Single centre experience with basiliximab in paediatric renal transplantation.

BACKGROUND: Introduction of IL-2-receptor antagonists has led to significantly decreasing numbers of acute rejection episodes in renal transplantation in adults. No data are available in paediatric recipients. METHODS: Between 1997 and 2000, 78 renal transplantations were performed in 77 children aged 0.5-16 years. Basiliximab, cyclosporin A (CsA) and prednisolone were administered in 48 children (age 7.8 +/- 5.3 years) and compared with 29 children (age 7.3 +/- 5.2 years) receiving CsA and prednisolone only. The number of acute rejections, survival, glomerular filtration rate (GFR) and side effects were determined for 3 years after transplantation. RESULTS: All 77 patients survived the observation period. One year graft survival in the basiliximab group was 95%, which is similar to the comparison group (93%). Children receiving basiliximab showed a lower incidence of acute rejection than the comparison group (14% vs 34%). The calculated GFR was lower in the basiliximab group when discharging from hospital, with 51 compared with 66 ml/min/1.73 m(2) in the non-basiliximab group. This was associated with higher CsA trough levels (214 vs 174 ng/ml) in the basiliximab patients. After 1 year the GFR was comparable in both groups (58 vs 52 ml/min/1.73 m(2)). CONCLUSIONS: Basiliximab offers excellent allograft survival, a lower incidence of acute rejections and almost no side effects. Therefore it can be recommended for routine immunosuppressive therapy in paediatric renal transplantation.     

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

BACKGROUND: Acute rejection remains a major problem in renal transplantation. Immunoprophylaxis with basiliximab (Simulect) has achieved significant reductions in acute rejection episodes in renal allograft recipients receiving dual immunosuppression. This study explored the tolerability and cumulative benefit of combining basiliximab with triple-drug therapy-cyclosporine (USP Modified, Neoral), mycophenolate mofetil, and steroids. METHODS: In a randomized, double-blind, placebo-controlled, multicenter study, 123 kidney transplant recipients received either basiliximab at 20 mg before transplantation (day 0) and 20 mg on day 4 (n=59), or placebo (n=64). All received triple-drug immunosuppression and were followed for 6 months. RESULTS: Tolerability of basiliximab was equivalent to placebo, with no increase in serious adverse events, infection, malignancy, or posttransplant lymphoproliferative disorder. At 6 months, there were trends in favor of basiliximab over placebo in the incidences of first biopsy-confirmed acute rejection (15.3% vs. 26.6%, P=NS) and of acute rejection treated with antibody (5.1% vs. 15.6%, P=NS). Kaplan-Meier estimates at 4 weeks and 6 months were significantly in favor of basiliximab treatment for first acute rejection, biopsy-confirmed rejection, rejection episodes treated with antibody therapy, and treatment failure. Renal function improved more rapidly in the basiliximab group, with mean creatinine clearance at week 2 being 54.7 mL/min versus 43.2 mL/min for placebo (P=0.034). At 12 months, patient survival was 100% in both groups; graft survival was 94.9% with basiliximab and 92.2% with placebo. CONCLUSIONS: Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.     

Triple immunosuppression with tacrolimus in pediatric renal transplantation: single-center experience

AIM: In this single-center cohort, we retrospectively analyzed the efficacy and safety of tacrolimus in pediatric renal transplantation. METHODS: We examined the medical records of 22 consecutive renal transplantation recipients (12 boys, 10 girls) receiving tacrolimus, to evaluate occurrence of acute rejection (AR) episodes, glomerular filtration rates (GFR), and side effects. RESULTS: The mean recipient age was 15.07 +/- 3.96 years. Seven grafts came from cadaveric, and 15 from living related donors. The patients were placed on immunosuppression with prednisolone and tacrolimus plus azathioprine (n = 8) or mycophenolate mofetil (MMF) (n = 12) or enteric-coated mycophenolate sodium (n = 2). Eighteen patients received basiliximab on days 0 and 4. There were three AR episodes at 5, 9, and 12 months. Mean GFR at the end of 1 and 2 years were 97.1 +/- 24.0 mL/min/1.73 m(2) and 116.9 +/- 42.2 mL/min/1.73 m(2), respectively. There was no graft loss. Hypertension, hyperlipidemia, and hyperglycemia were present in 14 (63.6%), 3 (13.6%), and 3 (13.6%) patients, respectively, without gingival hyperplasia, tremor, or hypertrichosis. Supraventricular tachycardia was noticed in five patients (22.7%), three of whom needed antiarrhythmic drugs (13.6%). CONCLUSION: Our single-center experience with tacrolimus, steroid plus azathioprine or MMF or enteric-coated mycophenolate sodium regimen in pediatric kidney recipients showed a low rate of AR with excellent graft survival and function at 1 and 2 year posttransplantation. The increased rate of supraventricular tachycardia in this regimen had not been previously reported; this association merits further studies.     

