title: Renal thrombotic microangiopathy and podocytopathy associated with the use of carfilzomib in a patient with multiple myeloma.
abstract: BACKGROUND
  Proteasome inhibitors are a relatively new class of chemotherapeutic agents. Bortezomib is the first agent of this class and is currently being used for the treatment of multiple myeloma. However, recent reports have linked exposure to bortezomib with the development of thrombotic microangiopathy. A new agent in this class, carfilzomib, has been recently introduced as alternative therapy for relapsing and refractory multiple myeloma. We report a case of renal thrombotic microangiopathy associated with the use of carfilzomib in a patient with refractory multiple myeloma.
  
  
  METHODS
  A 62 year-old Caucasian man with hypertension and a 4-year history of multiple myeloma, had been previously treated with lenalidomide, bortezomib and two autologous hematopoietic stem cell transplants. After the second hematopoietic stem cell transplant, he developed acute kidney injury secondary to septic shock and required dialysis for 4 weeks. Subsequently, his serum creatinine stabilized at 2.1 mg/dL (185.64 μmol/L). Seventeen months after the second hematopoietic stem cell transplant, he was initiated on carfilzomib for relapse of multiple myeloma. Six weeks later, he developed abrupt worsening of lower extremity edema and hypertension, and new onset proteinuria. His kidney function remained stable. Kidney biopsy findings were consistent with thrombotic microangiopathy. Eight weeks after discontinuation of carfilzomib, proteinuria and hypertension improved. Due to progression of multiple myeloma, he died a few months later.
  
  
  CONCLUSIONS
  In view of the previously reported association of bortezomib with thrombotic microangiopathy, the temporal association of the clinical picture with the initiation of carfilzomib, and the partial resolution of symptoms after discontinuation of the drug, we conclude that carfilzomib may have precipitated a case of clinically evident renal thrombotic microangiopathy in our patient.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, 615 South Preston Street, Louisville, KY 40202, USA. liliane.hobeika@louisville.edu.
authors.forename: Liliane
authors.initials: L
authors.lastname: Hobeika
authors.forename: Sally E
authors.initials: SE
authors.lastname: Self
authors.forename: Juan Carlos Q
authors.initials: JC
authors.lastname: Velez
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D004487:Edema / Q000209:etiology; D017809:Fatal Outcome; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy / Q000628:therapy; D009842:Oligopeptides / Q000009:adverse effects* / Q000627:therapeutic use; D050199:Podocytes / Q000187:drug effects / Q000473:pathology; D061988:Proteasome Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011507:Proteinuria / Q000209:etiology; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D012772:Shock, Septic / Q000209:etiology; D013713:Teniposide / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D057049:Thrombotic Microangiopathies / Q000139:chemically induced* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; C524865:carfilzomib; D003907:Dexamethasone; D003520:Cyclophosphamide; D013713:Teniposide; D000077269:Lenalidomide