Format

Send to

Choose Destination
J Immunother Cancer. 2019 Jan 6;7(1):2. doi: 10.1186/s40425-018-0478-8.

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

Author information

1
Department of Nephrology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
2
Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
3
Institute for Academic Medicine and Weill Cornell Medical College, Houston Methodist Cancer Center, Houston, TX, USA.
4
Department of Pathology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
5
Department of Pathology, Houston Methodist Hospital, Houston, TX, USA.
6
Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1468, Houston, TX, 77030, USA.
7
Rheumatology and Rehabilitation Department, Assiut University Hospitals, Faculty of Medicine, Assiut, Egypt.
8
Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
10
Department of Melanoma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
11
Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1468, Houston, TX, 77030, USA. aabudayyeh@mdanderson.org.

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

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center