Research Progress on Cytomegalovirus and Chronic Kidney Disease
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v7i2.5276
Abstract
Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease (ESRD), and its prevalence continues to rise. Increasing evidence suggests that cytomegalovirus (CMV) is not only a common opportunistic pathogen but also a potential pathogenic factor involved in the progression of CKD.CMV infection is characterized by lifelong latency, periodicity, and reactivation, which can cause continuous immune activation and inflammatory states. This article reviews the biological characteristics, latent infection, reactivation mechanisms, microRNAs, and immune cells associated with CMV, aiming to explore the potential mechanisms of kidney disease progression from a new perspective of viral infection and immune regulation, and to provide new insights and potential intervention targets for the prevention and treatment of CKD.
Keywords
chronic kidney disease, cytomegalovirus, immune cells, microRNAs
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[28]Munks M W, Rott K, Nesterenko P A, et al. Latent CMV infection of lymphatic endothelial cells is sufficient to drive CD8 T cell memory inflation[J]. PLoS pathogens, 2023, 19(1): e1010351.
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[34]Chang J H, Husain S A, Santoriello D, et al. Donor’s APOL1 risk genotype and “second hits” associated with de novo collapsing glomerulopathy in deceased donor kidney transplant recipients: a report of 5 cases[J]. American Journal of Kidney Diseases, 2019, 73(1): 134-139.
[35]Shabir S, Smith H, Kaul B, et al. Cytomegalovirus-associated CD4+ CD28null cells in NKG2D-dependent glomerular endothelial injury and kidney allograft dysfunction[J]. American Journal of Transplantation, 2016, 16(4): 1113-1128.
[36]Iwatani Y, Amemiya N, Nokiba H, et al. Risk factors for cytomegalovirus reactivation in patients with kidney disease under immunosuppressive therapy[J]. Clinical and Experimental Nephrology, 2022, 26(1): 22-28.
[37]Heald-Sargent T A, Forte E, Liu X, et al. New insights into the molecular mechanisms and immune control of cytomegalovirus reactivation[J]. Transplantation, 2020, 104(5): e118-e124.
[38]Ahn R, Schaenman J, Qian Z, et al. Acute and chronic changes in gene expression after CMV DNAemia in kidney transplant recipients[J]. Frontiers in immunology, 2021, 12: 750659.
[39]Han S H, Kumar D, Ferreira V H, et al. Human microRNA responses predict cytomegalovirus replication following solid organ transplantation[J]. The Journal of infectious diseases, 2017, 215(4): 537-546.
[40]Soffritti I, D’Accolti M, Ravegnini G, et al. Modulation of micrornome by human cytomegalovirus and human herpesvirus 6 infection in human dermal fibroblasts: Possible significance in the induction of fibrosis in systemic sclerosis[J]. Cells, 2021, 10(5): 1060.
[41]Afshari A, Yaghobi R, Golshan M. Cytomegalovirus microRNAs level determination in kidney recipients post transplantation[J]. Virology journal, 2022, 19(1): 147.
[42]Fernández-Ruiz M, López-García Á, Valverde-Manso A, et al. Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation[J]. American Journal of Transplantation, 2024, 24(7): 1180-1192.
[43]López-Botet M, De Maria A, Muntasell A, et al. Adaptive NK cell response to human cytomegalovirus: Facts and open issues[C]//Seminars in immunology. Academic Press, 2023, 65: 101706.
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[45]Zeng J, Zhang Y, Huang C. Macrophages polarization in renal inflammation and fibrosis animal models[J]. Molecular Medicine Reports, 2023, 29(2): 29.
[46]Zahradka I, Tichanek F, Majercikova L, et al. Composition of peripheral blood immune cell compartment in stage 5 chronic kidney disease is affected by smoking and other risk factors associated with systemic inflammatory response[J]. Frontiers in immunology, 2025, 16: 1608206.
[47]Betjes M G H, Weimar W, Litjens N H R. CMV seropositivity determines epoetin dose and hemoglobin levels in patients with CKD[J]. Journal of the American Society of Nephrology, 2009, 20(12): 2661-2666.
[48]Meijers R W J, Litjens N H R, Hesselink D A, et al. Primary cytomegalovirus infection significantly impacts circulating T cells in kidney transplant recipients[J]. American Journal of Transplantation, 2015, 15(12): 3143-3156.
[49]Bhargava R, Li H, Tsokos G C. Pathogenesis of lupus nephritis: the contribution of immune and kidney resident cells[J]. Current Opinion in Rheumatology, 2023, 35(2): 107-116.
[2]Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host[J]. Nature Reviews Microbiology, 2021, 19(12): 759-773.
[3]De Luca F, Camporeale V, Leccese G, et al. From Senescent Cells to Systemic Inflammation: The Role of Inflammaging in Age-Related Diseases and Kidney Dysfunction[J]. Cells, 2025, 14(22): 1831.
[4]Hsu C C, Li H P, Hung Y H, et al. Targeted methylation of CMV and E1A viral promoters[J]. Biochemical and biophysical research communications, 2010, 402(2): 228-234.
