Skip to main content
SpringerLink
Log in

Pathogenesis of Chronic Allograft Dysfunction Progress to Renal Fibrosis

  • Chapter
  • First Online:
Renal Fibrosis: Mechanisms and Therapies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1165))

Abstract

Kidney transplantation is a life-change measurement for the patients of end-stage renal disease (ESRD). However, the renal allograft cannot avoid initial acute kidney injury (AKI) and subsequent chronic allograft dysfunction (CAD), gradually develops fibrosis and eventually loses function. It is imperative to disclose the pathogenesis of AKI and CAD in order to facilitate interventions. We have studied the involvement of immunity, inflammation, and apoptosis in ischemia-reperfusion injury (IRI) and/or immunosuppressant induced AKI models, with associated chronic damage. Our research mainly focused on tubular epithelial cells (TECs) that are passive victims and also active participators in injury and mediate following repair or fibrosis. Targeting not only fibroblasts/myofibroblasts, but also TECs, might be a fundamental strategy to prevent and treat renal fibrosis. We have also evaluated the potential application of siRNA targeting caspase-3 and tissue protective erythropoietin derivatives, HBSP and CHBP, aiming to treat AKI and prevent CAD. Significant improvements have been obtained, but timely diagnosis and precise therapy of AKI and prevention of CAD progressing to ESRD are still very challenging. Modern technologies such as microarray and sequencing analysis have been used to identify biomarkers and potentially facilitate individual cell target treatment for transplant patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anders HJ, Ryu M (2011) Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis. Kidney Int 80:915–925

    Article  CAS  Google Scholar 

  • Baisantry A, Bhayana S, Rong S, Ermeling E, Wrede C et al (2016) Autophagy induces prosenescent changes in proximal tubular S3 segments. J Am Soc Nephrol JASN 27:1609–1616

    Article  CAS  Google Scholar 

  • Brooks CR, Yeung MY, Brooks YS, Chen H, Ichimura T et al (2015) KIM-1-/TIM-1-mediated phagocytosis links ATG5-/ULK1-dependent clearance of apoptotic cells to antigen presentation. EMBO J 34:2441–2464

    Article  CAS  Google Scholar 

  • Chevalier RL (2017) Evolutionary nephrology. Kidney Int Rep 2:302–317

    Article  Google Scholar 

  • Collino M, Thiemermann C, Cerami A, Brines M (2015) Flipping the molecular switch for innate protection and repair of tissues: long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Pharmacol Ther 151:32–40

    Article  CAS  Google Scholar 

  • Dahan A, Brines M, Niesters M, Cerami A, van Velzen M (2016) Targeting the innate repair receptor to treat neuropathy. Pain Rep 1:e566

    Article  Google Scholar 

  • Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13:722–737

    Article  CAS  Google Scholar 

  • di Paolo S, Teutonico A, Stallone G, Infante B, Schena A et al (2004) Cyclosporin exposure correlates with 1 year graft function and histological damage in renal transplanted patients. Nephrol Dial Transplant 19:2107–2112

    Article  Google Scholar 

  • Du C, Ren Y, Yao F, Duan J, Zhao H et al (2017) Sphingosine kinase 1 protects renal tubular epithelial cells from renal fibrosis via induction of autophagy. Int J Biochem Cell Biol 90:17–28

    Article  CAS  Google Scholar 

  • Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B et al (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357:2562–2575

    Article  CAS  Google Scholar 

  • Ekberg H, Bernasconi C, Tedesco-Silva H, Vitko S, Hugo C et al (2009) Calcineurin inhibitor minimization in the symphony study: observational results 3 years after transplantation. Am J Transplant (Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons) 9:1876–1885

    Article  CAS  Google Scholar 

  • Elliott MR, Koster KM, Murphy PS (2017) Efferocytosis signaling in the regulation of macrophage inflammatory responses. J Immunol 198:1387–1394

    Article  CAS  Google Scholar 

  • Gilboa D, Haim-Ohana Y, Deshet-Unger N, Ben-Califa N, Hiram-Bab S et al (2017) Erythropoietin enhances Kupffer cell number and activity in the challenged liver. Sci Rep 7:10379

    Article  Google Scholar 

  • Gobe GC, Bennett NC, West M, Colditz P, Brown L et al (2014) Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury. Am J Physiol Renal Physiol 306:F681–F692

    Article  CAS  Google Scholar 

  • Gorsuch WB, Chrysanthou E, Schwaeble WJ, Stahl GL (2012) The complement system in ischemia-reperfusion injuries. Immunobiology 217:1026–1033