Reduced acute rejection and superior 1-year renal allograft survival with basiliximab in patients with diabetes mellitus. The Global Simulect Study Group

BACKGROUND: Renal allograft recipients with diabetes mellitus often demonstrate poorer clinical outcomes than nondiabetic patients. Basiliximab (Simulect), a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection in renal allograft recipients in 2 multicenter, placebo-controlled, phase III trials. METHODS: An analysis of pooled results from the 2 trials was conducted to compare the efficacy and safety of basiliximab with placebo in renal transplant recipients with and without prior diabetes. Patients received either basiliximab (20 mg on day 0 and day 4 posttransplantation) or placebo in combination with cyclosporine for microemulsion (Neoral) and steroids. RESULTS: A total of 722 patients (150 diabetic, 572 nondiabetic) were eligible for intent-to-treat analysis. At 12 months, basiliximab as compared with placebo reduced the proportion of patients experiencing first acute rejection by 41% in diabetics (P<0.01) and by 29% in nondiabetics (P<0.001). Biopsy-confirmed rejection was reduced by 44% in diabetics (P<0.01) and by 26% in nondiabetics (P<0.01). The first acute rejection episode requiring augmented immunosuppression other than steroids was reduced by 49% in diabetics (P<0.01) and by 41% in nondiabetics (P<0.001); death, graft loss, or first rejection episode was reduced by 43% in diabetics (P=0.001) and by 22% in nondiabetics (P<0.01). Superior graft survival was maintained in diabetic recipients treated with basiliximab versus placebo (96% vs. 86%; P=0.022). There were no significant differences in safety between basiliximab and placebo in both diabetic and nondiabetic patients. CONCLUSIONS: Basiliximab is associated with a significant reduction in acute rejection and an excellent safety profile in renal transplant recipients with and without diabetes mellitus. Superior graft survival was evident in diabetic patients.     

Basiliximab (Simulect) in renal transplantation with high risk for delayed graft function

BACKGROUND: Basiliximab (Simulect) is effective in reducing episodes of acute rejection in renal transplantation. Delayed graft function (DGF) predisposes to acute rejection and shortens graft survival. The aim of this study was to determine the effects of basiliximab in renal transplantation recipients at high risk for DGF. METHODS: We studied 87 patients (mean age, 59 years), 42 of whom received basiliximab, 20 mg before transplantation and 20 mg on day 4. This cohort was compared with 45 patients without basiliximab. All received cyclosporine (51%) or tacrolimus (49%), mycophenolate mofetil, and steroids. DGF was defined as the requirement for dialysis within the first week after transplantation or failure to improve preexisting renal function. High-risk factors for DGF were cold ischemia time, recipient and donor age, non-heart-beating donor, HLA matching, and panel reactive antibody (PRA). RESULTS: The incidence of DGF was 18 (43%) in the basiliximab group versus 28 (62%) in the other patients (P = .07). When allografts from non-heart-beating donors were excluded, this incidence was 14 (38%) in the basiliximab group versus 28 (62%) in the other patients (P = .04). Regression analysis showed basiliximab to be a protective factor: 0.26 (range, 0.09-0.76). Basiliximab was well tolerated, and complications were similar in both groups. CONCLUSIONS: Basiliximab reduced the incidence of DGF in patients who received a high-risk allograft. It was well tolerated, and no adverse events were reported. The use of basiliximab may be considered in patients receiving an allograft who are at high risk for DGF.     

