Nephrotoxin Stewardship

Dr. Yash Javeri

Director- CCM and Emergency Medicine
Regency Super Specialty Hospital  – Lucknow, India
Dean-The Indian College Of Emergency Medicine
Vice President -Indian Society of Critical Care Medicine
Convener – Indian Sepsis Forum


Nephrotoxin agents add significantly to risk of acute kidney injury (AKI) development. AKI is often multifactorial and complex syndrome. One significant predictor of AKI development in both the inpatient and outpatient settings is nephrotoxin exposure. Drug-induced AKI (D-AKI) is increasingly being recognized as a relatively common adverse drug event in clinical practice, with approximately 30% of AKI cases being attributable to drugs. We must be cognizant of the mechanisms of drug-induced nephrotoxicity. Nephrotoxic drugs prescriptions must be safely prioritized with stringent monitoring of medication and other patient factors responsible for AKI. Each drug’s inherent nephrotoxic potential (NxP) must be thought of before prescription.

Stewardship is “the conducting, supervising, or managing of something; especially the careful and responsible management of something entrusted to one’s care”
Nephrotoxin stewardship aims to ensure safe medication use, promote kidney health, and prevent adverse drug events related to nephrotoxins and renally eliminated drugs.


The goals of nephrotoxin stewardship are:

  • Medication safety is appropriate drug dosing (both overdosing and underdosing to be avoided) and preventing/ameliorating adverse drug events.
  • Ensuring kidney health by preventing AKI, AKI to CKD transition, or worsening of CKD.
  • Cost effectiveness in treatment, investigations and other interventions

Scope and Considerations:

Nephrotoxin stewardship goes beyond individual drugs and considers drug burden and drug-drug interactions. Renal friendly strategies are designed to prevent AKI or to minimize the injury. Hypervigilant monitoring using both traditional functional biomarkers and novel damage biomarkers is crucial for effective stewardship. Nephrotoxin stewardship ensures a structured and consistent approach to safe medication use and prevention of patient harm. Comprehensive nephrotoxin stewardship must have coordinated patient centric individualized care plans, management strategies for medication safety, ensuring kidney health, and cost effectiveness. Implementing nephrotoxin stewardship reduces medication errors and adverse drug events, prevents or reduces the severity of drug-associated AKI, prevents progression to or worsening of chronic kidney disease, and alleviates the financial burden on the health care system.

General Principles:

Be vigilant: Monitor renal function closely when introducing any drug, especially known nephrotoxic agents.

Risk stratification: Analyze risks and benefits for potentially nephrotoxic drugs in high-risk patients. Renal perfusion should be optimized and dysfunction should be actively looked for with early AKI biomarkers.

Polypharmacy increases risk: Caution is necessary when using multiple medications. Specifically, if more nephrotoxic agents are prescribed adds to risk.
Nephrotoxin burden is the cumulative or aggregate exposure to nephrotoxins, with consideration to nephrotoxic potential for each drug, evaluated at a given time or within a reasonable time frame depending on the elimination half-life of the drug

Precautions: Implement measures to prevent or attenuate toxicity for common drugs

Risk Reduction:

Fluid Management: In situations where AKI risk exists (e.g., hypovolemia), fluid administration is crucial. Careful monitoring is essential to prevent fluid overload, which can worsen AKI .Euvolemia is desired in vast majority of case scenarios in order to minimize AKI risk in hospitalized patients.
Pretreatment hydration can reduce the nephrotoxic potential of many drugs. Early diagnosis is critical, so physicians must be aware of the nephrotoxic potential of prescribed medications and the risk status of their patients.

Biomarkers and Genetic Predisposition: Digital tools can enhance the detection of kidney injury by incorporating biomarkers and genetic information. Identifying patients at higher risk for nephrotoxicity allows for personalized and timely interventions.

Medication safety

  • Standardize a minimum list of renally adjusted drugs to target for surveillance
  • Recommendations for/or verification of initial and maintenance dose
    Check to dose when changes (improve or decline) in kidney function with use estimates (i.e. Cockcroft Gault; CKD-EPI 2021; kinetic eGFR for unstable SCr)
  • Therapeutic monitoring for non-nephrotoxic drugs (i.e. digoxin) Monitoring for adverse drug events (ADEs) and therapeutic failures


Contrast injury: Hydration strategies are needed for preventing contrast-induced acute kidney injury. Usage of relatively safer contrast or avoidance of contrast studies in high-risk groups.

Prioritization: Institutions can use a nephrotoxin potential index rating to prioritize targeted drugs with higher nephrotoxic potential.
Nephrotoxin Potential Index: Prioritizes targeted drugs with greater nephrotoxic potential for institutional stewardship programs

Drug Selection: Non-nephrotoxic or less nephrotoxic equivalents are preferred over highly nephrotoxic drugs.
Essential drugs should not be withheld due to fear of AKI. Risk- benefit of each neprotoxic agent must be weighed.
Antibiotic stewardship programs aim to optimize antibiotic use, improve patient outcomes, and prevent adverse effects. While they don’t directly reduce nephrotoxicity, they indirectly contribute by promoting appropriate antibiotic selection, dosing, and monitoring. By minimizing unnecessary exposure to nephrotoxic antibiotics, these programs help protect kidney function.

Electronic Surveillance: Digital health systems allow for real-time monitoring of patients’ medication use. By tracking drug exposure and identifying nephrotoxic drugs, healthcare providers can promptly intervene if adverse effects occur.

Implementing nephrotoxin stewardship reduces medication errors and adverse drug events, prevents or reduces the severity of drug-associated AKI, prevents progression to or worsening of chronic kidney disease, and alleviates the financial burden on the health care system.

Overall, nephrotoxin stewardship plays a vital role in optimizing patient care and preventing kidney-related complications.