How should rosuvastatin be managed in a patient with acute kidney injury (AKI) and reduced estimated glomerular filtration rate?

Rosuvastatin Management in Acute Kidney Injury

Primary Recommendation

Continue rosuvastatin at a reduced dose (5-10 mg daily maximum) in patients with AKI, unless the patient has severe renal impairment (creatinine clearance <30 mL/min) or the AKI is progressing to stage 2-3, in which case temporary discontinuation should be considered. 1

Dosing Adjustments Based on Renal Function

Severe Renal Impairment (CrCl <30 mL/min)

• Initiate at 5 mg once daily and do not exceed 10 mg once daily per FDA prescribing information 1
• This applies to patients with established severe renal impairment, not those on hemodialysis 1

Moderate Renal Impairment (eGFR 30-60 mL/min)

• KDIGO guidelines recommend avoiding high-intensity statins (including rosuvastatin >20 mg) in patients with eGFR <60 mL/min/1.73 m² 2
• However, FDA labeling for rosuvastatin does not recommend dose adjustment until creatinine clearance is <30 mL/min/1.73 m² 2
• The conservative approach is to reduce to 5-10 mg daily when eGFR drops below 60 mL/min 2

AKI Staging and Management Decisions

Stage 1 AKI (SCr increase 1.5-1.9× baseline or ≥0.3 mg/dL within 48h)

• Continue rosuvastatin at reduced dose (5-10 mg) if SCr remains <1.5 mg/dL 2
• Monitor creatinine every 2-4 days during hospitalization 2
• Review all nephrotoxic medications and consider rosuvastatin as a potential contributor if no other cause identified 2, 3

Stage 1B AKI (SCr ≥1.5 mg/dL but <2× baseline)

• Consider temporary discontinuation of rosuvastatin as this threshold predicts progression to higher AKI stages 2
• Reassess need for continuation based on cardiovascular risk versus renal risk 2

Stage 2-3 AKI (SCr ≥2× baseline or ≥4.0 mg/dL)

• Discontinue rosuvastatin temporarily until renal function stabilizes 2, 1
• Rosuvastatin should be temporarily discontinued in patients experiencing acute conditions at high risk of developing renal failure secondary to rhabdomyolysis (sepsis, shock, severe hypovolemia, major surgery, trauma, severe metabolic/electrolyte disorders) 1

Special Clinical Contexts

Contrast-Induced AKI Prevention

• High-dose rosuvastatin (40 mg on admission, then 20 mg daily) reduces CI-AKI risk in acute coronary syndrome patients 4
• The incidence of CI-AKI was 6.7% with rosuvastatin versus 15.1% in controls (adjusted OR 0.38,95% CI 0.20-0.71) 4
• Similar protective effects seen with rosuvastatin 10 mg daily for 5 days (2 days before, 3 days after procedure) in diabetic patients with CKD (2.3% vs 3.9% CI-AKI, p=0.01) 5
• This represents a unique scenario where rosuvastatin should be continued or initiated despite AKI risk 4, 5

Sepsis-Associated ARDS

• Rosuvastatin does not protect against de novo AKI in sepsis-associated ARDS and may worsen preexisting stage 1 AKI (adjusted OR 3.06,95% CI 1.14-8.22) 6
• Avoid initiating rosuvastatin in critically ill septic patients with AKI 6

Monitoring for Statin-Induced Renal Toxicity

Direct Tubular Toxicity

• Rosuvastatin can cause non-rhabdomyolysis-mediated acute tubular injury, particularly at 40 mg dose 7
• Monitor for proteinuria and hematuria on urinalysis, which were more frequent with rosuvastatin 40 mg 1
• If unexplained AKI occurs with abnormal urine sediment suggesting tubular injury and no rhabdomyolysis (normal CK), consider rosuvastatin as the causative agent 7

Myopathy and Rhabdomyolysis Risk

• Check CK levels if patient reports muscle pain, tenderness, or weakness 1
• Risk factors include age ≥65 years, uncontrolled hypothyroidism, renal impairment, and higher rosuvastatin doses 1
• Discontinue immediately if markedly elevated CK or myopathy diagnosed 1

Medication Interactions Requiring Dose Adjustment

Contraindicated or Severely Limited Combinations

• Avoid gemfibrozil with rosuvastatin; if unavoidable, initiate at 5 mg daily and do not exceed 10 mg daily 1
• Multiple antiviral medications (sofosbuvir/velpatasvir/voxilaprevir, ledipasvir/sofosbuvir) have concomitant use not recommended 1
• Atazanavir/ritonavir and lopinavir/ritonavir: initiate at 5 mg daily, do not exceed 10 mg daily 1

Moderate Restrictions

• Darolutamide: do not exceed 5 mg rosuvastatin daily 1
• Regorafenib: do not exceed 10 mg rosuvastatin daily 1
• Febuxostat: do not exceed 20 mg rosuvastatin daily 1

Algorithm for Decision-Making

1. Assess AKI stage using KDIGO criteria (SCr increase ≥0.3 mg/dL within 48h or ≥1.5× baseline within 7 days) 2

2. Calculate creatinine clearance or eGFR to determine severity of renal impairment 2, 1

3. Review medication list for nephrotoxic drugs and potential interactions 2, 3, 1

4. Determine clinical context:

   • If pre-procedure for coronary angiography: continue/initiate high-dose rosuvastatin 4, 5
   • If sepsis/critical illness: discontinue rosuvastatin 6
   • If stable medical patient: adjust dose based on renal function 1

5. Apply dose modifications:

   • CrCl ≥30 mL/min + Stage 1A AKI (SCr <1.5 mg/dL): continue at 5-10 mg daily 2
   • CrCl ≥30 mL/min + Stage 1B-3 AKI: temporarily discontinue 2
   • CrCl <30 mL/min: maximum 10 mg daily if continuing 1

6. Monitor closely: SCr every 2-4 days, urinalysis for proteinuria/hematuria, CK if muscle symptoms 2, 1

Common Pitfalls to Avoid

• Do not rely on serum creatinine alone to estimate renal function, as it underestimates impairment in elderly patients with reduced muscle mass 8
• Do not continue high-dose rosuvastatin (40 mg) in patients with established AKI outside the contrast-prevention context 1, 7
• Do not overlook rosuvastatin as a cause of unexplained AKI with tubular injury pattern, especially at 40 mg dose 7
• Do not forget to adjust for drug interactions that increase rosuvastatin levels and myopathy risk 1
• Do not initiate or continue rosuvastatin in hemodynamically unstable patients or those with sepsis-associated AKI 6