    Article  CAS  Google Scholar 

  • Haylor JL, Harris KP, Nicholson ML, Waller HL, Huang Q et al (2011) Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats. Exp Biol Med (Maywood) 236:755–763

    Article  CAS  Google Scholar 

  • Hu L, Yang C, Zhao T, Xu M, Tang Q et al (2012) Erythropoietin ameliorates renal ischemia and reperfusion injury via inhibiting tubulointerstitial inflammation. J Surg Res 176:260–266

    Article  CAS  Google Scholar 

  • Humphreys BD, Czerniak S, DiRocco DP, Hasnain W, Cheema R et al (2011) Repair of injured proximal tubule does not involve specialized progenitors. Proc Natl Acad Sci USA 108:9226–9231

    Article  CAS  Google Scholar 

  • Ising C, Heneka MT (2018) Functional and structural damage of neurons by innate immune mechanisms during neurodegeneration. Cell Death Dis 9:120

    Article  Google Scholar 

  • Jia Y, Zheng Z, Guan M, Zhang Q, Li Y et al (2018) Exendin-4 ameliorates high glucose-induced fibrosis by inhibiting the secretion of miR-192 from injured renal tubular epithelial cells. Exp Mol Med 50:56

    Article  Google Scholar 

  • Johnston JR, Brenner BM, Hebert SC (1987) Uninephrectomy and dietary protein affect fluid absorption in rabbit proximal straight tubules. Am J Physiol 253:F222–F233

    CAS  PubMed  Google Scholar 

  • Kang HM, Ahn SH, Choi P, Ko YA, Han SH et al (2015) Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med 21:37–46

    Article  CAS  Google Scholar 

  • Krauskopf A, Lhote P, Petermann O, Ruegg UT, Buetler TM (2005) Cyclosporin A generates superoxide in smooth muscle cells. Free Radic Res 39:913–919

    Article  CAS  Google Scholar 

  • Kriz W, Kaissling B, Le Hir M (2011) Epithelial-mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy? J Clin Investig 121:468–474

    Article  CAS  Google Scholar 

  • Kusaba T, Lalli M, Kramann R, Kobayashi A, Humphreys BD (2014) Differentiated kidney epithelial cells repair injured proximal tubule. Proc Natl Acad Sci USA 111:1527–1532

    Article  CAS  Google Scholar 

  • Lee TS, Lu KY, Yu YB, Lee HT, Tsai FC (2015) β common receptor mediates erythropoietin-conferred protection on OxLDL-induced lipid accumulation and inflammation in macrophages. Mediators Inflamm 2015:439759

    PubMed  PubMed Central  Google Scholar 

  • Li H, Peng X, Wang Y, Cao S, Xiong L et al (2016) Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis. Autophagy 12:1472–1486

    Article  CAS  Google Scholar 

  • Lifshitz L, Tabak G, Gassmann M, Mittelman M, Neumann D (2010) Macrophages as novel target cells for erythropoietin. Haematologica 95:1823–1831

    Article  CAS  Google Scholar 

  • Liu A, Wu J, Yang C, Wu Y, Zhang Y et al (2018a) TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury. Sci Rep 8:5510

    Article  Google Scholar 

  • Liu BC, Tang TT, Lv LL, Lan HY (2018b) Renal tubule injury: a driving force toward chronic kidney disease. Kidney Int 93:568–579

    Article  CAS  Google Scholar 

  • Livingston MJ, Ding HF, Huang S, Hill JA, Yin XM et al (2016) Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy 12:976–998

    Article  CAS  Google Scholar 

  • Luo B, Jiang M, Yang X, Zhang Z, Xiong J et al (2013) Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis. Biochem Biophys Acta 1832:1260–1270

    CAS  PubMed  Google Scholar 

  • Luo B, Gan W, Liu Z, Shen Z, Wang J et al (2016a) Erythropoeitin signaling in macrophages promotes dying cell clearance and immune tolerance. Immunity 44:287–302

    Article  CAS  Google Scholar 

  • Luo B, Wang J, Liu Z, Shen Z, Shi R et al (2016b) Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution. Nat Commun 7:12177

    Article  Google Scholar 

  • Lv LL, Feng Y, Wen Y, Wu WJ, Ni HF et al (2018) Exosomal CCL2 from tubular epithelial cells is critical for albumin-induced tubulointerstitial inflammation. J Am Soc Nephrol JASN 29:919–935

