Pamidronate-induced Collapsing FSGS



Pamidronate-induced Collapsing FSGS


A. Brad Farris, III, MD










In a 67-year-old woman with multiple myeloma who received pamidronate and developed 50 g/d proteinuria requiring hemodialysis, glomerular capillary loops show segmental occlusion image.






On high power, glomerular capillary loops are segmentally occluded image. Tubular injury was present with flattened tubular epithelium image.


TERMINOLOGY


Abbreviations



  • Focal segmental glomerulosclerosis (FSGS)


Definitions



  • Collapsing FSGS secondary to bisphosphonates such as pamidronate (Aredia) used in the treatment of osteolytic metastases, Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis (PMO)


ETIOLOGY/PATHOGENESIS


Mechanism Uncertain



  • Bisphosphonate binds calcium phosphate crystals within bone matrix, thus inhibiting osteoclast activity


  • Podocyte dysfunction is thought to be cause of collapsing FSGS



    • Pamidronate is thought to interfere with podocyte function and metabolism, similar to its metabolic effects on osteoclasts


    • Hypothesis: Podocytes leave their terminally differentiated state and enter the cell cycle, acquiring a more immature phenotype



      • Evidenced by loss of podocyte synaptopodin and increased Ki-67 expression


  • Tubular and podocyte mitochondrial injury may also be present


  • No evidence of immunologic mechanism (scant infiltrate)

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Pamidronate-induced Collapsing FSGS
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