Abstract: TH-PO642
Light Chain Cast Nephropathy and Vascular Limited Renal Amyloidosis Occurring Simultaneously in a Patient
Session Information
- Fellows/Residents Case Reports: Genetic Diseases, Pregnancy, Monoclonal Gammopathy
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Nephrology Education
- 1302 Fellows and Residents Case Reports
Authors
- Sury, Krishna, Yale University School of Medicine, New Haven, Connecticut, United States
- Moeckel, Gilbert W., Yale University School of Medicine, New Haven, Connecticut, United States
- Turner, Jeffrey M., Yale University School of Medicine, New Haven, Connecticut, United States
Background
Bence Jones proteins can lead to renal injury by multiple mechanisms; the biochemical properties of the immunoglobulin light chain play a central role in determining which type of kidney insult occurs. We present a case in which a patient simultaneously had vascular limited AL amyloidosis and light chain cast nephropathy. This sparked our interest in the molecular characteristics that, when present, might allow an immunoglobulin light chain to concurrently cause two distinct types of injury in separate compartments of the kidney.
Methods
A 53-year-old man presented with acute kidney injury (AKI) in the setting of six months of dizziness and progressively worsening pain from lower extremity claudication. Imaging revealed lucent lesions in the vertebrae, prompting a bone marrow biopsy that was diagnostic for multiple myeloma. The Congo red stain was negative for amyloid. Treatment of myeloma was delayed by onset of severe, symptomatic orthostatic hypotension. Workup including echocardiogram and cosyntropin stimulation test was unrevealing, and administration of intravenous fluids, fludrocortisone and midodrine was ineffective. His AKI progressed and he required dialysis but could not tolerate treatment due to severe hypotension. We attributed his renal decline to untreated myeloma, but this did not explain the orthostasis. Kidney biopsy revealed both light chain cast nephropathy and vascular-limited AL amyloidosis. Sadly, shortly thereafter the patient developed bradyarrhythmias and died of bradycardic arrest.
Conclusion
Multiple myeloma can present with a variety of renal manifestations; the type of injury depends upon the biochemical properties of the causative immunoglobulin light chain. AL amyloidosis occurs when the specific amino acid sequences and charge properties present promote the conformational change of light chains into amyloid fibrils. Alternatively, cast nephropathy occurs when there is an amino acid segment that stimulates light chain binding to uromodulin within the tubules. Rarely, these two distinct lesions occur simultaneously, as seen in our patient. We speculate that this occurs when a single species of monoclonal light chain possesses biochemical properties encompassing characteristics of both AL amyloidosis and cast nephropathy.