Podocyte Injury Associated Glomerulopathies Induced by Pamidronate

Background: Pamidronate has been demonstrated to decrease bone-related complications in multiple myeloma and delay progression of the disease. This has led to its use in supportive and maintenance therapy of myeloma in conjunction with steroids and chemotherapy. It has also been selectively used in patients with breast cancer and other neoplasms.

Methods: We report on five patients who developed glomerular disease induced by pamidronate. Pamidronate was the only drug common to all patients. Tests for hepatitis B and C and human immunodeficiency virus (HIV) were negative for all patients. The first two patients received a high dose of pamidronate for 8 weeks, whereas the other three patients were on monthly therapy for a prolonged period of time. Sources of data included chart review and pathologic analysis of kidney biopsy.

Results: Three patients were female and two were males and all were Caucasian, ranging in age from 58 to 71 years. Renal biopsy findings included minimal change disease in two, focal segmental glomerulosclerosis in two, and collapsing focal segmental glomerulosclerosis in one. Immunofluorescence was essentially negative in all cases. Electron microscopy showed variable podocyte injury and extensive foot process effacement. There was no evidence of multiple myeloma-related renal disease. After the biopsy, pamidronate was discontinued and renal function stabilized in all patients except the one with the collapsing variant of focal segmental glomerulosclerosis who required hemodialysis. Three patients had resolution of proteinuria, one patient continued to have proteinuria without deterioration in renal function.

Conclusion: Pamidronate has been mainly associated with collapsing focal segmental glomerulosclerosis. This report expands that relationship and adds other glomerular diseases linked with podocyte injury. Additional studies are needed to define the cause of the variability of renal histology with this agent.