Multiple Myeloma Kidney Disease

Multiple myeloma kidney disease covers the spectrum of renal lesions caused by monoclonal immunoglobulins or light chains, including cast nephropathy, light chain proximal tubulopathy, AL amyloidosis, monoclonal immunoglobulin deposition disease, hypercalcaemic nephropathy, and plasma cell infiltration.

• Renal impairment (creatinine over 2 mg/dL) at diagnosis in about 20%, and in up to 50% over the disease course; part of myeloma-defining CRAB features.
• Cast nephropathy accounts for 40 to 60%; AL amyloidosis and monoclonal immunoglobulin deposition disease 20 to 30%; proximal tubulopathy (Fanconi syndrome) in a minority.
• Other contributors: hypercalcaemia, dehydration, NSAIDs, contrast, bisphosphonates (zoledronic acid), hyperuricaemia, infection, hyperviscosity.
• Renal failure carries inferior survival unless renal recovery is achieved.
• Smouldering myeloma and MGUS with renal significance (monoclonal gammopathy of renal significance) require clone-directed therapy.

• Asymptomatic renal impairment with unexplained anaemia or hypercalcaemia.
• Nephrotic syndrome (amyloid, deposition disease), tubular syndromes (Fanconi: glycosuria, aminoaciduria, phosphaturia, acidosis, osteomalacia), AKI (cast nephropathy).
• Bone pain, fractures, fatigue, recurrent infections, neuropathy, macroglossia (amyloid).
• Hyperviscosity, bleeding.

• Serum protein electrophoresis and immunofixation, urine immunofixation, serum free light chains.
• Renal biopsy classification (immunofluorescence with light chain restriction, Congo red, electron microscopy, mass spectrometry typing of amyloid).
• Bone marrow examination with cytogenetics and FISH, skeletal imaging, calcium, beta-2 microglobulin, LDH.
• Urinalysis: dipstick under-detects light chains; quantify urinary protein by pyrogallol or sulfosalicylic acid methods.
• Exclude other causes (diabetes, hypertension, NSAIDs, obstruction).
• Cardiac assessment (NT proBNP, troponin, echo) in AL amyloid.

• Supportive: hydration, correct hypercalcaemia, avoid nephrotoxins, treat infection, treat hyperuricaemia, adjust drugs to GFR.
• Immediate clone-directed therapy, with renal recovery as an objective:
  • Cast nephropathy: bortezomib-based regimens (bortezomib 1.3 mg/m2 SC weekly or twice weekly, cyclophosphamide, dexamethasone), daratumumab-based triplets.
  • AL amyloidosis: daratumumab with cyclophosphamide, bortezomib and dexamethasone; autologous transplant for eligible.
  • Deposition disease/tubulopathy: bortezomib-based therapy, ASCT.
• Bisphosphonates: zoledronic acid 4 mg IV with renal dose adjustment (3 mg at eGFR 50 to 60, 3.3 mg 40 to 49, 3 mg 30 to 39), avoid if eGFR under 30; denosumab 120 mg SC monthly is an alternative in severe renal failure (monitor calcium).
• Renal replacement therapy as needed; transplant after sustained haematological remission.
• Prophylaxis: aciclovir 400 mg twice daily, antibiotic prophylaxis early in therapy (levofloxacin 500 mg daily for first 3 months), thromboprophylaxis (aspirin 75 to 100 mg, or enoxaparin 40 mg with IMiDs), vaccination.
• Monitor free light chains, creatinine and calcium regularly; response assessment by IMWG criteria and renal response (MDRD).