Nephrotoxicity of Immune Checkpoint Inhibitors

doi:10.19803/j.1672-8629.2019.10.12

Abstract

Abstract: The development of immune checkpoint inhibitors (ICIs) has revolutionized the field of cancer therapy. Despite the benefits, the use of ICIs is also accompanied by a unique spectrum of side effects, referred to as immune-related adverse events. Among them, ICIs-related kidney injury has been reported worldwide these years. Although uncommon, such injury may pose a threat to patients' drug treatment, quality of life and even life. So far, such adverse drug reactions have rarely been reported in China. In this paper, the characteristics, monitoring and treatment of ICIs-related kidney injury are summarized based on literature review in order to provide evidence for ICIs-related decision-making and adverse reaction management. Current clinical data suggests that the occurrence of acute kidney injury is relatively more common than other renal complications associated with ICIs use. There are also reports of ICIs-related nephrotic syndrome and kidney transplantation rejection. Glucocorticoid is the mainstay of current treatment. In addition, close monitoring of renal function during ICI treatment, early detection and intervention of kidney injury are critical to the outcome.

Key words: immune checkpoint inhibitor, immune-related adverse event, nephrotoxicity, acute kidney injury, onco-nephrology

CLC Number:

R994.11

FAN Qianqian, ZHANG Bo, ZHAO Bin, LI Qiuyue, LIU Fang, MA Jie. Nephrotoxicity of Immune Checkpoint Inhibitors[J]. Chinese Journal of Pharmacovigilance, 2019, 16(10): 632-638.

