Pediatric Nephrology

, Volume 33, Issue 7, pp 1105–1111 | Cite as

Bioengineering in renal transplantation: technological advances and novel options

Review
First Online:
Received:
Revised:
Accepted:

Abstract

End-stage kidney disease (ESKD) is one of the most prevalent diseases in the world with significant morbidity and mortality. Current modes of renal replacement therapy include dialysis and renal transplantation. Although dialysis is an acceptable mode of renal replacement therapy, it does have its shortcomings, which include poorer life expectancy compared with renal transplantation, risk of infections and vascular thrombosis, lack of vascular access and absence of biosynthetic functions of the kidney. Renal transplantation, in contrast, is the preferred option of renal replacement therapy, with improved morbidity and mortality rates and quality of life, compared with dialysis. Renal transplantation, however, may not be available to all patients with ESKD. Some of the key factors limiting the availability and efficiency of renal transplantation include shortage of donor organs and the constant risk of rejection with complications associated with over-immunosuppression respectively. This review focuses chiefly on the potential roles of bioengineering in overcoming limitations in renal transplantation via the development of cell-based bioartificial dialysis devices as bridging options before renal transplantation, and the development of new sources of organs utilizing cell and organ engineering.

Keywords

End-stage kidney disease Dialysis Renal transplantation Bioartificial dialysis devices Cell and organ engineering 
This is a preview of subscription content, log in to check access.

Notes

Compliance with ethical standards

Conflicts of interests

The authors declare that they have no conflicts of interest.

