Antipsychotics That Can Worsen Kidney Function
Antipsychotics that can worsen kidney function include lithium, clozapine, and quetiapine, with quetiapine carrying the highest risk of both acute kidney injury (AKI) and chronic kidney disease (CKD). 1
Mechanisms of Antipsychotic-Induced Kidney Damage
Antipsychotic medications can affect kidney function through several mechanisms:
- Systemic or renal/glomerular hemodynamic effects leading to kidney dysfunction 2
- Direct tubular or structural damage causing kidney injury 2
- Metabolic and inflammatory side effects that indirectly impact kidney function 3
- Drug accumulation in patients with existing renal impairment, creating a cycle of worsening kidney function 4
Specific Antipsychotics and Their Renal Effects
Lithium
- Causes diminution of renal concentrating ability, potentially presenting as nephrogenic diabetes insipidus with polyuria and polydipsia 5
- Associated with morphologic changes including glomerular and interstitial fibrosis and nephron atrophy in chronic therapy 5
- Kidney damage is common in long-term lithium treatment, affecting both glomerular and tubular function 6
- Renal function monitoring is essential as lithium toxicity is closely related to serum lithium levels 5
Clozapine
- Carries the highest individual risk among atypical antipsychotics with an odds ratio of 1.81 for developing CKD 7
- Higher plasma concentrations are likely in patients with significant renal impairment 4
- Requires dose adjustment in patients with renal impairment due to altered pharmacokinetics 4
- Inflammatory conditions may increase clozapine concentrations, potentially exacerbating renal effects 4
Quetiapine and Other Second-Generation Antipsychotics
- Quetiapine carries the highest overall risk of renal impairment among atypical antipsychotics 1
- Second-generation antipsychotics as a class are associated with a 34% increased risk of renal impairment 1
- Both short-term and long-term use of SGAs are associated with increased risk of CKD 7
- All investigated SGAs except aripiprazole have been associated with increased risk of CKD 7
Risk Factors and Monitoring
Risk Factors for Antipsychotic-Induced Kidney Damage
- Existing renal impairment 4
- Concomitant use of other nephrotoxic medications 2
- Advanced age 2
- Dehydration, especially with lithium therapy 5
- Inflammatory conditions that may alter drug metabolism 4
Monitoring Recommendations
- Monitor kidney function in all patients exposed to potentially nephrotoxic antipsychotics 2
- For lithium therapy, assess both tubular function (urine specific gravity, osmolality) and glomerular function (serum creatinine, creatinine clearance) 5
- Progressive or sudden changes in renal function, even within normal range, indicate need for treatment reevaluation 5
- Annual monitoring of serum creatinine levels for patients on lithium, with further evaluation when levels consistently rise above 140 μmol/L (1.6 mg/dL) 8
Prevention and Management Strategies
- Patients should receive potentially nephrotoxic medications only when necessary and for the shortest duration possible 2
- Consider alternative antipsychotics with lower renal risk (e.g., aripiprazole) in patients with existing kidney disease 7
- Avoid combinations of multiple nephrotoxic drugs when possible 2
- Maintain adequate hydration, especially in patients taking lithium 5
- Adjust dosages based on kidney function for antipsychotics eliminated by renal route 4
- Monitor for drug accumulation in patients with impaired renal function 4
Special Considerations in Elderly Patients
- Elderly patients are at higher risk due to age-related decline in kidney function (approximately 1% per year beyond age 30-40) 2
- The American Geriatrics Society Beers Criteria recommends careful monitoring of kidney function in older adults on psychotropic medications 2
- Avoid combinations of three or more CNS-active drugs (including antipsychotics) in elderly patients due to increased fall risk 2
- Consider dose adjustments for antipsychotics in elderly patients with reduced kidney function 2