One year results of preoperative single bolus ATG-Fresenius induction therapy in sensitized renal transplant recipients

Sensitization in kidney transplantation is associated with more acute rejections, inferior graft survival, and an increase in delayed graft function. This study was designed to evaluate the efficacy and safety of preoperative single bolus antithymocyte globulin (ATG) induction therapy in sensitized renal transplant recipients. METHODS: Fifty-six cadaveric donor kidney transplant recipients were divided into two groups: Group I (nonsensitized group, n = 30) and group II (sensitized group, PRA>10%, n = 26). ATG was given as a single preoperative bolus induction therapy to group II (ATG IV; 9 mg/kg). The group I patients were treated with mycophenolate mofetil preoperatively as induction therapy. The basic immunosuppressive regimen included tacrolimus (FK-506) or cyclosporine, mycophenolate mofetil, and prednisolone. After hospital discharge, patients were followed on a routine outpatient basis for 12 months. RESULTS: Acute rejection episodes (ARE) occurred in 20% (6/30) of group I and 15.38% (4/26) of group II patients (P = NS). Infections occurred in eight patients (26.7%) as 11 episodes (36.7%), averaging 1.4 episodes per infected patient in group 1, and 6 patients (23.1%) for a total of 10 episodes (38.5%), averaging 1.7 episodes per infected patient, in group II (P = NS). Occurrence of side effects and hospital stay were almost comparable in the two groups. No delayed graft function was observed in either group. The 12-month actuarial patient and graft survival were 100% in Group I and II. CONCLUSION: A preoperative single bolus ATG induction therapy was an effective and safe therapeutic measure, yielding an acceptable acute rejection rate in presensitized renal transplant recipients.     

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China

OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were assessed on human kidney allograft rejection and long-term survival. METHODS: This study compared treatment with T II(T II group, n=121) to that without T II(control group, n=102) among adult first cadaveric renal transplant recipients. The T II cohort of 121 recipients were divided into a regular dosage group (n=82) and a double dosage group (n=39). No antibody induction was administered to any patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1% of patients in the T II group versus 24.5% of patients in the control group. No rejection or repeated rejections occurred in the double dosage group at 3 months after transplantation. Acute rejection episodes were milder in the T II than the control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months after transplantation was lower in the T II group than the control group, 15% and 50%, respectively. All patients tolerated T II well over the 5 years of this study. The 5-year graft survival censored for death with function was 96.7% in the T II group and 80.4% in the control group. CONCLUSION: T II was effective to prevent renal allograft rejection and increase long-term renal allograft survival among adult cadaveric renal transplant recipients.     

Comparison of transplanted kidney function in patients on two different doses of mycophenolate mofetil

INTRODUCTION: Mycophenolate mofetil (MMF), an immunosuppressant that is widely used in renal transplant recipients, is associated with several dose-dependent hematologic and gastrointestinal side effects that lead to drug dose reduction or even discontinuation. The aim of this study was to compare the renal function and acute rejection rates of kidney allograft recipients who were on two different mycophenolate mofetil doses. METHODS: In a prospective study, 59 allograft kidney recipients who were on MMF 2 g/d were randomly selected and followed for evidences of acute rejection or drug side effects. Four patients were excluded from the study due to noncompliance, graft loss, and patient loss from opportunistic infection. Of the remaining 55 patients, 22 patients (40%) underwent MMF dose reduction to 1.35 +/- 0.23 g/d due to perceived side effects or economic reasons (group 1). The mean time for this change was 4.2 +/- 2.1 months after the kidney transplantation. The remaining patients (group 2, n = 33, 60%) had no change in MMF 2 g/d drug dosage. All patients were followed for at least 30 months after transplantation. Renal function tests (blood urea and serum creatinine) were measured monthly. Statistical analysis was performed using SPSS 11.0 (Student t test). A P value < .05 was considered significant. RESULTS: The two groups were comparable regarding age, gender, other immunosuppressive medications, and the time after transplantation. There were no episodes of acute rejection in group 1 after MMF dose reduction. The renal function (blood urea or serum creatinine levels) was comparable between the two groups at the end of study (P = .846 and .610, respectively). CONCLUSION: MMF dose reduction was not associated with an increased risk of acute renal allograft rejection or impaired graft function.     

Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation

INTRODUCTION: Because it is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have increased graft rejection rates, a serological crossmatch is routinely performed before kidney transplantation. But, the presence of these antibodies is not routinely monitored after transplantation. We investigated the panel-reactive antibody (PRA) response to know whether variations before or after kidney transplantation were associated with graft rejection. METHODS: We prospectively analyzed sera from 350 renal allograft recipients from September 1998 to March 2003. Pretransplantation and posttransplantation sera at 3 or 5 weeks postoperatively were tested in PRA. Recipients were stratified into 3 groups according to their PRA levels group I, PRA = 0; group II, PRA = less than 50%, and group III, PRA = more than 50%. RESULTS: The total graft rejection rate among 350 recipients was 9.4% (n = 33). Twenty-four pretransplantation PRA-positive recipients had a graft rejection rate of 20.8% (n = 5), compared with an 8.6% (n = 28) rate among 326 pretransplantation PRA-negative recipients. Six of 24 posttransplantation PRA-positive recipients (25%) experienced a graft rejection versus 27 (8.3%) of 326 posttransplantation PRA-negative subjects. Among the pretransplantation PRA stratae, the rejection rate in group III was 25% (1 of 4) versus 20% (4 of 20) in group II and 8.6% (28 of 326) in group I (P < .05). According to the postransplantation PRA level, 37.5% (3 of 8) in group III versus 18.8% (3 of 16) in group II and 8.3% (27 of 326) in group I (P < .05) had a graft rejection. CONCLUSION: Our study suggests that the PRA response pretransplantation and in the early posttransplantation period correlates with the kidney allograft rejection rate.     

Pancreas-after-kidney transplantation: an increasingly attractive alternative to simultaneous pancreas-kidney transplantation

BACKGROUND: Historically, the clinical acceptability of pancreas-after-kidney (PAK) transplantation has been hampered by relatively high acute rejection rates and lower pancreas graft survival rates when compared with the more commonly performed simultaneous pancreas-kidney (SPK) transplantation. The purpose of this study was to compare PAK transplantation to SPK transplantation in the Thymoglobulin induction era. METHODS: The authors reviewed all bladder-drained PAK (n=47) transplants receiving rabbit antithymocyte globulin induction from June 1998 to June 2002 and compared them with SPK (n=25) transplants during the same time period at their institution. The authors retrospectively studied data on demographics, patient survival, graft (pancreas and kidney) survival, complications, and biopsy-proven rejection episodes. RESULTS: The actuarial 1-year patient survival was 93% for the PAK group versus 100% for the SPK group (P =not significant [NS]). The actuarial 1-year pancreas graft survival was 87% for the PAK group versus 92% for the SPK group (P =NS). Waiting time for PAK was significantly shorter than for SPK (6.3 +/- 5.2 vs. 16.2 + -13.7 months, P <0.05). Clinical acute rejection rates were similar in the two groups (4.3% for PAK vs. 4.0% for SPK). PAK recipients demonstrated a greater decline in renal function after transplantation compared with SPK. A multivariate analysis failed to elucidate the cause. CONCLUSIONS: Newer immunosuppressive regimens allow PAK transplant patients to achieve immunologic outcomes similar to SPK transplant patients. Although the shorter waiting time and the ability to use living-donor kidneys make PAK an increasingly attractive alternative to SPK transplantation, its effect on renal allograft function deserves further attention.     

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.     

