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Diagnosis and management of immune checkpoint inhibitor-associated acute kidney injury

Nature Reviews Nephrology volume 18, pages 794–805 (2022)Cite this article

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Abstract

Since their introduction into clinical practice a decade ago, immune checkpoint inhibitors (ICIs) have had an overwhelming impact on cancer treatment. Use of these agents in oncology continues to grow; however, the increased use of these agents has been associated with a parallel increase in ICI-associated immune-related adverse events, which can affect virtually any organ, including the kidneys. ICI-associated acute kidney injury (ICI-AKI) occurs in 2–5% of patients treated with ICIs. Its occurrence can have important consequences, including the temporary or permanent discontinuation of ICIs or other concomitant anticancer therapies and the need for prolonged treatment with corticosteroids. Various mechanisms have been proposed to underlie the development of ICI-AKI, including loss of tolerance to self-antigens, reactivation of drug-specific effector T cells, and the production of kidney-specific autoantibodies. ICI-AKI most commonly manifests as acute tubulo-interstitial nephritis on kidney biopsy and generally shows a favourable response to early initiation of corticosteroids, with complete or partial remission achieved in most patients. The evaluation of patients with suspected ICI-AKI requires careful diagnostic work-up and kidney biopsy for patients with moderate-to-severe ICI-AKI to ensure accurate diagnosis and inform appropriate treatment.

Key points

  • Immune checkpoint inhibitors are frequently associated with the development of immune-related adverse events (irAEs).

  • Renal irAEs are rare, but potentially severe.

  • Acute tubulointerstitial nephritis is the most common irAE that affects the kidney, although other renal lesions have been described.

  • A kidney biopsy is central to making the correct diagnosis and guiding treatment in immune checkpoint inhibitor-associated acute kidney injury.

  • In general, the response of immune checkpoint inhibitor-associated acute kidney injury to corticosteroids is good and the prognosis is favourable.

  • The use of immune checkpoint inhibitors in kidney transplant recipients is associated with a significantly increased risk of allograft rejection.

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Fig. 1: Immune checkpoints and mechanism of immune evasion by cancer cells.
Fig. 2: Pathophysiology of immune checkpoint inhibitor-associated acute kidney injury.
Fig. 3: Proposed approach to the diagnosis and management of immune checkpoint inhibitor-associated acute kidney injury.
Fig. 4: Suggested approach to immune checkpoint inhibitor rechallenge in patients with biopsy-proven immune checkpoint inhibitor-associated acute kidney injury.

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References

  1. Matsushita, H. et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482, 400–404 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Robbins, P. F. et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat. Med. 19, 747–752 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. van Rooij, N. et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J. Clin. Oncol. 31, e439–e442 (2013).

    Article  PubMed  Google Scholar 

  4. Chen, D. S. & Mellman, I. Oncology meets immunology: the cancer-immunity cycle. Immunity 39, 1–10 (2013).

    Article  PubMed  Google Scholar 

  5. Kwon, E. D. et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. Proc. Natl Acad. Sci. USA 96, 15074–15079 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ahmadzadeh, M. et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114, 1537–1544 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Xu, C. et al. Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis. BMJ 363, k4226 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Postow, M. A., Sidlow, R. & Hellmann, M. D. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 378, 158–168 (2018).

    Article  CAS  PubMed  Google Scholar 

  9. Champiat, S. et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann. Oncol. 27, 559–574 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Khoja, L., Day, D., Wei-Wu, C. T., Siu, L. L. & Hansen, A. R. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann. Oncol. 28, 2377–2385 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Wolchok, J. D. et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 377, 1345–1356 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kanjanapan, Y. et al. Delayed immune-related adverse events in assessment for dose-limiting toxicity in early phase immunotherapy trials. Eur. J. Cancer 107, 1–7 (2019).

    Article  CAS  PubMed  Google Scholar 

  13. Salahudeen, A. K. et al. Incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a comprehensive cancer center. Clin. J. Am. Soc. Nephrol. 8, 347–354 (2013).

    Article  PubMed  Google Scholar 

  14. Manohar, S. et al. Acute interstitial nephritis and checkpoint inhibitor therapy. Kidney360 1, 16–24 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Seethapathy, H. et al. Incidence and clinical features of immune-related acute kidney injury in patients receiving programmed cell death ligand-1 inhibitors. Kidney Int. Rep. 5, 1700–1705 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sorah, J. D., Rose, T. L., Radhakrishna, R., Derebail, V. K. & Milowsky, M. I. Incidence and prediction of immune checkpoint inhibitor-related nephrotoxicity. J. Immunother. 44, 127–131 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Seethapathy, H. et al. The incidence, causes, and risk factors of acute kidney injury in patients receiving immune checkpoint inhibitors. Clin. J. Am. Soc. Nephrol. 14, 1692–1700 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Meraz-Munoz, A. et al. Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes. J. Immunother. Cancer 8, e000467 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Stein, C. et al. Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort. Nephrol. Dial. Transplant. 36, 1664–1674 (2021).

