Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience

Autor: Ala Abudayyeh, Cassian Yee, Nizar M. Tannir, Maria E. Suarez-Almazor, Shana Machado, Biruh Workeneh, Sheldon Chen, Amanda Tchakarov, Umut Selamet, Lillian W. Gaber, Huifang Lu, William F Glass, Amit Lahoti, Omar Mamlouk, Jamie S. Lin, Noha Abdel-Wahab, Maen Abdelrahim, Jean Tayar, Adi Diab
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Cancer Research
C3 Glomerulonephritis
Biopsy
medicine.medical_treatment
Gastroenterology
Antineoplastic Agents
Immunological
0302 clinical medicine
Glomerulonephritis
Neoplasms
Immunology and Allergy
Molecular Targeted Therapy
medicine.diagnostic_test
Acute tubulointerstitial nephritis
Acute kidney injury
Immunosuppression
Middle Aged
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
Female
Renal biopsy
Immunotherapy
Checkpoint inhibitors
Adult
medicine.medical_specialty
Immunology
Short Report
lcsh:RC254-282
Nephropathy
Immunomodulation
03 medical and health sciences
Internal medicine
Biomarkers
Tumor
medicine
Humans
Aged
Pharmacology
business.industry
medicine.disease
030104 developmental biology
Nephritis
Interstitial
business
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-13 (2019)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: Rationale & Objective The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects. Study design, setting, & participants We retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center. Results We identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77 years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14 weeks (range 6–56 weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16 days (range from 1 to 46 days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery. Conclusions Our data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.
Databáze: OpenAIRE
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