Journal Information
Vol. 29. Issue. S1.March 2009
Pages 1-77
Vol. 29. Issue. S1.March 2009
Pages 1-77
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PROGRESSION FACTORS IN CHRONIC KIDNEY DISEASE. IMMUNOLOGICAL MECHANISMS
Factores de progresión de la enfermedad renal crónica. Mecanismos inmunológicos
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4496
Luis Capdevila Plazaa, Juan José Cuberob, Enrique Lunab, Román Hernández-Gallegob
a Servicio de Nefrología, Hospital Vall d¿Hebron, Barcelona, Barcelona, España,
b Servicio de Nefrología, Complejo Hospitalario Universitario Infanta Cristina, Badajoz, España,
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Abstract
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El trasplante renal ofrece excelentes resultados a corto y medio plazo, tanto en la supervivencia del paciente como del injerto. Permanecen estabilizados los resultados a largo plazo. Las tasas de rechazo agudo están situadas a niveles muy reducidos: 8-15%. A pesar de los avances en el conocimiento de los mecanismos de la respuesta inmune, queda por resolver la disponibilidad de una monitorización inmunológica precisa y a tiempo real, que permita anticiparse a la aparición de lesiones histológicas, a la alteración de la función renal y que facilite seleccionar la inmunosupresión más idónea en el momento adecuado. Desde el punto de vista inmunológico, queda por solventar la prevención de las lesiones crónicas del injerto (fibrosis intersticial y atrofia tubular [FI y AT]) y la aparición del rechazo mediado por anticuerpos. La FI/AT es la principal causa de pérdida del injerto renal. En los resultados del trasplante renal, han contribuido de manera indiscutible los inmunosupresores (IS) inhibidores de la calcineurina (ciclosporina y tacrolimus), los antiproliferativos (micofenolato mofetil y micofenolato sódico) y anticuerpos mono y policlonales. La combinación tacrolimus con micofenolato mofetil o micofenolato sódico y esteroides es la que ofrece mejores resultados. El mantenimiento del equilibrio de la respuesta inmune es fundamental tanto para el paciente (prevención de infecciones y neoplasias) como para el injerto (mantenimiento de su función). Inmunosupresión en los trasplantados renales con insuficiencia renal: - Estadio 4: si la función se mantiene estable, no modificar la pauta de IS. Si el filtrado glomerular disminuye progresivamente, reducir los inhibidores de la calcineurina y los antiproliferativos.

In kidney transplantation patient and graft survival are excellent in short-term and mid-term, although they remain stable in the long-term. The incidence of acute rejection has decreased to 8%-15%. Despite marked progress in understanding immunologic mechanisms involved in transplantation, new tools are required to detect early changes that could affect allograft function allowing us to anticipate histological lesions and providing a more accurate use of immunosuppressive drugs. From an immunologic point of view, efforts should be directed to avoid interstitial fibrosis and tubular atrophy (IF/TA) and to prevent antibody-mediated rejection. The most frequent cause of late graft loss is IF/TA. Improvement in kidney transplant results have been achieved with calcineurin inhibitors -CNI- (cyclosporin and tacrolimus), antiproliferative agents (mycophenolate mofetil and enteric-coated mycophenolic acid) and T-cell-depleting antibodies. The combination of tacrolimus + mycophenolate mofetil + steroids has been the gold standard in kidney transplant immunosuppression. An adequate balance in order to maintain the appropiate immune response is essential to the patient to avoid infections or neoplasias as well to prevent rejection. In renal transplant recipients with chronic kidney disease stage 4T in which renal function remains stable, immuno-suppressive drugs can be continued at the usual maintenance doses. As GFR declines, CNI and antiproliferative drugs should be reduced.

Bibliography
[1]
Sayegh MH, Carpenter CB. Transplantation 50 Years Later ¿Progress, Challenges, and Promises. N Engl J Med 2004;351:2761-6. [Pubmed]
[2]
Port FK, Merion RM, Roys EC, Wolfe RA. Trends in Organ Donation and Transplantation in the United States, 1997¿2006. Am J Transplant 2008;8(Part 2):911-21.
[3]
Serón D, Arias M, Campistol JM, Morales JM, for the Spanish Chronic Allograft Nephropathy Study Group. Late renal allograft failure between 1990 and 1998 in Spain: a changing scenario. Transplantation 2003;76:1588-94. [Pubmed]
[4]
Danovitch G M. Handbook of kidney transplantation. 4th ed. Lippincott Williams & Wilkins; 2005.
