Improved Graft Survival after Renal Transplantation in the United States, 1988 to 1996
Sundaram Hariharan, M.D., Christopher P. Johnson, M.D., Barbara A. Bresnahan, M.D., Sarah E. Taranto, B.A., Matthew J. McIntosh, Ph.D., and Donald Stablein, Ph.D.
Background The introduction of cyclosporine has resulted inimprovement in the short-term outcome of renal transplantation,but its effect on the long-term survival of kidney transplantsis not known.
Methods We analyzed the influence of demographic characteristics(age, sex, and race), transplant-related variables (living orcadaveric donor, panel-reactive antibody titer, extent of HLAmatching, and cold-ischemia time), and post-transplantationvariables (presence or absence of acute rejection, delayed graftfunction, and therapy with mycophenolate mofetil and tacrolimus)on graft survival for all 93,934 renal transplantations performedin the United States between 1988 and 1996. A regression analysisadjusted for these variables was used to estimate the risk ofgraft failure within the first year and more than one year aftertransplantation.
Results From 1988 to 1996, the one-year survival rate for graftsfrom living donors increased from 88.8 to 93.9 percent, andthe rate for cadaveric grafts increased from 75.7 to 87.7 percent.The half-life for grafts from living donors increased steadilyfrom 12.7 to 21.6 years, and that for cadaveric grafts increasedfrom 7.9 to 13.8 years. After censoring of data for patientswho died with functioning grafts, the half-life for grafts fromliving donors increased from 16.9 years to 35.9 years, and thatfor cadaveric grafts increased from 11.0 years to 19.5 years.The average yearly reduction in the relative hazard of graftfailure after one year was 4.2 percent for all recipients (P<0.001),0.4 percent for those who had acute rejection (P=0.57), and6.3 percent for those who did not have acute rejection (P<0.001).
Conclusions Since 1988, there has been a substantial increasein short-term and long-term survival of kidney grafts from bothliving and cadaveric donors.
The number of patients with end-stage renal disease is increasingat the rate of 7 to 8 percent per year in the United States.1Renal transplantation is the treatment of choice for most ofthese patients, but the number of kidneys available for transplantationis limited.2 Since 1988, there has been a growing discrepancybetween the number of transplantations performed and the numberof patients awaiting transplantation, underscoring the needto maximize graft survival.2
The short-term outcome of renal transplantation has improvedsubstantially in the past 15 years. The introduction of cyclosporinefor the prevention of acute and chronic rejection in the early1980s and the introduction of muromonab-CD3 (OKT3 monoclonalantibody) for the treatment of acute rejection in the early1980s have increased the rate of graft survival at one year.3,4In recent years, use of newer immunosuppressive drugs such asmycophenolate mofetil and tacrolimus has been associated withfurther reduction in the incidence of acute rejection episodes.5,6
However, there has not been a noticeable improvement in long-termgraft survival.7 Long-term graft failure is usually due to deathwith a functioning graft, chronic rejection, or recurrent kidneydisease.8 Cyclosporine is nephrotoxic and has been thought toaggravate graft failure. Among these causes of long-term graftfailure, the most important and the most potentially remediableis chronic rejection.9 Graft failure due to chronic rejectionis a common reason for placing a patient on a waiting list forretransplantation.
The relation between acute and chronic rejection is not clear.Although acute rejection is considered the most important predictorof chronic rejection, no studies have demonstrated that a reductionin the incidence of acute rejection is associated with a reductionin the incidence of chronic rejection and an improvement inlong-term graft survival. We conducted a study to determinethe rate of long-term renal-allograft survival, as estimatedon the basis of the projected half-life, and to identify factorsthat may affect graft survival.
Methods
We studied all adults with available follow-up data who underwentprimary or repeated transplantation with a graft from a livingor cadaveric donor in the United States between 1988 and 1996.The data were obtained from 276 renal-transplantation centersthrough the United Network for Organ Sharing.
The KaplanMeier method was used to estimate the survivalof the transplants for each year.10 A maximum-likelihood estimateof the projected half-life (median value) was calculated withthe assumption of exponentially distributed graft-survival times.Graft loss was defined by the need for permanent dialysis, repeatedtransplantation, or death. We performed an additional analysisafter censoring data on patients who died while their graftswere functioning. The analysis of short-term graft survival(defined as survival for one year or less) included all patientswho received transplants between 1988 and 1996, and the analysisof long-term graft survival (defined as survival for more thanone year) included all patients who received transplants between1988 and 1995. To avoid a reporting bias associated with rapidnotification of critical events (death or graft failure) anddelayed notification of continued survival, follow-up time wasrestricted to two years before November 1998.