A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients

BACKGROUND: A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. METHODS: Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. RESULTS: During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. CONCLUSIONS: Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.     

Why do preemptive kidney transplant recipients have an allograft survival advantage?

BACKGROUND: Preemptive kidney transplantation is associated with an allograft survival advantage and is promoted in part because of this association. The basis for the allograft survival advantage in preemptive recipients is unclear. Possibilities include a lead time bias due to the earlier transplantation of patients with preserved native kidney function, less rapid loss of kidney function after transplantation, or the longer patient survival of preemptive recipients. METHODS: We compared the glomerular filtration rate (GFR) six months after transplantation and the subsequent rate of loss of kidney function as defined by the annualized change in GFR (mL/min/1.73 m2/year) in 5,966 preemptive and 34,997 non-preemptive recipients. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Multiple regression was used to determine the independent effect of preemptive transplantation upon the annualized change in GFR. RESULTS: The mean GFR six months after transplantation was similar among preemptive (49.5+/-15.7 mL/min/1.73 m2) and non-preemptive (49.2+/-14.7 mL/min/1.73 m2) recipients (P=0.37). In multivariate analysis, preemptive recipients had a slower decline in GFR (0.28 mL/min/year/1.73 m2; 95% confidence interval 0.11, 0.46; P=0.002). However, this difference was of modest clinical significance and would not explain the allograft survival advantage of preemptive transplantation. CONCLUSIONS: Neither the preservation of native kidney function nor differences in the rate of loss of kidney function explain the superior allograft survival of preemptive recipients. By exclusion, the allograft survival advantage associated with preemptive transplantation may be due to the longer survival of preemptive recipients.     

Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients

In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts. Eligible patients were randomized to induction with either basiliximab or daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral), mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejection episodes, the renal graft function, the safety, and the patient and graft survivals. Among 127 patients, six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute rejection at 12 months, in the basiliximab and the daclizumab groups, respectively. Two renal grafts were lost in the basiliximab and six in the daclizumab cohort, one of them due to rejection. One basiliximab and two daclizumab patients died. Hospital treatment was required for 25 and 33 infections in basiliximab and daclizumab groups, respectively. One basal cell carcinoma of skin was detected. One hypersensitivity reaction was observed with daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4% with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus 90.8%, respectively. No significant differences were observed between the groups. Basiliximab or daclizumab combined with triple therapy was an efficient and safe immunosuppression strategy, demonstrated with low incidence of acute rejection episodes, an acceptable adverse event profile, excellent graft function, and high survival rates in adult recipients within the first year after deceased donor renal transplantation.     

Graft function 5-7 years after renal transplantation in early childhood

BACKGROUND: Low recipient age is still a risk factor for graft failure after kidney transplantation (Tx). Detailed prospective reports on long-term graft function in small children after renal Tx are still lacking. METHODS: Forty-nine kidney allograft recipients who received transplants before the age of 5 years were followed prospectively. The most common disease was congenital nephrotic syndrome of the Finnish type. Twenty patients were recipients of living related donors (LRD), and 29 were cadaveric kidney (CAD) recipients. All patients received triple immunosuppression. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), sodium, urate, and potassium handling, and concentrating capacity were studied for up to 7 years after Tx. RESULTS: Patient survival 7 years after Tx was 100% for LRD and 96% for CAD recipients. Graft survival was 94% for LRD and 79% for CAD recipients (P=NS) and 89% and 83% for children >2 years and <2 years of age at Tx, respectively (P=NS). Five years after Tx, GFR was 70 vs. 64 and ERPF was 380 vs. 310 ml/min/1.73 m2 for LRD and CAD recipients, respectively (P=NS). Mean absolute GFR remained stable. GFR was lower in children who received transplants at <2 years than in children who received transplants at >2 years of age, 54 vs. 75 ml/min/1.73 m2 (P=0.02). Sodium handling remained intact, but hyperuricemia was seen in 43-67%; 17-33% showed abnormal handling of potassium; and most patients had a subnormal concentrating capacity. CONCLUSIONS: Excellent long-term graft survival and good graft function can be achieved with triple immunosuppression, even in young CAD kidney recipients.     

