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Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine...

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Autores principales: Palamaris, Kostas, Alexandris, Dimitrios, Stylianou, Kostas, Giatras, Ioannis, Stofas, Anastasios, Kaitatzoglou, Christina, Migkou, Magda, Goutas, Dimitrios, Psimenou, Erasmia, Theodoropoulou, Eleni, Theocharis, Stamatios, Alevizopoulos, Nektarios, Kastritis, Efstathios, Gerakis, Alexandros, Gakiopoulou, Harikleia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409791/
https://www.ncbi.nlm.nih.gov/pubmed/36013025
http://dx.doi.org/10.3390/jcm11164786
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author Palamaris, Kostas
Alexandris, Dimitrios
Stylianou, Kostas
Giatras, Ioannis
Stofas, Anastasios
Kaitatzoglou, Christina
Migkou, Magda
Goutas, Dimitrios
Psimenou, Erasmia
Theodoropoulou, Eleni
Theocharis, Stamatios
Alevizopoulos, Nektarios
Kastritis, Efstathios
Gerakis, Alexandros
Gakiopoulou, Harikleia
author_facet Palamaris, Kostas
Alexandris, Dimitrios
Stylianou, Kostas
Giatras, Ioannis
Stofas, Anastasios
Kaitatzoglou, Christina
Migkou, Magda
Goutas, Dimitrios
Psimenou, Erasmia
Theodoropoulou, Eleni
Theocharis, Stamatios
Alevizopoulos, Nektarios
Kastritis, Efstathios
Gerakis, Alexandros
Gakiopoulou, Harikleia
author_sort Palamaris, Kostas
collection PubMed
description We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.
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spelling pubmed-94097912022-08-26 Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases Palamaris, Kostas Alexandris, Dimitrios Stylianou, Kostas Giatras, Ioannis Stofas, Anastasios Kaitatzoglou, Christina Migkou, Magda Goutas, Dimitrios Psimenou, Erasmia Theodoropoulou, Eleni Theocharis, Stamatios Alevizopoulos, Nektarios Kastritis, Efstathios Gerakis, Alexandros Gakiopoulou, Harikleia J Clin Med Article We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition. MDPI 2022-08-16 /pmc/articles/PMC9409791/ /pubmed/36013025 http://dx.doi.org/10.3390/jcm11164786 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Palamaris, Kostas
Alexandris, Dimitrios
Stylianou, Kostas
Giatras, Ioannis
Stofas, Anastasios
Kaitatzoglou, Christina
Migkou, Magda
Goutas, Dimitrios
Psimenou, Erasmia
Theodoropoulou, Eleni
Theocharis, Stamatios
Alevizopoulos, Nektarios
Kastritis, Efstathios
Gerakis, Alexandros
Gakiopoulou, Harikleia
Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
title Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
title_full Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
title_fullStr Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
title_full_unstemmed Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
title_short Immune Checkpoint Inhibitors’ Associated Renal Toxicity: A Series of 12 Cases
title_sort immune checkpoint inhibitors’ associated renal toxicity: a series of 12 cases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409791/
https://www.ncbi.nlm.nih.gov/pubmed/36013025
http://dx.doi.org/10.3390/jcm11164786
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