The demographic characteristics used for covariate-adjustedanalyses included the age of the recipient and of the donorat the time of transplantation and the recipient's race andsex. Transplant-related variables included the source of theorgan (living or cadaveric donor), the titer of serum panel-reactiveantibody in the recipient, the duration of cold ischemia, andthe extent of HLA matching. We also included a variable forthe volume of transplantations at the center. Clinical variablesat the time of transplantation were the presence or absenceof multiple-organ transplantation, previous transplantationor blood transfusion, and an associated medical condition.
Post-transplantation variables included the presence or absenceof delayed graft function; treatment with antibody such as muromonab-CD3,antithymocyte globulin as induction therapy, or mycophenolatemofetil and tacrolimus for the prevention of acute rejection;and clinical acute rejection within one year after transplantation.Mean values were used for missing data. Clinical acute rejectionwas defined as confirmed or suspected acute rejection in patientswho received antirejection treatment.
The variables listed above were included in models with theyear of transplantation as an indicator variable, in order toassess their effect on short-term and long-term graft survival.The statistical analysis was performed with the use of proportional-hazardsregression models with adjustment for potential prognostic variables;post-transplantation variables were included only in the long-termanalysis. The relative hazard of graft failure was estimatedseparately for the first year (short-term survival) and morethan one year (long-term survival) after transplantation. Theannual change is reported as 1 minus the relative hazard peryear.
Results
All 93,934 renal transplantations performed in the United Stateswere included in the study. Selected variables at the time oftransplantation and transplant-related and post-transplantationvariables are shown in Table 1.
Table 1. Characteristics of Renal-Transplant Donors and Recipients, 1988 to 1996.
Figure 1 shows KaplanMeier estimates of survival oneyear after the transplantation of a renal graft from a livingor cadaveric donor during the period from 1988 to 1996. Thesurvival rate at one year for transplants from living donorsincreased from 88.8 percent in 1988 to 93.9 percent in 1996,an increase of 5.1 percentage points. The corresponding ratesfor transplants from cadaveric donors were 75.7 percent and87.7 percent, with an increase of 12.0 percentage points from1988 to 1996. After the censoring of data for transplants inpatients with incomplete follow-up (15,386 transplants), a totalof 13,455 transplants had failed and 65,093 were still functioningone year after transplantation. Of the 65,093 functioning transplants,12,562 (19.3 percent) subsequently failed. The long-term survivalof cadaveric transplants that were functioning at the end ofthe first year is shown in Figure 2. The survival curves areshorter for transplants received in recent years than for thosereceived earlier because there are fewer follow-up data forrecent years. The curves show a continuous trend toward improvedlong-term graft survival in recent years.
Figure 1. KaplanMeier Estimates of Graft Survival during the First Year after Transplantation for Grafts from Living Donors (Panel A) and Cadaveric Donors (Panel B) from 1988 to 1996.
Figure 2. KaplanMeier Estimates of Cadaveric-Graft Survival after One Year for All Grafts from Cadaveric Donors (Panel A) and after the Censoring of Data for Patients Who Died with Functioning Cadaveric Grafts (Panel B).
Table 2 shows the projected half-life of all transplants, withand without the censoring of data for patients who died withfunctioning grafts, from 1988 to 1995. The projected half-lifefor transplants from living donors was 12.7 years in 1988 and21.6 years in 1995, representing an increase of 70 percent in1995. After the censoring of data for patients who died withfunctioning grafts, the respective values were 16.9 years in1988 and 35.9 years in 1995, representing an increase of 112percent. The projected half-life for transplants from cadavericdonors was 7.9 years in 1988 and 13.8 years in 1995, representingan increase of 75 percent in 1995. After the censoring of datafor patients who died with functioning grafts, the respectivehalf-lives were 11.0 years and 19.5 years, representing an increaseof 77 percent. The difference in the projected half-life between1988 and 1995, with and without the censoring of data for patientswho died with functioning grafts, was greater for transplantsfrom living donors (42 percent) than for those from cadavericdonors (2 percent). The projected half-life for transplantsin nonblack recipients increased from 9.1 years to 13.3 yearsfrom 1988 to 1995, an increase of 46 percent. The correspondingvalues for transplants in blacks were 5.1 years and 7.2 years,an increase of 41 percent.