    Article  CAS  PubMed  Google Scholar 

  20. García-Carro, C. et al. Acute kidney injury as a risk factor for mortality in oncological patients receiving checkpoint inhibitors. Nephrol. Dial. Transplant. 37, 887–894 (2022).

    PubMed  Google Scholar 

  21. Manohar, S. et al. Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis. Nephrol. Dial. Transpl. 34, 108–117 (2019).

    Article  CAS  Google Scholar 

  22. Cortazar, F. B. et al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int 90, 638–647 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sznol, M. et al. Pooled analysis safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma. J. Clin. Oncol. 35, 3815–3822 (2017).

    Article  CAS  PubMed  Google Scholar 

  24. Wanchoo, R. et al. Adverse renal effects of immune checkpoint inhibitors: a narrative review. Am. J. Nephrol. 45, 160–169 (2017).

    Article  CAS  PubMed  Google Scholar 

  25. Gupta, S. et al. Acute kidney injury in patients treated with immune checkpoint inhibitors. J. Immunother. Cancer https://doi.org/10.1136/jitc-2021-003467 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wing, K. et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 322, 271–275 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Sharma, A. et al. Anti-CTLA-4 immunotherapy does not deplete FOXP3+ regulatory T cells (Tregs) in human cancers. Clin. Cancer Res 25, 1233–1238 (2019).

    Article  CAS  PubMed  Google Scholar 

  29. Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Robert, C. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372, 320–330 (2015).

    Article  CAS  PubMed  Google Scholar 

  31. Larkin, J., Hodi, F. S. & Wolchok, J. D. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 1270–1271 (2015).

    Article  PubMed  Google Scholar 

  32. Menke, J. et al. Programmed death 1 ligand (PD-L) 1 and PD-L2 limit autoimmune kidney disease: distinct roles. J. Immunol. 179, 7466–7477 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Nishimura, H., Nose, M., Hiai, H., Minato, N. & Honjo, T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11, 141–151 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Nishimura, H. et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291, 319–322 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Okazaki, T. et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat. Med. 9, 1477–1483 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Tivol, E. A. et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3, 541–547 (1995).

    Article  CAS  PubMed  Google Scholar 

  37. Waterhouse, P. et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270, 985–988 (1995).

    Article  CAS  PubMed  Google Scholar 

  38. Barreto, M. et al. Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. Eur. J. Hum. Genet. 12, 620–626 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Vaidya, B. et al. An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies. Rheumatology 41, 180–183 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Ueda, H. et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423, 506–511 (2003).

    Article  CAS  PubMed  Google Scholar 

  41. Prokunina, L. et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat. Genet. 32, 666–669 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Huang, C.-H. et al. Effects of genetic polymorphisms of programmed cell death 1 and its ligands on the development of ankylosing spondylitis. Rheumatology 50, 1809–1813 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. Boutros, C. et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat. Rev. Clin. Oncol. 13, 473–486 (2016).

    Article  CAS  PubMed  Google Scholar 

  44. Pillai, R. N. et al. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature. Cancer 124, 271–277 (2018).

    Article  CAS  PubMed  Google Scholar 

  45. Xu, H. et al. Antitumor activity and treatment-related toxicity associated with nivolumab plus ipilimumab in advanced malignancies: a systematic review and meta-analysis. Front. Pharmacol. 10, 1300 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lozano, A. X. et al. T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma. Nat. Med. 28, 353–362 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Subudhi, S. K. et al. Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities. Proc. Natl Acad. Sci. USA 113, 11919–11924 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Johnson, D. B. et al. Fulminant myocarditis with combination immune checkpoint blockade. N. Engl. J. Med. 375, 1749–1755 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ding, H., Wu, X. & Gao, W. PD-L1 is expressed by human renal tubular epithelial cells and suppresses T cell cytokine synthesis. Clin. Immunol. 115, 184–191 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Schoop, R. et al. Suppressed T-cell activation by IFN-γ-induced expression of PD-L1 on renal tubular epithelial cells. Nephrol. Dial. Transplant. 19, 2713–2720 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Starke, A. et al. Renal tubular PD-L1 (CD274) suppresses alloreactive human T-cell responses. Kidney Int 78, 38–47 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Jaworska, K. et al. Both PD-1 ligands protect the kidney from ischemia reperfusion injury. J. Immunol. 194, 325–333 (2015).

