Epidemiology

• Incidence: ~200,000 new cases/year in US; 10–20 cases/million/year
• Renal involvement: 20–50% of patients at diagnosis have AKI or baseline CKD
• Clinical significance: Renal impairment = adverse prognostic factor; impacts chemotherapy dosing & prognosis

Pathophysiology of Myeloma Kidney

The mechanism (step-by-step):

1. Clonal plasma cell proliferation → Produces large amounts of monoclonal immunoglobulin (usually IgG or IgA)
2. Free light chain production → Clones make excess κ or λ light chains (>20 mg/dL)
3. Glomerular filtration → Small light chains (22 kDa) filtered by glomerulus
4. Proximal tubule uptake → Light chains reabsorbed via endocytosis
5. Tubular cast formation → Light chains precipitate with Tamm-Horsfall protein (THP) to form refractory casts
6. Tubular obstruction → Casts occlude tubular lumen → AKI
7. Interstitial inflammation → Lytic lesions trigger innate immunity
8. Result: Acute tubular necrosis + interstitial nephritis

Clinical Presentation

Diagnosis

The gold standard: Kidney biopsy

Supporting labs: - SPEP: M-spike (monoclonal paraprotein) - UPEP: Bence Jones protein (free light chains in urine) - FLC assay: ↑ Involved light chain; abnormal ratio

Management of Acute Myeloma Kidney

Medical Management:

1. Hydration: Aggressive IV hydration (3–4 L daily) to ↑ GFR and dilute tubular fluid → ↓ cast precipitation
2. Loop diuretic: Furosemide to maintain high urine flow (200–300 mL/h goal)
3. Alkalinization: Sodium bicarbonate to alkalinize urine (target urine pH 6.5–7) — inhibits light chain precipitation
4. Avoid contrast, NSAIDs: ↓ GFR further
5. Anti-myeloma therapy: Prompt initiation of chemotherapy (bortezomib, lenalidomide, etc.) → ↓ light chain production → Resolution of casts

Renal Replacement Therapy: - Indications: Oliguric renal failure unresponsive to hydration, severe hyperkalemia, fluid overload - Modality: CRRT or hemodialysis (some argue CRRT preferred because continuous) - Outcome: 30–50% of oliguric patients recover renal function with supportive care + chemotherapy

Prognosis: - Early treatment: ~50–70% recover renal function if caught early - Delayed treatment: ~10–20% recover if AKI prolonged - Late diagnosis: Often results in permanent dialysis dependence

Long-Term Monitoring

• Serial Cr, FLC assay (response to therapy reflected in ↓ FLC)
• Suppress light chain production aggressively
• Avoid nephrotoxic drugs
• ACEi/ARB if proteinuria >1 g/day

What is MGRS?

Definition: Kidney disease caused by monoclonal immunoglobulin OR light chains deposited in glomeruli in the absence of overt hematologic malignancy. Usually a precursor to lymphoproliferative disorder.

Key distinction: MGRS ≠ Myeloma (no plasma cell clones >10% in marrow); MGRS is a renal-dominated disease

Pathology Patterns

Clinical Presentation

• Proteinuria: 0.5–5 g/day (often >1 g, sometimes nephrotic)
• Hematuria: Often present (RBC casts, dysmorphic RBCs)
• Renal function: Normal to impaired; variable AKI vs CKD
• Blood counts: Normal (no cytopenias; distinguishes from frank malignancy)

Diagnosis

Kidney biopsy is essential: - Light microscopy: GN pattern (MPGN, FSGS, or linear deposits) - Immunofluorescence: Monoclonal Ig or light chain deposition (κ or λ only, not polyclonal) - Electron microscopy: Confirms pattern (amyloid fibrils, electrodense deposits, etc.)