[5]Imlay H, Limaye A P. Current understanding of cytomegalovirus reactivation in critical illness[J]. The Journal of infectious diseases, 2020, 221(Supplement_1): S94-S102.
[6]Dhuruvasan K, Sivasubramanian G, Pellett P E. Roles of host and viral microRNAs in human cytomegalovirus biology[J]. Virus Research, 2011, 157(2): 180-192.
[7]Mohammad A A, Costa H, Landázuri N, et al. Human cytomegalovirus microRNAs are carried by virions and dense bodies and are delivered to target cells[J]. Journal of General Virology, 2017, 98(5): 1058-1072.
[8]Afshari A, Yaghobi R, Golshan M. Cytomegalovirus microRNAs level determination in kidney recipients post transplantation[J]. Virology Journal, 2022, 19(1): 147.
[9]Zhou W, Wang C, Ding M, et al. Different expression pattern of human cytomegalovirus-encoded microRNAs in circulation from virus latency to reactivation[J]. Journal of Translational Medicine, 2020, 18(1): 469.
[10]Sabbaghian M, Gheitasi H, Fadaee M, et al. Human cytomegalovirus microRNAs: Strategies for immune evasion and viral latency[J]. Archives of Virology, 2024, 169(8): 157.
[11]Yurochko A D. New mechanism by which human cytomegalovirus microRNAs negate the proinflammatory response to infection[J]. Mbio, 2017, 8(2): 10.1128/mbio. 00505-17.
[12]Heald-Sargent T A, Forte E, Liu X, et al. New insights into the molecular mechanisms and immune control of cytomegalovirus reactivation[J]. Transplantation, 2020, 104(5): e118-e124.
[13]Sun Y, Sen S, Parmar R, et al. Cytotoxic KLRG1+ IL-7R-effector CD8+ T cells distinguish kidney transplant recipients controlling cytomegalovirus reactivation[J]. Frontiers in Immunology, 2025, 16: 1542531.
[14]Zangger N, Oxenius A. T cell immunity to cytomegalovirus infection[J]. Current Opinion in Immunology, 2022, 77: 102185.
[15]Lim E Y, Jackson S E, Wills M R. The CD4+ T cell response to human cytomegalovirus in healthy and immunocompromised people[J]. Frontiers in cellular and infection microbiology, 2020, 10: 202.
[16]Hassan N, Eldershaw S, Stephens C, et al. CMV reactivation initiates long-term expansion and differentiation of the NK cell repertoire[J]. Frontiers in immunology, 2022, 13: 935949.
[17]Ng K R, Li J Y Z, Gleadle J M. Human cytomegalovirus encoded microRNAs: hitting targets[J]. Expert review of anti-infective therapy, 2015, 13(12): 1469-1479.
[18]Pickering H, Arakawa-Hoyt J, Llamas M, et al. Cytomegalovirus-associated CD57+ KLRG1+ CD8+ TEMRA T cells are associated with reduced risk of CMV viremia in kidney transplantation and chronic allograft dysfunction in lung transplantation[J]. Human Immunology, 2025, 86(3): 111285.
[19]Pickering H, Sen S, Arakawa-Hoyt J, et al. NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant[J]. JCi insight, 2021, 6(21): e153175.
[20]Charles C, Ferris A H. Chronic kidney disease[J]. Primary care, 2020, 47(4): 585-595.
[21]Grams M E, Melamed M L. Chronic kidney disease[J]. Annals of internal medicine, 2025, 178(9): ITC129-ITC144.
[22]Foresto-Neto O, Menezes-Silva L, Leite J A, et al. Immunology of kidney disease[J]. Annual Review of Immunology, 2024, 42(1): 207-233.
[23]Pace J, Paladugu P, Das B, et al. Targeting STAT3 signaling in kidney disease[J]. American Journal of Physiology-Renal Physiology, 2019, 316(6): F1151-F1161.
[24]Karangizi A H K, Chanouzas D, Fenton A, et al. Cytomegalovirus seropositivity is independently associated with cardiovascular disease in non-dialysis dependent chronic kidney disease[J]. QJM: An International Journal of Medicine, 2020, 113(4): 253-257.
[25]Zais I E, Sirotti A, Iesari S, et al. Human cytomegalovirus‐related gastrointestinal disease after kidney transplantation: A systematic review[J]. Clinical Transplantation, 2024, 38(1): e15218.
[26]Sun Y, Sen S, Parmar R, et al. Cytotoxic KLRG1+ IL-7R-effector CD8+ T cells distinguish kidney transplant recipients controlling cytomegalovirus reactivation[J]. Frontiers in Immunology, 2025, 16: 1542531.
[27]Li S, Livingston M J, Ma Z, et al. Tubular cell senescence promotes maladaptive kidney repair and chronic kidney disease after cisplatin nephrotoxicity[J]. JCI insight, 2023, 8(8): e166643.
