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PubMed2002

Two-hour post-dose cyclosporine level is a better predictor than trough level of acute rejection of renal allografts.

Cyclosporine (CyA) trough concentrations are poor predictors for acute rejection post-transplant. Patients were part of a randomized trial of basiliximab (n=70) vs. anti-thymocyte globulin (ATGAM) (n=65), both in combination with Neoral, mycophenolate mofetil, and steroids, undergoing first or second, cadaveric or live donor renal transplants. Whole blood samples were collected just before (C0) and at 2 h after CyA dosing on day 4 and at the end of weeks 1, 2, 4, and 8. The CyA was measured by fluorescence polarization immunoassay (TDx). Mean CyA C0 and C2 concentrations were calculated. Logistic regression analysis revealed that mean C2 level was the only predictor of acute rejection (P < or = 0.001). Higher mean C2 levels predicted lower rejection probabilities. Linear regression analysis revealed that higher mean C2 levels were not related to higher serum creatinine levels at either week 4 or 24 or to incidence of headache or tremor. The CyA C2 levels predict the frequency of rejection postrenal transplant. Target C2 levels are in the range of 1500 ng/dL.

Antibodies, Monoclonal↗
PubMed2003

Decreased bone mineral density in the pediatric renal transplant population.

All renal transplant recipients at our centre have had bone mineral density assessment (BMD) by DEXA scans of their lumbar spine while on the transplant waitlist and at 6-month intervals post-transplant over the past 7 yr. Risk factors for osteopenia and osteoporosis including donor source, dialysis status prior to transplantation, prior renal disease, and biopsy confirmed rejection events and their relationship to BMD of the lumbar spine were assessed. Thirty-nine children transplanted over the past 7 yr were included in this study. In total, 127 BMD longitudinal assessments were performed. From 1990 to 1997, ATG/ALG was used as antibody induction therapy. From 1997 to 2002, Basiliximab was utilized. Cyclosporin A (CyA) was the primary immunosuppressant for most children with tacrolimus as primary (n = 2) and switch for CyA failure or toxicity (n = 16). Prednisone was administered at a dose of 1 mg/kg/day for the first week and tapered to 10 mg/m2/alternate day by 1 month post-transplant. Azathioprine 1.5 mg/kg/day was continued for 1 yr and discontinued in children who were rejection free. All rejections were biopsy confirmed and treated with a prednisone pulse. Using a repeated measures regression analysis, we have found that L1-L4 BMD z score is affected by height and transplant number. It is also related to time relative to transplant in a quadratic fashion. There was an inverse relationship between advancing patient age and L1-L4 BMD z score. L1-L4 BMD z score was not related to weight, pre-existing renal disease, gender, donor source, type of renal replacement therapy prior to transplantation, or rejection events.

Adolescent↗
PubMed2001

Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients.

Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined. Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/ d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression. Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (maximal concentration) by 13.5 +/- 24% (p =0.009), while C12 (trough level) was unchanged (p =0.42). Total and LDL cholesterol decreased by 26.8 +/- 8.4% (p < 0.0001) and 41.5 +/- 11.0% (p < 0.0001), respectively. Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.

Adult↗
PubMed2004

C2 blood concentrations of orally administered cyclosporine in pediatric liver graft recipients with a body weight below 10 kg.

Pharmacokinetic studies in adult and pediatric liver transplant recipients have shown that the C(2) monitoring is superior to the traditional determination of CsA trough levels (C(0)) as an estimate of CsA exposure. However, target reference values for C(2) in very small infants have not been established yet. The objective of our study was to assess the distribution of C(2) levels in the first week following Ltx and to analyze enteral absorption of CsA for this group of patients. We documented CsA C(0) and C(2) levels in 25 infants with a body weight below 10 kg (median 6.8 kg; range 3.0-9.8 kg) in the first 7 days after Ltx. The infants had a median age at transplantation of 7 months (range 0.3-20.0 months). The underlying diagnoses were biliary atresia (n = 17), acute liver failure (n = 4), metabolic disease (n = 4). All children received CsA microemulsion (Neoral, initial 10 mg/kg/day), prednisolone, and two single doses of basiliximab as immunosuppressive drugs. The mean C(0) and C(2) levels were as follows: day 1: C(0) 77.0 +/- 39.6, C(2) 340.5 +/- 140.0 ng/mL; day 2: C(0) 135.5 +/- 53.2, C(2) 467.0 +/- 168.2 ng/mL; day 3: C(0) 146.5 +/- 70.8, C(2) 519.0 +/- 219.1 ng/mL; day 4: C(0) 168.5 +/- 55.1, C(2) 570.0 +/- 163.7 ng/mL; day 5: C(0) 156.5 +/- 38.0, C(2) 612.0 +/- 132.4 ng/mL; day 6: C(0) 177.0 +/- 41.1, C(2) 606.0 +/- 149.2 ng/mL; day 7: C(0) 174.0 +/- 27.2, C(2) 622.0 +/- 98.8 ng/mL (r = 0.82, p < 0.05). This analysis demonstrates that there is a good enteral absorption of CsA in very small children post-Ltx in the early post-operative period. Based on the C(2) levels achieved, we conclude that there is a good correlation between C(0) and C(2) levels even in very small infants.