    Article  CAS  PubMed  Google Scholar 

  53. Hakroush, S. et al. Variable expression of programmed cell death protein 1-ligand 1 in kidneys independent of immune checkpoint inhibition. Front. Immunol. 11, 624547 (2020).

    Article  CAS  PubMed  Google Scholar 

  54. Cortazar, F. B. et al. Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: a multicenter study. J. Am. Soc. Nephrol. 31, 435–446 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Koda, R. et al. Immune checkpoint inhibitor (nivolumab)-associated kidney injury and the importance of recognizing concomitant medications known to cause acute tubulointerstitial nephritis: a case report. BMC Nephrol. 19, 48 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dimitriou, F. et al. Cytokine release syndrome during sequential treatment with immune checkpoint inhibitors and kinase inhibitors for metastatic melanoma. J. Immunother. 42, 29–32 (2019).

    Article  CAS  PubMed  Google Scholar 

  57. Bridge, J. A., Lee, J. C., Daud, A., Wells, J. W. & Bluestone, J. A. Cytokines, chemokines, and other biomarkers of response for checkpoint inhibitor therapy in skin cancer. Front. Med. 5, 351 (2018).

    Article  Google Scholar 

  58. Wang, H. et al. Interleukin-10 is a promising marker for immune-related adverse events in patients with non-small cell lung cancer receiving immunotherapy. Front. Immunol. 13, 840313 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hailemichael, Y. et al. Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity. Cancer Cell 40, 509–523.e506 (2022).

    Article  CAS  PubMed  Google Scholar 

  60. Fadel, F., El Karoui, K. & Knebelmann, B. Anti-CTLA4 antibody-induced lupus nephritis. N. Engl. J. Med. 361, 211–212 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Leaf, D. E. Excessive diagnostic testing in acute kidney injury. BMC Nephrol. 17, 9 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Muriithi, A. K., Nasr, S. H. & Leung, N. Utility of urine eosinophils in the diagnosis of acute interstitial nephritis. Clin. J. Am. Soc. Nephrol. 8, 1857–1862 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Kitchlu, A. et al. A systematic review of checkpoint inhibitor-associated glomerular disease. KI Rep. 6, 66–77 (2020).

    PubMed  PubMed Central  Google Scholar 

  64. Schneider, B. J. et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J. Clin. Oncol. 39, 4073–4126 (2021).

    Article  CAS  PubMed  Google Scholar 

  65. Thompson, J. A. et al. Management of immunotherapy-related toxicities, version 1.2019. J. Natl Compr. Canc. Netw. 17, 255–289 (2019).

    Article  CAS  PubMed  Google Scholar 

  66. Brahmer, J. R. et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J. Immunother. Cancer 9, e002435 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Thompson, J. et al. NCCN Guidelines Version 1.2022: Management of Immunotherapy-Related Toxicities. https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1486 (2022).

  68. Haanen, J. et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 28, iv119–iv142 (2017).

    Article  CAS  PubMed  Google Scholar 

  69. Oleas, D. et al. Acute interstitial nephritis associated with immune checkpoint inhibitors: a single-centre experience. Clin. Kidney J. 14, 1364–1370 (2021).

    Article  CAS  PubMed  Google Scholar 

  70. Andrulli, S. et al. The risks associated with percutaneous native kidney biopsies: a prospective study. Nephrol. Dial. Transplant. https://doi.org/10.1093/ndt/gfac177 (2022).

    Article  PubMed  Google Scholar 

  71. Qualls, D. et al. Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis. J. Immunother. Cancer 7, 356 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Lee, M. D. et al. Rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis: a single-center retrospective cohort study. J. Immunother. Cancer 9, e002292 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Waljee, A. K. et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 357, j1415 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Zhang, H. et al. Impact of corticosteroid use on outcomes of non-small-cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. J. Clin. Pharm. Ther. 46, 927–935 (2021).

    Article  CAS  PubMed  Google Scholar 

  75. Baker, M. L. et al. Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy. J. Immunother. Cancer https://doi.org/10.1136/jitc-2021-004421 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Lin, J. S. et al. Infliximab for the treatment of patients with checkpoint inhibitor-associated acute tubular interstitial nephritis. Oncoimmunology 10, 1877415 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Dimitriou, F., Hogan, S., Menzies, A. M., Dummer, R. & Long, G. V. Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy. Eur. J. Cancer 157, 214–224 (2021).

    Article  CAS  PubMed  Google Scholar 

  78. Allouchery, M. et al. Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade ≥2 immune-related adverse events in patients with cancer. J. Immunother. Cancer 8, e001622 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Perazella, M. A. & Sprangers, B. AKI in patients receiving immune checkpoint inhibitors. Clin. J. Am. Soc. Nephrol. 14, 1077–1079 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Mamlouk, O. et al. Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience. J. Immunother. Cancer 7, 2 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Abdelahim, M. et al. Incidence, predictors, and survival impact of acute kidney injury in patients with melanoma treated with immune checkpoint inhibitors: a 10-year single-institution analysis. Oncoimmunology 10, 1927313 (2021).

