How does quinine affect kidney function?

Quinine's Effects on Kidney Function

Quinine can cause significant kidney dysfunction and should be used cautiously in patients with renal impairment, with appropriate dose adjustments and monitoring of kidney function. 1, 2

Pharmacokinetics and Renal Handling

• In patients with severe chronic renal failure, quinine clearance is decreased, resulting in higher plasma concentrations and potential toxicity 2
• After a single oral 600 mg dose of quinine in subjects with severe chronic renal failure (not on dialysis), the median AUC was 195% higher and median Cmax was 79% higher compared to subjects with normal renal function 2
• The mean plasma half-life in subjects with severe chronic renal impairment is prolonged to 26 hours compared to 9.7 hours in healthy controls 2

Dose Adjustments in Renal Impairment

• For patients with severe chronic renal failure, a modified dosing regimen consisting of one loading dose of 648 mg followed 12 hours later by a maintenance dosing regimen of 324 mg every 12 hours is recommended 2
• Negligible to minimal amounts of circulating quinine are removed by hemodialysis or hemofiltration, with only about 6.5% of quinine removed in 1 hour during hemodialysis 2
• Plasma quinine concentrations do not change significantly during or shortly after hemofiltration in subjects with chronic renal failure 2

Nephrotoxic Effects

• Quinine can cause immune-mediated thrombotic microangiopathy (TMA), which can lead to severe acute kidney injury requiring dialysis 3
• Quinine-induced TMA commonly results in chronic kidney disease, with some cases progressing to end-stage renal disease 3
• Quinine-induced hemolytic uremic syndrome (HUS) has been reported, characterized by glomerular and arteriolar endothelial swelling, capillary loop thrombi, mesangiolysis, segmental sclerosis, and segmental ischemia 4

Monitoring Recommendations

• Kidney function must be monitored in patients exposed to quinine to limit the risk and progression of acute kidney injury (AKI) and acute kidney disease (AKD) 1
• Patients receiving quinine should be monitored for signs of quinine-induced immune reactions that could affect kidney function 3
• Monitoring should include regular assessment of serum creatinine, blood urea nitrogen, and urine output 1

Risk Factors and Precautions

• Patients with pre-existing renal impairment are at higher risk for quinine-related adverse effects 2
• Quinine, like other potentially nephrotoxic agents, should not be withheld in life-threatening conditions (such as severe malaria) due to concern for AKI 1
• In patients with malaria and renal failure requiring dialysis, some evidence suggests that normal quinine dosing (2 x 15 mg/kg per day) may still be necessary to achieve therapeutic plasma levels (5-15 mg/L) 5

Special Considerations

• In patients with chronic renal failure on hemodialysis, there is increased plasma protein binding of quinine (particularly to alpha1-acid glycoprotein) and increased clearance of free drug, potentially resulting in lower plasma concentrations of free quinine 6
• The kynurenine pathway, which is involved in tryptophan metabolism, may be affected by quinine and is known to be disturbed in kidney diseases 7
• Careful fluid management is essential when administering IV quinine to maintain adequate renal perfusion while avoiding fluid overload 1

Clinical Pearls and Pitfalls

• Quinine-induced TMA is often initially misdiagnosed as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), delaying proper management 3
• Quinine-induced immune reactions can occur with even small exposures, including quinine in tonic water 3
• Women appear to be at higher risk for quinine-induced TMA 3
• Early recognition of quinine-induced kidney injury and prompt discontinuation of the drug are essential to prevent progression to chronic kidney disease 3, 4