Administration, Oral↗
PubMed2000

Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team.

BACKGROUND: On the basis of positive results in studies of the transplantation of pig extremities and the information exchanged at an international symposium on composite tissue transplantation, we developed a protocol for human hand transplantation. METHODS: After a comprehensive pretransplantation evaluation and informed-consent process, the left hand of a 58-year-old cadaveric donor, matched for size, sex, and skin tone, was transplanted to a 37-year-old man who had lost his dominant left hand 13 years earlier. Immunosuppression consisted of basiliximab for induction therapy and tacrolimus, mycophenolate mofetil, and prednisone for maintenance therapy. RESULTS: The cold-ischemia time of the donor hand was 310 minutes. There were no intraoperative or early postoperative complications. Moderate acute cellular rejection of the skin of the graft developed 6, 20, and 27 weeks after transplantation. All three episodes resolved completely after treatment with intravenous methylprednisolone and topical tacrolimus and clobetasol. Temperature, pain, and pressure sensation had developed in the hand and fingers by one year. At one year, the patient had regained the ability to perform many functional activities with his left hand that he had not been able to perform with his prosthesis, such as throwing a baseball, turning the pages of a newspaper, writing, and tying his shoelaces. CONCLUSIONS: Early success has been achieved in hand transplantation with the use of currently available immunosuppressive drugs.

Adult↗
PubMed2002

Anti-CD25 monoclonal antibody coverage allows for calcineurin inhibitor "holiday" in solid organ transplant patients with acute renal dysfunction.

BACKGROUND: Solid organ transplant (Tx) patients on calcineurin inhibitors (CNI) can develop acute renal dysfunction (ARD), which could be improved by reducing or withholding ("holiday") CNI dose. METHODS: We used anti-CD25 monoclonal antibodies to prevent acute rejection in 11 adult Tx patients (7 heart, 2 liver, 2 heart-renal Tx), requiring a CNI "holiday" because of 15 events of ARD after the initial postTx hospitalization. An event of ARD was defined as an increase in serum creatinine (Scr)>25% vs. baseline. The CNI "holiday" was implemented until Scr had decreased to baseline. Basiliximab was used in 7 patients (11 events), and daclizumab was used in 4 patients (4 events). RESULTS: The CNI "holiday" was implemented over 21+/-51 days. Anti-CD25 mAb were well tolerated with no episodes of acute rejection. Scr (micromol/liter) increased from 145+/-48 to 301+/-92 (P<0.0001), and decreased to 143+/-55 with the CNI "holiday." CONCLUSIONS: Our results suggest that a CNI "holiday" may improve ARD after solid organ Tx without rejection under anti-CD25 mAb coverage.

Acute Disease↗
PubMed2005

Steroid-free living-donor liver transplantation in adults.

To examine the benefits of steroid avoidance in adult living donor liver transplantation, we compared the clinical courses of nine recipients receiving basiliximab or daclizumab and 13 historical patients who received steroids. The 1-year patient and graft survival and the incidence of acute cellular rejection were similar in both groups. The side effects of immunosuppression tended to be more frequent in the steroid group. Hepatitis C virus (HCV)-RNA levels measured early after transplantation remained suppressed in the steroid-free group. Steroid avoidance was beneficial in the recipients, as both steroid side effects and recurrence of HCV could be avoided.

Acute Disease↗
PubMed2006

Safety and efficacy of steroid withdrawal two days after kidney transplantation: analysis of results at three years.