Supporting labs: - SPEP/UPEP: Small M-spike or absence thereof - FLC assay: Usually abnormal ratio (elevated involved light chain) - Bone marrow: <10% plasma cells (by definition)

Management

1. Treat underlying clone:
   • Chemotherapy if light chain/myeloma-like (bortezomib, lenalidomide)
   • Rituximab if B-cell proliferation
2. Supportive: ACEi/ARB for renal protection, BP control
3. Monitor renal function & proteinuria closely
4. Long-term surveillance: 10–20% progress to frank myeloma over 5 years

Types & Mechanisms

Clinical Features

High-grade (Burkitt, aggressive): - Peak risk: TLS (see prior handout) - AKI common (20–30% of patients) - Monitors: K+, uric acid, PO4 closely

Indolent (Low-grade): - Gradual proteinuria, hematuria - CKD progression over years - May have cryoglobulinemia (RNP, C4 ↓, Cr, mixed cryoglobulins)

Management

• Chemotherapy → Cell destruction, monitor for TLS
• Supportive: Hydration, rasburicase (if high risk)
• Renal-specific: ACEi/ARB, BP control
• Monitor: Renal function, UA, electrolytes q 1–2 weeks during/after chemotherapy

Mechanisms

AML-Specific

• Higher TLS risk if WBC >100,000 and high LDH
• Bladder involvement: Hemorrhagic cystitis (from chemotherapy)
• AKI incidence: 20–50% of hospitalized AML patients

ALL-Specific

• Highest TLS risk — ALL cells most chemosensitive
• Risk factors: Age <10 or >50, WBC >100,000, bulky disease, elevated LDH
• Management: Rasburicase prophylaxis, aggressive hydration, ICU monitoring (see TLS handout)

Management

• Prevention: Rasburicase, aggressive hydration BEFORE chemo starts
• Monitor: Baseline K+, uric acid, FLC; q6h labs during first 48 h
• RRT threshold: K+ >6.5 OR uric acid >8 with AKI OR anuria → Dialysis
• Duration: Usually 5–7 days of intensive monitoring

Timing & Complications

Acute Kidney Injury in SCT

Incidence: 40–50% of SCT patients develop AKI; 10–15% require dialysis

Causes: - Chemotherapy nephrotoxicity (conditioning regimens contain high-dose cyclophosphamide, busulfan) - Sepsis (immune reconstitution not complete; infection risk high) - Aminoglycoside antibiotics (empiric for fever) - Amphotericin B (fungal prophylaxis) - Calcineurin inhibitors (graft-versus-host disease prophylaxis) - TLS (from rapid leukemic cell kill if allogeneic transplant for hematologic malignancy)

Chronic Kidney Disease in SCT

Long-term renal outcomes: - 5-year CKD incidence: 20–30% - Risk factors: High-dose conditioning, older age, GVHD, multiple nephrotoxic drugs, TBI (total body irradiation) - Mechanism: CNI toxicity (cyclosporine/tacrolimus) → Hyaline arteriosclerosis, glomerulosclerosis, tubular atrophy

Management Strategies

Prevention: - Minimize CNI exposure; use lowest effective dose - Alternate CNIs with sirolimus if tolerated - Avoid concurrent nephrotoxic drugs (NSAIDs, contrast agents) - Monitor BP closely (control with ACEi/ARB)

Monitoring: - Baseline renal function before conditioning - Daily Cr during conditioning & early engraftment (first 30 days) - q 1–2 week labs during months 1–3 - q 1–3 month labs long-term (look for CKD progression)

Management of AKI: - Discontinue nephrotoxic drugs if possible - Hydration (unless fluid overloaded from sepsis/capillary leak) - RRT if oliguric or severe electrolyte derangements - Empiric antibiotics with renal dosing

Management of CKD: - ACEi/ARB to slow progression - BP target <130/80 (2025 AHA/ACC, ADA); KDIGO 2021 suggests systolic <120 on standardized measurement - Reduce CNI to lowest dose; consider switch to alternative agent - Avoid NSAIDs - Monitor for bone disease (CKD-MBD from chronic GFR reduction)

Red Flags

• ✗ Myeloma patient with rapid ↑ Cr → Consider myeloma kidney; start aggressive hydration immediately
• ✗ High-grade lymphoma + low K+/uric acid → Think TLS; prophylactic rasburicase
• ✗ AML with WBC >100k → Highest TLS risk; ICU-level monitoring
• ✗ SCT day +5 with ↑ Cr → Could be chemo, sepsis, CNI toxicity, or TLS overlap

Key Interventions by Scenario