Improved efficacy of basiliximab over antilymphocyte globulin induction therapy in paediatric renal transplantation.

BACKGROUND: Basiliximab is a chimeric human/mouse monoclonal antibody directed against the alpha chain of the IL-2 receptor, CD25, which has been reported as successfully reducing rejection in adult renal transplant recipients. Reported clinical experience of basiliximab in paediatric renal transplantation is limited. METHODS: Using two intravenous doses on day 0 (pre-operatively) and day 4 with prednisolone and cyclosporin A (dual) maintenance immunosuppression in 42 children undergoing renal transplantation in our unit (SIM group), we have compared patient and graft outcome, rejection rates in the first 6 months, renal function and the incidence of Cytomegalovirus (CMV) infection with 42 consecutive children who previously received antilymphocyte globulin immunoprophylaxis with prednisolone, cyclosporin A and azathioprine (triple) maintenance immunosuppression (ALG group). The two groups were similar, including HLA mismatching, apart from age and size at transplantation (SIM=10.3+/-5.4 years vs ALG=12.4+/-4.2 years, P<0.05). RESULTS: One patient in the SIM group died from food inhalation with a functioning kidney and one patient in the ALG group from Pneumocystis pneumonia and post-transplant lymphoproliferative disorders with a rejecting graft. Both 1- and 2-year actuarial graft survivals were 93% for the SIM group and 86% for the ALG group (NS). Three grafts were lost in the SIM group-none from rejection (thrombosis 2, death 1)-and seven in the ALG group-three from rejection. Occurrence of biopsy documented rejection in the first 6 months after transplantation was 0.15+/-0.22 for the SIM group and 0.35+/-0.51 episodes per pt-month at risk for ALG treatment (P<0.04). Early rejection within 30 post-operative days occurred in only four SIM patients, three of whom had undergone retransplantation. Forty-seven per cent of rejection episodes occurred between days 30 and 44 in SIM treated patients. Switching to tacrolimus was similar in both groups; 24% of the SIM groups were prescribed triple therapy. Estimated glomerular filtration rate was 46.0 and 46.2 ml/min for SIM and ALG groups, respectively, six months after transplantation. Ten per cent of SIM and 19% of ALG treated patients developed clinically significant CMV infection (NS) but none of 16 (R(+)) SIM children had CMV infection compared with 8 out of 15 (R(+)) ALG patients (P<0.01). CONCLUSIONS: Basiliximab immunoprophylaxis and dual therapy reduces rejection episodes in the first six months and maintains graft survival and function after paediatric renal transplantation. Seventy-six per cent of children receiving basiliximab immunoprophylaxis were successfully maintained on long-term dual immunosuppression. This immunosuppressive protocol reduces CMV disease in CMV(+) recipients compared with ALG induction and triple therapy.     

Basiliximab-chimeric anti-IL2-R monoclonal antibody in pediatric liver transplantation: comparative study

Basiliximab is a monoclonal antibody that binds to the alpha subunit (CD(25)) of the interleukin-2 receptor of activated T lymphocytes. The advantage of basiliximab in organ transplantation is the reduce possibility to calcineurin inhibitor dosages to avoid nephrotoxicity. Basiliximab has significantly reduced the incidence of acute rejection (AR) in renal transplant recipients; however, the results are uncertain in liver transplantation (LT). The objective of this investigation was to assess the effect of basiliximab to prevent AR in the first 6 months after pediatric LT. From March 2000 to October 2001, 32 recipients of a primary orthotopic cadaveric or living donor LT were given basiliximab by intravenous bolus injection on the day of transplantation (day 0) and on day 4. Four children who received one dose were excluded from the study. The rate and the intensity of AR episodes, the incidence of chronic rejection, serum creatinine level, incidence of infections, adverse side effects, and daily oral dosage of cyclosporine (Neoral) to maintain the target blood level of 850 to 1000 mg/dL at C2, 2 hours after the administration, were analyzed in the remaining 28 recipients. Results were compared to those obtained from a matched historical group (n = 28) of similar age, weight, and hepatic diseases distribution. None of the analyzed parameters was statistically significant (P >.05) except for the daily oral dose of cyclosporine (7 to 13 mg/kg/dose, P <.05). In our series, the addition of basiliximab to the immunosuppressive therapy did not reduce the incidence of AR in pediatric LT.     

