Intermediate-term outcomes with early steroid withdrawal in African-American renal transplant recipients undergoing surveillance biopsy

BACKGROUND: There is a paucity of data regarding the use of early corticosteroid withdrawal (ESW) in African-American renal allograft recipients, and very few reports with >or=1 year follow-up in all patients. METHODS: We examined the outcomes of 57 African-American renal allograft recipients with minimum follow-up 12 months who did not receive maintenance steroids after day 4 posttransplant. All patients received thymoglobulin induction, mycophenolate mofetil, and initial tacrolimus (n = 48) or sirolimus (n = 9). RESULTS: Patient and graft survival were 98% and 96% at 1 year, and 95% and 89% over the entire follow-up period (mean, 23 +/- 8 months). Incidence of acute rejection and cytomegalovirus infection were 18% and 7%, respectively, with mean serum creatinine 1.6 +/- 0.5 and 1.7 +/- 0.9 mg/dL at 6 and 12 months. Of patients with functioning grafts, 84% remained steroid free at 1 year, of which 11 (24%) were also calcineurin inhibitor free. Twenty-seven patients underwent surveillance biopsy at 1 month and 28 at 12 months, with 15 surveyed at both time points. There were significant increases in only 2 of the 6 1997 Banff chronic allograft nephropathy (CAN) category scores in this subgroup, with all mean values remaining <1 (mild in severity) at 1 year. Overall, from 82% to 96% of the 12-month scores were 相似文献   

National Survey of Anemia Prevalence After Kidney Transplantation in Argentina

Anemia is prevalent in kidney transplant recipients and likely contributes to morbidity and mortality. The definition of anemia as established by the World Health Organization and subsequently adopted by the American Society of Transplantation is a hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men. Using this definition, the prevalence of anemia is nearly 30%. The National Survey of Post Transplant Anemia (PTA) in kidney transplant recipients in Argentina was conducted to evaluate the incidence of PTA at 1 year and its relationship to variables that influence transplantation outcome. At 1 year posttransplantation, mean (SD) hemoglobin concentration was 12.43 (1.77) g/dL (n = 379), hematocrit concentration was 38.26% (5.59%) (n = 379), serum creatinine concentration was 1.51 (0.72) mg/dL (n = 380), and creatinine clearance was 60.8 (22.47) mL/min (n = 334). The prevalence of PTA in Argentina at 1 year posttransplantation was 42.25%. At univariate analysis, female sex, immunosuppression regimen (mycophenolate mofetil plus mammalian target of rapamycin), and pediatric age group were associated with anemia. At multivariate analysis, only renal function and pediatric age group were associated with anemia. The mean hemoglobin level at year of transplant was 12.43 g/dL +/−1.77 and the prevalence of PTA in Argentina at year of transplant is 42.25%. Results of our survey show a correlation between Hb levels and graft function and pediatric recipient.     

Tacrolimus (FK506) versus cyclosporine microemulsion (neoral) as maintenance immunosuppression therapy in kidney transplant recipients

The effects of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine (Neoral) on graft survival, function, and metabolic profile were evaluated in 69 patients receiving Neoral (group 1) and 54 patients receiving FK506 (group 2) for maintenance immunosuppression following kidney transplantation. Recipient and donor demographics and induction therapy were comparable, except for a higher number of sensitized patients in group 2 (n = 13). Acute rejection timing, severity, and infection rates and types were similar in both groups. During hospitalization, at 6 months, and at 1 year following transplantation, no significant differences were noted between groups in fasting glucose, serum cholesterol levels, triglyceride levels, or need for insulin or antihypertensive therapy. Mean serum creatinine levels on discharge (1.42 mg/dL +/- 0.14 vs 1.68 mg/dL +/- 0.3), at 1 month (1.45 mg/dL +/- 0.1 vs 1.39 mg/dL +/- 0.11), 3 months (1.46 mg/dL +/- 0.09 vs 1.32 mg/dL +/- 0.14), and 1 year (1.29 mg/dL +/- 0.08 vs 1.19 mg/dL +/- 0.09), but not at 6 months (1.42 +/- 0.37 vs 1.10 +/- 0.07; P = .001), were comparable between groups. The 1-year patient and graft survival rates were 98.3% for group 1 and 94.5% for group 2. When evaluated for acute rejection, infection, and metabolic differences, we conclude that both tacrolimus and cyclosporine are effective and safe calcineurin inhibitors for short-term use in kidney transplantation. A similar study is proposed to evaluate the long-term effects of both agents.     