    Article  CAS  Google Scholar 

  • Menon MC, Murphy B, Heeger PS (2017) Moving biomarkers toward clinical implementation in kidney transplantation. J Am Soc Nephrol 28:735–747

    Article  CAS  Google Scholar 

  • Mulay SR, Desai J, Kumar SV, Eberhard JN, Thomasova D et al (2016) Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. Nat Commun 7:10274

    Article  CAS  Google Scholar 

  • Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD et al (2003) The natural history of chronic allograft nephropathy. N Engl J Med 349:2326–2333

    Article  CAS  Google Scholar 

  • Nath KA, Croatt AJ, Hostetter TH (1990) Oxygen consumption and oxidant stress in surviving nephrons. Am J Physiol 258:F1354–F1362

    CAS  PubMed  Google Scholar 

  • Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, May 2018, Page i103, https://doi.org/10.1093/ndt/gfy104.FP214

    Article  Google Scholar 

  • Nicholson ML, McCulloch TA, Harper SJ, Wheatley TJ, Edwards CM et al (1996) Early measurement of interstitial fibrosis predicts long-term renal function and graft survival in renal transplantation. Br J Surg 83:1082–1085

    Article  CAS  Google Scholar 

  • Poon IK, Lucas CD, Rossi AG, Ravichandran KS (2014) Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 14:166–180

    Article  CAS  Google Scholar 

  • Ricklin D, Lambris JD (2013) Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol 190:3839–3847

    Article  CAS  Google Scholar 

  • Saqib N, Duling L, Krier K, Howdieshell TR (2009) Temporal and spatial expression of erythropoietin, erythropoietin receptor, and common beta receptor in wound fluid and granulation tissue. Wounds 21:164–171

    PubMed  Google Scholar 

  • Sato Y, Yanagita M (2013) Renal anemia: from incurable to curable. Am J Physiol Renal Physiol 305:F1239–F1248

    Article  CAS  Google Scholar 

  • Sato Y, Yanagita M (2017) Resident fibroblasts in the kidney: a major driver of fibrosis and inflammation. Inflamm Regen 37:17

    Article  Google Scholar 

  • Sis B, Einecke G, Chang J, Hidalgo LG, Mengel M et al (2010) Cluster analysis of lesions in nonselected kidney transplant biopsies: microcirculation changes, tubulointerstitial inflammation and scarring. Am J Transplant (Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons) 10:421–430

    Article  CAS  Google Scholar 

  • Solez K, Colvin RB, Racusen LC, Sis B, Halloran PF et al (2007) Banff ‘05 meeting report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (‘CAN’). Am J Transplant 7:518–526

    Article  CAS  Google Scholar 

  • Solez K, Colvin RB, Racusen LC, Haas M, Sis B et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant (Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons) 8:753–760

    Article  CAS  Google Scholar 

  • Takahashi A, Takabatake Y, Kimura T, Maejima I, Namba T et al (2017) Autophagy inhibits the accumulation of advanced glycation end products by promoting lysosomal biogenesis and function in the kidney proximal tubules. Diabetes 66:1359–1372

    Article  CAS  Google Scholar 

  • Thurman JM, Ljubanovic D, Edelstein CL, Gilkeson GS, Holers VM (2003) Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol 170:1517–1523

    Article  CAS  Google Scholar 

  • Thurman JM, Royer PA, Ljubanovic D, Dursun B, Lenderink AM et al (2006) Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injury. J Am Soc Nephrol 17:707–715

    Article  CAS  Google Scholar 

  • Ueba H, Shiomi M, Brines M, Yamin M, Kobayashi T et al (2013) Suppression of coronary atherosclerosis by helix B surface Peptide, a nonerythropoietic, tissue-protective compound derived from erythropoietin. Mol Med 19:195–202

    Article  Google Scholar 

  • Vanhove T, Goldschmeding R, Kuypers D (2017) Kidney fibrosis: origins and interventions. Transplantation 101:713–726

    Article  Google Scholar 

  • Varga ZV, Erdelyi K, Paloczi J, Cinar R, Zsengeller ZK et al (2018) Disruption of renal arginine metabolism promotes kidney injury in hepatorenal syndrome. Hepatology 68(4):1519–1533

    Article  CAS  Google Scholar 

  • Viau A, Bienaime F, Lukas K, Todkar AP, Knoll M et al (2018) Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney. EMBO J 37(15):e98615

