Multiple Myeloma associated renal injury
Multiple Myeloma (MM) is a plasma cell dyscrasia associated with malignant plasma cells producing excessive monoclonal proteins (immunoglobulin and free light chain).
Renal injury is commonly associated with Multiple Myeloma and has high mortality rates. More than 50% of cases of MM present with renal involvement.
Types of renal injury (monoclonal protein-associated injury) in Multiple Myeloma
- Cast Nephropathy
- Tubular defects
- Glomerular Deposition Disease
- Light Amyloidosis
Tubular Defects
Normal Plasma Cells produce the usual amount of Free light chains (FLCs) & Immunoglobulins (Ig) → FLCs & Ig in Ultrafiltrates→ Proximal Tubular Cells with Megalin/cubilin Receptors endocytose FLCs (Megalin/cubilin mediated endocytosis of FLCs) → Almost all endocytosed FLCs are degraded in the lysosome of the Proximal tubular cell.
In Multiple Myeloma
Plasma Cell Clones → Increased immunoglobulins and Free light chain (FLC) production → Increased FLCs and Immunoglobulins in Ultrafiltrate → FLCs are endocytosed by proximal tubular cells with the help of the cubilin-megalin complex → Excessive Endocytosis → Tubular Cells unable to degrade endocytosed FLCs →Stimulates → Tubular Cell Apoptosis → Proximal Tubulopathy (Fanconi Syndrome) and other tubular defects (depending upon the part involved)
Increased FLCs and Immunoglobulins in Ultrafiltrate → Activation of Pro-inflammatory pathways and Reactive oxidative species → Epithelial-Mesenchymal Transition → Progressive Renal Fibrosis → Interstitial Fibrosis → Tubulointerstitial nephritis
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Cast Nephropathy
Increased FLCs and Immunoglobulins in Ultrafiltrate → FLCs bind with Tamm-Horsfall Protein (THP) → Cast Formation → Tubular Obstruction →Giant Cell Reaction →Tubular Rupture due to increased backpressure → Ultrafiltrate leakage into interstitium →Activation of Pro-inflammatory pathways and Reactive oxidative species → Interstitial fibrosis → Tubulointerstitial nephritis
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Glomerular Deposition Disease (GDD)
Plasma cell dyscrasias are associated with dysproteinemia and the overproduction of monoclonal proteins. And their parts (light chain/heavy chain) cause injury in various parts of the kidney. This broad group of patients presenting with proteinuria and other renal dysfunction comes under the category of glomerular deposition disease. The deposition of serum amyloid A protein fragments associated with chronic inflammatory conditions (Rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) are also included in GDD.
Risk factor predisposing to Acute renal failure (ARF)
- Hypovolemia
- Loop diuretics
- Sepsis
- Hypercalcemia
- NSAIDs
- Radiographic Contrast Media
Diagnosis
Clinical presentation and laboratory values
- Signs and Symptoms of Multiple Myeloma – Anemia, Bone pain, Hypercalcemia, and Hypergammaglobulinemia
- Urine Dipstick is negative, but the Urine Spot test shows increased Protein - Highly suggestive of the presence of Free light chains / Bence-Jones proteins (BJP) in the urine.
- Protein Electrophoresis of Serum and Urine shows a Monoclonal band
- Immunofixation shows Monoclonal Band.
- Cast nephropathy and tubular defect cases have proteinuria but no albuminuria. The glomerular basement membrane (GBM) is intact, so it doesn't allow albumin to pass.
- Glomerular deposition disease and light chain amyloidosis have proteinuria and albuminuria because the glomerular basement membrane is damaged.
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Treatment
Manage precipitating factors
Discontinue Nephrotoxic agents
Treat underlying plasma cell dyscrasias (Chemotherapy)
Reduce the burden of monoclonal proteins
- Plasmapheresis
- Plasma exchange
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