Patterns of kidney injury
1. LIGHT CHAIN CAST NEPHROPATHY ('myeloma kidney'):
- Free monoclonal light chains precipitate with Tamm-Horsfall protein in distal tubule
- Causes obstruction, tubular injury, interstitial inflammation
- Presents as AKI with bland or near-bland urine (no significant albuminuria)
- Almost always in active multiple myeloma with very high SFLC (>500 mg/L)
2. Al Amyloidosis
- Misfolded light chain (more often lambda) forms amyloid fibrils
- Nephrotic-range proteinuria, often with preserved eGFR initially
- Cardiac, hepatic, autonomic involvement
- Refer to UK National Amyloidosis Centre, Royal Free
3. Light Chain Deposition Disease (Lcdd)
- Granular (non-fibrillar) light chain deposits along basement membranes
- Usually kappa
- Nephrotic-range proteinuria + CKD
4. Monoclonal Immunoglobulin MPGN / Pgnmid / C3gn With Monoclonal Gammopathy
- Various glomerular patterns driven by a small B-cell or plasma cell clone
- Typically MGRS rather than overt myeloma
5. Tubulopathy
- Fanconi syndrome (especially kappa light chains)
- Proximal tubular dysfunction: glycosuria, aminoaciduria, hypophosphataemia, RTA
6. CRYOGLOBULINAEMIC GN — type I (monoclonal):
- MPGN pattern
- Often associated with Waldenström or other lymphoplasmacytic disorders
7. HYPERCALCAEMIA + NEPHROCALCINOSIS:
- Contributes to AKI in active myeloma
When to suspect and how to investigate
RED FLAGS — always send a paraprotein screen:
- Unexplained AKI in adult >50
- CKD with anaemia disproportionate to eGFR
- Bone pain, lytic lesions, fractures
- Hypercalcaemia
- Nephrotic-range proteinuria + bland sediment
- Unexplained Fanconi syndrome
- Recurrent infections
First-line Bloods
- Serum protein electrophoresis + immunofixation
- Serum free light chains (SFLC) — Freelite assay; kappa:lambda ratio is key
- Urine protein electrophoresis + immunofixation (Bence Jones protein)
- 24h urine — quantify Bence Jones
- FBC, calcium, albumin, LDH, beta-2 microglobulin
- Hepatitis screen, HIV
- NT-proBNP and troponin (cardiac amyloid screen)
Imaging / Marrow
- Whole-body MRI or low-dose CT (skeletal survey is outdated)
- Bone marrow biopsy with flow cytometry + cytogenetics (FISH)
Kidney Biopsy
- Strongly recommended for AKI of unclear cause with paraproteinaemia, or for any MGRS suspicion
- Adequate Congo red staining, immunofluorescence with all chains (IgG, IgA, IgM, kappa, lambda, C3, C1q), electron microscopy
- Submit to a reference renal pathology centre for amyloid typing if needed (mass spectrometry)
Diagnostic Criteria Reminder
- Multiple myeloma: clonal plasma cells ≥10% + a CRAB feature or SLiM (sFLC ratio ≥100, ≥60% marrow plasma cells, or focal MRI lesion ≥5 mm)
- MGUS: clonal plasma cells <10%, M-protein <30 g/L, no CRAB — but can become MGRS if causing kidney damage
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Treatment
Urgent Supportive Care
- Stop NSAIDs and other nephrotoxins
- Avoid iodinated and gadolinium contrast
- IV hydration to ~3 L/day if no fluid overload — aim urine output >100 ml/h
- Treat hypercalcaemia: IV fluids, IV bisphosphonate (zoledronate dose-adjust for eGFR; denosumab if very low eGFR)
- Treat hyperuricaemia and tumour lysis risk before chemotherapy
- Renal replacement therapy if needed
CLONE-DIRECTED THERAPY (joint with haematology):
- Bortezomib-based induction is standard — VTD (bortezomib, thalidomide, dexamethasone) or VCD (bortezomib, cyclophosphamide, dexamethasone)
- Daratumumab now routinely added (Dara-VCD, Dara-VTD, or Dara-VRD) in line with NICE TA recommendations
- Lenalidomide-based regimens — dose-adjust for eGFR; cytopenias common
- Autologous stem cell transplant (ASCT) in fit patients after induction
- For relapsed/refractory: carfilzomib, pomalidomide, isatuximab, selinexor, CAR-T (idecabtagene, ciltacabtagene)
Mgrs-specific
- Treatment justified even with small clone if kidney damage proven on biopsy
- Plasma cell clone: bortezomib-based or daratumumab-based
- B-cell / lymphoplasmacytic clone: rituximab-based
- Treat to renal response and clone control, not standard 'CR' criteria
Dialysis
- Standard renal replacement therapy when indicated
- HIGH CUT-OFF (HCO) haemodialysis: removes light chains; the EuLITE and MYRE trials did not show improved dialysis-independence at 6 months when added to bortezomib; not routinely recommended; reserve for selected centres and clinical trials
- Plasma exchange — historical, not effective in cast nephropathy
Kidney Recovery
- 30-50% of dialysis-dependent cast nephropathy patients recover off dialysis with prompt bortezomib-based therapy
- Recovery is much less likely once >6 weeks on dialysis without treatment
Transplant
- Considered in selected patients with sustained complete haematological response and absent measurable clone
- MGRS transplant outcomes are improving with clone-directed prophylaxis
- Recurrence risk significant — refer specialist centre
Outlook and follow-up
Prognosis
- Cast nephropathy: 30-50% renal recovery if treated within days-weeks of presentation
- Untreated: rapid progression to dialysis dependence
- AL amyloidosis: cardiac involvement dominates prognosis
- MGRS: recovery depends on biopsy lesion and depth of haematological response
Monitoring
- SFLC ratio at every cycle
- Bone marrow on completion of induction and to assess CR
- eGFR, ACR/PCR every 2-4 weeks during treatment
- Vigilance for infection — myeloma + immunosuppression + CKD = high risk
- Vaccinations including pneumococcal, hepatitis B, COVID, flu, shingles (non-live)
- Long-term joint haematology-nephrology follow-up
KEY MESSAGE: kidney injury in plasma cell disease is a medical emergency. Every day on untreated cast nephropathy reduces the chance of getting off dialysis.