Table 2. Projected Half-Life of Renal Transplants, 1988 to 1995, before and after the Censoring of Data on Patients Who Died with Functioning Grafts.
Clinical acute rejection within the first year after transplantationhad a detrimental effect on long-term graft survival (Figure 3).Among patients who had an episode of clinical acute rejection,the projected half-life of cadaveric transplants was 7.0 yearsin 1988 and 8.8 years in 1995, an increase of 25 percent. Incontrast, the projected half-life for cadaveric transplantsin patients who did not have an episode of clinical acute rejectionin the first year after transplantation was 8.8 years in 1988and 17.9 years in 1995, an increase of 103 percent. After thecensoring of data for patients who died with functioning grafts,the projected half-life increased from 9.1 to 11.9 years, anincrease of 31 percent, in patients who had an episode of clinicalacute rejection, and from 12.9 to 27.1 years, an increase of110 percent, in those who did not have acute rejection. Theproportion of transplants from cadaveric donors who were morethan 50 years old increased from 10.4 percent in 1988 to 18.2percent in 1996 (Table 1), and the projected median half-lifeof the grafts from these donors was 5.5 years in 1988 and 7.5years in 1995, an increase of 36 percent.
Figure 3. Projected Half-Life of Grafts from Cadaveric Donors According to the Presence or Absence of Clinical Acute Rejection during the First Year after Transplantation.
After adjustment for the prognostic variables listed in theMethods section, the reduction in the relative hazard of graftfailure during the first year after transplantation was 7.1percent per year from 1988 to 1996 (P<0.001). After the firstyear, the mean reduction in the relative hazard of graft failurewas 4.2 percent per year (P<0.001). The analysis was furtherstratified according to whether there was clinical acute rejectionduring the first year after transplantation. Among patientswith an episode of clinical acute rejection, the reduction inthe relative hazard of graft failure was 0.4 percent per year(P=0.57), whereas among those without acute rejection, the reductionin the relative hazard was 6.3 percent per year (P< 0.001)(Figure 4A). After the censoring of data for patients who diedwith functioning grafts, the reduction in the relative hazardof graft failure was 2.4 percent per year among patients whohad an episode of clinical acute rejection (P=0.005) and 10.2percent per year among those who did not have acute rejection(P<0.001) (Figure 4B).
Figure 4. Relative Hazard of Graft Failure after the First Year, According to the Presence or Absence of Clinical Acute Rejection in the First Year.
For all grafts, the reduction in the relative hazard of graft failure was 0.4 percent per year for patients with acute rejection and 6.3 percent per year for those without acute rejection (Panel A). After the censoring of data for patients who died with functioning grafts, the reduction in the relative hazard was 2.4 percent per year for patients with acute rejection and 10.2 percent per year for those without acute rejection (Panel B).
Discussion
Renal transplantation is the treatment of choice for patientswith end-stage renal failure. Since the first report on renaltransplantation, in 1955, there has been a continuing effortto improve the short- and long-term survival of renal transplants.11Graft failure during the first year after transplantation isdue to acute rejection, primary nonfunction, graft thrombosis,recurrent kidney disease, or the death of a patient with a functioninggraft. The main obstacle to the success of transplantation hasbeen acute rejection. The introduction of cyclosporine in theearly 1980s for the prevention of acute rejection reduced therate of acute rejection and significantly improved graft survivalat one year.3 Nonetheless, even after the advent of cyclosporine-basedimmunosuppressive therapy in the mid-1980s, the prevalence ofacute rejection after the transplantation of a kidney from acadaveric donor ranged from 40 to 60 percent.12
Although treatment with cyclosporine has improved the rate ofgraft survival at one year, it has not substantially improvedlong-term graft survival.7 We found that from 1988 to 1996,the survival rate at one year improved by 5.1 percentage pointsfor transplants from living donors and by 12.0 percentage pointsfor those from cadaveric donors. The reduction in the relativehazard of graft failure within one year after transplantationwas 7.1 percent per year, after adjustment for multiple variables.We also found that since 1988, there has been steady improvementin long-term graft survival. The improvement is not due to areduction in the number of deaths, because the results of analysesperformed before and after the censoring of data for patientswho died with functioning grafts were similar.