Human platelet antigens: HPA-1, -2, -3, -4, and -5 polymorphisms in kidney transplantation

To investigate the association between kidney transplant rejection and polymorphisms of HPA-1, -2, -3, -4, and -5, the genomic DNA of 70 renal transplant recipients and 100 healthy blood donors was analyzed by polymerase chain reaction (PCR)-SSP. The patients were classified into two groups. Group 1 included 33 HLA-identical recipients and group 2, 37 one haplo-identical recipients. Thirty-one recipients experienced an acute rejection episode (ARE): 10 in group 1 and 21 in group 2. Ten group 2 patients developed chronic allograft dysfunction (CAD). Before transplantation, five patients in group 1 were lymphocytocytotoxic antibodies (LCT) positive, among them three developed an ARE. In group 2, seven recipients were LCT positive and four had an ARE. After transplantation, 29 patients were LCT positive: 11 in group 1 and 18 in group 2, among them: 6/11 and 11/18 had an ARE. The allelic frequencies of HPA-1, -2, and -5 among patients and controls did not reveal significant differences, whereas the HPA-3a and HPA-4b alleles were significantly more frequent among patients than controls: 91.4% and 27.8% versus 76.5% and 11.5% respectively (P < .05 and P < .001). The frequency of the HPA-3b allele was increased in patients with an ARE (11.3%) and those who developed CAD (20%) compared with those not affected by these complications (6.6% and 6.4%, respectively), but the difference was not significant. The genotype distribution of HPA-1, -3, and -4 genes of GPIIb/IIIa revealed that the most frequent genotype was HPA-1a1a/3a3a/4a4a (19%) among controls and HPA-1a1a/3a3a/4a4b (31.4%) among patients. This genotype was associated with an ARE in 25.8%, namely 50% of group 1 recipients and 14.28% of group 2. The HPA-4b polymorphism of GPIIb/IIIa receptor seem to be an independent risk factor for acute allograft rejection in kidney transplantation.     

Influence of cytomegalovirus disease on early and late renal graft function

The role of cytomegalovirus (CMV) disease to induce chronic nephropathy using new immunosuppressive regimens is debated. This study sought to assess the influence of CMV disease on early and late graft function in relation to immunosuppressive therapy. Among 456 renal recipients transplanted from 1997 to 2003, 95 were diagnosed with CMV disease on the basis of clinical symptoms and the presence of pp65 protein. The patients were divided into 2 groups according to their immunosuppressive regimen: group I included 43 patients treated with cyclosporine (CsA), azathioprine (AZA), and prednisone (P); group II, 52 patients treated with calcineurin inhibitor (CI), mycophenolate mofetil (MMF), and P. A control group of 90 CMV disease-free renal recipients were transplanted in 2001. CMV disease occurred in 20.8% of renal recipients: 14.8% from group I and 25.5% from group II. CMV disease was diagnosed in 73 patients (76.8%) before the third month after transplantation. An acute rejection episode (ARE) appeared in 42 patients, of whom 31 had CMV disease diagnosed within 1 month after ARE, while 5 before an ARE. In six patients ARE was not time related to CMV disease. The serum creatinine values at 6 months after transplantation were significantly higher among the CMV versus control groups: 1.69 and 1.76 vs 1.49 (P < .05). In patients with ARE and CMV disease, the serum creatinine value was also higher at 6 and 12 months after transplantation compared with patients without an ARE (P < .03). One- and 3-year graft survival rates were 95.1% and 83.7% in group I versus 93.4% and 86.5% in group II versus 95.4% and 90.2% in the control group. In conclusion, CMV disease showed a negative impact on early graft function independent of the immunosuppressive regimen, an effect that was emphasized by an ARE.     