[5]
Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004;4:378-83. [Pubmed]
[6]
Mekeel K, Meier-Kriesche HU, Kaplan B. Are we making progress in kidney transplantation? Curr Opin Organ Transplant 2006;11:1-6.
[7]
Kasiske BL, Gaston RS, Gourishankar S, Halloran PH, Matas AJ, Jeffery J, et al. Long-term deterioration of kidney allograft function. Am J Transplant 2005;5:1405-14. [Pubmed]
[8]
San Segundo D, Ruiz JC, Izquierdo M, Fernández-Fresnedo G, Gómez-Alamillo C, Merino R, et al. Calcineurin Inhibitors, but not Rapamycin, Reduce Percentages of CD4 CD25 FOXP3 Regulatory T Cells in Renal Transplant Recipients. Transplantation 2006;82:550-7.
[9]
Rodrigo E, Arias M. Monitorización inmunológica en el trasplante renal. Actualizaciones científicas en trasplantes (2007). Cátedra UAM-Roche. www.roche- trasplantes.com.
[11]
Bestard O, Nickel P, Cruzado JM, Schoenemann C, Boenisch O, Sefrin A, et al. Circulating Alloreactive T Cells Correlate with Graft Function in Longstanding Renal Transplant Recipients J Am Soc Nephrol 2008;19(7):1419-29.
[12]
Roslyn B, Mannon and Allan D, Kirk. Beyond Histology: Novel Tools to Diagnose Allograft Dysfunction. Clin J Am Soc Nephrol 2006;1:358-66.
[13]
Poggio ED, Augustine JJ, Clemente M, Danzig J M, Volokh N, Zand MS, et al. Pretransplant Cellular Alloimmunity as Assessed by a Panel of Reactive T Cells Assay Correlates With Acute Renal Graft Rejection. Transplantation 2007;83(7):847-52.
[14]
Serón D, Moreso F. Protocol biopsies in renal transplantation: Prognostic value of structural monitoring. Kidney Int 2007;72:690-7. [Pubmed]
[15]
14.Mueller TF, Einecke G, Reeve J, Sis B, Mengel M, Jhangri GS, et al. Microarray Analysis of Rejection in Human Kidney Transplants Using Pathogenesis-Based Transcript Sets Am J Transplant 2007;7:2712-22.
[16]
Abulezz S. KIM-1 expression in kidney allograft biopsies: Improving the gold standard. Kidney Int 2008;73:522-3. [Pubmed]
[17]
Strom TB. Rejection: more than eye can see. N Engl J Med 2005;353:2394-6. [Pubmed]
[18]
Solez K, Colvin RB, Racusen LC, Sis B, Halloran PF, Birk PE, et al. Banff ¿05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy (¿CAN¿). Am J Transplant 2007;7:518-26.
[19]
Solez K, Colvin RB Racusen LC, et al. Banff 07 Classification of Renal Allograft Pathology: Updates and Future Directions. Am J Transplant 2008;8:753-60.
[20]
Pallardó LM, Sancho A, Capdevila LL, Franco A. Acute rejection in kidney transplantation. Risk factors and prognostic value. Nephrol Dial Transplant 2004;19(4):38-42.
[21]
Kuypers DRJ. Immunosuppressive Drug Therapy and Subclinical Acute Renal Allograft Rejection: Impact and Effect. Transplantation 2008;85(7S):S25-30.
[22]
Opelz G, Döhler B, for the Collaborative Transplant Study Report. Influence of time of rejection on long-term graft survival in renal transplantation.  Transplantation 2008;85:661-6.
[23]
Rush DN for the Winnipeg Transplant Group. Impact of subclinical rejection on transplantation. Trends in Transplantation 2007;1:56-60.
[24]
23.Moreso F, Ibernon M, Gomà M, Carrera M, Fulladosa X, Hueso M, et al. Subclinical Rejection Associated with Chronic Allograft Nephropathy in Protocol Biopsies as a Risk Factor for Late Graft Loss. Am J Transplant 2006;6:747-52. [Pubmed]
[25]
Chapman JR. Introduction: Targets for Improving Outcomes in Renal Allografts Transplanted During the Next Ten Years. Transplantation 2008;85:S1-S2.
[26]
Jevnikar AM, Mannon RB. Late Kidney Allograft Loss: What We Know about It, and What We Can Do about It. Clin J Am Soc Nephrol 2008;3:S56-S67. [Pubmed]
[27]
Nankivell BJ, Chapman JR. Chronic Allograft Nephropathy: Current Concepts and Future Directions. Transplantation 2006;81:643-54.
