# Student Handout: Hematologic Malignancies & Kidney Disease

> **Learning objective:** Understand renal complications of blood cancers, focusing on myeloma kidney, MGRS, lymphoma/leukemia effects, and stem cell transplant-related nephropathy

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## Overview

Blood cancers have unique mechanisms of causing kidney disease due to high protein production, immune dyscrasia, and treatment-related complications. This handout covers the major entities:

1.  **Multiple Myeloma** → Myeloma kidney (cast nephropathy)
2.  **Monoclonal Gammopathy of Renal Significance (MGRS)**
3.  **Lymphomas** → Immune complex disease, TLS
4.  **Acute Leukemias** → TLS, blast lysis
5.  **Stem Cell Transplantation** → TLS, thrombotic complications

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## MULTIPLE MYELOMA & MYELOMA KIDNEY

### 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

| Feature | Details |
|----|----|
| **Acute presentation** | Rapid ↑ Cr (days to weeks); oliguric AKI possible |
| **Chronic** | Progressive CKD over months; proteinuria \<1 g/day (not nephrotic) |
| **Labs** | ↑ Cr, ↑ BUN, normal anion gap often; abnormal SPEP/UPEP |
| **Urinalysis** | **Crystal-like casts**, epithelial cells; NOT typically hematuria/RBC casts |
| **Light chains** | Serum free light chain ratio abnormal (κ/λ \>100 or \<0.01) |

### Diagnosis

**The gold standard: Kidney biopsy**

| Modality | Finding |
|----|----|
| **Light microscopy** | **Fractured light-chain casts**, often with an associated inflammatory reaction; typically in distal tubules and collecting ducts |
| **Electron microscopy** | Cast ultrastructure varies; interpret with light microscopy and light-chain staining |
| **Immunofluorescence** | Casts stain with **κ or λ light chain antibodies** (usually one predominates) |

**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:** Correct depletion with fluid therapy tailored to urine output, cardiac status, and repeated assessment for overload.
2.  **Diuretics:** Do not use furosemide routinely to force urine flow in cast nephropathy. Treat congestion only for a separate clinical indication.
3.  **Alkalinization:** Routine urine alkalinization has no demonstrated renal recovery benefit in myeloma-related renal impairment.
4.  **Avoid contrast, NSAIDs:** ↓ GFR further
5.  **Anti-myeloma therapy:** Prompt initiation of chemotherapy (bortezomib, lenalidomide, etc.) → ↓ light chain production → Resolution of casts

[IMWG recommendations for myeloma-related renal impairment (2023).](https://pubmed.ncbi.nlm.nih.gov/37414019/)

**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

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## MGRS (Monoclonal Gammopathy of Renal Significance)

### What is MGRS?

A B-cell or plasma-cell clone produces a nephrotoxic monoclonal immunoglobulin, with related kidney injury, without otherwise meeting hematologic criteria for clone-directed treatment. Kidney injury can nevertheless require treatment. A marrow plasma-cell cutoff alone does not define MGRS.

### Pathology Patterns

Examples include AL amyloidosis, monoclonal immunoglobulin deposition disease, proliferative GN with monoclonal deposits, and light-chain proximal tubulopathy. Lesions may affect glomeruli, tubules, vessels, or several compartments. Some associated lesions lack monoclonal deposits.

### Clinical Presentation

Proteinuria, hematuria, tubular dysfunction, AKI, or CKD may occur. Normal blood counts do not establish or exclude MGRS.

### Diagnosis

Integrate kidney biopsy, immunofluorescence and ultrastructure with serum/urine immunofixation, free light chains interpreted in kidney context, and hematologic evaluation. A monoclonal band alone does not prove renal causation.

### Management

Coordinate renal and hematologic expertise for lesion- and clone-specific treatment, supportive care, and longitudinal monitoring.

[IKMG consensus: definition and evaluation of MGRS (2019).](https://pubmed.ncbi.nlm.nih.gov/30510265/)

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## LYMPHOMA & KIDNEY DISEASE

### Types & Mechanisms

| Lymphoma Type | Renal Complication | Mechanism |
|----|----|----|
| **Hodgkin Lymphoma** | Immune complex GN, FSGS | Circulating immune complexes, nephrotic syndrome common |
| **Non-Hodgkin (Burkitt)** | **TLS** (high risk), immune complex GN | Massive cell turnover → hyperkalemia, hyperuricemia, AKI |
| **Non-Hodgkin (Indolent)** | Cryoglobulinemia, MPGN | Monoclonal Ig deposition similar to MGRS |
| **Post-transplant lymphoproliferative** | Glomerular disease, interstitial nephritis | EBV-driven; responds to reduction of immunosuppression |

### 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

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## ACUTE LEUKEMIA & KIDNEY DISEASE

### Mechanisms

| Complication | Details |
|----|----|
| **TLS** | **HIGH RISK** — Acute leukemias have highest TLS incidence; rapid cell death post-chemo → hyperkalemia, hyperuricemia |
| **Leukostasis** | WBC obstruction of renal vessels → AKI (rare but severe) |
| **Uric acid nephropathy** | Massive purine load from blasts → Urate crystal obstruction |
| **Blast infiltration** | Direct renal parenchymal infiltration (rare) |

### 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:** Assess TLS risk and select prophylaxis, hydration, and monitoring accordingly; rasburicase is appropriate for selected high-risk patients with attention to G6PD safety.