References

  1. 1.
    National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratificationGoogle Scholar
  2. 2.
    United States Renal Data System 2016 (2016) USRDS annual data report: epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, BethesdaGoogle Scholar
  3. 3.
    United States Renal Data System 2015 (2015) USRDS annual data report: epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, BethesdaGoogle Scholar
  4. 4.
    ERA-EDTA Registry (2016) ERA-EDTA Registry Annual Report 2014. Academic Medical Center, Department of Medical Informatics, Amsterdam, the NetherlandsGoogle Scholar
  5. 5.
    Harambat J, van Stralen KJ, Kim JJ, Tizard EJ (2012) Epidemiology of chronic kidney disease in children. Pediatr Nephrol 27:363–373CrossRefPubMedGoogle Scholar
  6. 6.
    Orr NI, McDonald SP, McTaggart S, Henning P, Craig JC (2009) Frequency, etiology and treatment of childhood end-stage kidney disease in Australia and New Zealand. Pediatr Nephrol 24:1719–1726CrossRefPubMedGoogle Scholar
  7. 7.
    Zaritsky JJ, Salusky IB, Gales B, Ramos G, Atkinson J, Allestead A, Brandt ML, Goldstein SL (2008) Vascular access complications in long-term pediatric hemodialysis patients. Pediatr Nephrol 23:2061–2065CrossRefPubMedGoogle Scholar
  8. 8.
    Hayes WN, Watson AR, Callaghan N, Wright E, Stefanidis CJ, European Pediatric Dialysis Working Group (2012) Vascular access: choice and complications in European paediatric haemodialysis units. Pediatr Nephrol 27:999–1004CrossRefPubMedGoogle Scholar
  9. 9.
    Schaefer F, Feneberg R, Aksu N, Donmez O, Sadikoglu B, Alexander SR, Mir S, Ha IS, Fischbach M, Simkova E, Watson AR, Moller K, von Baum H, Warady BA (2007) Worldwide variation of dialysis-associated peritonitis in children. Kidney Int 72:1374–1379CrossRefPubMedGoogle Scholar
  10. 10.
    Sethna CB, Bryant K, Munshi R, Warady BA, Richardson T, Lawlor J, Newland JG, Neu A, SCOPE Investigators (2016) Risk factors for and outcomes of catheter-associated peritonitis in children: the SCOPE collaborative. Clin J Am Soc Nephrol 11:1590–1596CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wartman SM, Rosen D, Woo K, Gradman WS, Weaver FA, Rowe V (2014) Outcomes with arteriovenous fistulas in a pediatric population. J Vasc Surg 60:170–174CrossRefPubMedGoogle Scholar
  12. 12.
    Regus S, Almási-Sperling V, Lang W (2016) Pediatric patients undergoing arteriovenous fistula surgery without intraoperative heparin. J Vasc Access 17:494–498CrossRefPubMedGoogle Scholar
  13. 13.
    Goldstein SL, Graham N, Burwinkle T, Warady B, Farrah R, Varni JW (2006) Health-related quality of life in pediatric patients with ESRD. Pediatr Nephrol 21:846–850CrossRefPubMedGoogle Scholar
  14. 14.
    Goldstein SL, Graham N, Warady BA, Seikaly M, McDonald R, Burwinkle TM, Limbers CA, Varni JW (2008) Measuring health-related quality of life in children with ESRD: performance of the generic and ESRD-specific instrument of the Pediatric Quality of Life Inventory (PedsQL). Am J Kidney Dis 51:285–297CrossRefPubMedGoogle Scholar
  15. 15.
    Riaño-Galán I, Málaga S, Rajmil L, Ariceta G, Navarro M, Loris C, Vallo A (2009) Quality of life of adolescents with end-stage renal disease and kidney transplant. Pediatr Nephrol 24:1561–1568CrossRefPubMedGoogle Scholar
  16. 16.
    McDonald SP, Craig JC, Australian and New Zealand Paediatric Nephrology Association (2004) Long-term survival of children with end-stage renal disease. N Engl J Med 350:2654–2662CrossRefPubMedGoogle Scholar
  17. 17.
    Groothoff JW (2005) Long-term outcomes of children with end-stage renal disease. Pediatr Nephrol 20:849–853CrossRefPubMedGoogle Scholar
  18. 18.
    Mitsnefes MM (2008) Cardiovascular complications of pediatric chronic kidney disease. Pediatr Nephrol 23:27–39CrossRefPubMedGoogle Scholar
  19. 19.
    Laupacis A, Keown P, Pus N, Krueger H, Ferguson B, Wong C, Muirhead N (1996) A study of the quality of life and cost-utility of renal transplantation. Kidney Int 50:235–242CrossRefPubMedGoogle Scholar
  20. 20.
    Loubeau PR, Loubeau JM, Jantzen R (2001) The economics of kidney transplantation versus hemodialysis. Prog Transplant 11:291–297CrossRefPubMedGoogle Scholar
  21. 21.
    Wolfe RA, Roys EC, Merion RM (2010) Trends in organ donation and transplantation in the United States, 1999–2008. Am J Transplant 10:961–972CrossRefPubMedGoogle Scholar
  22. 22.
    Saeed B (2012) Pediatric renal transplantation. Int J Organ Transplant Med 3:62–73PubMedPubMedCentralGoogle Scholar
  23. 23.
    Fletcher JT, Nankivell BJ, Alexander SI (2009) Chronic allograft nephropathy. Pediatr Nephrol 24:1465–1471CrossRefPubMedGoogle Scholar
  24. 24.
    Smith JM, Dharnidharka VR (2015) Viral surveillance and subclinical viral infection in pediatric kidney transplantation. Pediatr Nephrol 30:741–748CrossRefPubMedGoogle Scholar
  25. 25.
    Mynarek M, Hussein K, Kreipe HH, Maecker-Kolhoff B (2014) Malignancies after pediatric kidney transplantation: more than PTLD? Pediatr Nephrol 29:1517–1528CrossRefPubMedGoogle Scholar
  26. 26.
    Garro R, Warshaw B, Felner E (2015) New-onset diabetes after kidney transplant in children. Pediatr Nephrol 30:405–416CrossRefPubMedGoogle Scholar