A calcineurin inhibitor-sparing regimen with sirolimus, mycophenolate mofetil, and anti-CD25 mAb provides effective immunosuppression in kidney transplant recipients with delayed or impaired graft function

Delayed graft function (DGF) after renal transplantation is a significant risk factor for early acute rejection and graft loss. Sirolimus (SRL) can be administered in the setting of DGF without exacerbating the impaired renal function after transplantation. We examined a calcineurin-sparing regimen using SRL during the early post-operative period in renal transplant patients with delayed or impaired graft function. A retrospective review of 14 consecutive kidney transplant recipients with delayed or impaired graft function who received SRL was performed. The immunosuppressive regimen consisted of daclizumab induction (2 mg/kg), SRL (5-15 mg load followed by 2 5 mg daily maintenance therapy), corticosteroids, and mycophenolate mofetil (MMF, 1.5-3 g/d). Patients were monitored for allograft function, acute rejection, graft survival, thrombocytopenia, and leukopenia. Serum levels of SRL were determined by high-performance liquid chromatography performed at an independent commercial laboratory. Donors were cadaveric in 13 cases and living related in one. The duration of follow-up was 0.5-5.2 months. Nine patients required hemodialysis after transplantation. The mean time to initiation of calcineurin inhibitors was 21 +/- 13 d. Average serum creatinine levels at the initiation of SRL and at 1 month after transplantation were 8.4 +/- 2.7 and 2.1 +/- 1.2 mg/dL, respectively. There were 2 patients (14%) who experienced acute rejection within the first month after transplantation -1 with type I (steroid therapy) and 1 with type II (anti-thymocyte therapy). Serum levels of SRL were initially undetectable in the 2 patients with acute rejection. No grafts were lost during the period of follow-up. Three patients developed thrombocytopenia (platelets < 100 x 10(9)) and no patients developed leukopenia. The combination of SRL with anti-CD25 mAb, MMF, and corticosteroids appears to provide effective non-nephrotoxic immunosuppression for kidney transplantation without the need for a lymphocyte-depleting regimen. However, it is important to monitor serum SRL levels to determine the optimal dosing regimen. Furthermore, long-term follow-up of these patients will be helpful to determine whether improved immunosuppression can be achieved with a fully calcineurin-sparing regimen using SRL.     

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.     

Late calcineurin inhibitor withdrawal as a strategy to prevent graft loss in patients with suboptimal kidney transplant function

Chronic allograft nephropathy is a major cause of progressive renal failure in renal transplant recipients. Its etiology is multifactorial and may include both immunologic and nonimmunologic causes. In this observational cohort study we set out to see if calcineurin inhibitor withdrawal would reduce the likelihood of graft loss. METHODS: One hundred and five renal transplant recipients with impaired kidney function (mean serum creatinine 3.0 +/- 0.1 mg/dl) and biopsy-proven chronic allograft nephropathy had the dose of their calcineurin inhibitors, cyclosporine (CSA), or tacrolimus (FK), reduced or discontinued with either the addition of, or continuation of mycophenolate mofetil and low-dose corticosteroids. This intervention occurred at a mean of 29.0 +/- 2.7 months after transplantation. Follow-up after intervention was 54.3 +/- 4.1 months in the reduced CSA group (n = 64), 41.6 +/- 3.2 months in the reduced FK group (n = 28), and 75.5 +/- 6.7 months in the calcineurin inhibitor withdrawal group (n = 13). RESULTS: There were 24 graft failures in the reduced CSA group, 9 graft failures in the reduced FK group, and 1 graft lost in the calcineurin inhibitor withdrawal group. The unadjusted relative risk for graft failure in the CSA and FK groups combined (confidence interval 1.05-31.6), was 4.07 using the calcineurin inhibitor withdrawal group as the reference, p = 0.05. A Cox proportional hazards model adjusting for baseline covariates including age, gender, race, type of transplant, delayed graft function, baseline blood pressure and random serum glucose and cholesterol demonstrated that only calcineurin inhibitor dose reduction but not withdrawal, older age, delayed graft function, higher serum creatinine at the time of intervention, and higher diastolic blood pressure and serum glucose, correlated with graft loss. Only 6 of the 105 patients developed Banff grade acute rejection. All responded to steroid therapy. We conclude that although this observational cohort study may have a selection bias, late calcineurin inhibitor withdrawal in patients with chronic allograft nephropathy and impaired kidney function appears safe and durable as a treatment strategy to reduce the likelihood of graft failure.     

Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors.

Early renal dysfunction following liver transplantation is associated with increased morbidity and mortality. To evaluate the impact of delayed initiation of calcineurin inhibitor on renal function, we conducted a retrospective study comparing 118 liver transplant recipients who received rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitor with 80 liver transplant recipients who received no antibody and early initiation of calcineurin inhibitor (control group). All patients received mycophenolate mofetil and steroids. Delayed calcineurin inhibitor initiation with anti-thymocyte globulin was associated with significant improvement in renal function throughout the first year post-transplant. At 12 months post-transplant, patients treated with this regimen experienced lower serum creatinine (1.4 +/- 0.5 versus 1.7 +/- 0.5 mg/dL, P < 0.001), a higher estimated glomerular filtration rate (57.4 +/- 20.5 versus 43.7 +/- 14.4 mL/min/1.73 m(2), P < 0.001), and less dependence on dialysis (0.8% versus 13%, P < 0.001) in comparison with no antibody and early calcineurin inhibitor initiation. Patient survival and graft survival were similar between groups; however, there was a trend of a lower incidence of early biopsy-proven acute rejection with anti-thymocyte globulin. Overall infection and cytomegalovirus infection were significantly lower in anti-thymocyte globulin-treated patients, and there was no increased incidence of hepatitis C recurrence in comparison with controls. In conclusion, delayed initiation of calcineurin inhibitor with anti-thymocyte globulin in liver transplant recipients is safe and is associated with improvements in renal function and a lower incidence of early acute rejection in comparison with no antibody and early initiation of calcineurin inhibitor.     

Triple immunosuppression with or without basiliximab in pediatric renal transplantation: acute rejection rates at one year

Acute rejection (AR) is a major determinant of chronic allograft dysfunction and graft survival. This study evaluated the effect of basiliximab on AR in pediatric renal transplantation on triple immunosuppression. Forty-three transplantations (25 males and 18 females; mean age 14.9 +/- 3.6 years) were performed between 1996 and 2002. Thirteen of the grafts came from cadaveric donors and 30 from living-related donors. All patients were placed on immunosuppression with prednisolone + (azathioprine or mycophenolate mofetil) + (cyclosporine [CYA] or tacrolimus). Basiliximab was also administered in 20 cases. The respective rates of biopsy-proven AR in the basiliximab group (BG) and the standard-regimen group (N-BG) were 0% vs 17.4% (P >.05) at 1 month posttransplantation; 0% vs 26.1% (P <.05) at 3 months; 0% vs 26.1% (P <.05) at 6 months, and 7.1% vs 26.1% (P >.05) at 12 months. In the N-BG group the 1- and 3-year graft survival rates were 91.3% (21/23) and 83.3% (15/18), respectively. The mean glomerular filtration rate (GFR) in the first year after the transplantation was 75 +/- 33 mL/min/1.73 m(2) in the N-BG and 98 +/- 21 mL/min/1.73 m(2) in the BG patients (P <.05).Basiliximab significantly reduced the rates of acute rejection at 3 and 6 months after pediatric renal transplantation. The GFR in the first year was significantly higher among the patients treated with basiliximab, which was well tolerated by all patients and caused no significant adverse effects. The effect of basiliximab on long-term graft survival and chronic allograft dysfunction deserves further investigation.     

Conversion from azathioprine to mycophenolate mofetil followed by calcineurin inhibitor minimization or elimination in patients with chronic allograft dysfunction

The purpose of this study was to evaluate the effects of the conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) followed by calcineurin inhibitor (CNI) elimination or minimization in patients with progressive chronic allograft dysfunction (CAD). METHODS: Between November 6, 1999 and February 12, 2003, 169 patients receiving CNI/AZA/prednisone (153 CsA; 14 tacrolimus) were included in this study. Demographics, immunosuppression, graft function, hematology, and biochemistry were obtained before (-6, -3, and -1 month) and 1, 3, 6, 9 and 12 months after and at last follow-up visit after conversion. RESULTS: Mean age was 34 +/- 12 years, 66% males, 51% Caucasian, and 72% living allograft recipients. Mean follow-up times before and after conversion were 32.4 and 19.4 months; 10 patients completed 3 years of follow-up. CNI elimination was performed in 39% and minimization in 61% of patients. Overall there was significantly improved graft function at 1 year after conversion (2.6 +/- 1.0 vs 2.1 +/- 0.6 mg/dL, P = .038). The slopes of the regression lines of 1/Cr vs time were significantly improved from preconversion to after conversion (-0.026 vs +0.007 mg(-1)/dL per day(-1), P = .001). There was a significant decrease in mean systolic (141 +/- 21 vs 135 +/- 22 mm Hg, P = .015) and diastolic (89 +/- 15 vs 84 +/- 14 mm Hg, P = .005) blood pressure values at 1 year. There were four episodes of acute rejection (Banff IA) treated with steroids. Three years after conversion, patient and graft survivals were 95% and 79%, respectively. One patient developed posttransplant lymphoproliferative disease. CONCLUSION: Among patients with CAD, conversion from AZA to MMF followed by CNI minimization or elimination was a safe and effective strategy to preserve or improve graft function.     