Renal retransplantation: a retrospective monocentric study

Approximately 10% to 20% of all annual renal transplantations are retransplantations and up to 20% of patients on waiting lists need a repeat kidney because of previous graft failure. The immunological risk is much greater among retransplanted patients than first-time kidney recipients. It is likely that retransplantation will become even more prevalent in the future. However, clinical studies or retrospective data are rare in this patient population. We retrospectively investigated 50 recipients after second or third renal transplantations in our center since 2001. Immunosuppression was performed with corticosteroids, mycophenolate mofetil (MMF), tacrolimus, and induction therapy with either thymoglobulin (2.5 mg/kg body weight; n = 27) or 20 mg basiliximab on days 0 and 4 (n = 22) after renal transplantation; 1 patient was treated with antithymoglobulin Fresenius after combined liver-kidney transplantation. Acute rejection occurred in 12 recipients (44.4%) after thymoglobulin and in 7 recipients (31.8%) after basiliximab induction therapy (P < .05). In 4 (14.8%) thymoglobulin- and 5 (22.7%) basiliximab-treated recipients, vascular rejections were observed (P = NS). Patients with basiliximab treatment showed improved renal function at 1 year after transplantation: serum creatinine 134.3 mumol/L versus 199.6 mumol/L in the thymoglobulin group (P < .05). Over the observation period the renal function remained stable or improved in both groups if rejection treatment was successful. However, allograft failure was higher in the basiliximab-treated group, namely, 18.1% versus 14.8% in thymoglobulin-treated patients, but the difference did not reach statistical significance. In 3 (11.1%) thymoglobulin- and 4 (18.2%) basiliximab-treated patients cytomegalovirus (CMV) infections complicated the follow-up (P = NS). In the follow-up period of 5 years, no malignant diseases were seen in either group. Three basiliximab-treated recipients died in the first year due to sepsis or cardiovascular complications. Two thymoglobulin-treated patients developed BK virus nephropathy in the follow-up period. In conclusion, we observed a high immunological risk and rejection risk among retransplanted kidney recipients in our center. Particularly, severe vascular rejections with a harmful long-term impact on allograft function were observed in this population. Induction treatment seems to be successful to reduce risk and achieve better results. Single-shot thymoglobulin may be preferable to reduce severe vascular rejection and prevent allograft failure than basiliximab with the same infection rate.     

Long-term results (10 years) of a prospective trial comparing Lo-tact-1 monoclonal antibody and anti-thymocyte globulin induction therapy in kidney transplantation

To evaluate long-term patient and graft survival, and the incidence of acute and chronic rejection, infectious diseases and malignancies following induction therapy with a rat monoclonal interleukin 2 receptor antibody, Lo-Tact-1, or anti-thymocyte globulin (ATG). Forty first-time kidney transplant patients were prospectively randomized to two groups between May 1990 and June 1991. Twenty recipients were treated with Lo-Tact-1 (group 1) and the other 20, with ATG (group 2) during the first 14 days of the transplantation protocol. All patients were treated with azathioprine, steroids and cyclosporin A. Data were collected over 10 years. Median age was 42.1 years in group 1 and 39.3 years in group 2. Six recipients died during the 10 years of follow-up. All had functioning grafts. Death-censored graft survival was 35% in group 1 and 45% in group 2 after 10 years (P = NS). The number of acute rejection was similar in the two groups. Chronic allograft rejection was significantly more frequent in group 2 (n = 9) than in group 1 (n = 3), P < 0.05. Viral and bacterial infections were more frequent in group 2 than in group 1 (respectively 8 vs. 2 and 16 vs. 10, P < 0.05). Three patients had cancer. Although both Lo-tact-1 and ATG effectively prevented acute renal rejection, fewer bacterial and viral infections and cases of chronic allograft rejection were observed in Lo-tact-1-treated patients after 10 years of follow-up, demonstrating the potential value of this treatment for kidney transplantation.     

Preemptive living donor kidney transplantation: do the benefits extend to all recipients?

BACKGROUND: Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients. METHODS: We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months). RESULTS: Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37). CONCLUSION: With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.     

Renal allograft outcomes in African American versus Caucasian transplant recipients in the tacrolimus era

METHODS: Between January 1995 and December 1999, 185 kidney transplants were performed with tacrolimus (TAC)-based immunosuppression including 120 African American (AA, 65%) and 65 Caucasian recipients (C, 35%). Mean follow-up was 34 months. The AA group was characterized by a higher incidence of renal disease due to hypertension (72% AA vs 37% C, P <.001), pretransplant dialysis (95% AA vs 82% C, P =.003), waiting time (1.9 years AA vs 1.1 years C, P =.02), cadaveric donation (88% AA vs 68% C, P =.01), HLA mismatching (mean 3.5 AA vs 2.4 C, P <.001), and delayed graft function (DGF; 50% AA vs 22% C, P =.001). RESULTS: The 5-year actuarial patient and graft survival rates were 96% AA versus 83% C (P = NS) and 83% AA versus 75% C, (P = NS), respectively. The incidence of acute rejection (21% AA vs 12% C, P = NS) and mean time to acute rejection (12 months AA vs 11 months C) were similar. Although the incidence of chronic allograft nephropathy (CAN) was comparable (7% AA vs 5% C), the mean time to CAN was shorter in AA recipients (18 months AA vs 37 months C, P =.03). CONCLUSIONS: These results suggest marked improvement in post-transplant outcomes in the TAC era in patients with multiple immunologic risk factors including AA ethnicity, cadaveric donor source, DGF, and HLA mismatching.     

