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Technology Insight: innovative options for end-stage renal disease—from kidney refurbishment to artificial kidney

Nature Clinical Practice Nephrology volume 3, pages 564–572 (2007)Cite this article

Abstract

The steadily growing number of patients with chronic kidney disease who will eventually develop end-stage renal disease, together with the qualitative limitations of currently available renal replacement therapies, have triggered the exploration of innovative strategies for renal replacement therapy and for salvage of renal function. Currently, new hemodialysis modalities and membranes are being used with the aim of increasing clearance of uremic toxins to afford better metabolic control. In addition to these conventional approaches, there are four innovative potential solutions to the problem of replacing renal function when kidneys fail. The first is a small, implantable device with the potential to be supplemented with human cells ('artificial kidney'). The second involves restoration of the damaged kidney by harnessing recent advances in stem-cell technology and knowledge of developmental programing ('refurbished kidney'). The third is (partially) growing a kidney in vitro with the use of therapeutic cloning ('cultured kidney'). The fourth innovative solution involves the use of other organs to replace various renal functions ('distributed kidney'). In this article we review the efforts that have been made to improve renal replacement therapies, and explore innovative approaches. We will not cover all potential solutions in detail. Rather, we aim to indicate directions of future endeavor and arouse enthusiasm in clinicians and scientists for exploration of these exciting avenues.

Key Points

  • Unless conventional dialysis techniques can be considerably improved, the ever-increasing burden of chronic kidney disease will necessitate the development of innovative new renal replacement therapies

  • The use of xenotransplantation continues to be investigated

  • Nanotechnology could be a platform for the development of a lightweight and reliable artificial kidney that could be worn or implanted

  • The integration of new nephrons, repair of native renal tissue by using stem cells derived from bone marrow or kidney, and generation of replacement tissue using nuclear transplantation and embryonic stem cells, are all promising avenues of investigation

  • The 'hosting' of renal functions in nonrenal tissues, and harnessing of developmental plasticity in adults, might also help to overcome kidney dysfunction

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Figure 1: Principle of a mechanical two-step filter device.
Figure 2: The developmental plasticity continuum, from the perinatal programing hypothesis to refurbishment strategies.
Figure 3: Persistent lowering of arterial pressure with brief antihypertensive therapy (30 mg/kg/day enalapril plus low salt intake [ELS]) in adult spontaneously hypertensive rats (CON).

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References

  1. Vanholder R et al. (2005) The European artificial organ scene: present status. Artif Organs 29: 498–506

    Article  Google Scholar 

  2. Humes HD et al. (2006) The future of hemodialysis membranes. Kidney Int 69: 1115–1119

    Article  CAS  Google Scholar 

  3. Kooistra MP (2003) Frequent prolonged home haemodialysis: three old concepts, one modern solution. Nephrol Dial Transplant 18: 16–19

    Article  Google Scholar 

  4. Eknoyan G et al. (2002) Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 347: 2010–2019

    Article  Google Scholar 

  5. Penne EL et al. (2005) Resolving controversies regarding hemodiafiltration versus hemodialysis: the Dutch Convective Transport Study. Semin Dial 18: 47–51

    Article  Google Scholar 

  6. Ward RA (2005) Protein-leaking membranes for hemodialysis: a new class of membranes in search of an application? J Am Soc Nephrol 16: 2421–2430

    Article  CAS  Google Scholar 

  7. Leonard EF et al. (2004) Dialysis without membranes: how and why? Blood Purif 22: 92–100

    Article  Google Scholar 

  8. Humes HD et al. (1999) Tissue engineering of a bioartificial renal tubule assist device: in vitro transport and metabolic characteristics. Kidney Int 55: 2502–2514

    Article  CAS  Google Scholar 

  9. Diaz-Buxo JA (2005) Access and continuous flow peritoneal dialysis. Perit Dial Int 25 (Suppl 3): S102–S104

    PubMed  Google Scholar 

  10. Hoff CM and Shockley TR (2002) Peritoneal dialysis in the 21st century: the potential of gene therapy. J Am Soc Nephrol 13 (Suppl 1): S117–S124

    CAS  PubMed  Google Scholar 

  11. Kozlowski T et al. (1998) Depletion of anti-Gal(alpha)1-3Gal antibody in baboons by specific alpha-Gal immunoaffinity columns. Xenotransplantation 5: 122–131

    Article  CAS  Google Scholar 

  12. McKenzie IF et al. (1999) Definition and characterization of chicken Gal alpha(1,3)Gal antibodies. Transplantation 67: 864–870

