scholarly journals Paraneoplastic tubulointerstitial nephritis exacerbated by immune checkpoint inhibitor

2021 ◽  
pp. 239936932110563
Author(s):  
Thomas Paul Scherer ◽  
Karim Alexander Saba ◽  
Raeto Thomas Strebel ◽  
Ariana Gaspert ◽  
Richard Cathomas ◽  
...  
Keyword(s):  
Paraneoplastic Syndrome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Paraneoplastic Syndromes ◽  
Prior Literature ◽  
Metastasized Renal Cell Carcinoma ◽  
Work Up

Background: With the expanding indications and thus broader use of immune checkpoint inhibitors, clinicians are faced with a new kind of immune-related adverse events. Because of their immune modulating effects, immune checkpoint inhibitors have the potential to worsen autoimmunity in general. Paraneoplastic syndromes can be caused by tumor-induced autoimmune mechanisms. The use of immune-activating substances such as checkpoint inhibitors might lead to exacerbation of paraneoplastic syndromes causing premature discontinuation of the immunotherapy. Case presentation: We report on a 64-year-old patient with metastasized renal cell carcinoma who developed acute kidney failure after cytoreductive nephrectomy. Work-up revealed a paraneoplastic syndrome that caused tubulointerstitial nephritis (TIN). Glucocorticoid therapy successfully reversed the acute kidney injury. However, adjuvant therapy with Nivolumab provoked a flare-up of the paraneoplastic syndrome on two occasions, eventually leading to a treatment discontinuation. Conclusions: Many cases of Nivolumab-induced TIN have been described lately. However, our case demonstrates therapy failure due to a flare-up of a pre-existing paraneoplastic syndrome of the renal cancer. Against this background, it can only be speculated that some of the TIN cases discussed in prior literature might also have been flare-ups of subclinical autoimmunity.

Tubulitis in a patient treated with nivolumab: Case report and literature review

2018 ◽  
Vol 2 (2-3) ◽  
pp. 107-112
Author(s):  
Viral Vakil ◽  
Mark Birkenbach ◽  
Katti Woerner ◽  
Lihong Bu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitors ◽  
Kidney Biopsy ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

Avoiding immunogenic drugs is key to preserve renal function in patients receiving immune checkpoint inhibitors: Lessons learned from three illustrative cases

2021 ◽  
pp. 239936932110485
Author(s):  
Laura Martínez Valenzuela ◽  
Paula Antón ◽  
Ariel Tango ◽  
Francisco Gómez ◽  
Xavier Fulladosa ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Lessons Learned ◽  
Temporal Association ◽  
Preserve Renal Function ◽  
Concomitant Medications ◽  
Cancer Immunosurveillance

Background: In the recent years, new immunotherapy agents are showing promising results in the treatment of cancer. Immune checkpoint inhibitors (ICI), which block neoplasm-induced lymphocyte inhibition and enhance cancer immunosurveillance mechanisms, are associated to acute tubulointerstitial nephritis (ATIN). The mechanisms of this adverse effect are debated. Methods: We present a three-case series of ATIN in the setting of ICI therapy managed in our Nephrology department. We detail the clinical course of the episodes, emphasizing on the concomitant medications administered. We also conducted a literature review of the altered drug immunogenicity in patients under immunotherapy drugs. Results: The three reported ATIN cases illustrate closer temporal association with the concomitant medication rather than the ICI itself. This suggests a scenario where the tolerance to previously accepted drugs seems to be lost. Moreover, one of the patients presented an ATIN flare after ICI discontinuation, suggesting an state of leukocyte hyperactivation. Conclusions: Unraveling the exact patho-mechanisms by which ICI-related ATIN occurs will allow the prevention of the development of this side effect and determine whether ICI re-challenge in patients previously affected by ICI-ATIN is safe.

scholarly journals Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors

2016 ◽  
Vol 90 (3) ◽  
pp. 638-647 ◽  
Author(s):  
Frank B. Cortazar ◽  
Kristen A. Marrone ◽  
Megan L. Troxell ◽  
Kenneth M. Ralto ◽  
Melanie P. Hoenig ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Clinicopathological Features

MO404ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS (CPIS) NEPHROTOXICITY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Fausta Catapano ◽  
Elisa Persici ◽  
Giulia Ubaldi ◽  
Francesca Romani ◽  
Elena Mancini
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Long Term Follow Up

Abstract Background and Aims The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related toxicities associated with CPIs can limit its efficacy. Case Report. A 52 year-old female diagnosed with left ocular melanoma and treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The main damage was interstitial and characterized by tubulitis, tubular necrosis, non-isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4+, inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda light chains). On the basis of these histological findings, Nivolumab-induced Acute Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient was treated by steroids and she achieved almost complete renal function recovery (Figure 3). Conclusions. CPIs can induce a long-term Acute Kidney Injury. Histological features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve renal outcome. In patients treated with CPIs a multidisciplinary management between oncologists and nephrologists is desirable for monitoring renal function at basal, after drug administration and in the long-term follow-up.

scholarly journals A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

2019 ◽  
Vol 13 (1) ◽  
pp. 42-45
Author(s):  
Xavier Charmetant ◽  
Cécile Teuma ◽  
Jennifer Lake ◽  
Frédérique Dijoud ◽  
Vincent Frochot ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Renal Toxicity ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Tubular Dysfunction ◽  
Distal Tubular Acidosis

Abstract The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

Endocrine adverse events related with immune checkpoint inhibitors: an update for clinicians

Immunotherapy ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 481-510 ◽  
Author(s):  
Maria V Deligiorgi ◽  
Mihalis I Panayiotidis ◽  
Dimitrios T Trafalis
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Future Perspective ◽  
Programmed Cell Death 1 ◽  
Diagnostic Work ◽  
Work Up

Designated as scientific breakthrough of current decade, immune checkpoint inhibitors attenuate the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1)/ligand 1 (PD-L1) pathways, depriving cancer cells of a key strategy of evasion from immunosurveillance. The reinvigoration of immune response translates into clinical success, inevitably entwined with a novel constellation of immune-related adverse events. The present review dissects the endocrine immune-related adverse events, emphasizing their unique profile featured by unpredictable onset, irreversibility, nonspecific symptoms, wide clinical spectrum and sophisticated diagnostic work-up. Guidelines advocate individualized decision-making process guided by clinicians' judgement. Future perspective should be governed by five principles – prevention, anticipation, detection, treatment, monitoring – aiming to gain the optimal profit diminishing immunotoxicity.

scholarly journals Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

2017 ◽  
Vol 45 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Rimda Wanchoo ◽  
Sabine Karam ◽  
Nupur N. Uppal ◽  
Valerie S. Barta ◽  
Gilbert Deray ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Incidence Rates ◽  
Primary Data ◽  
Medline Search ◽  
Main Adverse Effect

Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.

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