment therapy does not automatically mean that it should be discontinued. Instead, the indication, dose, dosing interval, treatment duration, and concomitant therapies need to be systematically reassessed as kidney function evolves. Whenever possible, KDIGO guidelines recommend limiting exposure to nephrotoxic agents and ensuring that drug dosing remains appropriate for the patient’s kidney function.¹

How drug exposure changes during hospitalization

Drug therapy can change considerably over the course of hospitalization: new drugs may be introduced, others discontinued, and others continued for extended periods. Risk assessment therefore cannot be limited to the presence of a single drug. It must also consider changes over time in the number of potentially nephrotoxic drugs, the duration of exposure, and the concomitant use of multiple drugs.

A prospective multicenter study involving 1,001 patients admitted to ten intensive care units examined exposure to potentially nephrotoxic drugs. During the first seven days of hospitalization, 62% of patients had received at least one potentially nephrotoxic drug, while 30% had received two or more.²

These findings indicate that exposure to potentially nephrotoxic drugs is common as early as the first week of hospitalization and may involve the concurrent use of multiple drugs. The study does not allow the onset of AKI to be attributed to any specific drug, but it highlights the importance of reassessing the entire medication therapy over time. This means determining which treatments are still necessary, how long they have been administered, and whether concomitant drug use may be relevant to kidney risk. Alongside reviewing drugs that may contribute to kidney injury, it is also essential to assess treatments whose dose or dosing interval depends on kidney function.

Adapting drug therapy as kidney function evolves

In patients with AKI, kidney function may worsen, remain stable, or recover during hospitalization. Consequently, the dose and dosing interval of ongoing treatments may need to be reassessed more than once. If therapy is not adjusted to reflect changes in kidney function, drug exposure may be insufficient, potentially reducing therapeutic efficacy, or excessive, increasing the risk of toxicity.³

Reassessing drug dosing, however, does not mean automatically reducing the dose of every treatment. For treatments that need to be started promptly, the initial dose is intended to rapidly achieve effective therapeutic exposure and should not be delayed simply because kidney function is unstable. After treatment initiation, the dose and interval of subsequent administrations should be reassessed according to the clinical indication, the pharmacokinetic and pharmacodynamic characteristics of the medication, and the patient’s clinical course and kidney function. The aim is to maintain a balance between efficacy and safety. When available and clinically indicated, therapeutic drug monitoring based on plasma concentrations can provide a more direct measure of whether drug exposure is appropriate.³

A single assessment may therefore be insufficient. As kidney function and drug therapy evolve, even an initially appropriate prescription may need to be reviewed again over the following hours or days. Medication reconciliation and review should therefore continue throughout the patient’s clinical course, rather than being limited to an isolated check.

Why continuous monitoring can make a difference in clinical practice

In this context, the KDIGO Bundle, a module of the U-Care Renal Platform, is designed to integrate the monitoring of prescriptions classified as potentially nephrotoxic and their associated dosing into the clinical workflow. The module flags drugs for which discontinuation or reassessment may be appropriate and provides guidance on potential dose adjustments based on current glomerular filtration rate values. It also monitors episodes of hypotension and hyperglycemia, generating timely alerts to support clinical management. The system does not automatically discontinue drugs or modify prescriptions. The physician remains responsible for assessing the indication, dose, and whether treatment should be continued, using the information provided by the platform to support clinical decision-making.⁴

The use of the platform in clinical practice was assessed in an implementation study involving 202 adult postoperative patients admitted to intensive care. Among patients who developed AKI of any stage during their ICU stay, the median number of daily administrations of medications classified as nephrotoxic in the study decreased from 9 before implementation to 6.5 after implementation, representing an observed relative reduction of 28%.⁴

The role of the KDIGO Bundle module is therefore not to replace clinical judgment, but to automate continuous monitoring of prescriptions, dosages, and relevant clinical conditions. Integrating the module into the clinical workflow can make it easier to identify treatments and conditions that require reassessment as kidney function and the patient’s clinical condition evolve. In this way, KDIGO recommendations for medication management can be translated more effectively into everyday clinical practice.

To learn more about how the KDIGO Bundle module, integrated into the U-Care Renal Platform, can support medication management in critically ill patients with AKI, request a demo.