Campath-1H in renal transplantation: The University of Wisconsin experience

BACKGROUND: Immune cell depletion is known to prevent renal allograft rejection and injury. We evaluated the humanized monoclonal antibody Campath-1H (alemtuzumab; ILEX Oncology, San Antonio, Texas) in renal transplant recipients for its safety and efficacy in preventing rejection when used in combination with a calcineurin inhibitor, mycophenolate mofetil, and low-dose steroid therapy. METHODS: One hundred twenty-six consecutive renal allograft recipients received 2 doses of Campath-1H antibody on days 0 and 1. Outcomes were compared to patients who received an anti-CD25 antibody (n=799), Thymoglobulin (n=160), or other antibody treatment (n=156) in combination with a calcineurin inhibitor, mycophenolate mofetil, and higher dose steroids. RESULTS: The Campath-1H group overall experienced less rejection than the other 3 groups (P=.037). Patients with delayed graft function experienced less rejection with Campath-1H than control groups (P=.0096) and improved graft survival (P=.0119). There was no difference in infection or malignancies between the 4 groups. CONCLUSIONS: Campath-1H was well tolerated in renal transplant patients and led to significant reductions in incidence of rejection. Patients with delayed graft function experienced significantly improved graft survival.     

Early withdrawal of cyclosporine A improves 1-year kidney graft structure and function in sirolimus-treated patients

BACKGROUND: Chronic allograft nephropathy (CAN) represents the most common cause of late graft loss. Nephrotoxicity from chronic use of calcineurin inhibitors (CNI) has the potential to contribute to CAN. The present investigation aimed to evaluate the impact of early CNI withdrawal on kidney graft function and structure at 1 year in sirolimus (SRL)-treated patients. METHODS: Forty consecutive kidney transplant recipients were initially treated with corticosteroids, cyclosporine A (CsA), and SRL (2 mg/day). After 3 months, patients were randomly assigned to either continue the same treatment (group I) or to withdraw CsA and continue SRL (group II). All patients underwent kidney graft biopsy immediately after graft reperfusion (0-hr biopsy) and 12 months after engraftment. RESULTS: Baseline graft biopsy showed a higher degree of renal damage in group II patients (total score, 4+/-1.6 vs. 2+/-0.9; P<0.05). Twelve months after engraftment, CAN was diagnosed in 55% of all patients, of whom 64% were in group I and 36% in group II. CAN lesions were scored as moderate to severe in 90% of group I patients but only 32% of group II patients (P<0.05). A vascular score greater than or equal to 2 occurred in 90% of group I patients and in 38% of group II patients (P<0.05). At 1 year, group I patients showed a significantly worse kidney graft function (serum creatinine, 2.0+/-0.3 vs. 1.3+/-0.3 mg/dL; creatinine clearance, 54+/-14 vs. 66+/-17 mL/min; both P<0.002). CONCLUSIONS: These results suggest that early withdrawal of CsA is a safe option, which allows a significant reduction of chronic histologic damage, particularly vascular injury, of cadaveric kidney allografts.     

The use of an anti-CD25 monoclonal antibody and mycophenolate mofetil enables the use of a low-dose tacrolimus and early withdrawal of steroids in renal transplant recipients