[28]
Vongwiwatana A, Tasanarogn A, Rayner DC, Melk A, Halloran PE. Epitelial to mesenchymal transition during late deterioration of human kidney transplants: The role of tubular cells in fibrogenesis. Am J Transplant 2005;5:1367-74. [Pubmed]
[29]
Hertig A, Verine J, Mougenot B, Jouanneau C, Ouali N, Sebe P, et al. Risk Factors for Early Epithelial to Mesenchymal Transition in Renal Grafts. Am J Transplant 2006;6:2937-46. [Pubmed]
[30]
Kerjaschki D, Regele HM, Moosberger I, Nagy-Bojarski K, Watschinger B, Soleiman A, et al. Lymphatic Neoangiogenesis in Human Kidney Transplants Is Associated with Immunologically Active Lymphocytic Infiltrates J Am Soc Nephrol 2004;15:603-12.
[31]
Colvin RB. Antibody-Mediated Renal Allograft Rejection: Diagnosis and Pathogenesis J Am Soc Nephrol 2007;18:1046-56.
[32]
Gloor JM, Sethi S, Stegall MD, Park WD, Moore SB, DeGoey S, et al. Transplant Glomerulopathy: Subclinical Incidence and Association with Alloantibody Am J Transplant 2007;7:212-32.
[33]
Cosio FG,Gloor JM, Sethi S, Stegall MD. Transplant Glomerulopathy. Am J Transplant 2008;8:492-6.
[34]
33.Mengel M, Gwinner W, Schwarz A, Bajeski R, Franz I, Bröcker V, et al. Infiltrates in Protocol Biopsies from Renal Allografts Am J Transplant 2007;7:356-65.
[35]
González Molina M, Seron D, García del Moral R, Carrera M, Sola E, Alférez MJ, et al. Mycophenolate mofetil reduces deterioration of renal function in patients with chronic allograft nephropathy. A follow-up study by the Spanish Cooperative Study Group of chronic allograft nephropathy. Transplantation 2004;77:215-20. [Pubmed]
[36]
35.Mannon RB. Therapeutic Targets in the Treatment of Allograft Fibrosis. Am J Transplant 2006;6:867-75. [Pubmed]
[37]
González Molina M, Morales JM, Marcen T, Campistol JM, Oppenheimer F, Serón D, et al. Renal Function in Patients With Cadaveric Kidney Transplants Treated With Tacrolimus or Cyclosporine. Transplant Proc 2007;39:2167-9. [Pubmed]
[38]
Ciancio G, Burke GW, Gaynor JJ, Ruiz P, Roth D, Kupin W, et al. A Randomized Long-Term Trial of Tacrolimus/Sirolimus versus Tacrolimus/Mycophenolate versus Cyclosporine/Sirolimus in Renal Transplantation: Three-Year Analysis. Transplantation 2006;81:845-52. [Pubmed]
[39]
Osuna A, Gentil MA, Capdevila L, Cantarell C, Mazuecos A, Pereira P, Rodríguez-Algarra G, et al. and the Spanish Kidney Transplant of Elderly Donor Study Group. Two Doses of Daclizumab With Delayed Introduction of low ¿dose Tacrolimus in elderly recipients of cadaveric renal transplants from donors >55 years of age. Transplant Proc 2005;37:1438-40. [Pubmed]
[40]
Srinivas TR, Schold JD, Guerra G, Eagan A, Bucci CM, Meier- Kriesche HU. Mycophenolate Mofetil/Sirolimus Compared to Other Common Immunosuppressive Regimens in Kidney Transplantation. Am J Transplant 2007;7:586-94. [Pubmed]
[41]
Srinivas TR, Meier-Kriesche HU. Minimizing Immunosuppression, an Alternative Approach to Reducing Side Effects: Objectives and Interim Result. Clin J Am Soc Nephrol 2008;3:S101-S116. [Pubmed]
[42]
Rostaing L, Cantarovich D, Mourad G, Budde K, Rigotti P, Mariat C, et al. CARMEN Study Group: Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation 2005;79:807-14. [Pubmed]
[43]
Bosmans JL, Ysebaert DK, Verpooten GA. Chronic Allograft Nephropathy: What Have We Learned From Protocol Biopsies? Transplantation 2008;85:S38-S41.
[44]
Guerra G, Srinivas TR, Meier-Kriesche HU. Calcineurin inhibitor-free immunosuppression in kidney transplantation. Transplant Int 2007;20:813-27.
[45]
Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B, Gurkan A, et al. ELITE-Symphony Study: Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007;357:2562-75. [Pubmed]
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