References

[1] Postow M A, Callahan M K, Wolchok J D.Immune checkpoint blockade in cancer therapy[J]. J Clin Oncol, 2015, 33(17):1974-1982.
[2] 张志仁. 免疫检查点抑制剂及其心血管不良反应研究进展[J]. 药学进展,2018,42(7):492-499.
[3] Heinzerling L, de Toni E N, Schett G, et al. Checkpoint inhibitors[J]. Dtsch Arztebl Int, 2019, 116(8): 119-126.
[4] Postow M A, Sidlow R, Hellmann M D.Immune-related adverse events associated with immune checkpoint blockade[J]. NEngl J Med, 2018, 378(2): 158-168.
[5] Mason N T, Khushalani N I, Weber J S, et al.Modeling the cost of immune checkpoint inhibitor-related toxicities[J].J Clin Oncol, 2016, 34(15 suppl): 6627.
[6] Cortazar F B, Marrone K A, Troxell M L, et al.Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors[J]. Kidney Int, 2016, 90(3): 638-647.
[7] US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0[S]. 2009.
[8] Murakami N, Motwani S, Riella L V.Renal complications of immune checkpoint blockade[J]. Curr Probl Cancer, 2017, 41(2): 100-110.
[9] Wanchoo R, Karam S, Uppal N N, et al.Adverse renal effects of immune checkpoint inhibitors: a narrative review[J]. Am J Nephrol,2017,45(2):160-169.
[10] EI Rassy E, Bakouny Z, Yared F, et al.The nephrotoxicity of immune checkpoint inhibitor-based combinations[J]. Eur J Cancer, 2018, (103): 274-278.
[11] Shirali A C, Perazella M A, Gettinger S.Association of acute interstitial nephritis with programmed cell death 1 inhibitor therapy in lung cancer patients[J]. Am J Kidney Dis, 2016, 68(2): 287-291.
[12] Murakami N, Borges T, Yamashita M, et al.Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma[J]. Clin Kidney J, 2016, 9(3): 411-417.
[13] Belliere J, Meyer N, Mazieres J, et al.Acute interstitial nephritis related to immune checkpoint inhibitors[J]. Br J Cancer, 2016, 115(12): 1457-1461.
[14] Izzedine H, Mathian A, Champiat S, et al.Renal toxicities associated with pembrolizumab[J]. Clin Kidney J, 2019, 12(1): 81-88.
[15] MamLouk O, Selamet U, Machado S, et al. Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience[J]. J Immunother Cancer, 2019, 7(1): 2.
[16] Kidd J M, Gizaw A B.Ipilimumab-associated minimal-change disease[J]. Kidney Int, 2016, 89(3): 720.
[17] Kitchlu A, Fingrut W, Avila-Casado C, et al.Nephrotic syndrome with cancer immunotherapies: a report of 2 cases[J].Am J Kidney Dis, 2017, 70(4): 581-585.
[18] Gao B, Lin N, Wang S, et al.Minimal change disease associated with anti-PD1 immunotherapy: a case report[J]. BMC Nephrol, 2018, 19(1): 156.
[19] Bickel A, Koneth I, Enzler-Tschudy A, et al.Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma[J]. BMC Cancer, 2016,(16): 656.
[20] Daanen R A, Maas R J H, Koornstra R H T, et al. Nivolumab-associated nephrotic syndrome in a patient with renal cell carcinoma: a case report[J]. J Immunother, 2017, 40(9): 345-348.
[21] Fadel F, El Karoui K, Knebelmann B.Anti-CTLA4 antibody-induced lupus nephritis[J]. N Engl J Med, 2009, 361(2): 211-212.
[22] Glassock R J.Secondary minimal change disease[J]. Nephrol Dial Transplant, 2003, 18(suppl6): 52-58.
[23] Auguet T, Lorenzo A, Colomer E, et al.Recovery of minimal change nephrotic syndrome and acute renal failure in a patient with renal cell carcinoma[J]. Am J Nephrol, 1998, 18(5): 433-435.
[24] Audard V, Larousserie F, Grimbert P, et al.Minimal change nephrotic syndrome and classical Hodgkin’s lymphoma: report of 21 cases and review of the literature[J]. Kidney Int, 2006, 69(12): 2251-2260.
[25] Kittai A S, Oldham H, Cetnar J, et al.Immune checkpoint inhibitors in organ transplant patients[J]. J Immunother, 2017, 40(7): 277-281.
[26] Lesouhaitier M, Dudreuilh C, Tamain M, et al.Checkpoint blockade after kidney transplantation[J]. Eur J Cancer, 2018,(96): 111-114.
[27] Jose A, Yiannoullou P, Bhutani S, et al.Renal allograft failure after ipilimumab therapy for metastatic melanoma: a case report and review of the literature[J]. Transplant Proc, 2016, 48(9): 3137-3141.
[28] Zehou O, Leibler C, Arnault J P, et al.Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients[J]. Am J Transplant, 2018, 18(12): 3065-3071.
[29] Iannello A, Thompson T W, Ardolino M, et al.Immunosurveillance and immunotherapy of tumors by innate immune cells[J]. Curr Opin Immunol, 2016,(38): 52-58.
[30] Waeckerle-Men Y, Starke A, Wuthrich RP.PD-L1 partially protects renal tubular epithelial cells from the attack of CD8+ cytotoxic T cells[J]. Nephrol Dial Transplant, 2007, 22(6): 1527-1536.
[31] Koda R, Watanabe H, Tsuchida M, 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[J]. BMC Nephrol, 2018, 19(1): 48.
[32] Lute K D, May K F Jr, Lu P, et al. Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies[J]. Blood, 2005, 106(9): 3127-3133.
[33] Barnett R, Barta V S, Jhaveri K D.Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab[J]. N Engl J Med, 2017, 376(2): 191-192.
[34] Morita M, Fujino M, Jiang G, et al.PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft[J]. Am J Transplant, 2009, 10(1): 40-46.
[35] Spain L, Higgins R, Gopalakrishnan K, et al.Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma[J]. Ann Oncol, 2016, 27(6): 1135-1137.
[36] Riella L V, Paterson A M, Sharpe AH, et al.Role of the PD-1 pathway in the immune response[J]. Am J Transplant, 2012, 12(10): 2575-2587.
[37] Brahmer J R, Lacchetti C, Schneider B J, et al.Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline[J]. J Clin Oncol, 2018, 36(17): 1714-1768.