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myeloma cast nephropathy; light chain cast nephropathy

Etiology: - always associated with multiple myeloma. Epidemiology: - 20% of patients with multiple myeloma Pathology: - Ig light chains in urine - renal tubular injury - obstructive uropathy of tubular origin - filtered light chains endocytosed by proximal tubule cells are nephrotoxic, resulting in proximal tubular dysfunction - always associated with multiple myeloma Clinical manifestations: - acute or slowly progressive kidney injury Laboratory: - 24 hour urine protein - high levels of Ig light chains in urine - albumin in urine may be normal - nephrotic level proteinuria, but not nephrotic syndrome (no edeme - urine dipstick detects albumin, not Ig light chains - serum protein electrophoresis - high serum free light chains - urine protein electrophoresis - immunofixation electrophoresis - hypercalcemia - anemia Radiology: - lytic bone lesions may be noted Differential diagnosis: - AA amyloidodsis - frequently present with the nephrotic syndrome - history of an inflammatory disease, edema, hypoalbuminemia - monoclonal gammopathy of renal significance - no hypercalcemia, anemia, or lytic bone lesions - fibrillary glomerulopathy - hematuria, hypertension Management: - treatment of multiple myeloma - reduce free Ig light chains with chemtherapy - avoid bisphosphonates - pamidronate may induce acute renal failure & nephrotic syndrome - zoledronate may induce acute tubular necrosis - contraindicated if GFR > 30 mL/min - avoid NSAIDs, especially in patients with volume depletion

General

multiple myeloma; plasmacytoma/plasma cell myeloma nephropathy

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025
  2. Mene P, Stoppacciaro A, Lai S, et al. Light chain cast nephropathy in multiple myeloma: prevalence, impact and management challenges. Int J Nephrol Renovasc Dis. 2022;15:173-183. PMID: 35592304