BACKGROUND: Reducing calcineurin-inhibitor-induced nephrotoxicity and simultaneously avoiding long-term steroid related side-effects is a desirable goal in renal transplantation. We examined the hypothesis that using anti-CD25 monoclonal antibody induction and mycophenolate mofetil (MMF) would allow the lowering of target pre-dose blood concentrations of tacrolimus immediately after transplantation and subsequently stopping steroids at 5 months. METHODS: Eighty-two kidney recipients were enrolled in a single-center study comparing two tacrolimus-based protocols. Group I (n = 41) patients received a standard-dose tacrolimus (blood concentration 10-15 ng/mL) with MMF and a standard dose corticosteroid. Group II (n = 41) patients were treated with a low-dose tacrolimus (blood concentration 5-10 ng/mL) and MMF, a low-dose corticosteroid (stopped after 5 months) and induction with daclizumab. RESULTS: Patient (95.1 versus 100%) and graft survival (92.6 versus 97.5%) at 1 yr were not different between groups. Patients of group II experienced significantly less acute rejections than group I (17.1 versus 41.4% p = 0.03). Delayed graft function occurred less often in group II (5 versus 12% p = 0.43). Graft function at 1 yr was significantly better in group II (serum creatinine 1.49 versus 1.69 mg/dL and creatinine clearance 59.6 versus 49 mL/min; p < 0.05). Corticosteroids could be stopped after 5 months in 82.9% of group II patients. CONCLUSION: A regimen consisting of anti-CD25 monoclonal antibody induction and MMF allows the safe and efficient use of low-target pre-dose trough concentrations of tacrolimus and enables the early discontinuation of steroids. Preliminary results indicate a better 1-yr graft function compared to a normal-dose tacrolimus regimen.     

Worse renal transplant outcomes observed among Afro-Brazilian patients on prospective registry data of 2461 renal transplants at least 1 year follow-up

We present prospective registry data of 2461 (live donor = 1753 and deceased donor = 08) renal transplants performed between 1999 and 2003. All subjects were followed for more than 1 year after transplantation and most were treated with a calcineurin inhibitor and azathioprine. Afro-Brazilian, white, and mixed patients constituted 11% (272), 67.1% (1651), and 14.9% (367) of the population respectively. Mean dialysis time was 42.3 +/- 32.9 months and delayed graft function, occurred in more than 60%. Three-year patient survival rates were 96.3%, 92.8%, and 86.7% for living-related, living-unrelated, and deceased donors, respectively. Corresponding 3-year graft survival rates were 87.3%, 82.1%, and 71.3% and functional graft survival rates were 90.2%, 88.8%, and 81.5%. The poorer transplant outcome observed among Afro-Brazilian patients has been mainly attributed to differences in absorption of cyclosporine, tacrolimus, and mycophenolate mofetil.     

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.     

A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year

BACKGROUND: This is the 1-year report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. METHODS: Prior to transplantation, recipients were randomized to receive tacrolimus plus corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study. Patient and graft survival, renal function, study drug dosing and discontinuations were evaluated at 1 year. RESULTS: At 1 year, there was no difference in patient survival (95.7% sirolimus vs. 97.2% MMF; P=0.45) or graft survival (90.8% sirolimus vs. 94.3% MMF; P=0.22). Patients without delayed graft function (DGF) receiving MMF had significantly better graft survival (99% vs. 93%; P=0.01). Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus (98% vs. 91%; P=0.07). Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation (26.5% vs. 14.8% MMF; P=0.006). Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels (1.3 mg/dL vs. 1.5 mg/dL; P=0.03) and a trend towards higher calculated creatinine clearance (CrCl), (58.4 ml/min vs. 54.3 ml/min; P=0.06). More patients in the sirolimus group had a serum creatinine >2.0 mg/dL, (20.4% vs. 11.0%; P=0.02). CONCLUSIONS: Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF. Patient and graft survival were excellent in both arms. Renal function is superior for patients treated with tacrolimus + MMF combination.     

Impact of anti-hepatitis C virus (HCV) antibody on outcomes in renal transplant recipients infected with HCV

