Collapsing Focal Segmental Glomerulosclerosis Following Treatment with High-Dose Pamidronate

Abstract

Abstract. Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.

Crystal-Induced Podocytopathy Producing Collapsing Focal Segmental Glomerulosclerosis in Monoclonal Gammopathy of Renal Significance: A Case Report

“…However, only 3 cases (including ours) presented as collapsing FSGS, 7 , 19 a seldom described variant characterized by marked wrinkling and collapse of glomerular basement membranes plus hypertrophy and hyperplasia of overlying podocytes. 8 , 9 Nasr et al 7 and Akilesh et al 19 described 2 cases of crystalloid podocytopathy causing collapsing FSGS in a 54-year-old woman and a 45-year-old man, respectively. Both had IgGκ multiple myelomas and presented with nephrotic-range proteinuria and acute kidney injury.…”

“…Collapsing FSGS was first described in patients with HIV-associated nephropathy in African American patients. However, there has been increasing recognition of collapsing FSGS associated with patients with multiple myeloma treated with pamidronate, 7 , 8 , 9 which used to be widely prescribed for the treatment of multiple myeloma–associated hypercalcemia. 7 , 8 , 9 Interestingly, crystalloid podocytopathy causing collapsing FSGS in the absence of pamidronate, viral infection, or toxins has only been described by Akilesh et al 19 and our present case.…”

“…However, there has been increasing recognition of collapsing FSGS associated with patients with multiple myeloma treated with pamidronate, 7 , 8 , 9 which used to be widely prescribed for the treatment of multiple myeloma–associated hypercalcemia. 7 , 8 , 9 Interestingly, crystalloid podocytopathy causing collapsing FSGS in the absence of pamidronate, viral infection, or toxins has only been described by Akilesh et al 19 and our present case. This prompted us to consider that collapsing FSGS manifestations were caused by the paraproteinemia itself because no other causative factors were involved.…”

“…Collapsing focal segmental glomerulosclerosis (FSGS) is a rare disease associated with viruses such as HIV and parvovirus or drugs like bisphosphonates, particularly pamidronate, used for treatment of multiple myeloma–associated hypercalcemia. 7 , 8 , 9 However, crystal-induced podocytopathy causing FSGS without the use of these drugs is extremely rare.…”

Patient-reported effectiveness and safety of Pamidronate in NSAIDs-refractory chronic recurrent multifocal osteomyelitis in children

“…In contrast to other studies, our research reveals a greater number of patients (9 out of 42—19%) complaining about their drug-related dermatological conditions. Renal insufficiency is rare, yet a very severe complication, which is proven to be associated with Pamidronate treatment [ 40 ]. A systematic review proposed by Tanvetyanon et al [ 41 ] shows that acute renal failure occurred rather sporadically and usually after at least 11 months of continuous therapy.…”