Chronic rejection remains the most important cause of graftloss in long-term studies. The prevalence of chronic rejectionranges from 10 percent to 80 percent, depending on the durationof follow-up.9,13,14 The most important predictor of chronicrejection is a previous episode of acute rejection.13,15,16,17,18Apart from clinical acute rejection, patients may have subclinicalrejection that causes ongoing immunologic injury, leading tochronic rejection.19,20 Black transplant recipients are morelikely than white recipients to have chronic rejection, a findingthat may be due to differences in immunologic responsiveness,HLA matching, or control of blood pressure.21,22,23 Our studyshows an improvement in the projected half-life of grafts inblacks as well as in other patients, but graft survival in blackscontinues to be poor.
Our study also shows the decline in the relative hazard of graftfailure during long-term follow-up a reduction of approximately4.2 percent per year from 1988 to 1995. Among patients who hadone or more episodes of clinical acute rejection, the reductionin the relative hazard of graft failure was only 0.4 percentper year, as compared to 6.3 percent per year among those whodid not have clinical acute rejection. Among patients who underwenttransplantation in recent years, the projected half-life ofgrafts in patients who did not have an episode of clinical acuterejection was nearly double that for those who did have suchan episode. Thus, it seems clear that the reduction in the rateof acute rejection from 1988 to 1996 has resulted in lower ratesof graft failure due to chronic rejection. These results indicatethat the long-term toxicity of cyclosporine does not blunt itsshort-term benefit.24
Data from various studies make it clear that immunologic factorssuch as higher values for serum panel-reactive antibody, prolongedcold-ischemia time, and nonimmunologic factors, including delayedgraft function, can increase the incidence of acute rejectionand reduce long-term graft survival.25,26,27 We found that thecold-ischemia time and the titer of serum panel-reactive antibodyin recipients have decreased over time, which may have contributedto the lower rate of acute rejection in the recent cohorts ofpatients, but there has been little change in either the racialdistribution of recipients or the extent of HLA matching.
The limited availability of organs has prompted many centersto use organs from older cadaveric donors. Kidneys from suchdonors have a lower survival rate than those from younger cadavericdonors.2,28 From 1988 to 1996, the proportion of grafts fromolder cadaveric donors increased from 10.4 to 18.2 percent.
The introduction of mycophenolate mofetil and tacrolimus inthe 1990s has also been associated with a reduction in the incidenceof acute rejection during the first year after transplantation.5,6This finding does not explain the results reported here, however,because the overall proportion of patients in our study whoreceived either drug was small. The drugs may have been introducedat a later date after transplantation, but in the group of patientswho had an episode of clinical acute rejection thosewho may have been switched to these drugs there wasno substantial improvement in the graft half-life. Long-termfollow-up studies of treatment with mycophenolate mofetil inthe United States have not revealed any effect of this drugon graft survival or the prevalence of chronic rejection.29Higher doses of cyclosporine improve graft survival,30 and theincreased bioavailability of cyclosporine has been correlatedwith a reduction in episodes of acute rejection.31 However,data on cyclosporine doses and blood concentrations were notavailable for the patients in our study, so we could not determinewhether this factor contributed to the improvement in graftsurvival.
In conclusion, between 1988 and 1996, there was a steady improvementin the short-term and long-term survival of renal grafts fromboth living and cadaveric donors.
Supported by a grant (N01-AI-25132) from the National Institutesof Health.
We are indebted to Mary Ellison from the United Network forOrgan Sharing for providing study data, and to Linda Eisertand Katie Landa for assisting with the preparation of the manuscript.
Source Information
From the Divisions of Nephrology (S.H., B.A.B.) and Transplant Surgery (C.P.J.), Medical College of Wisconsin, Milwaukee; the United Network for Organ Sharing, Richmond, Va. (S.E.T.); and the EMMES Corporation, Potomac, Md. (M.J.M., D.S.). Presented at the 18th Annual Meeting of the American Society of Transplantation, Chicago, May 1519, 1999.
Address reprint requests to Dr. Hariharan at the Medical College of Wisconsin, Division of Nephrology, 9200 W. Wisconsin Ave., Milwaukee, WI 53226, or at hari{at}mcw.edu.
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Furuichi, K., Gao, J.-L., Murphy, P. M.
(2006). Chemokine Receptor CX3CR1 Regulates Renal Interstitial Fibrosis after Ischemia-Reperfusion Injury. Am. J. Pathol.
