After cyclosporine and muromonab-CD3 (OKT3 monoclonal antibody)were introduced into clinical practice in the early 1980s, one-yearsurvival rates for renal allografts improved from approximately60 percent to between 80 and 90 percent.1,2,3 However, the incidenceof acute rejection in the first six months after transplantationremained high; approximately half the recipients had at leastone episode of acute rejection. In the 1990s, the introductionof new immunosuppressive agents led to a decrease in the incidenceof acute rejection.4 Although long-term allograft survival hasimproved,1 chronic rejection and death with a functioning graftremain leading causes of the late loss . . . [Full Text of this Article]
The Problem of Late Allograft Loss
Chronic Rejection in Renal Transplantation
Death with a Functioning Allograft
Current Strategies to Prevent Late Allograft Loss
Perioperative Management and HLA Matching
Pharmacologic Prevention of Acute Rejection
Tacrolimus
Mycophenolate Mofetil
Sirolimus
Monoclonal Antibodies against the Interleukin-2 Receptor
Treatment of Severe or Refractory Acute Rejection
Optimal Dose of Calcineurin Inhibitors beyond the First Year after Transplantation
Discontinuation of Corticosteroids
Treatment of Hypertension and Hyperlipidemia
Future Strategies to Minimize Late Allograft Loss
Avoidance of Calcineurin Inhibitors or Corticosteroids
Hyporesponsiveness, or the Induction of Tolerance
Conclusions
Source Information
From the Renal Unit (M.P., N.T.-R.) and the Transplantation Unit (M.P., T.T., T.K., N.T.-R., A.B.C.), Departments of Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston.
Address reprint requests to Dr. Pascual at the Renal Unit, Box MZ 70, Massachusetts General Hospital, Boston, MA 02114, or at mpascual@partners.org.
Bestard, O., Cruzado, J. M., Rama, I., Torras, J., Goma, M., Seron, D., Moreso, F., Gil-Vernet, S., Grinyo, J. M.
(2008). Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts. J. Am. Soc. Nephrol.
19: 2020-2026
[Abstract][Full Text]
Seron, D., Arns, W., Chapman, J. R.
(2008). Chronic allograft nephropathy--clinical guidance for early detection and early intervention strategies. Nephrol Dial Transplant
23: 2467-2473
[Full Text]
Ashton-Chess, J., Giral, M., Mengel, M., Renaudin, K., Foucher, Y., Gwinner, W., Braud, C., Dugast, E., Quillard, T., Thebault, P., Chiffoleau, E., Braudeau, C., Charreau, B., Soulillou, J.-P., Brouard, S.
(2008). Tribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection. J. Am. Soc. Nephrol.
19: 1116-1127
[Abstract][Full Text]
Jevnikar, A. M., Mannon, R. B.
(2008). Late Kidney Allograft Loss: What We Know about It, and What We Can Do about It. CJASN
3: S56-S67
[Abstract][Full Text]
Srinivas, T. R., Meier-Kriesche, H.-U.
(2008). Minimizing Immunosuppression, an Alternative Approach to Reducing Side Effects: Objectives and Interim Result. CJASN
3: S101-S116
[Abstract][Full Text]
Kawai, T., Cosimi, A. B., Spitzer, T. R., Tolkoff-Rubin, N., Suthanthiran, M., Saidman, S. L., Shaffer, J., Preffer, F. I., Ding, R., Sharma, V., Fishman, J. A., Dey, B., Ko, D. S.C., Hertl, M., Goes, N. B., Wong, W., Williams, W. W. Jr., Colvin, R. B., Sykes, M., Sachs, D. H.
(2008). HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression. NEJM
358: 353-361
[Abstract][Full Text]
Mariat, C., Maillard, N., Phayphet, M., Thibaudin, L., Laporte, S., Alamartine, E., Berthoux, F.
(2008). Estimated glomerular filtration rate as an end point in kidney transplant trial: where do we stand?. Nephrol Dial Transplant
23: 33-38
[Full Text]
Ekberg, H., Tedesco-Silva, H., Demirbas, A., Vitko, S., Nashan, B., Gurkan, A., Margreiter, R., Hugo, C., Grinyo, J. M., Frei, U., Vanrenterghem, Y., Daloze, P., Halloran, P. F., the ELITE-Symphony Study,
(2007). Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation. NEJM
357: 2562-2575
[Abstract][Full Text]
Djamali, A.