BACKGROUND: Chronic steroid therapy in spite of myriad side effects is widely used in kidney transplantation. This prospective controlled study evaluated safety and efficacy of steroid withdrawal at 2 days in kidney recipients monitored by surveillance biopsy. METHODS: In all, 300 kidney recipients were studied; 150 in second-day steroid withdrawal group and 150 in steroid treated group (control group). Immunosuppression was basiliximab induction and maintenance was a calcineurin inhibitor and mycophenolate mofetil or sirolimus. Biopsy-proven acute rejection (BPAR) was treated by methylpredisolone. Surveillance biopsies were completed to evaluate subclinical acute rejection (SCAR) and chronic allograft nephropathy (CAN). Primary end point was acute rejection. Three-year patient and graft survival, new onset diabetes mellitus (NODM), serum creatinine and creatinine clearance were evaluated. RESULTS: Acute rejection was diagnosed in 14% in control group and 16% in steroid withdrawal group. Three-year patient and graft survival was 89% and 79% in control and 91% and 78% in steroid withdrawal group. Serum creatinine and creatinine clearance was 1.9+/-0.8 and 59+/-11 in control group and 1.8+/-0.9 mg/dl and 61+/-10 mls/minute in steroid withdrawal group. Incidence of SCAR and progression of CAN were comparable in the 2 groups. At 3-years NODM was diagnosed in 21% in control group and 4% in steroid withdrawal group (P<0.01). CONCLUSIONS: Two-day steroid withdrawal in kidney transplant recipients did not affect BPAR, SCAR, CAN, graft function and patient and graft survival compared to control group up to 3 years. NODM was significantly less in steroid withdrawal group. Two-day steroid withdrawal is safe and beneficial in kidney transplant recipients.

Acute Disease↗
PubMed2004

Cost-minimization study comparing Simulect vs. Thymoglobulin in renal transplant induction.

PURPOSE: Based on the data of clinical trial CHI-F-02 comparing the efficacy and safety of basiliximab (Simulect) vs. anti-thymocyte globulin (Thymoglobulin) in renal transplant induction, we carried out an economic evaluation. METHOD: This pharmacoeconomic study was a cost-minimization study, i.e. given the equivalent efficacy of the products, the strategy that minimized the cost of care was considered better. The cost of care was analyzed from the hospital perspective. MATERIAL: This 'piggyback' study of 100 patients estimated the direct medical costs incurred over 6 months of use of two strategies for renal transplant induction therapy. Direct medical costs are those of utilized medical resources: medications, hospital stays, dialysis, and physician visits and investigations not scheduled in the protocol. RESULTS: In the Simulect arm, significant reductions were found in the initial hospital stay duration and number of infectious episodes. Therefore, although the average cost of treatment was slightly higher with Simulect) than with Thymoglobulin (2964 vs. 2298 Euros), the cost of the initial hospitalization was significantly lower in the Simulect arm (10 907 vs. 11 967 Euros; p = 0.02). Furthermore the mean cost of infectious episodes was significantly lower in the Simulect arm (1056 vs. 1790 Euros, p = 0.03). Cytomegalovirus infection accounted for a significantly smaller proportion of this cost in the Simulect arm than in the Thymoglobulin arm (30% vs. 53%, p = 0.001). CONCLUSION: This study showed direct medical cost savings of 1159 Euros per patient in the Simulect arm, which more than compensated for the higher price of this immunosuppressive drug.

Adult↗
PubMed2004

Rapid steroid withdrawal in hepatitis C virus-positive kidney transplant recipients.

The effects of rapid steroid withdrawal (SW) on kidney transplantation (KT) outcome were investigated in 12 HCV+ patients in a prospective cohort study. These results were compared with 17 HCV+ patients who received KT in the prior 2 yr and treated with a standard prednisone taper protocol. SW patients received only 6 d of steroid treatment after transplantation. Eleven received Thymoglobulin and one Basiliximab induction treatment along with a calcineurin inhibitor and mycophenolate mofetil. Patient and graft survival was 92% in SW group (median follow-up 12 months, range 6-17), and 92 and 82% in the historic control group respectively (median follow-up 21 months, range 11-27). In the SW and control group, acute rejection rates were 9 and 18%, and mean creatinine levels at last follow-up 1.30 +/- 0.36 and 1.68 +/- 0.58 mg/dL respectively. Only two SW patients had an increase in liver function tests during follow-up (18%), compared with six patients in the control group (43%). This study demonstrates that rapid SW is safe for HCV+ KT recipients, without an increase in acute rejection episodes or liver function abnormalities in the short term.

Adult↗
PubMed2005

Airway cellular response to two different immunosuppressive regimens in lung transplant recipients.

