Melatonin Use in Metabolic Encephalopathy and Acute Kidney Injury

Rationale for Use

Melatonin is not classified as a nephrotoxin in major nephrology guidelines, according to the National Kidney Foundation 1, 2, 3
Unlike many medications that require avoidance in AKI, melatonin does not appear on lists of drugs to discontinue during acute kidney disease episodes, as stated by the American Society of Nephrology 1, 2, 4

AKI significantly impairs cytochrome P450 activity and drug metabolism, which can affect melatonin clearance and potentially increase drug levels, as reported by the National Institute of Diabetes and Digestive and Kidney Diseases 1, 2, 3
The effects of AKI on drug metabolism are clinically relevant but poorly characterized compared to chronic kidney disease, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 1, 3
Organ crosstalk between liver and kidney during AKI can influence drug metabolism through effects on hepatic blood flow, metabolic acidosis, and changes in protein binding, as described by the European Renal Association 1, 2, 4

Regular monitoring of renal function (serum creatinine and electrolytes) should be performed while on any medication during AKI, as recommended by the American College of Physicians 5, 6
Assess for signs of excessive sedation or altered mental status, particularly important given the baseline metabolic encephalopathy, according to the Neurocritical Care Society 1

Reassess need for continuation once AKI resolves and metabolic encephalopathy improves, as suggested by the National Kidney Foundation 1

Do not assume standard dosing is appropriate—AKI alters drug metabolism unpredictably, requiring dose reduction, as warned by the American Society of Nephrology 1, 3
Do not combine melatonin with multiple other sedating medications without careful monitoring, as drug interactions may be amplified in AKI, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 1, 3
Do not use melatonin as a substitute for treating the underlying causes of metabolic encephalopathy and AKI, as emphasized by the National Institute of Diabetes and Digestive and Kidney Diseases 1

No absolute contraindications exist for melatonin use in AKI based on available guidelines, as stated by the European Renal Association 1, 2, 3
Exercise caution if the patient is on other medications metabolized by cytochrome P450 enzymes, as AKI impairs this pathway, according to the American College of Clinical Pharmacy 1, 3
Consider delaying initiation if the patient has severe hemodynamic instability or requires multiple nephrotoxic medications, as recommended by the Society of Critical Care Medicine 1, 3