    Article  Google Scholar 

  • Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B et al (2005) Costimulation blockade with belatacept in renal transplantation. N Engl J Med 353:770–781

    Article  CAS  Google Scholar 

  • Vitalone MJ, Ganguly B, Hsieh S, Latek R, Kulbokas EJ et al (2014) Transcriptional profiling of belatacept and calcineurin inhibitor therapy in renal allograft recipients. Am J Transplant (Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons) 14:1912–1921

    Article  CAS  Google Scholar 

  • Wang S, Zhang C, Hu L, Yang C (2016) Necroptosis in acute kidney injury: a shedding light. Cell Death Dis 7:e2125

    Article  CAS  Google Scholar 

  • Wu Y, Zhang J, Liu F, Yang C, Zhang Y et al (2013) Protective effects of HBSP on ischemia reperfusion and cyclosporine a induced renal injury. Clin Dev Immunol 2013:758159

    PubMed  PubMed Central  Google Scholar 

  • Wu Q, Wang X, Nepovimova E, Wang Y, Yang H et al (2018) Mechanism of cyclosporine A nephrotoxicity: oxidative stress, autophagy, and signalings. Food Chem Toxicol 118:889–907

    Article  CAS  Google Scholar 

  • Yang B, El Nahas AM, Thomas GL, Haylor JL, Watson PF et al (2001) Caspase-3 and apoptosis in experimental chronic renal scarring. Kidney Int 60:1765–1776

    Article  CAS  Google Scholar 

  • Yang B, Johnson TS, Haylor JL, Wagner B, Watson PF et al (2003) Effects of caspase inhibition on the progression of experimental glomerulonephritis. Kidney Int 63:2050–2064

    Article  CAS  Google Scholar 

  • Yang B, El Nahas AM, Fisher M, Wagner B, Huang L et al (2004) Inhibitors directed towards Caspase-1 and -3 are less effective than pan caspase inhibition in preventing renal proximal tubular cell apoptosis. Nephron Exp Nephrol 96:E39–E51

    Article  CAS  Google Scholar 

  • Yang B, Jain S, Pawluczyk IZ, Imtiaz S, Bowley L et al (2005) Inflammation and caspase activation in long-term renal ischemia/reperfusion injury and immunosuppression in rats. Kidney Int 68:2050–2067

    Article  CAS  Google Scholar 

  • Yang B, Harris KP, Jain S, Nicholson ML (2007) Caspase-7, Fas and FasL in long-term renal ischaemia/reperfusion and immunosuppressive injuries in rats. Am J Nephrol 27:397–408

    Article  CAS  Google Scholar 

  • Yang B, Hosgood SA, Harper SJ, Nicholson ML (2010) Leucocyte depletion improves renal function in porcine kidney hemoreperfusion through reduction of myeloperoxidase + cells, caspase-3, IL-1beta, and tubular apoptosis. J Surg Res 164:e315–e324

    Article  CAS  Google Scholar 

  • Yang B, Elias JE, Bloxham M, Nicholson ML (2011a) Synthetic small interfering RNA down-regulates caspase-3 and affects apoptosis, IL-1 beta, and viability of porcine proximal tubular cells. J Cell Biochem 112:1337–1347

    Article  CAS  Google Scholar 

  • Yang B, Hosgood SA, Bagul A, Waller HL, Nicholson ML (2011b) Erythropoietin regulates apoptosis, inflammation and tissue remodelling via caspase-3 and IL-1beta in isolated hemoperfused kidneys. Eur J Pharmacol 660:420–430

    Article  CAS  Google Scholar 

  • Yang B, Hosgood SA, Nicholson ML (2011c) Naked small interfering RNA of caspase-3 in preservation solution and autologous blood perfusate protects isolated ischemic porcine kidneys. Transplantation 91:501–507

    Article  CAS  Google Scholar 

  • Yang B, Hosgood SA, Da Z, Harper SJ, Waller HL et al (2012) Biomarkers assessing warm ischemic injury using an isolated porcine kidney hemoreperfusion model. Exp Biol Med 237:1462–1473

    Article  CAS  Google Scholar 

  • Yang C, Jia Y, Zhao T, Xue Y, Zhao Z et al (2013a) Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys. J Surg Res 181:342–354

    Article  CAS  Google Scholar 

  • Yang C, Li L, Xue Y, Zhao Z, Zhao T et al (2013b) Innate immunity activation involved in unprotected porcine auto-transplant kidneys preserved by naked caspase-3 siRNA. J Transl Med 11:210

