Can multiple myeloma cause kidney disease?

Multiple Myeloma and Kidney Disease

Yes, multiple myeloma directly causes kidney disease through several mechanisms, with light chain cast nephropathy being the most common form of renal damage, occurring in approximately 90% of myeloma patients with kidney involvement. 1

Mechanisms of Kidney Damage in Multiple Myeloma

Light Chain Cast Nephropathy

• Overproduced monoclonal free light chains (FLCs) interact with Tamm-Horsfall protein in the loop of Henle to form casts that obstruct renal tubules 1
• These casts cause tubular rupture, triggering an immune response that further damages the tubules 1
• Tubular obstruction leads to progressive interstitial inflammation and fibrosis 1

Direct Tubular Toxicity

• High concentrations of FLCs directly injure proximal tubular cells through:
  • Activation of redox pathways with increased expression of NFκB and MAPK 1
  • Production of hydrogen peroxide 1
  • Activation of inflammatory and profibrotic cytokine pathways 1

Other Mechanisms of Renal Damage

• Light chain deposition disease (LCDD): monoclonal light chains deposit in kidney tissue 1
• AL amyloidosis: light chains form amyloid fibrils that deposit in organs including kidneys 1
• Fanconi syndrome: FLCs impair proximal tubule reabsorptive capacity, causing glucosuria, aminoaciduria, and hypophosphatemia 1

Risk Factors and Predictors of Kidney Injury

• Serum FLC concentrations >50 mg/dL significantly increase risk of acute kidney injury 1, 2
• Risk dramatically increases when FLC concentration exceeds 80-200 mg/dL 1
• High urinary FLC excretion appears necessary for AKI development 1
• Contributing factors include dehydration, hypercalcemia, infections, and nephrotoxic medications (particularly NSAIDs) 1

Epidemiology and Impact

• Renal impairment occurs in 25-50% of multiple myeloma patients during their disease course 3, 4
• Approximately 10% of myeloma patients have advanced kidney disease requiring dialysis at presentation 4
• Severe renal impairment significantly reduces overall survival 3, 4
• Recovery of kidney function reverses the negative impact on survival 1

Diagnosis and Assessment

• Renal impairment in MM is defined by eGFR <40 ml/min/1.73 m² or serum creatinine >2 mg/dL 1
• The IMWG recommends using the MDRD equation for estimating GFR in MM patients 1
• Kidney biopsy may be necessary when the cause of renal insufficiency cannot be clearly attributed to myeloma 5
• Serum free light chain assay is essential for diagnosis and monitoring 2, 5

Management Approach

• MM patients with renal impairment should be considered a medical emergency 1

• Treatment should focus on:

  • Adequate hydration (at least 3 liters daily) 1
  • Urine alkalinization 1
  • Treatment of hypercalcemia if present 1
  • Discontinuation of nephrotoxic medications 1
  • Prompt anti-myeloma therapy to rapidly reduce FLC levels 1

• Bortezomib-based regimens are recommended as first-line therapy for MM patients with renal impairment as they:

  • Do not require dose adjustment in renal failure 1, 5
  • Are not nephrotoxic 1
  • Can significantly improve renal recovery rates 1, 6

Monitoring and Prognosis

• A minimum reduction of 50-60% of serum FLC is associated with renal recovery 1
• Achieving serum FLC concentration <50 mg/dL by the end of cycle 1 of chemotherapy improves renal recovery 1
• Earlier FLC reduction (by day 12 vs. day 21) is associated with better kidney function recovery 1
• Regular monitoring of renal function and serum FLC levels is essential 5

Clinical Pearls and Pitfalls

• Renal impairment alters FLC concentration due to impaired clearance, affecting interpretation of results 5
• Normal kappa:lambda ratio is 0.26-1.65, but in severe renal impairment (CKD stage 5), the normal ratio can rise to 0.34-3.10 2, 5
• High-dose therapy and autologous stem cell transplantation can be considered for selected patients with renal impairment under age 65 7
• Kidney transplantation remains an option to consider in carefully selected patients with improved myeloma control 4, 6