(2007). Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts. Am. J. Physiol. Renal Physiol.
293: F445-F455
[Abstract][Full Text]
Codarri, L., Vallotton, L., Ciuffreda, D., Venetz, J.-P., Garcia, M., Hadaya, K., Buhler, L., Rotman, S., Pascual, M., Pantaleo, G.
(2007). Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7R{alpha}high cell population in solid organ transplant recipients. J. Exp. Med.
204: 1533-1541
[Abstract][Full Text]
Remuzzi, G., Cravedi, P., Costantini, M., Lesti, M., Ganeva, M., Gherardi, G., Ene-Iordache, B., Gotti, E., Donati, D., Salvadori, M., Sandrini, S., Segoloni, G., Federico, S., Rigotti, P., Sparacino, V., Ruggenenti, P., for the MYSS Follow-Up Study Group,
(2007). Mycophenolate Mofetil versus Azathioprine for Prevention of Chronic Allograft Dysfunction in Renal Transplantation: The MYSS Follow-Up Randomized, Controlled Clinical Trial. J. Am. Soc. Nephrol.
18: 1973-1985
[Abstract][Full Text]
Salama, A. D., Womer, K. L., Sayegh, M. H.
(2007). Clinical Transplantation Tolerance: Many Rivers to Cross. J. Immunol.
178: 5419-5423
[Abstract][Full Text]
Goes, N. B., Colvin, R. B.
(2007). Case 12-2007 -- A 56-Year-Old Woman with Renal Failure after Heart-Lung Transplantation. NEJM
356: 1657-1665
[Full Text]
Djamali, A., Sadowski, E. A., Muehrer, R. J., Reese, S., Smavatkul, C., Vidyasagar, A., Fain, S. B., Lipscomb, R. C., Hullett, D. H., Samaniego-Picota, M., Grist, T. M., Becker, B. N.
(2007). BOLD-MRI assessment of intrarenal oxygenation and oxidative stress in patients with chronic kidney allograft dysfunction. Am. J. Physiol. Renal Physiol.
292: F513-F522
[Abstract][Full Text]
van Ree, R. M., Oterdoom, L. H., de Vries, A. P. J., Gansevoort, R. T., van der Heide, J. J. H., van Son, W. J., Ploeg, R. J., de Jong, P. E., Gans, R. O. B., Bakker, S. J. L., , on behalf of the Renal Transplant Program, Unive,
(2007). Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients. Nephrol Dial Transplant
22: 246-253
[Abstract][Full Text]
Khoriaty, R., Otrock, Z. K., Medawar, W. A., Khauli, R. B., Bazarbachi, A.
(2006). A case of successful double sequential bone marrow and kidney transplantations in a patient with multiple myeloma. Nephrol Dial Transplant
21: 3585-3588
[Full Text]
Morales, J. M., Dominguez-Gil, B.
(2006). Impact of Tacrolimus and Mycophenolate Mofetil Combination on Cardiovascular Risk Profile after Kidney Transplantation. J. Am. Soc. Nephrol.
17: S296-S303
[Abstract][Full Text]
Scholten, E. M., Rowshani, A. T., Cremers, S., Bemelman, F. J., Eikmans, M., van Kan, E., Mallat, M. J., Florquin, S., Surachno, J., ten Berge, I. J., Bajema, I. M., de Fijter, J. W.
(2006). Untreated Rejection in 6-Month Protocol Biopsies Is Not Associated with Fibrosis in Serial Biopsies or with Loss of Graft Function. J. Am. Soc. Nephrol.
17: 2622-2632
[Abstract][Full Text]
Furuichi, K., Gao, J.-L., Murphy, P. M.
(2006). Chemokine Receptor CX3CR1 Regulates Renal Interstitial Fibrosis after Ischemia-Reperfusion Injury. Am. J. Pathol.
169: 372-387
[Abstract][Full Text]
Fitau, J., Boulday, G., Coulon, F., Quillard, T., Charreau, B.
(2006). The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-{alpha}-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways. J. Biol. Chem.
