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Basiliximab Versus Daclizumab Combined With Triple Immunosuppression in Deceased Donor Renal Transplantation: A Prospective, Randomized Study

Kandus, Aljoša1,4; Arnol, Miha1; Omahen, Katarina1; Oblak, Manca1; Vidan-Jeras, Blanka2; Kmetec, Andrej3; Bren, Andrej F.1

doi: 10.1097/TP.0b013e3181d02496
Clinical and Translational Research
Free
SDC

Background. In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies combined with triple immunosuppression.

Methods. The adult recipients of at least one human leukocyte antigen-mismatched deceased donor renal graft on cyclosporine microemulsion, mycophenolate mofetil, and methylprednisolone were randomized to induction with basiliximab or daclizumab, given in standard doses. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejections, graft function, patient and graft survival, and safety of this therapy.

Results. Two hundred twelve patients were studied. At 12 months, 11 (10.3%) and 10 (9.5%) patients experienced biopsy-confirmed first acute rejection in basiliximab and daclizumab groups, respectively. Estimated glomerular filtration rate was 69±19 mL/min/1.73 m2 in the basiliximab and 66±21 mL/min/1.73 m2 in the daclizumab group. Patient survival was 97.2% with basiliximab and 97.1% with daclizumab, and graft survival was 94.4% vs. 90.5%, respectively. Hospital treatment was required for 50 and 59 infections in basiliximab and daclizumab groups, respectively. One renal cell carcinoma of native kidney and one basal cell carcinoma were detected in the basiliximab group, and one melanoma of skin in the daclizumab group. One hypersensitivity reaction was observed with daclizumab. No significant differences were found between the groups.

Conclusion. Basiliximab or daclizumab combined with triple therapy was an efficient and a safe immunosuppression strategy, demonstrated with low incidence of acute rejections, excellent graft function, high survival rates, and acceptable adverse event profile in adult recipients within the 1st year after deceased donor renal transplantation.

1 Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

2 Tissue Typing Centre, Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia.

3 Department of Urology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

4 Address correspondence to: Aljoša Kandus, M.D., Ph.D., Department of Nephrology, University Medical Centre Ljubljana, Zaloška 7, Ljubljana 1525, Slovenia.

A.K. participated in research design and writing of the paper; M.A. participated in research design, writing of the paper, and participated in data analysis; K.O. participated in the performance of the research, M.O. participated in the performance of the research; B.V.-J. participated in the performance of the research and contributed the analytic tools; A.K. participated in the performance of the research; A.F.B. participated in research design and in the performance of the research.

The authors declare no conflict of interest.

E-mail: aljosa.kandus@guest.arnes.si

Received 9 October 2009. Revision requested 8 November 2009.

Accepted 8 December 2009.

Two monoclonal antibodies against the alpha subunit (CD25) of the interleukin-2 receptor on activated T lymphocytes have been available for induction immunosuppression: a chimeric antibody, basiliximab, and a humanized antibody, daclizumab. When combined with these antibodies, the receptors are not available for interleukin-2 binding, and proliferation of activated T cells is inhibited. Both antibodies are used to supplement standard immunosuppressive therapy after renal transplantation (1–3). At a dose of 20 mg administered intravenously before transplantation and on day 4, basiliximab maintains interleukin-2 receptor saturation for 4 to 6 weeks (1, 2, 4). The average duration of this saturation seemed to be prolonged by 39% and 64% in the presence of azathioprine and mycophenolate mofetil (MMF), respectively (5). Five doses of daclizumab at 1 mg/kg given intravenously before transplantation and every 2 weeks thereafter achieved adequate interleukin-2 receptor saturation for more than 12 weeks (2, 3, 6). Basiliximab and daclizumab were proven to be effective for acute rejection prophylaxis after renal transplantation, and they were well tolerated in clinical trials (6–13). The incidence of infections and other adverse events was similar between treatment groups (6–9, 11–13). These favorable results support the use of basiliximab or daclizumab in combination with standard immunosuppression. So far, there are no relevant randomized studies comparing efficacy and safety of the two antibodies in renal transplant recipients. However, important differences between the two antibodies are the duration of interleukin-2 receptor saturation, dose administration regimens, and costs of treatment (14).