[28]Munks M W, Rott K, Nesterenko P A, et al. Latent CMV infection of lymphatic endothelial cells is sufficient to drive CD8 T cell memory inflation[J]. PLoS pathogens, 2023, 19(1): e1010351.
[29]Dedeoglu B, de Weerd A E, Huang L, et al. Lymph node and circulating T cell characteristics are strongly correlated in end-stage renal disease patients, but highly differentiated T cells reside within the circulation[J]. Clinical & Experimental Immunology, 2017, 188(2): 299-310.
[30]FARRUGIA E, SCHWAB T R. Management and prevention of cytomegalovirus infection after renal transplantation[C]//Mayo Clinic Proceedings. Elsevier, 1992, 67(9): 879-890.
[31]Sadeghi M, Lahdou I, Opelz G, et al. IL-23 plasma level is strongly associated with CMV status and reactivation of CMV in renal transplant recipients[J]. BMC immunology, 2016, 17(1): 35.
[32]Ishikawa S, Tasaki M, Saito K, et al. Long-term CMV monitoring and chronic rejection in renal transplant recipients[J]. Frontiers in cellular and infection microbiology, 2023, 13: 1190794.
[33]Song JR, Li YF. Research progress on renal fibrosis in IgA nephropathy[J]. Journal of Modern Medicine & Health, 2026,42(1).
[34]Chang J H, Husain S A, Santoriello D, et al. Donor’s APOL1 risk genotype and “second hits” associated with de novo collapsing glomerulopathy in deceased donor kidney transplant recipients: a report of 5 cases[J]. American Journal of Kidney Diseases, 2019, 73(1): 134-139.
[35]Shabir S, Smith H, Kaul B, et al. Cytomegalovirus-associated CD4+ CD28null cells in NKG2D-dependent glomerular endothelial injury and kidney allograft dysfunction[J]. American Journal of Transplantation, 2016, 16(4): 1113-1128.
[36]Iwatani Y, Amemiya N, Nokiba H, et al. Risk factors for cytomegalovirus reactivation in patients with kidney disease under immunosuppressive therapy[J]. Clinical and Experimental Nephrology, 2022, 26(1): 22-28.
[37]Heald-Sargent T A, Forte E, Liu X, et al. New insights into the molecular mechanisms and immune control of cytomegalovirus reactivation[J]. Transplantation, 2020, 104(5): e118-e124.
[38]Ahn R, Schaenman J, Qian Z, et al. Acute and chronic changes in gene expression after CMV DNAemia in kidney transplant recipients[J]. Frontiers in immunology, 2021, 12: 750659.
[39]Han S H, Kumar D, Ferreira V H, et al. Human microRNA responses predict cytomegalovirus replication following solid organ transplantation[J]. The Journal of infectious diseases, 2017, 215(4): 537-546.
[40]Soffritti I, D’Accolti M, Ravegnini G, et al. Modulation of micrornome by human cytomegalovirus and human herpesvirus 6 infection in human dermal fibroblasts: Possible significance in the induction of fibrosis in systemic sclerosis[J]. Cells, 2021, 10(5): 1060.
[41]Afshari A, Yaghobi R, Golshan M. Cytomegalovirus microRNAs level determination in kidney recipients post transplantation[J]. Virology journal, 2022, 19(1): 147.
[42]Fernández-Ruiz M, López-García Á, Valverde-Manso A, et al. Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation[J]. American Journal of Transplantation, 2024, 24(7): 1180-1192.
[43]López-Botet M, De Maria A, Muntasell A, et al. Adaptive NK cell response to human cytomegalovirus: Facts and open issues[C]//Seminars in immunology. Academic Press, 2023, 65: 101706.
[44]Cojohari O, Mahmud J, Altman A M, et al. Human cytomegalovirus mediates unique monocyte-to-macrophage differentiation through the PI3K/SHIP1/Akt signaling network[J]. Viruses, 2020, 12(6): 652.
[45]Zeng J, Zhang Y, Huang C. Macrophages polarization in renal inflammation and fibrosis animal models[J]. Molecular Medicine Reports, 2023, 29(2): 29.
[46]Zahradka I, Tichanek F, Majercikova L, et al. Composition of peripheral blood immune cell compartment in stage 5 chronic kidney disease is affected by smoking and other risk factors associated with systemic inflammatory response[J]. Frontiers in immunology, 2025, 16: 1608206.
[47]Betjes M G H, Weimar W, Litjens N H R. CMV seropositivity determines epoetin dose and hemoglobin levels in patients with CKD[J]. Journal of the American Society of Nephrology, 2009, 20(12): 2661-2666.
[48]Meijers R W J, Litjens N H R, Hesselink D A, et al. Primary cytomegalovirus infection significantly impacts circulating T cells in kidney transplant recipients[J]. American Journal of Transplantation, 2015, 15(12): 3143-3156.
[49]Bhargava R, Li H, Tsokos G C. Pathogenesis of lupus nephritis: the contribution of immune and kidney resident cells[J]. Current Opinion in Rheumatology, 2023, 35(2): 107-116.
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