Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: Single-center experience 11 Medical and Health Sciences 1103 Clinical Sciences

Omar Mamlouk, Umut Selamet, Shana Machado, Maen Abdelrahim, William F. Glass, Amanda Tchakarov, Lillian Gaber, Amit Lahoti, Biruh T Workeneh, Sheldon Chen, Jamie Lin, Noha Abdelwahab Hassan Ali Hassan, Jean H Tayar, Huifang Lu, Maria Suarez-Almazor, Nizar M Tannir, Cassian Yee, Adi Diab, Ala Abudayyeh

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Abstract

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.

Original languageEnglish (US)
Article number2
JournalJournal for immunotherapy of cancer
Volume7
Issue number1
DOIs
StatePublished - Jan 6 2019

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Interstitial Nephritis
Glomerulonephritis
Biopsy
Acute Kidney Injury
Health
Kidney
Therapeutics
IGA Glomerulonephritis
Pathology
Membranous Glomerulonephritis
Amyloidosis
Hematologic Neoplasms
Amyloid
Immunosuppression
Neoplasms
Adrenal Cortex Hormones
Biomarkers
Steroids
Urine
Inflammation

Keywords

  • Acute tubulointerstitial nephritis
  • Checkpoint inhibitors
  • Glomerulonephritis
  • Immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

@article{641fe32da2434c229aaa28d769d29ffd,
title = "Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: Single-center experience 11 Medical and Health Sciences 1103 Clinical Sciences",
abstract = "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.",
keywords = "Acute tubulointerstitial nephritis, Checkpoint inhibitors, Glomerulonephritis, Immunotherapy",
author = "Omar Mamlouk and Umut Selamet and Shana Machado and Maen Abdelrahim and Glass, {William F.} and Amanda Tchakarov and Lillian Gaber and Amit Lahoti and Workeneh, {Biruh T} and Sheldon Chen and Jamie Lin and Hassan, {Noha Abdelwahab Hassan Ali} and Tayar, {Jean H} and Huifang Lu and Maria Suarez-Almazor and Tannir, {Nizar M} and Cassian Yee and Adi Diab and Ala Abudayyeh",
year = "2019",
month = "1",
day = "6",
doi = "10.1186/s40425-018-0478-8",
language = "English (US)",
volume = "7",
journal = "Journal for ImmunoTherapy of Cancer",
issn = "2051-1426",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis

T2 - Single-center experience 11 Medical and Health Sciences 1103 Clinical Sciences

AU - Mamlouk, Omar

AU - Selamet, Umut

AU - Machado, Shana

AU - Abdelrahim, Maen

AU - Glass, William F.

AU - Tchakarov, Amanda

AU - Gaber, Lillian

AU - Lahoti, Amit

AU - Workeneh, Biruh T

AU - Chen, Sheldon

AU - Lin, Jamie

AU - Hassan, Noha Abdelwahab Hassan Ali

AU - Tayar, Jean H

AU - Lu, Huifang

AU - Suarez-Almazor, Maria

AU - Tannir, Nizar M

AU - Yee, Cassian

AU - Diab, Adi

AU - Abudayyeh, Ala

PY - 2019/1/6

Y1 - 2019/1/6

N2 - 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.

AB - 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.

KW - Acute tubulointerstitial nephritis

KW - Checkpoint inhibitors

KW - Glomerulonephritis

KW - Immunotherapy

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