What are the guidelines for treating arthritis in a patient with End-Stage Renal Disease (ESRD)?

Treatment of Arthritis in ESRD Patients

In patients with ESRD and arthritis, avoid NSAIDs and methotrexate entirely, use hydroxychloroquine as the preferred DMARD with careful monitoring, and consider biologics (rituximab, belimumab) which require no dose adjustment in renal failure. 1, 2

Critical Medication Contraindications in ESRD

Methotrexate is absolutely contraindicated in ESRD patients due to renal elimination and risk of severe toxicity 3, 1. The FDA label explicitly warns that methotrexate requires close monitoring of renal function, and reduced renal clearance leads to toxic accumulation 3.

NSAIDs must be avoided in ESRD as they can precipitate acute kidney injury and worsen renal function, even in patients already on dialysis 4, 5, 2. While NSAIDs are recommended for symptomatic relief in arthritis with normal renal function 4, 5, this recommendation does not apply to ESRD patients where renal toxicity is a critical concern 2.

Bucillamine is also contraindicated in ESRD 1.

Preferred Pharmacologic Options

First-Line: Hydroxychloroquine

• Hydroxychloroquine is the most commonly used DMARD in ESRD patients (13.5% utilization rate) and does not require dose adjustment 6.
• However, more frequent monitoring for adverse drug reactions is required in ESRD, particularly for retinal toxicity 1.
• This should be the anchor drug for inflammatory arthritis in ESRD when methotrexate cannot be used 1, 6.

Biologic Agents (No Dose Adjustment Required)

• Rituximab and belimumab have pharmacokinetics unaffected by ESRD and require no dose adjustments 1.
• These are preferred biologic options when hydroxychloroquine alone is insufficient 1.
• Etanercept and adalimumab are used infrequently (2.5% and 1.5% respectively) but can be considered 6.

DMARDs Requiring Dose Adjustment or Special Monitoring

• Leflunomide and sulfasalazine do not require significant dose reduction and can be used, though leflunomide should be administered carefully 1.
• Mycophenolate mofetil, cyclosporine A, and tacrolimus require therapeutic drug monitoring in ESRD 1.
• Cyclophosphamide and azathioprine need dose adjustments based on renal function 1.

Glucocorticoid Use

• Systemic glucocorticoids (prednisone/prednisolone) are the most commonly prescribed anti-rheumatic medication in ESRD patients (45.9% utilization) 6.
• Use at the lowest effective dose for the shortest duration (<6 months) as temporary adjunctive therapy 4, 7.
• Intra-articular glucocorticoid injections are preferred for oligoarticular involvement to minimize systemic exposure 4, 7.

Non-Pharmacologic Interventions

• Dynamic exercises focusing on range of motion and strengthening should be prescribed as they are as effective as pharmacologic interventions 8.
• Occupational therapy for joint protection techniques is recommended as adjunctive treatment 4, 8.
• Weight control is essential if BMI >25, as each kilogram lost reduces joint loading by 3-4 kilograms 8.

Disease Activity Monitoring

• Monitor disease activity every 1-3 months using composite measures (tender/swollen joint counts, patient/physician global assessments, ESR/CRP) 4, 7.
• Target clinical remission or lowest disease activity possible 4, 7.
• Note that disease activity of most rheumatic diseases tends to decrease after hemodialysis initiation, but may still flare requiring ongoing immunosuppression 1.

Critical Pitfalls to Avoid

• Never use methotrexate in ESRD - it is renally eliminated and causes severe toxicity 3, 1.
• Never prescribe NSAIDs for symptomatic relief - the standard arthritis recommendation does not apply to ESRD patients 4, 5, 2.
• Do not assume biologics need dose reduction - rituximab and belimumab specifically do not require adjustment 1.
• Recognize that diabetes (33.5%) and hypertension (30.6%) are the most common causes of ESRD in RA patients, not the arthritis itself 6.

Multidisciplinary Collaboration

• Collaboration between rheumatology and nephrology is essential for optimal management of arthritis in ESRD 1.
• Refer to rheumatology if multiple joints become involved or if inflammatory markers are elevated despite treatment 8, 7.
• Consider palliative care consultation for patients with limited life expectancy or severe comorbidities who may not benefit from aggressive immunosuppression 9.