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.



  • Focal segmental glomerulosclerosis (FSGS)


  • 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)


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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