Light Chain Cast Nephropathy

Light chain cast nephropathy (myeloma cast nephropathy) is the commonest renal lesion in multiple myeloma, caused by intratubular precipitation of monoclonal free light chains with Tamm-Horsfall protein, obstructing distal tubules.

• Renal impairment at diagnosis in 20 to 40% of myeloma patients, with AKI requiring dialysis in 5 to 10%.
• Precipitants: dehydration, hypercalcaemia, infection, NSAIDs, contrast, loop diuretics, ACE inhibitors, acid urine.
• Pathology: fractured, "fractured glass" casts with giant cell reaction, tubular atrophy and interstitial fibrosis.
• High serum free light chain burden (involved free light chain over 500 mg/L) predicts cast formation.
• Renal recovery depends on rapid reduction of light chains: about 60 to 80% recover if free light chains fall by 60% or more within 21 days.

• Rapid or subacute loss of renal function with minimal proteinuria on dipstick (light chains not detected), bland sediment.
• Features of myeloma: bone pain, anaemia, hypercalcaemia, recurrent infections, fatigue.
• Hypercalcaemia (polyuria, confusion, constipation), hyperviscosity (rare).
• AKI after precipitating event.

• Serum free light chain assay with ratio, serum and urine protein electrophoresis with immunofixation (Bence Jones proteinuria), 24-hour urinary light chain excretion; urine albumin low relative to total protein by sulfosalicylic acid test discordance.
• Calcium, creatinine, haemoglobin, LDH, beta-2 microglobulin, albumin.
• Bone marrow biopsy (clonal plasma cells ≥ 10%), skeletal survey/whole body low-dose CT or PET/MRI.
• Renal biopsy to confirm cast nephropathy and exclude light chain deposition disease, AL amyloid, acute tubular injury (indicated if free light chain involved level below 500 mg/L, albuminuria over 1 g/day, or atypical features).
• Ultrasound: normal or enlarged kidneys.

• Urgent combined approach (within 24 to 48 hours): supportive care plus effective anti-myeloma therapy.
• Hydration: fluid to maintain urine output 2 to 3 L/day, correct hypercalcaemia (saline, zoledronic acid 4 mg IV renally dose adjusted or pamidronate 30 to 90 mg, calcitonin, dexamethasone, denosumab 120 mg), alkalinise urine not routinely.
• Stop nephrotoxins (NSAIDs, contrast, aminoglycosides, loop diuretics unless overload, ACE inhibitors during AKI).
• Chemotherapy rapidly lowering free light chains: bortezomib 1.3 mg/m2 SC on days 1, 4, 8, 11 (no renal adjustment) with dexamethasone 20 to 40 mg weekly or daily initially, plus cyclophosphamide or thalidomide/lenalidomide (renal dosing) or daratumumab 16 mg/kg weekly; triplet regimens (bortezomib, cyclophosphamide, dexamethasone; daratumumab-VCd) achieve renal response in 60 to 80%.
• Extracorporeal light chain removal: high cut-off haemodialysis (Theralite) with chemotherapy in selected dialysis-dependent patients (benefit uncertain; MYRE trial negative for independence), plasma exchange not recommended routinely.
• Renal replacement therapy for standard indications; some become dialysis-independent after 3 months.
• Autologous stem cell transplantation for eligible patients, with melphalan dose reduction (140 mg/m2).
• Prophylaxis: aciclovir 400 mg twice daily, bone protection, thromboprophylaxis with immunomodulatory agents.
• Monitor serum free light chains, creatinine, and calcium every 1 to 2 weeks initially.