    Article  CAS  Google Scholar 

  13. Zhong R et al. (2003) Improvement in human decay accelerating factor transgenic porcine kidney xenograft rejection with intravenous administration of gas914, a polymeric form of alphaGAL. Transplantation 75: 10–19

    Article  CAS  Google Scholar 

  14. Lai L et al. (2002) Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295: 1089–1092

    Article  CAS  Google Scholar 

  15. Yamada K et al. (2005) Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med 11: 32–34

    Article  CAS  Google Scholar 

  16. Soin B et al. (2001) Physiological aspects of pig-to-primate renal xenotransplantation. Kidney Int 60: 1592–1597

    Article  CAS  Google Scholar 

  17. Butler D (1998) Last chance to stop and think on risks of xenotransplants. Nature 391: 320–324

    CAS  PubMed  Google Scholar 

  18. Paradis K et al. (1999) Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. Science 285: 1236–1241

    Article  CAS  Google Scholar 

  19. Wilson CA et al. (2000) Extended analysis of the in vitro tropism of porcine endogenous retrovirus. J Virol 74: 49–56

    Article  CAS  Google Scholar 

  20. Nissenson AR et al. (2005) The human nephron filter: toward a continuously functioning, implantable artificial nephron system. Blood Purif 23: 269–274

    Article  Google Scholar 

  21. Drexler KE (2003) If atomic precision is unfeasible, so is life. Nature 422: 257

    Article  CAS  Google Scholar 

  22. Shin M et al. (2004) Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane). Biomed Microdevices 6: 269–278

    Article  CAS  Google Scholar 

  23. Brodie JC and Humes HD (2005) Stem cell approaches for the treatment of renal failure. Pharmacol Rev 57: 299–313

    Article  Google Scholar 

  24. Atala A and Koh CJ (2004) Tissue engineering applications of therapeutic cloning. Annu Rev Biomed Eng 6: 27–40

    Article  CAS  Google Scholar 

  25. Laflamme MA and Murry CE (2005) Regenerating the heart. Nat Biotechnol 23: 845–856

    Article  CAS  Google Scholar 

  26. Steer DL and Nigam SK (2004) Developmental approaches to kidney tissue engineering. Am J Physiol Renal Physiol 286: F1–F7

    Article  CAS  Google Scholar 

  27. Woolf AS et al. (1990) Creation of a functioning chimeric mammalian kidney. Kidney Int 38: 991–997

    Article  CAS  Google Scholar 

  28. Rogers SA et al. (1998) Transplantation of developing metanephroi into adult rats. Kidney Int 54: 27–37

    Article  CAS  Google Scholar 

  29. Dekel B et al. (2002) Engraftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal human kidney development. J Am Soc Nephrol 13: 977–990

    CAS  PubMed  Google Scholar 

  30. Schmidt-Ott KM et al. (2005) Novel regulators of kidney development from the tips of the ureteric bud. J Am Soc Nephrol 16: 1993–2002

    Article  CAS  Google Scholar 

  31. Rookmaaker MB et al. (2002) Bone-marrow-derived cells contribute to endothelial repair after thrombotic microangiopathy. Blood 99: 1095

    Article  CAS  Google Scholar 

  32. Cornacchia F et al. (2001) Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors. J Clin Invest 108: 1649–1656

    Article  CAS  Google Scholar 

  33. Imasawa T et al. (2001) The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells. J Am Soc Nephrol 12: 1401–1409

    CAS  PubMed  Google Scholar 

  34. Kale S et al. (2003) Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest 112: 42–49

    Article  CAS  Google Scholar 

  35. Gupta S et al. (2002) A role for extrarenal cells in the regeneration following acute renal failure. Kidney Int 62: 1285–1290

    Article  Google Scholar 

  36. Feng Z et al. (2005) Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors. Am J Pathol 167: 355–363

    Article  Google Scholar 

  37. Oliver JA et al. (2004) The renal papilla is a niche for adult kidney stem cells. J Clin Invest 114: 795–804

    Article  CAS  Google Scholar 

  38. Maeshima A et al. (2006) Adult kidney tubular cell population showing phenotypic plasticity, tubulogenic capacity, and integration capability into developing kidney. J Am Soc Nephrol 17: 188–198

    Article  CAS  Google Scholar 

  39. Lange C et al. (2005) Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int 68: 1613–1617

    Article  Google Scholar 

  40. Little MH (2006) Regrow or repair: potential regenerative therapies for the kidney. J Am Soc Nephrol 17: 2390–2401

    Article  Google Scholar 

  41. Choi JH et al. (2004) Decreased number and impaired angiogenic function of endothelial progenitor cells in patients with chronic renal failure. Arterioscler Thromb Vasc Biol 24: 1246–1252