No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas transplantation: a comparative analysis

The optimal immunosuppressive regimen for simultaneous kidney pancreas transplantation (SKPT) is still not established. We conducted a study to compare the safety and efficacy of no induction versus anti-IL-2 receptor induction protocols in SKPT recipients receiving the same maintenance regimen. METHODS: Sixty-three SKPT recipients were divided into two groups: no induction group (n = 42) and anti-IL-2 receptor induction group (n = 21). All patients were maintained on tacrolimus, mycophenolate mofetil, and prednisone. Primary endpoints were 1-year acute rejection incidence and patient and graft survivals. RESULTS: Demographic characteristics were similar between the groups. Acute rejection incidence at 1 year was equal in both groups (28.6%). Kidney and pancreas allograft survival in the no induction group were 78.6% and 76.2%, and in the anti-IL-2R induction group, 81% and 71.4%, respectively (P = NS). Patient survival was also similar: 83.3% in the no induction versus 85.7% in the anti-IL-2R induction group. Deaths due to sepsis were higher in the anti-IL-2R induction group, albeit not significantly. CONCLUSION: The use of a no-induction protocol in SKPT is safe and effective immunosuppression that also reduces transplantation costs.     

Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation

BACKGROUND: Combined liver-kidney transplantation (LKT) is the accepted treatment for patients with liver failure and irreversible renal insufficiency. Controversy exists as to whether simultaneous LKT with organs from the same donor confers immunologic and graft survival benefit to the kidney allograft. This study compares the outcomes of simultaneous LKT with the contralateral kidneys used for kidney alone transplantation (KAT) or combined pancreas-kidney transplantation (PKT) to understand the factors that account for the differences in survival. METHODS: From October 1987 to October 2001, LKTs with organs from 899 cadaver donors were reported to the United Network for Organ Sharing; 800 contralateral kidneys from these donors were used in 628 KAT and 172 PKT recipients. These 800 paired control patients were the basis of this analysis. RESULTS: Graft and patient survival rates were lower among LKT recipients compared with KAT (P<0.001) and PKT recipients (P<0.001), because of a higher patient mortality rate during the first 3 months posttransplant. Among human leukocyte antigen-mismatched transplants, LKT recipients demonstrated the highest 1-year rejection-free survival rate (LKT 70%, KAT 61%, and PKT 57% ) (P=0.005 vs. KAT, P=0.005 vs. PKT). There was a lower incidence of renal graft loss resulting from chronic rejection among LKT recipients (LKT 2% vs. KAT 8% vs. PKT 6%, P<0.0001). CONCLUSIONS: Patients undergoing LKT exhibit a higher rate of mortality during the first year posttransplant compared with patients undergoing KAT and KPT. Analysis of the data indicates an allograft-enhancing effect of liver transplantation on the renal allograft.     

Transplantation of the spleen: effect of splenic allograft in human multivisceral transplantation

OBJECTIVES: To describe the effect of the splenic allograft in human multivisceral transplantation. SUMMARY BACKGROUND DATA: We performed transplants of the spleen as part of a multivisceral graft in an attempt to decrease both the risk of infection from an asplenic state and the risk of rejection by a possible tolerogenic effect. To our knowledge, this is the first report of human splenic transplantation in a large series. METHODS: All primary multivisceral recipients who received a donor spleen (N = 60) were compared with those who did not receive a spleen (N = 81). RESULTS: Thirty-five of 60 (58%) are alive in the spleen group, and 39 of 81 (48%) are alive in control group (P = 0.98). In univariate analysis, splenic recipients showed superiority in freedom-from-any rejection (P = 0.02) and freedom-from-moderate or severe rejection (P = 0.007). No significant differences were observed in analyses of infectious complications between the spleen and control groups. Both platelet and leukocyte counts became normal in splenic patients, whereas these counts were significantly increased in nonsplenic recipients. Observed incidence of graft versus host disease (GVHD) was 8.25% (5 of 60) in the spleen group and 6.2% (5 of 81) in the control group (P = 0.70). Increased incidence of autoimmune hemolysis was observed in the spleen group. CONCLUSIONS: Allograft spleen can be transplanted within a multivisceral graft without significantly increasing the risk of GVHD. The allogenic spleen seems to show a protective effect on small bowel rejection. Further investigation with longitudinal follow-up is required to precisely determine the immunologic and hematologic effects of the allograft spleen.     