In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of basiliximab versus daclizumab combined with cyclosporine (CsA), MMF, and methylprednisolone in adult-mismatched deceased donor renal graft recipients during a 12-month period of follow-up.

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PATIENTS AND METHODS

Study Design and Inclusion Criteria

This investigator-driven study was undertaken at one renal transplant center at the Department of Nephrology, University Medical Centre Ljubljana, Slovenia and was approved by the Institutional Ethical Committee. The design, data collection, analysis, and writing were performed by the investigators. Informed consent was obtained from each patient. The study was registered at the Cochrane Renal Group database (CRG030600052) and received no special funding.

Adult renal transplant recipients, each assigned to receive isolated renal graft from a deceased donor with at least one human leukocyte antigen mismatch, were eligible for the study. Patients received basiliximab or daclizumab, according to a 1:1 randomization procedure. The randomization was performed by the use of table of random numbers and sealed envelopes were used to conceal the allocation from the investigators. The numbered envelopes kept at local pharmacy were opened just before transplantation by personnel who were not involved in the study.

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Immunosuppression and Concomitant Medications

Basiliximab (Simulect, Novartis, Basel, Switzerland) infusion of 20 mg was given immediately before transplantation and again on day 4. Daclizumab (Zenapax, Hoffmann-La Roche, Basel, Switzerland) infusion of 1 mg/kg was administered immediately before transplant surgery and 2, 4, 6, and 8 weeks after transplantation. All study patients received the same triple immunosuppression: CsA, MMF, and methylprednisolone. Continuous infusion of CsA (Sandimmun, Novartis, Basel, Switzerland) at 0.08 mg/kg per hour was started at operation and followed by CsA microemulsion (Sandimmun Neoral, CsA Neoral, Novartis) at 3 mg/kg twice daily on day 2. CsA Neoral dose was adjusted to achieve blood trough levels from 100 to 170 ng/mL during first 3 months after transplantation and 70 to 130 ng/mL after the 3rd month. CsA concentrations were measured by an enzyme-multiplied immunoassay technique using monoclonal antibodies. MMF (CellCept, Hoffmann-La Roche, Basel, Switzerland) was given at 0.75 g three times daily (0.5 g three times daily in patients with body weight <50 kg) from day 1. Methylprednisolone at 0.4 mg/kg was injected at operation and from day 1 to day 3. Oral methylprednisolone was started on day 4 at 0.4 mg/kg per day and tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg per day.

All patients received diltiazem. Continuous infusion of diltiazem at 0.0022 mg/kg per minute was started at operation and was replaced by oral diltiazem given at 60 to 90 mg three times daily on day 4. Prophylaxis with trimethoprim-sulfamethoxazole for 12 months was also a part of treatment in all patients. Patients who were positive for tuberculin received isoniazid for 12 months. Patients at high risk of cytomegalovirus (CMV) infection (donor seropositive and recipient seronegative) were given ganciclovir or valganciclovir for 100 days after transplantation.

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Efficacy Endpoints

The primary efficacy endpoint of the study was the incidence of biopsy-confirmed first acute rejection episodes at 12 months. Secondary endpoints included the proportion of patients with early acute rejections (in the first 3 months), the time of occurrence of the first rejection episode, the comparison of the histologic severity of the acute rejections, the incidence of delayed graft function, the renal graft function up to the end of 12th month, the number and causes of graft loss and death of patients, and the patient and graft survival at 12 months.

Patients with suspected rejection episode underwent graft core biopsy before antirejection treatment. Biopsy samples were evaluated in accordance with available Banff classification of renal transplant histopathology (15–17). Steroid-resistant acute cellular rejections were treated with the antithymocyte globulin or the muromonab-CD3. High doses of intravenous immune globulin or plasmapheresis combined with low dose of CMV hyperimmune globulin were used for treatment of acute antibody-mediated rejections. Graft function was evaluated by estimated glomerular filtration rate (eGFR) calculated by abbreviated Modification of Diet in Renal Disease formula (18). Clinical evaluations of signs and symptoms, laboratory variables, graft function, as well as patient and graft survivals were made regularly during follow-up.

