The nephrotoxicity of immune checkpoint inhibitor–based combinations

Rassy, Elie El; Bakouny, Ziad; Yared, Fares; Chelala, Dania; Karak, Fadi El; Ghosn, Marwan

doi:10.1016/j.ejca.2018.07.126

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…Despite their great success, ICI can cause serious inflammatory and immune-related adverse events (irAE), affecting almost any organ [2,4]. Most commonly involved areas are skin, colon, the endocrine system, liver, lungs, heart, musculoskeletal system, and central nervous system [5].…”

mentioning

confidence: 99%

Managing immune dysregulation resulting from immune checkpoint inhibitors: impact of the ASCO guidelines and key take-homes for immunologists

Kim

Suarez‐Almazor

2018

Expert Review of Clinical Immunology

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By targeting inhibitory checkpoint molecules, with resultant reinvigoration of antitumor immunity, immune checkpoint inhibitors (ICIs) have opened a new chapter in cancer treatment [1]. Full activation of T cells requires two signals: (i) binding of the T cell receptor (TCR) to the antigen-major histocompatibility complex in antigen-presenting cells and (ii) co-stimulation by engagement of CD28 on the T cell to CD80/86 on the antigenpresenting cell [2]. Upon activation, T cells express cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on their surface, a CD28 homolog with higher affinity for CD80/86 than CD28, attenuating and terminating T cell activation. Programmed death 1 (PD-1) is a surface molecule expressed on activated T cells, B cells, regulatory T cells, natural killer cells, natural killer T cells, maturing thymocytes, some myeloid and antigenpresenting cells, innate lymphoid cell progenitors, and some cancer cells [3]. PD-1 ligands, PD-L1 and PD-L2, are expressed by antigen-presenting cells, T cells, B cells, dendritic cells, macrophages, thymocytes, non-hematopoietic lineages, and some cancer cells [3]. By binding PD-1 ligands, PD-1 on activated T cells provides inhibitory signals and attenuates T cell activity. PD-1 ligands are expressed by various normal tissues as a physiologic mechanism to protect self, but they are also expressed in various tumor cells, helping tumor cells evade antitumor immunity. Antibodies against CTLA-4 (ipilimumab) and antibodies against PD-1/PD-L1 (hereon, anti-PD-1 antibodies, nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab) have shown paradigm-shifting therapeutic benefits in various cancers. Ipilimumab is approved for the treatment of melanoma, and anti-PD-1 antibodies for various tumors including melanoma, non-small-cell lung cancer, renal cell carcinoma, Hodgkin disease, head and neck cancer, and bladder cancer, among others [1]. New indications continue to be approved at a rapid pace. ICI-based combinations are also being approved including combination ICIs (nivolumab plus ipilimumab) in non-small-cell lung cancer, renal cell carcinoma, and melanoma; chemotherapy plus ICIs in non-small-cell lung cancer; chemotherapy plus ICIs plus bevacizumab in non-small-cell lung cancer; tyrosine kinase inhibitors plus ICIs in renal cell carcinoma.

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confidence: 99%

Managing immune dysregulation resulting from immune checkpoint inhibitors: impact of the ASCO guidelines and key take-homes for immunologists

Kim

Suarez‐Almazor

2018

Expert Review of Clinical Immunology

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“…Reported rates of nephrotoxicity are less than 1% for antictla-4 antibodies, but acute kidney injury is reported in 2.2% of patients treated with anti-PD-1 antibodies 4 . With combination immune checkpoint blockade, renal complications are seen in 4.2% of patients 49 . Renal toxicities include glomerulonephritis, hypertension, proteinuria, and acute interstitial nephritis, with cases of lupus nephritis also reported 49 .…”

Section: Renal Iraesmentioning

confidence: 99%

“…With combination immune checkpoint blockade, renal complications are seen in 4.2% of patients 49 . Renal toxicities include glomerulonephritis, hypertension, proteinuria, and acute interstitial nephritis, with cases of lupus nephritis also reported 49 .…”

