Consensus Obtained for the Nephrotoxic Potential of 167 Drugs in Adult Critically Ill Patients Using a Modified Delphi Method

Gray, Matthew P.; Barreto, Erin F.; Schreier, Diana J.; Kellum, John A.; Suh, Kangho; Kashani, Kianoush; Rule, Andrew D.; Kane‐Gill, Sandra L.

doi:10.1007/s40264-022-01173-4

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…A recent study aimed to assign a nephrotoxic potential for 167 drugs, rating these on a scale from 0 to 3, with 3 corresponding to a definite nephrotoxic potential. 41 However, the overall changes in nephrotoxic potential arising from changes in the sales of numerous drugs are difficult to assess. In addition, the aggregated data used in this study does not disclose patients receiving multiple potentially nephrotoxic drugs, which could in theory have synergistic (or antagonistic) effects on kidney function.…”

Section: Limitationsmentioning

confidence: 99%

Twenty-Three-Year Trends in the Use of Potentially Nephrotoxic Drugs in Denmark

Enevoldsen¹,

Christiansen²,

Jensen³

2023

CLEP

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Background:The occurrence of acute and chronic kidney diseases has been rising in the last decades. Although drug use is a common risk factor for impaired kidney function, changes in utilization of potential nephrotoxic drugs have received little attention. Purpose: To describe temporal trends in the utilization of potentially nephrotoxic drugs in Denmark between 1999 and 2021. Methods: Specific drugs known or suspected to be nephrotoxic were identified in the literature. Data on the sold defined daily doses (DDDs) of potentially nephrotoxic drugs between 1999 and 2021 were retrieved using the Danish Register of Medical Product Statistics. Trends in sales of DDDs per 1000 inhabitants per day were tabulated and illustrated graphically. Results: From 1999 to 2021, the total sale of all selected drugs increased from 286 to 457 DDDs per 1000 inhabitants per day. The overall sale reached a preliminary peak in 2012 with 449 DDDs per 1000 inhabitants per day and remained relatively stable thereafter until reaching an all-time high in 2021 with 457 DDDs per 1000 inhabitants per day. Contributing with the majority in volume, sales of drugs inhibiting the renin-angiotensin-aldosterone system (RAAS) increased dramatically throughout the period. The same was observed for acetaminophen, methotrexate, tacrolimus, and iodinated contrast dye. In contrast, the sales of diuretics, acetylsalicylic acid, and ciclosporin decreased during the last decade of the study period. Conclusion:From 1999-2021 considerable changes in sales of potentially nephrotoxic drugs were observed. In general, the sales increased, in volume predominated by RAAS inhibiting drugs. This increase in sales of potential nephrotoxins could contribute to an increasing occurrence of kidney diseases.

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Section: Limitationsmentioning

confidence: 99%

Twenty-Three-Year Trends in the Use of Potentially Nephrotoxic Drugs in Denmark

Enevoldsen¹,

Christiansen²,

Jensen³

2023

CLEP

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“…Indeed, up to 22% of the 100 most administered drugs in adult intensive care are potentially nephrotoxic [5]. In addition, the number of new medications, including chemotherapeutics and biological drugs with potential nephrotoxicities, continues to increase exponentially [6,7]. Hence, healthcare providers need to be familiar with the drugs that may cause nephrotoxicity to select appropriate medications for their patient scenario and tailor the drug therapy program accordingly (e.g., discontinuation, dose adjustment).…”

Section: Introductionmentioning

confidence: 99%

Drug-drug interaction and acute kidney injury development: A correlation-based network analysis

Zhu

Barreto

et al. 2023

PLoS ONE

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Background Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI. Methods We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis). Results Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR<90 vs. eGFR≥90 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered. Conclusions This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity.

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“…Within the intensive care unit (ICU), AKI occurs in 25–60% of patients [3,4 ▪ ]. Sustaining an AKI results in a significant economic burden and increased patient morbidity and mortality [5,6,7,8 ▪ ]. The current consensus definition of AKI is based on the Kidney Disease: Improving Global Outcomes (KDIGO) AKI Criteria [9].…”

Section: Introductionmentioning

confidence: 99%

“…In a recent assessment conducted by Gray et al [8 ▪ ], a nephrotoxic potential rating system was employed to evaluate commonly prescribed medications in the ICU. The findings identified 20 medications, including nine antimicrobial agents, with probable-to-probable/definite nephrotoxicity [8 ▪ ]. Similarly, a comparable pattern of high-risk nephrotoxic medications was also reported in paediatric inpatients [14].…”

Section: Introductionmentioning

confidence: 99%

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights

Karimzadeh,

Strader,

Kane-Gill

et al. 2023

Current Opinion in Critical Care

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Purpose of review Drug associated kidney injury (D-AKI) occurs in 19–26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important. Recent findings Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI. Summary The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.

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Consensus Obtained for the Nephrotoxic Potential of 167 Drugs in Adult Critically Ill Patients Using a Modified Delphi Method

Cited by 23 publications

References 35 publications

Twenty-Three-Year Trends in the Use of Potentially Nephrotoxic Drugs in Denmark

Twenty-Three-Year Trends in the Use of Potentially Nephrotoxic Drugs in Denmark

Drug-drug interaction and acute kidney injury development: A correlation-based network analysis

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights

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