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(2006). Steroid-free immunosuppression after renal transplantation--long-term experience from a single centre. Nephrol Dial Transplant
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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
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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
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Huurman, V. A.L., Kalpoe, J. S., van de Linde, P., Vaessen, N., Ringers, J., Kroes, A. C.M., Roep, B. O., De Fijter, J. W.
(2006). Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients. Diabetes Care
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Roos-van Groningen, M. C., Scholten, E. M., Lelieveld, P. M., Rowshani, A. T., Baelde, H. J., Bajema, I. M., Florquin, S., Bemelman, F. J., de Heer, E., de Fijter, J. W., Bruijn, J. A., Eikmans, M.
(2006). Molecular Comparison of Calcineurin Inhibitor-Induced Fibrogenic Responses in Protocol Renal Transplant Biopsies. J. Am. Soc. Nephrol.
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Mathew, T. H., Van Buren, C., Kahan, B. D., Butt, K., Hariharan, S., Zimmerman, J. J., for the Rapamune 309 Study Group,
(2006). A Comparative Study of Sirolimus Tablet Versus Oral Solution for Prophylaxis of Acute Renal Allograft Rejection. J Clin Pharmacol
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Muthukumar, T., Dadhania, D., Ding, R., Snopkowski, C., Naqvi, R., Lee, J. B., Hartono, C., Li, B., Sharma, V. K., Seshan, S. V., Kapur, S., Hancock, W. W., Schwartz, J. E., Suthanthiran, M.
(2005). Messenger RNA for FOXP3 in the urine of renal-allograft recipients.. NEJM
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Stallone, G., Infante, B., Schena, A., Battaglia, M., Ditonno, P., Loverre, A., Gesualdo, L., Schena, F. P., Grandaliano, G.
(2005). Rapamycin for Treatment of Chronic Allograft Nephropathy in Renal Transplant Patients. J. Am. Soc. Nephrol.
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White, C., Akbari, A., Hussain, N., Dinh, L., Filler, G., Lepage, N., Knoll, G. A.
(2005). Estimating Glomerular Filtration Rate in Kidney Transplantation: A Comparison between Serum Creatinine and Cystatin C-Based Methods. J. Am. Soc. Nephrol.
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Eikmans, M., Roos-van Groningen, M. C., Sijpkens, Y. W.J., Ehrchen, J., Roth, J., Baelde, H. J., Bajema, I. M., de Fijter, J. W., de Heer, E., Bruijn, J. A.
(2005). Expression of Surfactant Protein-C, S100A8, S100A9, and B Cell Markers in Renal Allografts: Investigation of the Prognostic Value. J. Am. Soc. Nephrol.
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Hale, D. A, Dhanireddy, K., Bruno, D., Kirk, A. D
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Moloney, F. J., Almarzouqi, E., O'Kelly, P., Conlon, P., Murphy, G. M.
(2005). Sunscreen Use Before and After Transplantation and Assessment of Risk Factors Associated With Skin Cancer Development in Renal Transplant Recipients. Arch Dermatol
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Kock, M. C. J. M., Ijzermans, J. N. M., Visser, K., Hussain, S. M., Weimar, W., Pattynama, P. M. T., Krestin, G. P., Hunink, M. G. M.
(2005). Contrast-Enhanced MR Angiography and Digital Subtraction Angiography in Living Renal Donors: Diagnostic Agreement, Impact on Decision Making, and Costs. Am. J. Roentgenol.
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Hauser, I. A., Spiegler, S., Kiss, E., Gauer, S., Sichler, O., Scheuermann, E. H., Ackermann, H., Pfeilschifter, J. M., Geiger, H., Grone, H.-J., Radeke, H. H.
(2005). Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-{gamma} (MIG). J. Am. Soc. Nephrol.
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Kramer, B. K., Montagnino, G., del Castillo, D., Margreiter, R., Sperschneider, H., Olbricht, C. J., Kruger, B., Ortuno, J., Kohler, H., Kunzendorf, U., Stummvoll, H.-K., Tabernero, J. M., Muhlbacher, F., Rivero, M., Arias, M., for the European Tacrolimus vs Cyclosporin Microem,
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Keith, D. S., deMattos, A., Golconda, M., Prather, J., Cantarovich, M., Paraskevas, S., Tchervenkov, J., Norman, D. J.
(2005). Factors Associated with Improvement in Deceased Donor Renal Allograft Function in the 1990s. J. Am. Soc. Nephrol.
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Saunders, R N, Karoo, R, Metcalfe, M S, Nicholson, M L
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Rao, P. S., Schaubel, D. E., Saran, R.