  27. 27.
    Kolff WJ, Berk HTJ (1943) De kunstmatige nier. Een dialysator met groot oppervlak. Ned Tijdschr Geneeskd 87:1684Google Scholar
  28. 28.
    Broers H (2006) Inventor for life, the story of W. J. Kolff, father of artificial organs. B&Vmedia, KampenGoogle Scholar
  29. 29.
    Kolff W (1946) De kunstmatige nier. Kok, KampenGoogle Scholar
  30. 30.
    Vienken J (2009) “Bioengineering for life”: a tribute to Willem Johan Kolff. Nephrol Dial Transplant 24:2299–2301CrossRefPubMedGoogle Scholar
  31. 31.
    Arai Y, Kanda E, Kikuchi H, Yamamura C, Hirasawa S, Aki S, Inaba N, Aoyagi M, Tanaka H, Tamura T, Sasaki S (2014) Decreased mobility after starting dialysis is an independent risk factor for short-term mortality after initiation of dialysis. Nephrology (Carlton) 19:227–233CrossRefGoogle Scholar
  32. 32.
    Humes HD, Buffington DA, MacKay SM, Funke AJ, Weitzel WF (1999) Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat Biotechnol 17:451–455CrossRefPubMedGoogle Scholar
  33. 33.
    Tumlin J, Wali R, Williams W, Murray P, Tolwani AJ, Vinnikova AK, Szerlip HM, Ye J, Paganini EP, Dworkin L, Finkel KW, Kraus MA, Humes HD (2008) Efficacy and safety of renal tubule cell therapy for acute renal failure. J Am Soc Nephrol 19:1034–1040CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Pino CJ, Yevzlin AS, Tumlin J, Humes HD (2012) Cell-based strategies for the treatment of kidney dysfunction: a review. Blood Purif 34:117–123CrossRefPubMedGoogle Scholar
  35. 35.
    Fissell WH, Fleischman AJ, Humes HD, Roy S (2007) Development of continuous implantable renal replacement: past and future. Transl Res 150:327–336CrossRefPubMedGoogle Scholar
  36. 36.
    Fissell WH, Dubnisheva A, Eldridge AN, Fleischman AJ, Zydney AL, Roy S (2009) High-performance silicon nanopore hemofiltration membranes. J Memb Sci 326:58–63CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Conlisk AT, Datta S, Fissell WH, Roy S (2009) Biomolecular transport through hemofiltration membranes. Ann Biomed Eng 37:722–736CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Fissell WH, Roy S (2009) The implantable artificial kidney. Semin Dial 22:665–670CrossRefPubMedGoogle Scholar
  39. 39.
    Fissell WH, Manley S, Westover A, Humes HD, Fleischman AJ, Roy S (2006) Differentiated growth of human renal tubule cells on thin-film and nanostructured materials. ASAIO J 52:221–227CrossRefPubMedGoogle Scholar
  40. 40.
    Kanani DM, Fissell WH, Roy S, Dubnisheva A, Fleischman A, Zydney AL (2010) Permeability—selectivity analysis for ultrafiltration: effect of pore geometry. J Memb Sci 349:405CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kensinger C, Karp S, Kant R, Chui BW, Goldman K, Yeager T, Gould ER, Buck A, Laneve DC, Groszek JJ, Roy S, Fissell WH (2016) First implantation of silicon nanopore membrane hemofilters. ASAIO J 62:491–495CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Buffington DA, Pino CJ, Chen L, Westover AJ, Hageman G, Humes HD (2012) Bioartificial renal epithelial cell system (BRECS): a compact, cryopreservable extracorporeal renal replacement device. Cell Med 4:33–43CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Johnston KA, Westover AJ, Rojas-Pena A, Buffington DA, Pino CJ, Smith PL, Humes HD (2016) Development of a wearable bioartificial kidney using the bioartificial renal epithelial cell system (BRECS). J Tissue Eng Regen Med. doi: 10.1002/term.2206 PubMedGoogle Scholar
  44. 44.
    Westover AJ, Buffington DA, Johnston KA, Smith PL, Pino CJ, Humes HD (2017) A bio-artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock. J Tissue Eng Regen Med 11:649–657CrossRefPubMedGoogle Scholar
  45. 45.
  46. 46.
    Magee CC, Pascual M (2004) Update in renal transplantation. Arch Intern med 164:1373–1388CrossRefPubMedGoogle Scholar
  47. 47.
    Al-Awqati Q, Oliver JA (2002) Stem cells in the kidney. Kidney Int 61:387–395CrossRefPubMedGoogle Scholar
  48. 48.
    Safirstein R (1999) Renal regeneration: reiterating a developmental paradigm. Kidney Int 56:1599–1600CrossRefPubMedGoogle Scholar
  49. 49.
    Nony PA, Schnellmann RG (2003) Mechanisms of renal cell repair and regeneration after acute renal failure. J Pharmacol Exp Ther 304:905–912CrossRefPubMedGoogle Scholar
  50. 50.
    Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G (2004) Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 14:1035–1041PubMedGoogle Scholar
  51. 51.
    Kunter U, Rong S, Djuric Z, Boor P, Müller-Newen G, Yu D, Floege J (2006) Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol 17:2202–2212CrossRefPubMedGoogle Scholar
  52. 52.
    Bussolati B, Hauser PV, Carvalhosa R, Camussi G (2009) Contribution of stem cells to kidney repair. Curr Stem Cell Res Ther 4:2–8CrossRefPubMedGoogle Scholar
  53. 53.
    Li L, Black R, Ma Z, Yang Q, Wang A, Lin F (2012) Use of mouse hematopoietic stem and progenitor cells to treat acute kidney injury. Am J Physiol Renal Physiol 302:F9–F19CrossRefPubMedGoogle Scholar
  54. 54.
    He J, Wang Y, Sun S, Yu M, Wang C, Pei X, Zhu B, Wu J, Zhao W (2012) Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton) 17:493–500CrossRefGoogle Scholar
