In a patient with known multiple myeloma who now has an elevated erythrocyte sedimentation rate and chronic kidney disease, what is the most urgent management priority and recommended treatment regimen?

Management of Multiple Myeloma with Elevated ESR and Chronic Kidney Disease

The most urgent priority is immediate initiation of bortezomib-based chemotherapy combined with aggressive IV hydration to rapidly reduce serum free light chains and prevent irreversible renal damage. 1, 2

Immediate Management Priorities

Treat as Medical Emergency

• Multiple myeloma patients presenting with renal impairment must be considered a medical emergency requiring prompt intervention to prevent progression to dialysis-dependent end-stage renal disease 1
• The elevated ESR reflects high disease activity and inflammatory burden, which correlates with increased free light chain production driving the renal injury 1

Aggressive Hydration Protocol

• Establish IV access immediately and begin normal saline at 150-200 mL/hour to achieve urine output >100 mL/hour 2, 3
• High fluid intake alone is insufficient—it must be combined with prompt anti-myeloma therapy 1
• Correct hypercalcemia if present, as this exacerbates renal dysfunction 1

Tumor Lysis Syndrome Prophylaxis

• Administer rasburicase 0.2 mg/kg IV as a single dose (or 3-6 mg fixed dose) before initiating chemotherapy in patients with high tumor burden, renal insufficiency, or elevated LDH 2
• Multiple myeloma patients with CKD are at significant risk for tumor lysis syndrome due to approximately 30% having renal insufficiency at diagnosis 2

First-Line Chemotherapy Regimen

Bortezomib-Based Therapy (Preferred)

Bortezomib-based regimens are the foundation of treatment for MM patients with renal impairment because they do not require dose adjustment even in dialysis-dependent patients 4

• Recommended regimen: Bortezomib 1.3 mg/m² subcutaneously on days 1,8,15,22 plus dexamethasone 1, 2
• Bortezomib has no nephrotoxic potential and rapidly reduces serum free light chains, which is critical for renal recovery 1, 4
• Early reduction of serum free light chain concentration directly correlates with kidney function recovery 5

Dose Adjustments for Other Agents

Lenalidomide requires careful dose reduction based on creatinine clearance: 1

• CrCl 30-60 mL/min: 10 mg daily
• CrCl <30 mL/min without dialysis: 15 mg every other day
• CrCl <30 mL/min on dialysis: 5 mg daily after dialysis

Thalidomide can be used without dose adjustment in renal impairment but monitor for hyperkalemia 4, 6

Critical Pitfall to Avoid

Do not delay chemotherapy for extended periods while attempting conservative measures alone—this worsens outcomes, particularly in patients with renal involvement 2. The pathophysiology involves free light chains forming tubular casts with Tamm-Horsfall protein, causing tubular obstruction and progressive interstitial inflammation 1. Time is kidney function.

Renal Replacement Therapy Considerations

• Initiate hemodialysis for severe AKI or end-stage renal disease 4, 5
• Use high flux or high cut-off membranes because routine hemodialysis cannot effectively remove serum free light chains 4, 5
• Plasmapheresis is recommended for patients with hyperviscosity syndrome or cast nephropathy presenting with AKI, as it may increase dialysis independence 4
• However, the role of therapeutic plasma exchange remains controversial for routine use 1

Monitoring Renal Function

• Use MDRD or CKD-EPI formulas to estimate GFR, not serum creatinine alone 1, 4
• The CKD-EPI-cystatin C equation provides independent prognostic value and more sensitive detection of renal impairment 1
• Stage renal injury according to 2013 KDIGO CKD guidelines 4

Transplant Eligibility

High-dose melphalan (200 mg/m²) with autologous stem cell transplantation remains standard of care for eligible patients, even those with CKD 4, 6

• Should not be withheld from patients with CKD, even those on dialysis 6
• Treatment can improve renal disease, especially if started early 6
• Consider more prudently in patients with severe renal insufficiency (GFR <30 mL/min) 4

Supportive Care

• Long-term bisphosphonates to reduce skeletal-related events, but use with caution as they can cause renal failure in CKD patients 2, 6
• Monitor renal function mandatorily when using bisphosphonates 1
• Maintain adequate hydration of at least 3 liters daily or 2 L/m²/day 4

Diagnostic Workup While Initiating Treatment

• Serum free light chain assay with kappa/lambda ratio (though sensitivity/specificity decreased in renal failure) 7, 8
• 24-hour urine protein electrophoresis and immunofixation 3, 9
• Bone marrow biopsy to quantify plasma cell infiltration 2
• FISH for high-risk cytogenetics: t(4;14), del(17p), t(14;16) 2