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Giral, M., Nguyen, J. M., Karam, G., Kessler, M., de Ligny, B. H., Buchler, M., Bayle, F., Meyer, C., Foucher, Y., Martin, M. L., Daguin, P., Soulillou, J. P.
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Halloran, P. F.
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(2004). Renal transplantation 2004: where do we stand today?. Nephrol Dial Transplant
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Doyle, A. M., Lechler, R. I., Turka, L. A.
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Kaplan, B., Meier-Kriesche, H.-U.
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(2004). Mycophenolate mofetil vs azathioprine in a large population of elderly renal transplant patients. Nephrol Dial Transplant
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Lentine, K. L., Brennan, D. C.
(2004). Statin use after renal transplantation: a systematic quality review of trial-based evidence. Nephrol Dial Transplant
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(2004). Centre-specific variation in renal transplant outcomes in Canada. Nephrol Dial Transplant
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Poggio, E. D., Clemente, M., Riley, J., Roddy, M., Greenspan, N. S., Dejelo, C., Najafian, N., Sayegh, M. H., Hricik, D. E., Heeger, P. S.
(2004). Alloreactivity in Renal Transplant Recipients with and without Chronic Allograft Nephropathy. J. Am. Soc. Nephrol.
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Fabrizii, V., Winkelmayer, W. C., Klauser, R., Kletzmayr, J., Saemann, M. D., Steininger, R., Kramar, R., Horl, W. H., Kovarik, J.
(2004). Patient and Graft Survival in Older Kidney Transplant Recipients: Does Age Matter?. J. Am. Soc. Nephrol.
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Womer, K. L., Sayegh, M. H.
(2004). Donor Antigen and Transplant Tolerance Strategies: It Takes Two to Tango!. J. Am. Soc. Nephrol.
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(2004). Paid transplants in India: the grim reality. Nephrol Dial Transplant
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(2004). Long-Term Benefits with Sirolimus-Based Therapy after Early Cyclosporine Withdrawal. J. Am. Soc. Nephrol.
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Bruno, S., Remuzzi, G., Ruggenenti, P.
(2004). Transplant Renal Artery Stenosis. J. Am. Soc. Nephrol.
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(2004). Proteomic-Based Detection of Urine Proteins Associated with Acute Renal Allograft Rejection. J. Am. Soc. Nephrol.
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Ii, M., Losordo, D. W.
(2003). Transplant Graft Vasculopathy: A Dark Side of Bone Marrow Stem Cells?. Circulation
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Harris, J
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Abbott, K. C., Yuan, C. M., Taylor, A. J., Cruess, D. F., Agodoa, L. Y. C.
(2003). Early Renal Insufficiency and Hospitalized Heart Disease after Renal Transplantation in the Era of Modern Immunosuppression. J. Am. Soc. Nephrol.
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Knoll, G. A., MacDonald, I., Khan, A., van Walraven, C.
(2003). Mycophenolate Mofetil Dose Reduction and the Risk of Acute Rejection after Renal Transplantation. J. Am. Soc. Nephrol.
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Gourishankar, S., Hunsicker, L. G., Jhangri, G. S., Cockfield, S. M., Halloran, P. F.
(2003). The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving. J. Am. Soc. Nephrol.
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Heine, G. H., Girndt, M., Sester, U., Kohler, H.
(2003). No rise in renal Doppler resistance indices at peak serum levels of cyclosporin A in stable kidney transplant patients. Nephrol Dial Transplant
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Heine, G. H., Girndt, M., Sester, U., Kohler, H.
(2003). No rise in renal Doppler resistance indices at peak serum levels of cyclosporin A in stable kidney transplant patients. Nephrol Dial Transplant
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Bakker, R. C., Koop, K., Sijpkens, Y. W., Eikmans, M., Bajema, I. M., de Heer, E., Bruijn, J. A., Paul, L. C.
(2003). Early Interstitial Accumulation of Collagen Type I Discriminates Chronic Rejection from Chronic Cyclosporine Nephrotoxicity. J. Am. Soc. Nephrol.
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Floege, J.
(2003). Recurrent glomerulonephritis following renal transplantation: an update. Nephrol Dial Transplant
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Cremers, S. C. L. M., Scholten, E. M., Schoemaker, R. C., Lentjes, E. G. W. M., Vermeij, P., Paul, L. C., den Hartigh, J., de Fijter, J. W.