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Safety Endpoints

Safety assessments included the occurrence of those adverse events possibly associated with the usage of two different antibodies, that is, infections requiring hospital treatment, malignancies, hypersensitivity reactions, and occurrence of new-onset diabetes mellitus after transplantation. CMV disease was defined as an active CMV infection combined with the occurrence of additional CMV-related clinical or laboratory manifestations (19). The diagnostic criteria for diabetes mellitus as recommended by the 2003 international consensus guidelines for new-onset diabetes mellitus after transplantation were used (20).

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Statistical Analysis

The working hypothesis was the equivalence of both therapies in the prevention of biopsy-confirmed first acute rejection episode. We predicted that acute rejection incidence would approximate 15% and calculated that 137 patients were needed in each group with a noninferiority difference set at 10%, an alpha risk set at 5%, and a power of 80%. Because the study was performed in a small-volume single renal transplant center, the study design included an interim assessment and subsequent readjustment of enrollment if the interim differences between the two groups were negligible. The investigators decided to discontinue the study after more than 200 patients had been enrolled. This decision was made because of the statistical improbability of showing a change in the primary efficacy endpoint if more patients were enrolled.

All study endpoints were analyzed on the basis of the intention-to-treat principle. Categorical variables were summarized as counts and percentages or medians with interquartile ranges and continuous variables as means with standard deviation. Categorical data were compared with Fisher's exact test and continuous variables with the t test for unpaired data or the Wilcoxon-Mann-Whitney test as appropriate. The incidences of graft rejection, graft loss, and death were calculated with the use of Kaplan-Meier survival analysis and compared with the log-rank test.

All tests were two tailed, and a P value of less than 0.05 was considered to indicate statistical significance. Analyses were performed using the SPSS statistical software (version 16.0, SPSS Inc., Chicago, IL).

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RESULTS

Demographic and Immunosuppressant Data

Figure 1 shows the patient flow throughout the trial. A total of 229 patients were transplanted at our renal transplant center between June 2002 and December 2007. Two patients, younger than 18 years, and 15 patients with zero human leukocyte antigen mismatch did not meet the inclusion criteria. One hundred seven patients in the basiliximab arm and 105 patients in the daclizumab arm subsequently entered the trial and are reported here. Overall, 196 (92.5%) patients completed 12-month period of follow-up with functioning graft.

FIGURE 1.

FIGURE 1.

Both patient groups were well balanced with respect to patient and donor demographics (Table 1). With regard to baseline immunologic parameters, patients were considered of low-immunological risk, as reflected by median current panel reactive antibodies of 0%. Among 212 patients analyzed in the study, 20 patients (9.4%) were recipients of a second graft and only 13 (6.1%) had a current panel reactive antibody level above 10%. The minority of patients were transplanted from expanded criteria donors (21).

TABLE 1

TABLE 1

An intergroup comparison of the mean doses of the immunosuppressant agents administered during the study (i.e., CsA Neoral, MMF) showed that doses were similar in both groups at all times with the exception of higher mean MMF dose in basiliximab group at month 6 (Table 2). A similar intergroup comparison showed that blood CsA trough level was higher in daclizumab group at month 2 but that no intergroup differences occurred at any other time point (Table 2).

TABLE 2

TABLE 2

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Efficacy Endpoints

The primary endpoint, biopsy-confirmed first acute rejection, was observed in 11 (10.3%) basiliximab patients and 10 (9.5%) daclizumab patients (P=0.85; Fig. 2 and Table 3). The median time between transplantation and rejection occurrence was similar in the basiliximab and the daclizumab arm (138 vs. 102 days; P=0.17). Rejection gradings are shown in Table 3. The severity of rejection, as scored by the Banff criteria, was similar among the basiliximab and the daclizumab patients. Of the daclizumab patients, one experienced three rejection episodes, and two patients experienced rejections that were diagnosed as antibody mediated. Only one patient (in the daclizumab arm) experienced an episode of biopsy-confirmed acute rejection that was left untreated (due to concomitant sepsis). All patients received steroid boluses as a first-line treatment of rejection. Additional therapy was administered to two basiliximab patients (1.9%) and three daclizumab patients (2.9%). In the basiliximab group, one patient received antithymocyte globulin, and one patient received muromonab-CD3. Of the daclizumab patients, one patient received muromonab-CD3, one patient received muromonab-CD3 and high dose of intravenous immunoglobulin, and one patient was treated using plasmapheresis and low dose of CMV hyperimmune globulin. All rejections, but one, were satisfactorily treated.

