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A Systematic Review of Immune Checkpoint Inhibitor–Associated Glomerular Disease

ABSTRACT:

Introduction

Immune checkpoint inhibitors (ICIs) are increasingly used to treat cancers. Kidney immune-related adverse events (IRAEs) are now well recognized, with the incidence of IRAEs ranging from 2% to 5%. Most of the initial data related to kidney IRAEs have focused on acute interstitial nephritis (AIN). There are minimal data on the types and relative frequencies of glomerular diseases associated with ICIs, their treatment, and outcomes.

Methods

We performed a systematic review and meta-analysis of all biopsy-proven published cases/series of glomerular pathology associated with ICIs. We searched the MEDLINE, EMBASE, and Cochrane databases from inception to February 2020. We abstracted patient-level data, including demographics, cancer and ICI therapy details, and characteristics of kidney injury.

Results

After screening, 27 articles with 45 cases of biopsy-confirmed ICI-associated glomerular disease were identified. Several lesion types were observed, with the most frequent being pauci-immune glomerulonephritis (GN) and renal vasculitis (27%), podocytopathies (24%), and complement 3 GN (C3GN; 11%). Concomitant AIN was reported in 41%. Most patients had ICIs discontinued (88%), and nearly all received corticosteroid treatment (98%). Renal replacement therapy (RRT) was required in 25%. Most patients had full (31%) or partial (42%) recovery from acute kidney injury (AKI), although 19% remained dialysis-dependent, and approximately one-third died. Complete or partial remission of proteinuria was achieved in 45% and 38%, respectively.

Conclusion

Multiple forms of ICI-associated glomerular disease have been described. Pauci-immune GN, podocytopathies, and C3GN are the most frequently reported lesions. ICI-associated glomerular disease may be associated with poor kidney and mortality outcomes. Oncologists and nephrologists must be aware of glomerular pathologies associated with ICIs and consider obtaining a kidney biopsy specimen when features atypical for AIN are present. Graphical abstract

SUBMITTER: Kitchlu A

PROVIDER: S-EPMC7783581 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Project description:BackgroundImmune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease.MethodsWe comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded.ResultsWe identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD.ConclusionIAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.