A number of new immunosuppressive drugs have become available in transplant medicine. We investigated the effects of two different immunosuppressive protocols on bronchoalveolar lavage fluid cellular characteristics in 34 lung transplant recipients who were treated with anti-thymocyte globulin induction therapy, cyclosporine, azathioprine (AZA), and prednisolone (regimen I), compared with 17 recipients receiving basiliximab induction, tacrolimus, AZA, and prednisolone (regimen II). We performed bronchoalveolar lavages between 15 and 40 d post-transplantation, in stable clinical condition and no acute rejection, cytomegalovirus, and/or respiratory tract infection. The regimen II treatment was associated with a significantly lower percentage lavage fluid lymphocytes than with regimen I. The CD4/CD8 ratio was significantly higher with regimen II than with regimen I: 1.56 (range 0.41-2.16) and 0.33 (0.04-0.95) respectively; p < 0.001, mainly because of a lower percentage CD8(+) cells with regimen II: 25% (12-51) vs. regimen I: 60% (34-77); p < 0.001. The percentage CD4(+) CD25(+) cells appeared lower with regimen II: 21% (10-88) vs. regimen I: 50% (0-87); p = 0.04. Overall survival was similar between the groups, whereas a beneficial trend in freedom of bronchiolitis obliterans syndrome was observed with regimen II. Airway lymphocyte subtypes are affected by the immunosuppressive protocol used. This observation should be taken into account when studying transplant recipients, and may contribute to our understanding of alloreactive airway disease.

Adult↗
PubMed2005

Cytomegalovirus prophylaxis with valganciclovir in African-American renal allograft recipients based on donor/recipient serostatus.

There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African-American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 +/- 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R-) received 900 mg (n = 12); moderate risk (D+/R+, D-/R+) received 450 mg (n = 60); and low risk (D-/R-) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R- serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients.

Adult↗
PubMedDate not supplied

Infectious complications after kidney transplantation: current epidemiology and associated risk factors.

BACKGROUND: The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. METHODS: This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. RESULTS: We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR=4.5 and 2.9, p=0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR=3.3 and 2.5, p=0.009 and 0.047, respectively). CONCLUSION: This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal.

Adult↗
PubMed2005

Development of growth and body mass index after pediatric renal transplantation.

Suboptimal final height and marked weight gain after renal transplantation (RTx) are common and may result in obesity. Steroid free immunosuppression has been advocated to improve growth and limit weight gain. We evaluated retrospectively the evolution of growth and body mass index (BMI) after renal transplantation to study risk factors for weight gain under steroid based treatment. Sixty-four pediatric patients (age 9.9 +/- 5.0 yr) were included in the study. To allow comparison between different age groups, standard deviation scores (SDS) for height and BMI for height age were calculated at time of transplantation and 3, 6, 9, 12, 24, 36, 48 and 60 months later. Induction immunosuppression consisted of basiliximab, cyclosporine and prednisone. Growth retardation at time of RTx was obvious with a SDS for height of -2.20 +/- 1.34. Height during the first year improved to an SDS of -2.0 +/- 1.27 (p < 0.01) but did further not increase in year 2 and 3. More than 40% of all patients remained 2 SDS below normal mean. SDS BMI for height age at transplantation was -0.19 +/- 0.98 and increased significantly during the first 3 months after transplantation to +0.64 +/- 1.07 (p < 0.01). Thereafter, BMI remained stable but did not decline to pretransplant values. A SDS BMI for height age of more than 2 SDS was observed in 2, 6, 9 and 11% of children at RTx and 1, 2 and 3 yr later respectively. BMI gain over 3 yr was significantly enhanced in children whose parents (especially the mother) were overweight. No influence of gender, BMI at RTx, dialysis modality prior to RTx or rejection episodes could be detected. We conclude that after RTx children exhibit some improvement in growth but height remains suboptimal. The BMI does increase significantly during the first months after RTx and does not return to baseline values under steroid-based immunosuppression. Obesity (>2 SDS above normal) does not occur more often than in the normal population. The most predictive parameter of inappropriate weight gain during 3 yr is the BMI of the mother. We would speculate that steroids may play a major role in weight gain in the early phase after RTx. However, genetic or environmental factors predict the long-term weight development.

Antibodies, Monoclonal↗
PubMed2005

Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation.

UNLABELLED: Between May 2001 and January 2003, 132 live donor renal allotransplant recipients were included in a prospective, randomized controlled trial where they were divided into two groups. All patients received steroids and basiliximab induction therapy. For maintenance immunosuppression, tacrolimus and sirolimus were used in group A. In group B, mycophenolate mofetil (MMF) and sirolimus were utilized. Patients were followed up for a minimum of 24 months. One-year patient and graft survival rates were not significantly different between group A (96.9%, 92.3%) and group B (100%, 98.4%), respectively. However, the incidence of biopsy-proven acute rejection was less in group B but the difference was not statistically significant (13.5% vs. 18.5% in group A). Statistically significant better renal function was encountered among group B patients at two years post-transplantation as measured by serum creatinine (1.25 vs. 1.43 mg/dl; P = 0.017) and calculated glomerular filtration rate (GFR) (94.9 vs. 79.6 ml/min; P = 0.005). One year protocol biopsies showed insignificant differences relative to chronic allograft damage index (CADI) between either group (Group A: 2.41 vs. Group B: 2.69; P = 0.436). CONCLUSION: Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen. The long term impact of this observation on graft survival and function needs longer follow up.