FIGURE 2.

FIGURE 2.

TABLE 3

TABLE 3

Delayed graft function, defined as the need for dialysis within the first week after transplantation, occurred in 21.5% of basiliximab patients and 20.0% of daclizumab patients (P=0.79). Renal graft function as assessed by eGFR was similar in both patient groups at all times (Table 3). Up to 1 year, 16 grafts were lost: 6 in the basiliximab (5.6%) and 10 in the daclizumab (9.5%) group (P=0.28). In explanted grafts after vascular thrombosis or technical failure, the acute rejection was excluded by histopathologic examination. Six patients died: three in the basiliximab (2.8%) and three in the daclizumab (2.9%) group (P=0.98; Table 3). At 1 year, overall graft survival rates in the basiliximab and daclizumab groups were 94.4% and 90.5%, respectively (P=0.29), and patient survival rates were 97.2% and 97.1%, respectively (P=0.98).

To elucidate whether rejection had a negative impact on the overall cohort of 196 patients who completed 12-month period of follow-up with functioning graft, we performed a post hoc analysis to compare graft function in those patients who had experienced rejection (n=19) with those who remained rejection free (n=177) at 1 year. The eGFR at 1 year was 69±19 mL/min/1.73 m2 among rejection-free patients, compared with eGFR of 54±18 mL/min/1.73 m2 among patients with rejection episodes (P=0.002).

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Safety Endpoints

The number of infections requiring hospitalization was similar in both patient groups (50 in the basiliximab and 59 in the daclizumab arm; Table 4). The percentage of CMV disease was numerically more frequent in the daclizumab group when compared with the basiliximab group (21.9% vs. 13.1%, P=0.09). One patient in the basiliximab arm developed basal cell carcinoma, and one patient in the daclizumab arm developed melanoma of the skin. One patient in the basiliximab arm developed renal cell carcinoma of the native kidney. None of the patients developed posttransplant lymphoproliferative disorder.

TABLE 4

TABLE 4

The proportion of patients with new-onset diabetes mellitus after transplantation was similar in both patient groups (Table 4). One hypersensitivity reaction was observed during the fourth administration of daclizumab. It manifested mainly with dyspnea and flush. The fifth dose of daclizumab was omitted in this patient.

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DISCUSSION

This is the largest documented study of head-to-head comparison between basiliximab and daclizumab in deceased donor renal transplantation. The main result from this study is that basiliximab and daclizumab were similarly effective in protecting low-immunological risk renal graft recipients from the 1st-year acute rejection.

It is well appreciated that acute rejection is strongly related to the development of chronic rejection and subsequent graft failure (22, 23). Because of its potential harmful effect, one of the main aims of current immunosuppression is to avoid acute rejection to improve renal graft survival. The majority of acute rejection episodes occur in the early posttransplant period (22). It is common to differentiate early and late acute rejections. The latter are more resistant to treatment and are stronger predictor of chronic rejection. However, the terms early and late acute rejection are not consistently defined and range of early rejection is 2 to 6 months after transplantation (22, 24). Because of this inconsistency, the limitation of acute rejection to the first 3 posttransplant months could be acceptable. This period is similar to duration of interleukin-2 receptor saturation with daclizumab.

Immunosuppression with basiliximab or daclizumab in combination with CsA Neoral, MMF, and low doses of methylprednisolone seems to be promising therapy due to low incidence of early acute rejection episodes and low overall incidence of acute rejections in our study. Supporting the efficacy of our immunosuppression was also excellent renal graft function at the end of follow-up. A post hoc analysis of the patient population who completed 1 year of follow-up also revealed that graft function was significantly better among patients who remained rejection free. Two randomized, placebo-controlled trials evaluated addition of anti- interleukin-2 receptor monoclonal antibodies induction to CsA, MMF, and steroids (9, 25). These showed a relative reduction in acute rejection of 42.5% (15.3% vs. 26.6%, n=123) at 6 months (9) and 30% (14% vs. 20%, n=75) at 12 months (25), respectively but were not powered to show statistically significant difference. Despite lack of the statistical significance in the above studies, we believe that the addition of these antibodies to CsA, MMF, and steroids is beneficial and clinically relevant.