    Article  Google Scholar 

  • Yang C, Zhao T, Lin M, Zhao Z, Hu L et al (2013c) Helix B surface peptide administered after insult of ischemia reperfusion improved renal function, structure and apoptosis through beta common receptor/erythropoietin receptor and PI3K/Akt pathway in a murine model. Exp Biol Med 238:111–119

    Article  CAS  Google Scholar 

  • Yang C, Zhao T, Zhao Z, Jia Y, Li L et al (2014) Serum-stabilized naked caspase-3 siRNA protects autotransplant kidneys in a porcine model. Mol Ther J Am Soc Gene Ther 22:1817–1828

    Article  CAS  Google Scholar 

  • Yang C, Hosgood SA, Meeta P, Long Y, Zhu T et al (2015a) Cyclic helix B peptide in preservation solution and autologous blood perfusate ameliorates ischemia-reperfusion injury in isolated porcine kidneys. Transplant Direct 1:e6

    Article  Google Scholar 

  • Yang C, Zhang C, Zhao Z, Zhu T, Yang B (2015b) Fighting against kidney diseases with small interfering RNA: opportunities and challenges. J Transl Med 13:39

    Article  Google Scholar 

  • Yang B, Lan S, Dieude M, Sabo-Vatasescu JP, Karakeussian-Rimbaud A et al (2018) Caspase-3 is a pivotal regulator of microvascular rarefaction and renal fibrosis after ischemia-reperfusion injury. J Am Soc Nephrol 29:1900–1916

    Article  CAS  Google Scholar 

  • Zhang Y, Chen W, Wu Y, Yang B (2017) Renoprotection and mechanisms of erythropoietin and its derivatives helix B surface peptide in kidney injuries. Curr Protein Pept Sci 18:1183–1190

    CAS  PubMed  Google Scholar 

  • Zipfel PF, Skerka C (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9:729–740

    Article  CAS  Google Scholar 

  • Zwaini Z, Dai H, Stover C, Yang B (2017) Role of complement properdin in renal ischemia-reperfusion injury. Curr Gene Ther 17:411–423

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The studies cited in this chapter were supported by the Zhongshan Hospital of Fudan University; the Affiliated Hospital of Nantong University and the Medical School of Nantong University; and the University Hospitals of Leicester (UHL) and the University of Leicester. We also would like to acknowledge the support of various project grants such as the Kidney Care Appeal from UHL (to BY), the UK–China Fellowship for Excellence from the Department for Business Innovation and Skills (to BY), the National Natural Foundation of China (81400752 and 81770746 to CY and 81170689, 81570677 and 81873622 to BY), the National Key R&D Program of China (2018YFA0107502 to CY), the Medical and Health Talents Training Plan for the Excellent Youth of Shanghai Municipal (2018YQ50 to CY) and Shanghai Rising-Star Program (19QA1406300 to CY).

Author information

Authors and Affiliations

  1. Department of Urology, Zhongshan Hospital, Zhangjiang Technology Institute, Fudan University, Shanghai, China

    Cheng Yang & Ruochen Qi

  2. Shanghai Key Laboratory of Organ Transplantation, Shanghai, China

    Cheng Yang & Ruochen Qi

  3. Nantong-Leicester Joint Institute of Kidney Science, Department of Nephrology, Affiliated Hospital of Nantong University, Renal Group, Basic Medical Research Centre, Medical College of Nantong University, Nantong, 226001, Jiangsu, China

    Bin Yang

  4. Department of Cardiovascular Sciences, University of Leicester, University Hospitals of Leicester, Leicester, LE1 7RH, UK

    Bin Yang

Authors
  1. Cheng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruochen Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bin Yang .

Editor information

Editors and Affiliations

  1. Zhongda Hospital, Southeast University School of Medicine, Southeast University, Nanjing, Jiangsu, China

    Bi-Cheng Liu

  2. Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, Hong Kong

    Hui-Yao Lan

  3. Zhongda Hospital, Southeast University School of Medicine, Southeast University, Nanjing, Jiangsu, China

    Lin-Li Lv

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yang, C., Qi, R., Yang, B. (2019). Pathogenesis of Chronic Allograft Dysfunction Progress to Renal Fibrosis. In: Liu, BC., Lan, HY., Lv, LL. (eds) Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology, vol 1165. Springer, Singapore. https://doi.org/10.1007/978-981-13-8871-2_6

Download citation

Publish with us

Policies and ethics

Search

Navigation