Can a patient with chronic kidney disease stage 3b (eGFR ≈ 37 mL/min) safely continue hydroxychloroquine (Plaquenil) and tocilizumab (Actemra)?

Hydroxychloroquine and Tocilizumab Safety in CKD Stage 3b

Both hydroxychloroquine (Plaquenil) and tocilizumab (Actemra) can be safely continued in a patient with CKD stage 3b (eGFR 37 mL/min/1.73 m²), but hydroxychloroquine requires dose adjustment and enhanced retinopathy monitoring due to increased toxicity risk at this level of kidney function.

Hydroxychloroquine (Plaquenil) Management

Dose Adjustment Required

• Hydroxychloroquine requires dose reduction in CKD stage 3b because the drug and its metabolites are renally excreted, and impaired clearance increases the risk of retinal toxicity 1.
• Prescribers must account for GFR when dosing medications, particularly those with narrow therapeutic ranges or significant renal excretion 2.

Enhanced Retinopathy Monitoring

• CKD stage 3 or greater (eGFR <60 mL/min/1.73 m²) independently increases the risk of hydroxychloroquine retinopathy by approximately 2-fold (HR 1.95% CI 1.25-3.04) 3.
• This elevated risk persists even after accounting for dose and duration of use, making annual ophthalmologic screening with spectral-domain optical coherence tomography and automated visual field testing mandatory 3.
• The risk compounds with other factors including age >45 years, female sex, and tamoxifen use 3.

Renal Benefits

• Hydroxychloroquine demonstrates anti-inflammatory and immunomodulatory properties that may actually benefit kidney function, with emerging evidence showing proteinuria reduction in IgA nephropathy and potential cardiovascular risk reduction in CKD 4.
• The drug inhibits macrophage activation and attenuates renal fibrosis through TLR-9 pathway modulation, suggesting potential nephroprotective effects 5.

Tocilizumab (Actemra) Management

No Dose Adjustment Needed

• Tocilizumab does not require dose adjustment in CKD stage 3b as it is a monoclonal antibody cleared through proteolytic catabolism rather than renal excretion.
• The KDIGO guidelines emphasize dose adjustment only for drugs with significant renal clearance 2.

Monitoring Considerations

• Standard monitoring for tocilizumab includes complete blood count, liver function tests, and lipid panel, but no specific additional monitoring is required for CKD stage 3b.
• Watch for infection risk, which may be slightly elevated in CKD patients due to underlying immune dysfunction 6.

Practical Management Algorithm

For Hydroxychloroquine:

1. Calculate ideal body weight-based dosing (not actual body weight) to minimize retinopathy risk
2. Reduce dose to ≤5 mg/kg/day of ideal body weight in CKD stage 3b 3
3. Ensure annual ophthalmologic screening with both spectral-domain OCT and automated visual fields 3
4. Monitor serum creatinine and eGFR every 3-6 months to detect progression 6

For Tocilizumab:

1. Continue standard dosing (162 mg subcutaneously weekly or 4-8 mg/kg IV every 4 weeks depending on indication)
2. Monitor CBC, liver enzymes, and lipids per standard protocols
3. Assess for signs of infection at each visit

Critical Caveats

Avoid Premature Discontinuation

• Do not discontinue either medication solely based on eGFR of 37 mL/min unless specific complications develop (symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms) 2.
• The threshold for considering medication discontinuation in CKD is eGFR <15 mL/min/1.73 m², not stage 3b 7.

Nephrotoxin Avoidance

• Ensure avoidance of NSAIDs, which are nephrotoxic and contraindicated in CKD stage 3b 6.
• Review all concomitant medications for potential drug-drug interactions and nephrotoxic agents 2.

Optimize CKD Management

• Ensure the patient is on appropriate CKD-protective therapies including ACE inhibitor or ARB (if albuminuria present), SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²), and statin for cardiovascular protection 2, 8.
• Target blood pressure <130/80 mmHg if albuminuria ≥30 mg/24 hours 8.

Consider Nephrology Referral

• Refer to nephrology if proteinuria >1 g/day, rapidly declining eGFR (>20% drop), or refractory hypertension on 4+ agents 8.