What is the renal manifestation of multiple myeloma called?

Light Chain Cast Nephropathy: The Primary Renal Manifestation of Multiple Myeloma

The renal manifestation of multiple myeloma is called light chain cast nephropathy (LCCN), which is the most common form of renal damage in multiple myeloma, accounting for approximately 90% of cases 1.

Pathophysiology of Light Chain Cast Nephropathy

• LCCN occurs when excess monoclonal free light chains (FLCs) produced by myeloma cells interact with Tamm-Horsfall protein in the loop of Henle, forming obstructive casts that damage renal tubules 1, 2
• The light chain casts obstruct the tubules causing rupture, which induces an inflammatory response, further injuring the tubules 1
• Additional injury mechanisms include:
  • Production of hydrogen peroxide by the FLCs 1
  • Activation of inflammatory pathways including NF-κB and ASK1 1
  • Induction of apoptosis, inflammation, and tubulointerstitial fibrosis 1

Clinical Significance

• LCCN is a leading cause of acute kidney injury (AKI) in multiple myeloma patients 1
• It is defined as a myeloma defining event (MDE) by the International Myeloma Working Group 1
• Renal impairment imposes the greatest impact on overall survival among all myeloma defining events (hyperCalcemia, Renal impairment, Anemia, and Bone lytic lesions) 1
• Short-term mortality remains significantly higher in patients with LCCN, especially if renal failure is not reversed 1

Risk Factors and Predictors

• Serum FLC concentrations >80-200 mg/dL significantly increase the risk of AKI 1, 2
• AKI is rare when serum FLC concentration is <50 mg/dL 1
• High urinary FLC excretion appears necessary for AKI to occur 1
• Incidence of AKI at diagnosis is 16-31% when measured by serum creatinine >1.4 mg/dL 1

Diagnosis

• Renal impairment in MM is defined by an eGFR of <40 mL/min/1.73 m² or a serum creatinine >2 mg/dL 1
• Diagnostic workup should include:
  • Serum creatinine, electrolytes, estimated GFR 2
  • 24-hour urine collection 2
  • Serum protein electrophoresis and serum free light chain measurement 2
• Renal biopsy may not be necessary if proteinuria predominantly consists of light chains with high serum FLC levels but should be considered when etiology is unclear 2, 3

Management Principles

• Recovery of renal function requires rapid and significant reduction of the involved serum free light chain 1
• A minimum reduction of 50-60% of serum FLC is associated with renal recovery 1
• Bortezomib-based regimens should be initiated immediately as they do not require dose adjustment in renal impairment 2, 4
• Target >50% reduction of involved FLC from baseline and an FLC level <50 mg/dL by the end of cycle 1 2
• For patients with FLC >150 mg/dL, extracorporeal therapies like plasma exchange or high cut-off hemodialysis should be considered 2

Prognosis

• Recovery of kidney function reverses the negative impact on overall survival 1
• Factors associated with renal recovery include lower baseline creatinine and ≥50% drop in serum FLC levels 2
• Recent data shows excellent 6-month renal recovery without early mortality in LCCN patients treated with modern anti-myeloma therapies 4

Other Renal Manifestations in Multiple Myeloma

• FLCs can also cause Fanconi's syndrome, characterized by failure of the reabsorptive capacity of proximal renal tubules 1
• Deposition of monoclonal light chains can lead to amyloid light chain (AL) amyloidosis or light chain deposition disease (LCDD) 1
• Rare cases of combined cast nephropathy, amyloidosis, and LCDD have been reported 5

Light chain cast nephropathy represents a medical emergency requiring prompt intervention to prevent irreversible kidney damage and improve survival outcomes in multiple myeloma patients.