Basiliximab does not reduce the early rejection incidence in high-risk kidney recipients under tacrolimus-based immunosuppression

This study sought to evaluate the benefit of addition of basiliximab to tacrolimus-based immunosuppression among high-risk renal transplantations. We retrospectively analyzed the clinical data of the basiliximab induction group (n = 55) and a risk-matched control group (n = 57). Graft survivals rates at 1, 3, and 5 years were 100%, 98.1%, and 91.8%, respectively, for the control and 96.2%, 93.9%, and 76.4%, respectively, for the basiliximab group (P = .083). Patient survivals rates at 1, 3, and 5 years were 98.3%, 98.3%, and 98.3%, respectively, for the control group and 98.2%, 94.2%, and 94.2%, respectively, for the basiliximab group (P = .277). Biopsy-proven acute rejection (AR) within 12 months occurred among 24.6% and 18.2% for the control and induction groups, respectively (P = .492). Serum creatinine levels at 1, 3, 6, and 12 months were 1.23 +/- 0.30, 1.38 +/- 0.41, 1.47 +/- 0.61, and 1.44 +/- 0.67 mg/dL, respectively, among the control and 1.24 +/- 0.28, 1.40 +/- 0.38, 1.40 +/- 0.36, and 1.63 +/- 1.62 mg/dL, respectively, among the induction group. In conclusion, this study showed that the addition of basiliximab to tacrolimus-based immunosuppression did not further improve the results of high-risk kidney transplantations in terms of reducing AR, prolonging graft survival, or improving renal function.     

Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.     

Kidney transplantation with sirolimus and mycophenolate mofetil-based immunosuppression: 5-year results of a randomized prospective trial compared to calcineurin inhibitor drugs

BACKGROUND: We report the 5-year outcomes from a randomized prospective trial in primary adult renal allograft recipients, designed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function. METHODS: Sixty-one patients were randomized to either sirolimus (n=31) or cyclosporine (n=30) after basiliximab induction and mycophenolate mofetil (MMF) with steroids. Sirolimus was concentration controlled at 10-12 ng/mL for at least 6 months. RESULTS: After 5 years, sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival (87.1 vs. 90%, P=0.681), acute rejection rates (12.9 vs. 23.3%, P=0.22), total cholesterol (209.1 vs. 204.3 mg/dL, P=0.973), urine protein/creatinine ratios (0.398 vs. 0.478 mg/dL, P=0.72), and overall medical and surgical morbidity (P=NS). Although unadjusted patient survival was similar, sirolimus based CNI-free patients had longer death censored graft survival (96.4 vs. 76.7%, P=0.0265), higher glomerular filtration rate (GFR) by the abbreviated Modified Diet in Renal Disease (66.7 vs. 50.7 cc/min, P=0.0075), and fewer graft losses from chronic allograft nephropathy. The Banff chronic scores at two years were strong predictors of 5-year GFR. At 5 years, there were six de novo (three solid organ, three skin) cancers in the CNI group and only two de novo (one skin, one leukemia, no solid organ) cancers in the sirolimus group (P=NS). CONCLUSIONS: This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs, when therapeutic drug monitoring of sirolimus is employed. The application of CNI drug avoidance protocols to high-risk recipients (retransplants, highly sensitized, etc.), extrarenal allograft recipients, or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials.     

Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation

BACKGROUND: Calcineurin inhibitor(CNI)-free protocols using sirolimus (SRL) in kidney transplantation have proven effective, although reports have linked SRL to proteinuria. We sought to investigate this link and its impact on graft function. METHODS: We retrospectively analyzed 184 live donor kidney transplant recipients who exclusively received de novo CNI-based (n = 106) or SRL-based (n = 78) regimens. Estimated glomerular filtration rate (GFR) and semi-quantitative dipstick proteinuria measurements were obtained at one, six, 12, and 24 months and six and 12 months, respectively. RESULTS: SRL-treated patients had higher frequencies of proteinuria (> or =1+) at 6 months (40.8% vs. 21.4%, P = 0.006) and 12 months (37.8% vs. 18.4%, P = 0.004) than those treated with CNI. Independent predictors of proteinuria at 12 months were GFR at one month (OR 0.62 per 10 ml/min/1.73 m, P<0.001), delayed graft function (OR 11.5, P = 0.02), and a SRL-based regimen (OR 4.18, P=0.002). By univariable analysis, SRL vs. CNI patients had higher GFR at each point. SRL-treated patients without proteinuria had higher GFR at 12 months compared to CNI-treated patients with and without proteinuria (66 vs. 50 or 56 ml/min/1.73 m, P < 0.05). No difference in GFR was seen between SRL-treated patients with proteinuria vs. CNI-treated patients without proteinuria (57 vs. 56 ml/min/1.73 m, P > 0.05). Absence of proteinuria and a SRL-based regimen remained independently associated FS with higher GFR at 12 months by multivariable analyses. CONCLUSIONS: De novo SRL-based immunosuppression is associated with a higher frequency of semi-quantitative proteinuria, however, estimated graft function at 1 year posttransplant remains superior to that of CNI-treated patients. Nevertheless, the long-term implications of these findings need to be determined.     

The advanced age deceased kidney donor: current outcomes and future opportunities

BaCKGROUND: Due to the aging general population, deceased donors > or =55 years will form an increasingly larger proportion of the deceased kidney donor pool. METHODS: Using data from the United States Renal Data System, we determined the change in graft survival between 1996 and 2000 among 32,557 recipients of donors aged <55 years and > or =55 years in univariate and multivariate survival analyses. We identified donor risk factors for graft loss that might influence the decision to accept or reject donors <55 and > or =55 years. The initial glomerular filtration rate established 6 months after transplantation (initial GFR), and the stability of GFR in the first post-transplant year (GFR at 12 months post-transplantation-GFR at six months post-transplantation) were compared between recipients of donors <55 and > or =55 years and the association of these factors with graft survival was determined. RESULTS: In 2000, one-year graft survival in donors > or =55 years was 86.7%. Between 1996 and 1999 the projected graft half life improved from 11.4 to 14.5 years for recipients of donors <55 years (P < 0.01); however, there was no improvement for recipients of donors > or =55 years (8.2 to 9.2 year, P= 0.46). Among donor factors studied, only cold ischemic time >24 hours identified recipients of donors > or =55 years at risk for graft loss. Compared to recipients of donors <55 years, recipients of donors > or =55 years established a lower initial GFR (42 vs. 56 mL/min/1.73 m(2), P < 0.0001), and had less stable GFR in the first post-transplant year (-1.5 vs. -0.6 mL/min/1.73 m(2), P <.0001). Recipients from donors > or =55 years with initial GFR > or =50 mL/min/1.73 m(2) and no drop GFR during the first post-transplant year had graft survival that was superior to that of donors <55 years with either initial GFR <50 mL/min/1.73 m(2) or a drop in GFR during the first post-transplant year. CONCLUSION: Donors > or =55 years are a valuable resource. Despite improvements in immunosuppression, rejection, and delayed graft function, the projected increase in long-term graft survival among recipients of donors <55 years was not shared among recipients of donors > or =55 years. Recipients of donors > or =55 years had lower initial GFR, and less stable GFR during the first post-transplant year. Limiting cold ischemic time to <24 hours may improve outcomes among recipients of donors > or =55 years. Future studies to maximize initial GFR and minimize early loss of GFR in recipients of donors > or =55 years may lead to improved outcomes from deceased donors > or =55 years.     

Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation

SUMMARY:   Simultaneous pancreas–kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte-depleting therapy is associated with a high incidence of side-effects. We performed a historical controlled trial to compare OKT3 versus anti-CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty-eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 ( n  = 12) and basiliximab was used after ( n  = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100 vs 100%), kidney (91.7 vs 91.7%) and pancreas (75 vs 83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximab vs 25% on OKT3, P  = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 ± 11.9 vs 54.5 ± 15.9 mL/min for  basiliximab vs OKT3, P  < 0.001). The incidence of major opportunistic infection was lower in basiliximab-treated patients (9 vs 50% in the OKT3 group, P  = 0.033). Basiliximab was associated with similar 6-month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.     

Posttransplant Prophylactic Intravenous Immunoglobulin in Kidney Transplant Patients at High Immunological Risk: A Pilot Study

The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p<0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p<0.01; class II: from 25 +/- 30% to 7 +/- 16%, p<0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy.     

The change in allograft function among long-term kidney transplant recipients

Long-term kidney allograft survival continues to remain an elusive goal. Kidney transplant recipients are believed to be at high risk for loss of allograft function, and new, potentially non-nephrotoxic immunosuppressive medications are advocated to improve long-term allograft survival. To evaluate the efficacy of such therapeutic interventions, information regarding the change in GFR among kidney transplant recipients with long-term allograft survival is needed. We studied 40,963 transplant recipients between 1987 and 1996 with allograft survival of at least 2 yr in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation. The baseline mean GFR at 6 mo after transplantation was 49.6 +/- 15.4 ml/min per 1.73 m(2). During the mean follow-up of 5.7 +/- 2.3 yr, the mean +/- standard error of the change in GFR was -1.66 +/- 6.51 ml/min per 1.73 m(2) per year (median, -0.94 L/min per 1.73 m(2) per year). A total of 12,583 (30%) of patients had improvement in GFR, 8133 (20%) patients had no change in GFR, and 20,247 (50%) patients had decline in GFR. It is concluded that, although most patients had significant impairment of GFR at baseline, the decline in GFR was slow and many patients had either no change or improvement in GFR. Strategies to improve long-term kidney allograft survival that increase baseline allograft function may be more effective than strategies to slow the decline in GFR.     

Chronic kidney disease in renal transplant recipients

The aim of the present study was to investigate the utility in renal transplant patients of the guidelines for the diagnosis and classification of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (GFR) elaborated by the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation. PATIENTS AND METHODS: Four hundred forty-seven cadaveric kidney transplants performed between 1980 and 1994 with graft function at 12 months were included in the study. The GFR was calculated according to the MDRD equation. RESULTS: The mean GFR at 12 months was 54.5 +/- 20.3 mL/min/1.73 m(2): 23 patients (5.1%) had a GFR > or =90 mL/min/1.73 m(2); 136 patients (30.6%), 60-89; 246 (54.7%), 30-59; 35 patients (7.8%), 15-29; and 7 patients (1.6%), GFR <15. Similar distribution of CKD stages was observed at 5 and 10 years. Unadjusted graft survival at 10 years was better among patients with a higher GFR at 12 months: 87% in patients with GFR >90 mL/min/1.73 m(2); 83% of GFR 60-89 mL/min/1.73 m(2); 63%, GFR 30-59 mL/min/1.73 m(2); and 23%, GFR <30 mL/min/1.73 m(2) (P < .001). The association between GFR and graft survival persisted when adjusted by the age and gender of the recipients and donors, time on dialysis, body mass index, immunosuppression, delayed graft function, rejection, and HLA mismatches. The prevalence of complications, such as anemia, hypertension, dyslipidemias, and number of drugs increased as GFR declined. CONCLUSIONS: More than 60% of recipients presented chronic kidney disease. GFR was a predictive factor for graft survival at 10 years. The classification of renal transplant patients by CKD stages may help to identify patients with increased risk of graft loss and also to design strategies to improve outcomes.