    Article  CAS  Google Scholar 

  42. Lin F et al. (2005) Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 115: 1756–1764

    Article  CAS  Google Scholar 

  43. Duffield JS et al. (2005) Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 115: 1743–1755

    Article  CAS  Google Scholar 

  44. Thomson JA et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147

    Article  CAS  Google Scholar 

  45. Lanza RP et al. (2002) Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol 20: 689–696

    Article  CAS  Google Scholar 

  46. Koh CJ and Atala A (2004) Tissue engineering, stem cells, and cloning: opportunities for regenerative medicine. J Am Soc Nephrol 15: 1113–1125

    Article  Google Scholar 

  47. Okie S (2005) Stem-cell research—signposts and roadblocks. N Engl J Med 353: 1–5

    Article  CAS  Google Scholar 

  48. Chung Y et al. (2006) Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres. Nature 439: 216–219

    Article  CAS  Google Scholar 

  49. Solter D (2000) Mammalian cloning: advances and limitations. Nat Rev Genet 1: 199–207

    Article  CAS  Google Scholar 

  50. Hochedlinger K and Jaenisch R (2003) Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med 349: 275–286

    Article  CAS  Google Scholar 

  51. Tamashiro KL et al. (2002) Cloned mice have an obese phenotype not transmitted to their offspring. Nat Med 8: 262–267

    Article  CAS  Google Scholar 

  52. Gluckman PD and Hanson MA (2004) Living with the past: evolution, development, and patterns of disease. Science 305: 1733–1736

    Article  CAS  Google Scholar 

  53. Henderson LW (2000) Future developments in the treatment of end-stage renal disease: a North American perspective. Am J Kidney Dis 35 (Suppl S): S106–S116

    Article  CAS  Google Scholar 

  54. Bateson P et al. (2004) Developmental plasticity and human health. Nature 430: 419–421

    Article  CAS  Google Scholar 

  55. Barker DJ (2004) The developmental origins of well-being. Philos Trans R Soc Lond B Biol Sci 359: 1359–1366

    Article  CAS  Google Scholar 

  56. Racasan S et al. (2005) Programming blood pressure in adult SHR by shifting perinatal balance of NO and reactive oxygen species toward NO: the inverted Barker phenomenon. Am J Physiol Renal Physiol 288: F626–F636

    Article  CAS  Google Scholar 

  57. Racasan S et al. (2004) Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats. Hypertension 44: 83–88

    Article  CAS  Google Scholar 

  58. Lundie MJ et al. (1997) Long-term inhibition of the renin-angiotensin system in genetic hypertension: analysis of the impact on blood pressure and cardiovascular structural changes. J Hypertens 15: 339–348

    Article  CAS  Google Scholar 

  59. Smallegange C et al. (2004) Persistent lowering of pressure by transplanting kidneys from adult spontaneously hypertensive rats treated with brief antihypertensive therapy. Hypertension 44: 89–94

    Article  CAS  Google Scholar 

  60. Julius S et al. (2006) Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 354: 1685–1697

    Article  CAS  Google Scholar 

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Acknowledgements

B Braam was supported by a research fellowship from the Royal Netherlands Academy of Arts and Sciences. MC Verhaar is supported by the Netherlands Organization for Scientific Research (NWO grant 016.036.041). Studies cited in this report were supported by the Dutch Kidney Foundation (grants NS6013, C03.2039, PC127 and C04.2093).

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Authors and Affiliations

  1. B Braam is Associate Professor in the Division of Nephrology and Immunology, Department of Medicine, and Adjunct Associate Professor in the Department of Physiology, University of Alberta, Edmonton, Canada.,

    Branko Braam

  2. MC Verhaar is Associate Professor in the Department of Nephrology and Hypertension and in the Department of Vascular Medicine, WH Boer and JA Joles are Associate Professors in the Department of Nephrology and Hypertension, and P Blankestijn, University Medical Center Utrecht, The Netherlands.,

    Marianne C Verhaar, Peter Blankestijn, Walther H Boer & Jaap A Joles

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  1. Branko Braam
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Correspondence to Branko Braam.

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Braam, B., Verhaar, M., Blankestijn, P. et al. Technology Insight: innovative options for end-stage renal disease—from kidney refurbishment to artificial kidney. Nat Rev Nephrol 3, 564–572 (2007). https://doi.org/10.1038/ncpneph0600

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