Is colistin (polymyxin E) nephrotoxic, particularly in patients with pre-existing renal issues or impaired renal function?

Is Colistin Nephrotoxic?

Yes, colistin is definitively nephrotoxic, with a nephrotoxicity incidence of approximately 36% in critically ill patients, representing a 2.4-fold increased risk compared to β-lactam-based regimens. 1, 2

Magnitude of Nephrotoxicity Risk

The nephrotoxicity profile of colistin is substantial and well-documented:

• Incidence rates range from 31-39% in critically ill patients receiving standard dosing regimens 3, 2, 4, 5
• A 2021 meta-analysis of randomized controlled trials found colistin increased nephrotoxicity risk by 140% compared to β-lactam antibiotics (RR 2.40,95% CI 1.47-3.91), with a number needed to harm of only 5 patients 2
• Most nephrotoxicity is reversible, with 90% of patients recovering renal function within one month after discontinuation 5
• Only 4-20% of cases result in irreversible renal damage requiring ongoing renal replacement therapy 4, 5

Comparative Nephrotoxicity: Colistin vs Polymyxin B

Polymyxin B demonstrates significantly lower nephrotoxicity than colistin and should be strongly preferred when available, particularly in patients with renal impairment:

• Polymyxin B causes nephrotoxicity in 11.8% of patients versus 39.3% with colistin 6
• Polymyxin B requires no dose adjustment during continuous renal replacement therapy (CRRT), while colistin requires complex adjustments 6, 7
• Colistin-associated nephrotoxicity occurs earlier and more frequently than with polymyxin B 6

Mechanism and Clinical Characteristics

The nephrotoxic mechanism involves:

• Increased tubular epithelial cell membrane permeability leading to cation, anion, and water influx, resulting in cell swelling and lysis 8
• Oxidative stress and inflammatory pathways contributing to renal injury 8
• Nephrotoxicity is dose-dependent, with total cumulative dose being a critical predictor of kidney injury 3, 8
• Typically presents with preserved urine output, which can mask early detection 5

High-Risk Patient Populations

Patients with the following characteristics face substantially elevated nephrotoxicity risk and require intensified monitoring:

• Chronic kidney disease at baseline (40% nephrotoxicity rate vs 3% in those without) 4
• Hypertension (87% vs 56% in those without hypertension developed nephrotoxicity) 4, 5
• Hypoalbuminemia (significant independent risk factor, as free colistin causes renal toxicity) 5, 8
• Elderly patients (age >59 years) 8
• Hyperbilirubinemia 8
• Severe illness/septic shock 3

Concomitant Nephrotoxic Agents

The risk of nephrotoxicity increases 6.5-fold when colistin is combined with at least two other nephrotoxic agents 4:

• Avoid concurrent aminoglycosides (explicitly contraindicated due to additive nephrotoxicity) 9
• NSAIDs are a significant independent risk factor for colistin nephrotoxicity 5
• Intravenous contrast material increases risk (33% vs 0% nephrotoxicity) 4
• Sodium cephalothin enhances nephrotoxicity and should be avoided 9
• Second-generation fluoroquinolones show cumulative dose-related nephrotoxicity risk 5

Mandatory Monitoring Requirements

Renal function must be monitored closely during colistin therapy (strong recommendation, low-quality evidence) 1:

• Check baseline renal function before initiation 7
• Monitor 2-3 times per week during treatment 7
• Acute kidney injury during colistin treatment is a major factor related to clinical failure and mortality 1, 10

Dosing Considerations to Minimize Nephrotoxicity

While maintaining efficacy, consider these strategies:

• Always administer a loading dose of 9 million IU (300 mg colistin base activity) regardless of renal function to rapidly achieve therapeutic levels 1, 10
• For normal renal function: maintenance dose of 4.5 million IU every 12 hours 10
• Shorten treatment duration when possible, as total cumulative dose predicts kidney damage 3
• Adjust maintenance doses (not loading dose) based on creatinine clearance in renal impairment 7, 9

Critical Clinical Pitfall

Do not underdose colistin in an attempt to reduce nephrotoxicity, as subtherapeutic levels lead to treatment failure and increased mortality while still carrying nephrotoxic risk 1. The better strategy is to use alternative agents when available (ceftazidime-avibactam, ceftolozane-tazobactam) or switch to polymyxin B 1, 6.

Preferred Alternatives

When treating carbapenem-resistant infections, strongly consider ceftolozane-tazobactam over polymyxin-based regimens due to superior efficacy and dramatically lower nephrotoxicity (adjusted OR 0.08,95% CI 0.03-0.22) 6. Colistin should be regarded as a last-line agent 2.