281: 20148-20159
[Abstract][Full Text]
Djamali, A., Samaniego, M., Muth, B., Muehrer, R., Hofmann, R. M., Pirsch, J., Howard, A., Mourad, G., Becker, B. N.
(2006). Medical Care of Kidney Transplant Recipients after the First Posttransplant Year. CJASN
1: 623-640
[Abstract][Full Text]
Isobe, M., Kosuge, H., Suzuki, J.-i.
(2006). T Cell Costimulation in the Development of Cardiac Allograft Vasculopathy: Potential Targets for Therapeutic Interventions. Arterioscler. Thromb. Vasc. Bio.
26: 1447-1456
[Abstract][Full Text]
Goldfarb-Rumyantzev, A. S., Hurdle, J. F., Baird, B. C., Stoddard, G., Wang, Z., Scandling, J. D., Barenbaum, L. L., Cheung, A. K.
(2006). The role of pre-emptive re-transplant in graft and recipient outcome. Nephrol Dial Transplant
21: 1355-1364
[Abstract][Full Text]
Goldfarb-Rumyantzev, A. S., Smith, L., Shihab, F. S., Baird, B. C., Habib, A. N., Lin, S.-j., Barenbaum, L. L.
(2006). Role of Maintenance Immunosuppressive Regimen in Kidney Transplant Outcome. CJASN
1: 563-574
[Abstract][Full Text]
Diekmann, F., Campistol, J. M.
(2006). Conversion from calcineurin inhibitors to sirolimus in chronic allograft nephropathy: benefits and risks. Nephrol Dial Transplant
21: 562-568
[Full Text]
Bergman, A. J., Burke, J., Larson, P., Johnson-Levonas, A. O., Reyderman, L., Statkevich, P., Kosoglou, T., Greenberg, H. E., Kraft, W. K., Frick, G., Murphy, G., Gottesdiener, K., Paolini, J. F.
(2006). Effects of ezetimibe on cyclosporine pharmacokinetics in healthy subjects.. J Clin Pharmacol
46: 321-327
[Abstract][Full Text]
Saurina, A., Campistol, J. M., Piera, C., Diekmann, F., Campos, B., Campos, N., de las Cuevas, X., Oppenheimer, F.
(2006). Conversion from calcineurin inhibitors to sirolimus in chronic allograft dysfunction: changes in glomerular haemodynamics and proteinuria. Nephrol Dial Transplant
21: 488-493
[Abstract][Full Text]
Poggio, E. D., Clemente, M., Hricik, D. E., Heeger, P. S.
(2006). Panel of Reactive T Cells as a Measurement of Primed Cellular Alloimmunity in Kidney Transplant Candidates. J. Am. Soc. Nephrol.
17: 564-572
[Abstract][Full Text]
Bumbea, V., Kamar, N., Ribes, D., Esposito, L., Modesto, A., Guitard, J., Nasou, G., Durand, D., Rostaing, L.
(2005). Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant
20: 2517-2523
[Abstract][Full Text]
Vallejos, A., Alperovich, G., Moreso, F., Canas, C., de Lama, M. E., Goma, M., Fulladosa, X., Carrera, M., Hueso, M., Grinyo, J. M., Seron, D.
(2005). Resistive index and chronic allograft nephropathy evaluated in protocol biopsies as predictors of graft outcome. Nephrol Dial Transplant
20: 2511-2516
[Abstract][Full Text]
Webster, A. C, Woodroffe, R. C, Taylor, R. S, Chapman, J. R, Craig, J. C
(2005). Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ
331: 810-
[Abstract][Full Text]
Holzmacher, R., Kendziorski, C., Michael Hofman, R., Jaffery, J., Becker, B., Djamali, A.
(2005). Low serum magnesium is associated with decreased graft survival in patients with chronic cyclosporin nephrotoxicity. Nephrol Dial Transplant
20: 1456-1462
[Abstract][Full Text]
Sayegh, M. H., Carpenter, C. B.
(2004). Transplantation 50 Years Later -- Progress, Challenges, and Promises. NEJM
351: 2761-2766
[Full Text]
Ponticelli, C.
(2004). Renal transplantation 2004: where do we stand today?. Nephrol Dial Transplant
19: 2937-2947
[Abstract][Full Text]
Magee, C. C., Pascual, M.