Excess risk of renal allograft loss associated with cigarette smoking.

BACKGROUND: Cigarette smoking contributes to a number of health-related problems, but its impact on renal transplant survival beyond accelerated patient death is unclear. METHODS: We performed a cohort study of 645 adult renal allograft recipients from 1985 to 1995 to evaluate the relationship between smoking and graft outcome. RESULTS: Twenty-four percent of recipients (156/645) were smokers at the time of transplant evaluation. Of these, 90% continued to smoke after transplantation. Pretransplant smoking was significantly associated with reduced overall graft and death-censored graft survival. Patients who were smokers at the time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48% at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death-censored graft survival in recipients of cadaveric (P=0.02) and of living donor kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be accounted for by differences in rejection (64% vs. 61%, P=0.35). In a multivariate analysis, pretransplant smoking was associated with a relative risk of 2.3 for graft loss. Among patients with a smoking history before transplantation, death-censored graft survival was significantly higher for those who quit smoking before transplant evaluation. CONCLUSIONS: Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival. These effects should be emphasized to patients with end-stage renal disease who are considering renal transplantation.     

Decreased short-term renal graft survival in Maghrebian recipients

The influence of race on renal allograft survival is disputed. We studied 16 cadaveric renal transplants in 14 Maghrebian patients, each matched with two controls of local origin. Patient survival at 12 months was 93% in the Maghreb group and 97% in the control group (NS). Graft survivals at 3 months for these two groups were 73% and 97%, respectively (P<0.01). At 6 months, graft survival in the control group remained unchanged at 97%, whereas in the case group it declined further to 59% (P<0.01). Overall graft failure in the Maghreb group amounted to 44% (seven of 16 transplants). In each case, failure was due to biopsy-proven acute rejection. Overall graft failure amongst the controls was only 6% (two of 32 transplants) (P=0.004) (only one case of acute rejection, or 3%) (P=0.01). This study provides evidence for significantly lower short-term renal graft survival in Maghrebian recipients of a Caucasian graft. Acute rejection seems to play a major causative role in graft loss in this group.     

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.     

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.     

Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus

BACKGROUND: We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol. METHODS: In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy. Eligible patients were withdrawn from prednisone between three and five months posttransplant, and followed for acute rejection and changes in renal function. Outcomes (group 1, n=32) were compared to those of patients deemed not to be candidates for steroid withdrawal (group 2, n=15). RESULTS: After a mean follow-up of 48.5 months, 13 of 32 patients (41%) in group 1 developed acute rejection; only 13 patients (41%) remain steroid-free. Nine of 13 rejection episodes were associated with noncompliance. Graft loss occurred in 8 of 32 patients (25%) in group 1 and in 5 of 15 patients (33%) in group 2 (P=NS). Serum creatinine rose from 1.4+/-0.41 to 2.45+/-1.7 mg/dL in group 1 (P=0.004) and from 2.1+/-0.45 to 2.62+/-1.2 mg/dL (P=NS) in group 2. Among 13 patients in group 1 who remain steroid-free, creatinine concentration has risen from 1.28+/-.0.37 prior to steroid withdrawal to 1.64+0.54 at last follow-up (P=0.027). CONCLUSIONS: Late noncompliance and/or rejection in African Americans withdrawn from steroids have a negative impact on long-term graft function and survival. Steroid withdrawal may be associated with long-term deterioration of renal function, even in the absence of overt acute rejection.