The incidence of acute rejection episodes was not significantly different between the basiliximab group and the daclizumab group in our study. The number of patients who would have to be enrolled for the study to reach statistical power was insufficient, but significant differences in acute rejection episodes between the basiliximab and daclizumab arms seemed to be improbable even if greater number of patients were enrolled. Any difference could hardly be expected taking into account mechanism of action of both monoclonal antibodies. Furthermore, there were no significant differences in combined immunosuppression, characteristics of patients and donors, or other events with a potential influence on the occurrence of rejection. In addition, an important reason for premature discontinuation of the study was the fact that daclizumab induction exceeded basiliximab therapy for approximately €277,000. In our country, the costs of treatment with basiliximab (two doses of 20 mg) amounted to €2482 when compared with €5125 (five doses of 75 mg) for treatment with daclizumab (2007 values).

Two smaller trials (n=82 total) compared basiliximab with daclizumab combined with calcineurin inhibitor (CsA or tacrolimus), MMF, and steroids. At 3 months, basiliximab was associated with significant decrease in acute rejection episodes when compared with daclizumab. However, this difference in efficacy cannot be convincing without close similarity of combined immunosuppression as well as the characteristics of patients and donors, which was not presented (26). No clear difference for any outcomes could be demonstrated in the other trial (27).

CsA Neoral doses used in our study and concomitant blood CsA trough levels were low and could possibly decrease the frequency and severity of adverse effects of this drug. At 12 months, CsA doses were at least two times lower than those associated with the best long-term renal graft survival in retrospective analysis (28). However, it must be mentioned that this analysis was completed before widespread usage of MMF and anti-interleukin-2 receptor monoclonal antibodies.

With regard to safety, hospital treatment was required for 50 and 59 infections in basiliximab and daclizumab groups, respectively. Patients in the daclizumab group showed a trend to a more frequent CMV disease. This could be related to a longer interleukin-2 receptor saturation associated with daclizumab. All infections, but two in daclizumab group, were successfully treated. The infections that occurred in patients with failed renal graft during the first 12 posttransplant months were also included in the presented numbers. No case of posttransplant lymphoproliferative disorder is in accordance with previous observation that among induction therapies, anti-interleukin-2 receptor antibodies were associated with the smallest risk of this disorder (29).

Beside already discussed lack of statistical power of our study, there are other noticeable limitations. First, it was an open-label trial. Blinding the two arms would have been logistically complex. Second, the majority of our patients was of low-immunological risk and transplanted from standard criteria donors. It is unclear whether immunologically high-risk patients would benefit from daclizumab rather than basiliximab because its administration schedule permits a longer duration of interleukin-2 receptor saturation. Finally, during the first years (2002–2004), donor-specific antibodies were not reported and C4d staining was not already available, and biopsies were still scored according to Banff 97 criteria and not by more recent classifications that take into account humoral rejection. This might have resulted in underreporting of humoral rejection. However, the responses to treatment appropriate for acute cellular rejection in our patients support the assumption that humoral rejections were not overlooked.

We concluded that both anti-interleukin-2 receptor monoclonal antibodies in combination with CsA Neoral, MMF, and low doses of methylprednisolone achieved an efficient and a safe immunosuppression, demonstrated with low incidence of acute rejections, excellent renal graft function, high survival rates during the first 12 posttransplant months, and an acceptable adverse events profile in immunologically low-risk adult recipients transplanted from deceased standard criteria donors. Although no significant differences were found between the two therapies, larger samples ought to be studied before definitive conclusions may be drawn. The simplicity of drug administration and substantially lower costs of treatment are currently the acknowledged advantages of basiliximab usage.