(2003). A compartmental pharmacokinetic model of cyclosporin and its predictive performance after Bayesian estimation in kidney and simultaneous pancreas-kidney transplant recipients. Nephrol Dial Transplant
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Gill, J. S., Tonelli, M., Mix, C. H., Pereira, B. J.G.
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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.
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Erin, C. A, Harris, J.
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Adu, D., Cockwell, P., Ives, N. J, Shaw, J., Wheatley, K.
(2003). Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trials. BMJ
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Morath, C., Ritz, E., Zeier, M.
(2003). Protocol biopsy: what is the rationale and what is the evidence?. Nephrol Dial Transplant
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Yilmaz, S., Tomlanovich, S., Mathew, T., Taskinen, E., Paavonen, T., Navarro, M., Ramos, E., Hooftman, L., Hayry, P.
(2003). Protocol Core Needle Biopsy and Histologic Chronic Allograft Damage Index (CADI) as Surrogate End Point for Long-Term Graft Survival in Multicenter Studies. J. Am. Soc. Nephrol.
14: 773-779
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Xu, H., Montgomery, S. P., Preston, E. H., Tadaki, D. K., Hale, D. A., Harlan, D. M., Kirk, A. D.
(2003). Studies Investigating Pretransplant Donor-Specific Blood Transfusion, Rapamycin, and the CD154-Specific Antibody IDEC-131 in a Nonhuman Primate Model of Skin Allotransplantation. J. Immunol.
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Hillebrands, J.-L., Klatter, F. A., Rozing, J.
(2003). Origin of Vascular Smooth Muscle Cells and the Role of Circulating Stem Cells in Transplant Arteriosclerosis. Arterioscler. Thromb. Vasc. Bio.
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Voiculescu, A., Ivens, K., Hetzel, G. R., Hollenbeck, M., Sandmann, W., Grabitz, K., Balzer, K., Schneider, F., Grabensee, B.
(2003). Kidney transplantation from related and unrelated living donors in a single German centre. Nephrol Dial Transplant
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Gourishankar, S., Jhangri, G. S., Cockfield, S. M., Halloran, P. F.
(2003). Donor Tissue Characteristics Influence Cadaver Kidney Transplant Function and Graft Survival but Not Rejection. J. Am. Soc. Nephrol.
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Mui, K. W., van Son, W. J., Tiebosch, A. T. M. G., van Goor, H., Bakker, W. W.
(2003). Clinical relevance of immunohistochemical staining for ecto-AMPase and ecto-ATPase in chronic allograft nephropathy (CAN). Nephrol Dial Transplant
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Jassal, S. V., Krahn, M. D., Naglie, G., Zaltzman, J. S., Roscoe, J. M., Cole, E. H., Redelmeier, D. A.
(2003). Kidney Transplantation in the Elderly: A Decision Analysis. J. Am. Soc. Nephrol.
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Bunnapradist, S., Cho, Y. W., Cecka, J. M., Wilkinson, A., Danovitch, G. M.
(2003). Kidney Allograft and Patient Survival in Type I Diabetic Recipients of Cadaveric Kidney Alone Versus Simultaneous Pancreas/Kidney Transplants: A Multivariate Analysis of the UNOS Database. J. Am. Soc. Nephrol.
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First, M. R.
(2003). Renal function as a predictor of long-term graft survival in renal transplant patients. Nephrol Dial Transplant
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Jurewicz, W. A.
(2003). Tacrolimus versus ciclosporin immunosuppression: long-term outcome in renal transplantation. Nephrol Dial Transplant
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Yang, H. C.
(2003). Tailoring tacrolimus-based immunotherapy in renal transplantation. Nephrol Dial Transplant
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Liem, Y. S., Kock, M. C. J. M., Ijzermans, J. N. M., Weimar, W., Visser, K., Hunink, M.G. M.
(2003). Living Renal Donors: Optimizing the Imaging Strategy--Decision- and Cost-effectiveness Analysis. Radiology
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Wong, C. F., Abraham, K. A., Dorman, A. M., Walshe, J. J.
(2002). Recurrence of familial interstitial nephritis following renal transplantation. Nephrol Dial Transplant
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Inston, N. G., Cockwell, P.
(2002). The evolving role of chemokines and their receptors in acute allograft rejection. Nephrol Dial Transplant
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(2002). Risk of Renal Allograft Loss from Recurrent Glomerulonephritis. NEJM
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