Adult↗
PubMed2004

Induction immunosuppression in kidney transplant recipients older than 60 years of age : safety and efficacy of ATGAM, OKT3 and Simulect.

BACKGROUND: The choice of induction immunosuppression for kidney transplantation in elderly recipients is dictated by the consideration of the risk of infection as well as efficacy in the prevention of acute rejection, thus allowing a reduction in subsequent maintenance immunosuppression and its attendant long-term adverse effects. OBJECTIVE: To compare the efficacy and safety of the antibody induction immunosuppression strategies in elderly recipients of kidney transplants. PATIENTS AND METHODS: We present retrospective data analysis on 183 kidney transplant recipients > or = 60 years of age at Hahnemann University Hospital (Philadelphia, PA, USA) over a 12-year period. We compared four consecutive cohorts of kidney transplant recipients receiving lymphocyte immune globulin, equine antithymocyte globulin (ATGAM) [n = 29]; muromonab CD3 (OKT3) [n = 45]; basiliximab (Simulect) with corticosteroid maintenance [n = 40]; and Simulect without corticosteroid maintenance (n = 69). RESULTS: Delayed graft function (DGF) was observed in 48% of patients receiving ATGAM, 35.6% in the OKT3 group and 35% in the Simulect group with corticosteroid maintenance and 36.2% in the Simulect group without corticosteroid maintenance. The rejection rate within the first 3 months was 31% in the ATGAM and OKT3 groups, 17.5% in the Simulect group with corticosteroid maintenance and 14.5% in the Simulect group without corticosteroid maintenance. These differences for DGF and acute rejection were statistically significant between patients receiving ATGAM and OKT3, ATGAM or OKT3 and both groups of Simulect (all p < 0.05). Patients receiving Simulect were free of adverse effects typically encountered by patients receiving polyclonal and monoclonal antibodies for induction. Patients receiving Simulect had much shorter hospital stays and benefited from significant reduction of costs compared with other groups. CONCLUSION: Our data indicate that kidney transplant recipients > or = 60 years of age benefit from induction therapy with Simulect followed by corticosteroid-free maintenance immunosuppression.

Adrenal Cortex Hormones↗
PubMed2001

[Antibodies and immunomodulation].

CURRENT SITUATION: When examining immunosuppressor induction one important question is to determine the efficacy of anti-CD25 antibodies or the new compound efalizumab compared with anti-lymphocyte globulins and anti-OKT3 agents known to be very effective but with important side effects. DACLIZUMAB: Recent work has shown that 2 injections at 1 mg/kg (one on day 1 the other between day 10 and day 14) completely block interleukin-2 receptor for more than 10 weeks in 98% of the recipients. Instead of the 5 injections every 15 days as indicated by the recommendations, this new protocol is easier to institute and less costly. The efficacy remains to be demonstrated. BASILIXIMAB: This chimeric monoclonal antibody has affinity for the IL-2 receptor. Balisiximab is administered in 2 doses at 20 mg, one on day 0 and the other one on day 4. A unique 40 mg dose on day 1 has a comparable efficacy. OTHER PROTOCOLS: Among the different induction molecules with promising properties, particular attention should be given to efalizumab. The antisense oligonucleotide (ICAM-1; ISIS 2302) appears to show relatively poor tolerance and no therapeutic efficacy. In association with plasmapheresis and intravenous immunoglobulins, it has been shown to be very effective when given to graft candidates with a positive cross match or after transplantation in case of acute rejection.

Antibodies, Monoclonal↗
PubMed2002

[Therapeutic strategy for acute rejection in organ transplantation--optimal use of monoclonal antibody].

Transplantation has now become the treatment of choice for end-stage organ failure. However, acute rejection still occurs in approximately 20-50% of cadaver or living donor kidney recipients during the first year post-transplantation and lead to permanent damage of graft function or loss. Recently chimeric(basiliximab) and the humanized(daclizumab) monoclonal antibodies against the alpha chain(CD25) of the interleukin 2 receptor(IL-2R) introduced in the late 1990s. Induction therapy with these antibodies results in a 15-20% reduction in acute rejection episodes after renal transplantation. The availability of anti-IL-2R monoclonal antibodies offers a further opportunity for graft-specific induction therapy.

Acute Disease↗