(2004). Update in Renal Transplantation. Arch Intern Med
164: 1373-1388
[Abstract][Full Text]
Ponticelli, C., Torras, J., Herrero-Fresneda, I., Grinyo, J. M., Pietrzyk, M., Hoffmann, U., Kramer, B. K., Nankivell, B. J., Chapman, J. R.
(2004). Chronic Allograft Nephropathy. NEJM
350: 1254-1256
[Full Text]
Chang, G.-C., Wu, C.-L., Pan, S.-H., Yang, T.-Y., Chin, C.-S., Yang, Y.-C., Chiang, C.-D.
(2004). The Diagnosis of Pneumonia in Renal Transplant Recipients Using Invasive and Noninvasive Procedures. Chest
125: 541-547
[Abstract][Full Text]
Schaub, S., Rush, D., Wilkins, J., Gibson, I. W., Weiler, T., Sangster, K., Nicolle, L., Karpinski, M., Jeffery, J., Nickerson, P.
(2004). Proteomic-Based Detection of Urine Proteins Associated with Acute Renal Allograft Rejection. J. Am. Soc. Nephrol.
15: 219-227
[Abstract][Full Text]
Boehler, A., Estenne, M.
(2003). Post-transplant bronchiolitis obliterans. Eur Respir J
22: 1007-1018
[Abstract][Full Text]
Magee, C., Pascual, M.
(2003). The Growing Problem of Chronic Renal Failure after Transplantation of a Nonrenal Organ. NEJM
349: 994-996
[Full Text]
Salama, A. D., Najafian, N., Clarkson, M. R., Harmon, W. E., Sayegh, M. H.
(2003). Regulatory CD25+ T Cells in Human Kidney Transplant Recipients. J. Am. Soc. Nephrol.
14: 1643-1651
[Abstract][Full Text]
Tsui, T.-Y., Wu, X., Lau, C.-K., Ho, D. W.Y., Xu, T., Siu, Y.-T., Fan, S.-T.
(2003). Prevention of Chronic Deterioration of Heart Allograft by Recombinant Adeno-Associated Virus-Mediated Heme Oxygenase-1 Gene Transfer. Circulation
107: 2623-2629
[Abstract][Full Text]
Morath, C., Ritz, E., Zeier, M.
(2003). Protocol biopsy: what is the rationale and what is the evidence?. Nephrol Dial Transplant
18: 644-647
[Full Text]
Gotti, E., Perico, N., Perna, A., Gaspari, F., Cattaneo, D., Caruso, R., Ferrari, S., Stucchi, N., Marchetti, G., Abbate, M., Remuzzi, G.
(2003). Renal Transplantation: Can We Reduce Calcineurin Inhibitor/Stop Steroids? Evidence Based on Protocol Biopsy Findings. J. Am. Soc. Nephrol.
14: 755-766
[Abstract][Full Text]
Burke, G. W.
(2003). Foreword. Nephrol Dial Transplant
18: i1-2
[Full Text]
First, M. R.
(2003). Renal function as a predictor of long-term graft survival in renal transplant patients. Nephrol Dial Transplant
18: i3-6
[Abstract][Full Text]
Jurewicz, W. A.
(2003). Tacrolimus versus ciclosporin immunosuppression: long-term outcome in renal transplantation. Nephrol Dial Transplant
18: i7-11
[Abstract][Full Text]
Yang, H. C.
(2003). Tailoring tacrolimus-based immunotherapy in renal transplantation. Nephrol Dial Transplant
18: i16-20
[Abstract][Full Text]
Watschinger, B., Pascual, M.
(2002). Capillary C4d Deposition as a Marker of Humoral Immunity in Renal Allograft Rejection. J. Am. Soc. Nephrol.
13: 2420-2423
[Full Text]
Rigatto, C., Parfrey, P., Montori, V. M., Basu, A., Kudva, Y. C., Baum, C. L., McGee, A. P., Friedman, A., Friedman, A., Pascual, M., Tolkoff-Rubin, N., Cosimi, A. B.
(2002). Strategies to Improve Outcomes after Renal Transplantation. NEJM
346: 2089-2092
[Full Text]