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REFERENCES

1. Onrust SV, Wiseman LR. Basiliximab. Drugs 1999; 57: 207.
2. Maes BD, Vanrenterghem YF. Anti-interleukin-2 receptor monoclonal antibodies in renal transplantation. Nephrol Dial Transplant 1999; 14: 2824.
3. Wiseman LR, Faulds D. Daclizumab. Drugs 1999; 58: 1029.
4. Kovarik JM, Kahan BD, Rajagopalan PR, et al. Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. Transplantation 1999; 68: 1288.
5. Kovarik JM, Pescovitz MD, Sollinger HW, et al. Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients. Clin Transplant 2001; 15: 123.
6. Vincenti F, Lantz M, Birnbaum J, et al. A phase I trial of humanized anti-interleukin 2 receptor antibody in renal transplantation. Transplantation 1997; 63: 33.
7. Kahan BD, Rajagopalan PR, Hall M. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. Transplantation 1999; 67: 276.
8. Ponticelli C, Yussim A, Cambi V, et al. A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients. Transplantation 2001; 72: 1261.
9. Lawen JG, Davies EA, Mourad G, et al. Randomized double-blind study of immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with mycophenolate mofetil-containing triple therapy in renal transplantation. Transplantation 2003; 75: 37.
10. Kovarik J, Wolf P, Cisterne JM, et al. Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts. Transplantation 1997; 64: 1701.
11. Nashan B, Moore R, Amlot P, et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet 1997; 350: 1193.
12. Vincenti F, Kirkman R, Light S, et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 1998; 338: 161.
13. Nashan B, Light S, Hardie IR, et al. Reduction of acute renal allograft rejection by daclizumab. Transplantation 1999; 67: 110.
14. van Gelder T, Warlé M, ter Meulen RG. Anti-interleukin-2 receptor antibodies in transplantation: What is the basis for choice? Drugs 2004; 64: 1737.
15. Racusen LC, Solez K, Colvin, RB, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999; 55: 713.
16. Racusen LC, Colvin RB, Solez K, et al. Antibody-mediated rejection criteria—An addition to the Banff 97 classification of renal allograft rejection. Am J Transplant 2003; 3: 708.
17. 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.
18. Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine [abstract]. J Am Soc Nephrol 2000; 11: 155A.
19. Tanabe K, Tokumoto T, Ishikawa N, et al. Comparative study of cytomegalovirus (CMV) antigenemia assay, polymerase chain reaction, serology, and shell vial assay in the early diagnosis and monitoring of CMV infection after renal transplantation. Transplantation 1997; 64: 1721.
20. Davidson J, Wilkinson A, Dantal J, et al. New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation 2003; 75(suppl 10): SS3.
21. Metzger RA, Delmonico FL, Feng S, et al. Expanded criteria donors for kidney transplantation. Am J Transplant 2003; 3(suppl 4): 114.
22. Basadonna GP, Matas AJ, Gillingham KJ, et al. Early versus late acute renal allograft rejection: Impact on chronic rejection. Transplantation 1993; 55: 993.
23. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342: 605.
24. Gjertson DW. Impact of delayed graft function and acute rejection on graft survival. Transplant Proc 2002; 34: 2432.
25. Pescovitz MD, Bumgardner G, Gaston RS, et al. Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation. Clin Transplant 2003; 17: 511.
26. Khan A-J, Sarkissian N, Brennen TS, et al. Comparison of two IL-2 receptor blockers in decreasing the incidence of acute rejection in early post-transplant time in renal transplant recipients [abstract]. J Am Soc Nephrol 2000; 11: 694A.
27. Nair MP, Nampoory MR, Johny KV, et al. Induction immunosuppression with interleukin-2 receptor antibodies (basiliximab and daclizumab) in renal transplant recipients. Transplant Proc 2001; 33: 2767.
28. Opelz G, Dohler B. Cyclosporine and long-term kidney graft survival. Transplantation 2001; 72: 1267.
29. Cherikh WS, Kauffman HM, McBride MA, et al. Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 2003; 76: 1289.
Keywords:

Renal transplantation; Immunosuppression; Basiliximab; Daclizumab; Kidney; IL-2 receptor; Rejection

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