    Article  Google Scholar 

  82. Perazella, M. A. & Shirali, A. C. Nephrotoxicity of cancer immunotherapies: past, present and future. J. Am. Soc. Nephrol. 29, 2039–2052 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Murakami, N. et al. A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant. Kidney Int. 100, 196–205 (2021).

    Article  CAS  PubMed  Google Scholar 

  84. Carroll, R. P. et al. Immune checkpoint inhibitors in kidney transplant recipients: a multicentre, single-arm, phase 1 study. Lancet Oncol. https://doi.org/10.1016/s1470-2045(22)00368-0 (2022).

    Article  PubMed  Google Scholar 

  85. Kitchlu, A., Jhaveri, K. D., Sprangers, B., Yanagita, M. & Wanchoo, R. Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review. Clin. Kidney J. 14, 2012–2022 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Chute, D. F. et al. Incidence and predictors of CKD and estimated GFR decline in patients receiving immune checkpoint inhibitors. Am. J. Kidney Dis. 79, 134–137 (2022).

    Article  CAS  PubMed  Google Scholar 

  87. Isik, B. et al. Biomarkers, clinical features, and rechallenge for immune checkpoint inhibitor renal immune-related adverse events. Kidney Int. Rep. 6, 1022–1031 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Moledina, D. G. et al. Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. JCI Insight 4, e127456 (2019).

    Article  PubMed Central  Google Scholar 

  89. Heybeli, C., Nathan, M. A. & Herrmann, S. Renal injury in the setting of immune checkpoint inhibitor: report of a case of hypothyroidism and the role of positron emission tomography. J. Onconephrol. 4, 112–116 (2020).

    Google Scholar 

  90. Herrmann, S. M., Alexander, M. P., Romero, M. F. & Zand, L. Renal tubular acidosis and immune checkpoint inhibitor therapy: an immune-related adverse event of PD-1 inhibitor-a report of 3 cases. Kidney Med. 2, 657–662 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Okawa, S. et al. Rapidly progressive acute kidney injury associated with nivolumab treatment. Case Rep. Oncol. 13, 85–90 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

B.S. is a senior clinical investigator of The Research Foundation Flanders (F.W.O. 1842919 N) and receives funding from the Foundation against Cancer (Stichting tegen Kanker; C/2020/1380). D.E.L. is funded by National Institutes of Health grants R01HL144566, R01DK125786 and R01DK126685. M.J.S. is funded by Fondo de Investigación Sanitaria-FEDER, ISCIII, PI17/00257, REDINREN, RD16/0009/0030 and EIN2020-112338. We would like to thank Albert Herelixka, University Hospitals Leuven, Belgium, for drawing the figures included in the original submission of this manuscript.

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Authors and Affiliations

  1. Division of Nephrology, Ziekenhuis Oost-Limburg, Genk, Belgium

    Ben Sprangers

  2. Biomedical Research Institute, Department of Immunology and Infection, UHasselt, Diepenbeek, Belgium

    Ben Sprangers

  3. Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA

    David E. Leaf

  4. Division of Medical Oncology, Azienda Ospedaliero-Universitaria Corsorziale Policlinico di Bari, Bari, Italy

    Camillo Porta

  5. Oncology, Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Bari, Italy

    Camillo Porta

  6. Nephrology Research Group, Vall d’hebrón Institut de Recerca (VHIR), Barcelona, Spain

    Maria José Soler

  7. Department of Nephrology, Hospital Universitari Vall d’Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain

    Maria José Soler

  8. Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA

    Mark A. Perazella

  9. Veterans Affairs Medical Center, West Haven, Connecticut, USA

    Mark A. Perazella

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Glossary

Immune checkpoints

Regulators of the immune system that can be activating (promoting immune cell activation) or negative (inhibiting immune cell activation).

T cell exhaustion

A state of T cell dysfunction arising during chronic infections and cancer, characterized by poor T cell effector function, continued expression of inhibitor receptors and a specific transcriptional signature.

Tumour-draining lymph nodes

Lymph nodes located immediately downstream of tumours and where the anti-tumour immune response will be activated.

Thymic negative selection

Process of intra-thymic deletion of self-reactive thymocytes (developing T cells).

Haptens

Small molecules that elicit an immune response only when bound to a large carrier such as a protein.

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Sprangers, B., Leaf, D.E., Porta, C. et al. Diagnosis and management of immune checkpoint inhibitor-associated acute kidney injury. Nat Rev Nephrol 18, 794–805 (2022). https://doi.org/10.1038/s41581-022-00630-8

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