Section: Renal Iraesmentioning

confidence: 99%

“…Nephrology consultation is advised, and renal biopsy might be required in some cases 4,15 . Other reported treatments include mycophenolate, rituximab with prednisone for cases of pauci-immune glomerulonephritis (with plasma exchange also used for a patient with positivity for anti-neutrophil cytoplasmic antibodies), and infliximab for a case of immunoglobulin A nephropathy 49,50 .…”

Section: Renal Iraesmentioning

confidence: 99%

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Diagnosis, Monitoring, and Management of Adverse Events From Immune Checkpoint Inhibitor Therapy

Khan

Monzon

2020

Current Oncology

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Immune checkpoint inhibitor therapy (ICIT) is now standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, it is imperative to understand the timing, epidemiology, monitoring, diagnosis, and management of immune related adverse events (irAEs) associated with ICIT. This article reviews specific irAEs by organ system, consolidating recommendations from multiple guidelines and incorporating data from case reports to highlight additional evolving therapeutic options for patients. Managing these adverse events requires early recognition, early intervention, and education of both patients and the multidisciplinary health care team. Given the durable responses observed with ICIT, and the irreversible nature associated with some of these irAEs, further research into management of the sequelae of ICIT is required.

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“…Another meta-analysis found the incidence of AKI in clinical trials to be 5% in patients administered nivolumab. 3…”

Section: Introductionmentioning

confidence: 99%

Cohort study on immune checkpoint inhibitor-associated acute kidney injury: Incidence, risk factors, and management strategies

Panich

Irwin

Bissonette

et al. 2023

J Oncol Pharm Pract

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Introduction Case studies and retrospective chart reviews of health system data have demonstrated an increased risk of nephrotoxicity in patients receiving immune checkpoint inhibitors compared to clinical trials. This study investigated the frequency, causes, and risk factors for acute kidney injury in a real-world, rural setting. Methods This was a retrospective cohort study of patients who received at least one dose of a checkpoint inhibitor at a rural health system from May 2013 to February 2020 and who received at least one dose of a checkpoint inhibitor. Electronic and manual chart review helped to determine the incidence of, risk factors for, and renal outcomes and management strategies of checkpoint inhibitor-related acute kidney injury. Multivariable Fine and Gray subdistribution hazard models were used to assess the impact of patient characteristics on the incidence of sustained acute kidney injury and checkpoint inhibitor-induced acute kidney injury. Results After exclusion criteria, 906 patients who received at least one dose of a checkpoint inhibitor at Marshfield Clinic Health System during the study period were included. The incidence of acute kidney injury of any duration and due to any cause was 36.1%, while sustained acute kidney injury occurred in 28.7% of patients. Checkpoint inhibitor-related acute kidney injury was thought to have occurred in 2.7% of patients. Baseline estimated glomerular filtration rate < 60 was the sole predictor of checkpoint inhibitors-related acute kidney injury. Most patients with suspected checkpoint inhibitor-related acute kidney injury were managed with corticosteroids, and 62.5% experienced complete renal recovery. Conclusions Ours is the first retrospective cohort study to test whether baseline Eastern Cooperative Oncology Group score and checkpoint inhibitor place in therapy were associated with checkpoint inhibitor-related acute kidney injury, and neither of these data points were found to be predictive. Even after expanding the parameters and methodologies of our study as compared to other retrospective cohort studies, we found only three baseline characteristics to be predictive of sustained acute kidney injury: Baseline eGFR, loop diuretic, and spironolactone use. For checkpoint inhibitor-related baseline, eGFR alone was predictive.

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The nephrotoxicity of immune checkpoint inhibitor–based combinations

Cited by 7 publications

References 28 publications

Managing immune dysregulation resulting from immune checkpoint inhibitors: impact of the ASCO guidelines and key take-homes for immunologists

Managing immune dysregulation resulting from immune checkpoint inhibitors: impact of the ASCO guidelines and key take-homes for immunologists

Diagnosis, Monitoring, and Management of Adverse Events From Immune Checkpoint Inhibitor Therapy

Cohort study on immune checkpoint inhibitor-associated acute kidney injury: Incidence, risk factors, and management strategies

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