  55. 55.
    Dorronsoro A, Robbins PD (2013) Regenerating the injured kidney with human umbilical cord mesenchymal stem cell-derived exosomes. Stem Cell Res Ther 4:39CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    He J, Wang Y, Lu X, Zhu B, Pei X, Wu J, Zhao W (2015) Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing. Nephrology (Carlton) 20:591–600CrossRefGoogle Scholar
  57. 57.
    Li Q, Tian SF, Guo Y, Niu X, Hu B, Guo SC, Wang NS, Wang Y (2015) Transplantation of induced pluripotent stem cell-derived renal stem cells improved acute kidney injury. Cell Biosci 5:45CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Jia X, Xie X, Feng G, Lű H, Zhao Q, Che Y, Zheng Y, Han Z, Xu Y, Li Z, Kong D (2012) Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury. BMC Nephrol 13:105CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Zhu XY, Lerman A, Lerman LO (2013) Concise review: mesenchymal stem cell treatment for ischemic kidney disease. Stem Cells 31:1731–1736CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Steenhard BM, Isom KS, Cazcarro P, Dunmore JH, Godwin AR, St John PL, Abrahamson DR (2005) Integration of embryonic stem cells in metanephric kidney organ culture. J Am Soc Nephrol 16:1623–1631CrossRefPubMedGoogle Scholar
  61. 61.
    Kobayashi T, Tanaka H, Kuwana H, Inoshita S, Teraoka H, Sasaki S, Terada Y (2005) Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells. Biochem Biophys Res Commun 336:585–595CrossRefPubMedGoogle Scholar
  62. 62.
    Kim D, Dressler GR (2005) Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia. J Am Soc Nephrol 16:3527–3534CrossRefPubMedGoogle Scholar
  63. 63.
    Morizane R, Monkawa T, Itoh H (2009) Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro. Biochem Biophys Res Commun 390:1334–1339CrossRefPubMedGoogle Scholar
  64. 64.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefPubMedGoogle Scholar
  65. 65.
    Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, Li W, Weng Z, Chen J, Ni S, Chen K, Li Y, Liu X, Xu J, Zhang S, Li F, He W, Labuda K, Song Y, Peterbauer A, Wolbank S, Redl H, Zhong M, Cai D, Zeng L, Pei D (2010) Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6:71–79CrossRefPubMedGoogle Scholar
  66. 66.
    Horster MF, Braun GS, Huber SM (1999) Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation. Physiol Rev 79:1157–1191CrossRefPubMedGoogle Scholar
  67. 67.
    Woolf AS, Palmer SJ, Snow ML, Fine LG (1990) Creation of a functioning chimeric mammalian kidney. Kidney Int 38:991–997CrossRefPubMedGoogle Scholar
  68. 68.
    Rogers SA, Lowell JA, Hammerman NA, Hammerman MR (1998) Transplantation of developing metanephroi into adult rats. Kidney Int 54:27–37CrossRefPubMedGoogle Scholar
  69. 69.
    Hammerman MR (2003) Therapeutic promise of embryonic kidney transplantation. Nephron Exp Nephrol 93:e58CrossRefPubMedGoogle Scholar
  70. 70.
    Gilbert TW, Sellaro TL, Badylak SF (2006) Decellularization of tissues and organs. Biomaterials 27:3675–3683PubMedGoogle Scholar
  71. 71.
    Ross EA, Williams MJ, Hamazaki T, Terada N, Clapp WL, Adin C, Ellison GW, Jorgensen M, Batich CD (2009) Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. J Am Soc Nephrol 20:2338–2347CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Nakayama KH, Batchelder CA, Lee CI, Tarantal AF (2010) Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. Tissue Eng Part A 16:2207–2216CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC (2013) Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med 19:646–651CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Ott HC (2015) Perfusion decellularization of discarded human kidneys: a valuable platform for organ regeneration. Transplantation 99:1753CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Mirmalek-Sani SH, Sullivan DC, Zimmerman C, Shupe TD, Petersen BE (2013) Immunogenicity of decellularized porcine liver for bioengineered hepatic tissue. Am J Pathol 183:558–565CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Salvatori M, Peloso A, Katari R, Soker S, Lerut JP, Stratta RJ, Orlando G (2015) Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand. Xenotransplantation 22:1–6CrossRefPubMedGoogle Scholar
  77. 77.
    Hull CW (1986) Apparatus for production of three-dimensional objects by stereolithography. US4575330 A (Google Patents, 1986)Google Scholar
  78. 78.
    Zopf DA, Hollister SJ, Nelson ME, Ohye RG, Green GE (2013) Bioresorbable airway splint created with a three-dimensional printer. N Engl J Med 368:2043–2045CrossRefPubMedGoogle Scholar
  79. 79.
    Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773–785CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Division of Pediatric Nephrology, Dialysis and Renal TransplantationShaw-National Kidney Foundation, National University Hospital Children’s Kidney Centre, Khoo Teck Puat-National University, Children’s Medical Institute, National University Health SystemSingaporeSingapore
  2. 2.Department of Pediatrics, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Personalised recommendations