### Management

- **Prevention:** Before therapy, assess disease, treatment, and patient-specific TLS risk. Select urate-lowering treatment and hydration accordingly.
- **Monitor:** Baseline K+, uric acid, FLC; q6h labs during first 48 h
- **Kidney replacement therapy:** Escalate refractory hyperkalemia, severe acidosis, fluid overload, or uncontrolled metabolic complications. Ongoing lysis and falling urine output warrant early nephrology involvement; uric acid alone is not an automatic dialysis trigger.
- **Duration:** Usually 5–7 days of intensive monitoring

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[BSH guideline: TLS risk assessment, prevention, and kidney support (2025).](https://pubmed.ncbi.nlm.nih.gov/40903841/)

## STEM CELL TRANSPLANTATION (SCT) & KIDNEY DISEASE

### Timing & Complications

| Phase | Complication | Mechanism |
|----|----|----|
| **Pre-transplant conditioning** | AKI from chemotherapy (TLS-like) | Myeloablative regimen toxicity |
| **Engraftment (days 0–30)** | Acute kidney injury, sepsis | Infection, medication nephrotoxicity (aminoglycosides, amphotericin) |
| **Early post-transplant (months 1–3)** | Calcineurin inhibitor (CNI) nephrotoxicity | Cyclosporine or tacrolimus → ↓ GFR, HTN |
| **Late post-transplant (\>3 months)** | Chronic kidney disease, GVHD-related | CNI toxicity, chronic GVHD, infections |

### 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)

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## Clinical Integration

### Red Flags

- ✗ Myeloma patient with rapid ↑ Cr → Urgent evaluation for cast nephropathy; assess perfusion and congestion while arranging disease-directed treatment.
- ✗ High-grade lymphoma with rising potassium, phosphate, uric acid, or AKI → Evaluate urgently for TLS.
- ✗ 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

| Scenario | Urgent Actions |
|----|----|
| **Suspected myeloma kidney** | Urgent hematology/nephrology care, individualized fluids, prompt antimyeloma treatment, and biopsy when indicated; no routine forced diuresis or urine alkalinization. |
| **High-grade lymphoma starting chemo** | Risk-based TLS prophylaxis, G6PD-aware rasburicase selection, individualized hydration, and monitored electrolytes and renal function. |
| **AML diagnosis with WBC \>100k** | High-risk TLS assessment, appropriate prophylaxis, hydration and monitoring; escalate critical-care and kidney support according to clinical need. |
| **SCT day +3 with AKI** | Hold nephrotoxic drugs, optimize hydration status, check uric acid/K+, consider RRT if worsening |

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## Key Clinical Pearls

✓ **Myeloma kidney = Casts** — Crystal-like tubular casts on biopsy; light chain staining confirms ✓ **MGRS = Biopsy essential** — Distinguishes monoclonal from polyclonal immunoglobulin ✓ **Lymphoma TLS = Highest risk** — Burk lymphoma + bulky disease = ICU monitoring ✓ **AML \> ALL for volume** — But ALL \> AML for TLS risk per cell chemosensitivity ✓ **SCT AKI multifactorial** — Chemo + drugs + infection; needs systematic evaluation ✓ **Early treatment = Better outcomes** — Prompt chemotherapy resolves myeloma kidney; delays worsen prognosis

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## Related Content

**Onconephrology Hub:** - Hematologic Malignancies & Kidney Disease — Comprehensive pathology and extended management - Tumor Lysis Syndrome — Detailed TLS pathophysiology and management

**Cross-Reference Student Handouts:** - Student Handout: Tumor Lysis Syndrome — TLS diagnosis, risk stratification, management - Student Handout: AKI Staging — General AKI assessment framework - Glomerular Disease Algorithm — MGRS differential from primary GN

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## References

- [Dimopoulos MA, et al. Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group.](https://pubmed.ncbi.nlm.nih.gov/37414019/) Lancet Oncology. 2023.
- [Leung N, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group.](https://pubmed.ncbi.nlm.nih.gov/30510265/) Nature Reviews Nephrology. 2019.
- [Chan YLT, et al. British Society for Haematology updated guidelines for the diagnosis and management of tumour lysis syndrome in adults and children with haematological malignancies: A focus on patient safety.](https://pubmed.ncbi.nlm.nih.gov/40903841/) British Journal of Haematology. 2025.
- [Wanchoo R, et al. Renal Toxicities of Novel Agents Used for Treatment of Multiple Myeloma.](https://pubmed.ncbi.nlm.nih.gov/27654928/) Clinical Journal of the American Society of Nephrology. 2017.
- [Kidney injury and disease in patients with haematological malignancies.](https://pubmed.ncbi.nlm.nih.gov/33785910/) Nature Reviews Nephrology. 2021.

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**Study Tips:** - **Myeloma kidney:** Fractured casts on kidney biopsy with restriction to one light chain (κ or λ), interpreted with the full pathology findings - **MGRS:** Link the kidney lesion to the nephrotoxic clone; no universal marrow cutoff - **Lymphoma:** Think TLS for high-grade, cryoglobulinemia for indolent - **AML/ALL:** TLS prevention depends on disease, treatment, and patient risk - **SCT:** Triplet problem — chemo + drugs + infection; manage all three

*Created: 2026-02-28*


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