Acute Tubular Necrosis in a Patient With Myeloma Treated With Carfilzomib

Liberman, V.; D’Agati, Vivette D.; Masani, Naveed; Drakakis, James; Mattana, Joseph

doi:10.1016/j.ekir.2016.06.002

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…A case report published by Liberman et al described biopsy proven acute tubular necrosis (ATN) following carfilzomib administration. 21 A study by Moreau et al found that the most common adverse event leading to carfilzomib discontinuation was AKI, regardless of dosing strategy. 22 Whether carfilzomib offers an acceptable therapeutic option for AMR in kidney and other solid organ transplant recipients will depend at least in part on whether AKI risk can be mitigated by alternative dosing and/or IVF administration.…”

Section: Discussionmentioning

confidence: 99%

Carfilzomib‐based antibody mediated rejection therapy in pediatric kidney transplant recipients

Cody

Varnell

Lazear

et al. 2023

Pediatric Transplantation

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BackgroundTo date, the evidence for proteasome‐inhibitor (PI) based antibody mediated rejection (AMR) therapy has been with the first‐generation PI bortezomib. Results have demonstrated encouraging efficacy for early AMR with lesser efficacy for late AMR. Unfortunately, bortezomib is associated with dose‐limiting adverse effects in some patients. We report use of the second generation proteosome inhibitor carfilzomib for AMR treatment in two pediatric patients with a kidney transplant.MethodsThe clinical data on two patients who experienced dose limiting toxicities from bortezomib were collected along with their short‐ and long‐term outcomes.ResultsA two‐year‐old female with simultaneous AMR, multiple de novo DSAs (DR53 MFI 3900, DQ9 MFI 6600, DR15 2200, DR51 MFI 1900) and T‐cell mediated rejection (TCMR) completed three carfilzomib cycles and experienced stage 1 acute kidney injury after the first two cycles. At 1 year follow up, all DSAs resolved, and her kidney function returned to baseline without recurrence. A 17‐year‐old female also developed AMR with multiple de novo DSAs (DQ5 MFI 9900, DQ6 MFI 9800, DQA*01 MFI 9900). She completed two carfilzomib cycles, which were associated with acute kidney injury. She had resolution of rejection on biopsy and decreased but persistent DSAs on follow‐up.ConclusionsCarfilzomib treatment for bortezomib‐refractory rejection and/or bortezomib toxicity may provide DSA elimination or reduction, but also appears to be associated with nephrotoxicity. Clinical development of carfilzomib for AMR will require a better understanding of efficacy and development of approaches to mitigate nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Carfilzomib‐based antibody mediated rejection therapy in pediatric kidney transplant recipients

Cody

Varnell

Lazear

et al. 2023

Pediatric Transplantation

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“…44 Initially, several reports showed that the injury might be pre-renal and/or acute tubular damage. [45][46][47] In the last few years, several case series have confirmed biopsy-proven TMA cases closely associated with this agent. [48][49][50][51] Most published cases speculate that carfilzomib, similar to bortezomib, causes TMA through a dose-dependent toxic mechanism in which plasmapheresis is unlikely to show any clinical benefit.…”

Section: Discussionmentioning

confidence: 99%

Case-based discussions in onco-nephrology

Henriksen

Hogan

Abudayyeh

et al. 2020

Journal of Onco-Nephrology

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Onco-nephrology encompasses a wide range of complex problems including nephrotoxicity from traditional chemotherapy and targeted therapies, paraneoplastic kidney diseases, tumor- or treatment-related microangiopathies and glomerulonephritis, and kidney injuries associated with dysproteinemia, among others. To bring these topics to life, we present a case-based discussion of clinicopathologic features that we have encountered in our daily practices. We hope these discussions of clinical presentation, kidney biopsy findings, underlying pathophysiology, and therapeutic considerations will provide insight into recognizing and treating this expanding spectrum of diseases.

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“…There are some reports of carfilzomib causing direct proximal tubular injury; however, the risk appears to be very small [70].…”

Section: Renalmentioning

confidence: 98%

What the Intensivists Need to Know About Critically Ill Myeloma Patients

Nair¹,

Patel²

2018

Oncologic Critical Care

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Multiple myeloma (MM) is a hematological malignancy characterized by an increase in aberrant plasma cells in the bone marrow leading to rising monoclonal protein in serum and urine. With the introduction of novel therapies with manageable side effects, this incurable disease has evolved into a chronic disease with an acceptable quality of life for the majority of patients. Accordingly, management of acute complications is fundamental in reducing the morbidity and mortality in MM. MM emergencies include symptoms and signs related directly to the disease and/or to the treatment; many organs may be involved including, but not limited to, renal, cardiovascular, neurologic, hematologic, and infectious complications. This review will focus on the numerous approaches that are aimed at managing these complications.

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Acute Tubular Necrosis in a Patient With Myeloma Treated With Carfilzomib

Cited by 10 publications

References 10 publications

Carfilzomib‐based antibody mediated rejection therapy in pediatric kidney transplant recipients

Carfilzomib‐based antibody mediated rejection therapy in pediatric kidney transplant recipients

Case-based discussions in onco-nephrology

What the Intensivists Need to Know About Critically Ill Myeloma Patients

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