OBJECTIVE: Hepatitis C virus (HCV) infection remains an important risk factor for mortality and morbidity in transplant recipients. In this study, we retrospectively analyzed the impact of pretransplantation hepatitis C antibody status in HCV-infected renal allograft recipients on graft and patient survivals. PATIENTS AND METHODS: From February 1998 to August 2007, 933 renal transplantations were performed at our center. Of these, 104 patients were identified to be harboring HCV infection: 59 (group I) were anti-HCV positive prior to transplantation and 45 (group II) were HCV RNA/antibody positive in the posttransplantation period. The patients transplanted in different eras received different immunosuppressive regimens. Complete follow-up data were available for 72.3% (43/59) in group I and 80% (36/45) in group II. Both groups had a similar number of patients on cyclosporine (62.8% vs 61.1%), tacrolimus (37.2% vs 38.8%), and mycophenolate mofetil (MMF; 58.1% vs 61.1%). These patients were analyzed for differences in patient and graft survivals by log-rank test. RESULTS: The overall mean ages were 35.1 +/- 10.4 and 32.4 +/- 10.4 years, male to female ratios 37:6 and 31:5, mean donor ages 41.5 +/- 10.9 and 41.2 +/- 13.1 years, and mean follow-up durations 29.4 +/- 24 (range, 1-107.7) and 32.6 +/- 24.2 (range, 3.1-97.2) months in groups I and II, respectively. The patients in group I had received a significantly greater number of blood transfusions compared with patients in group II (6.2 +/- 5.7 vs 2.1 +/- 2.9) and a significantly greater number of dialysis treatments prior to transplantation (84.5 +/- 62.0 vs 33.8 +/- 43.2), respectively. Liver function tests-SGOT (22.6 +/- 16.1 vs 18.3 +/- 12.1 IU/L) and SGPT (24.2 +/- 28.9 vs 20.4 +/- 20.2 IU/L)-were similar in the 2 groups in the pretransplantation period, respectively. The patient and graft survivals at 5 years were similar: 88.6% vs 82.3% (P = .81) and 60.1% vs 62.5% (P = .75) in groups I and II, respectively. The serum creatinine values at last follow-up were 1.38 +/- 0.6 vs 1.7 +/- 2.4 mg% (P = not significant), SGOT 33.4 +/- 25.6 vs 38.3 +/- 47 IU/L, and SGPT 39.3 +/- 46.7 vs 59.2 +/- 89 IU/L in groups I and II, respectively. Liver decompensation occurred in 4 patients, 2 in each group at a mean duration of 36.5 months. CONCLUSION: Absence of HCV antibody does not confer any survival disadvantage in HCV-infected renal allograft recipients undergoing renal transplantation.     

Impact of pregnancy on the outcome of kidney transplantation

BACKGROUND: There is still controversy over whether pregnancy adversely affects renal transplantation outcomes. We, thus, compared two groups of kidney transplant recipients in terms of patient survival and allograft function: those who did versus did not conceive posttransplant. METHODS: This historical cohort study conducted between 1996 and 2002, divided female kidney transplant recipients of reproductive age into group I (n=86, at least one posttransplant pregnancy) and group II (n=125, no posttransplant pregnancy). The two groups were matched for age, cause of end-stage renal disease (ESRD), treatment protocol, and first creatinine (Cr). All patients received a first transplant and all had a Cr less than 1.5 mg/dL on entry into the study. The subjects were followed for 45.4 +/- 22.0 and 46.3 +/- 19.8 months, respectively (P>.05). Five-year patient and graft survivals and Cr were considered to be the main outcome measures. RESULTS: Mean (SD) age in groups I and II was 26.6 +/- 6.6 and 26.9 +/- 8.1 years, respectively (P>.05). Five-year patient and graft survival rates were not significantly different between the study groups. Of the women in group 1, only 9 (10.5%) subjects displayed elevated serum Cr levels (>1.5 mg/dL) at the end of follow-up, while the serum Cr levels in 35 (28%) group II patients were above 1.5 mg/dL (P=.024). CONCLUSION: Our results indicates pregnancy did not seem to adversely affect patient and graft survival among kidney transplant recipients. Renal transplantation in stable women of childbearing age should not be a contraindication to pregnancy.     

Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: preliminary results of an open prospective study

As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI (n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose (n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 +/- 0.36 versus 1.58 +/- 0.33 mg/dL, P < .001) and BUN (39.2 +/- 11.8 versus 29.9 +/- 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 +/- 10.8 versus 61.6 +/- 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 +/- 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 +/- 19 versus 130 +/- 14 mm Hg, P < .01) and diastolic (82 +/- 9 to 74 +/- 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 +/- 25.9 versus 25.2 +/- 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.     

Effect of basiliximab on renal allograft rejection within 1 year after transplantation

Basiliximab is widely used in clinical practice for initial immunosuppressive treatment of renal transplant recipients, seeking to reduce the incidence of acute rejection episodes without adverse events. This retrospective study included 123 renal allograft recipients transplanted at a single center. All were followed for longer than 1 year after transplantation and treated with calcineurin inhibitor and steroid (methylprednisolone) for prophylactic immunosuppression, but basiliximab and mycophenolate mofetil were optional. We compared the outcomes of renal transplant recipients who were versus treated were not with basiliximab as initial immunosuppressive therapy. Basiliximab was used for initial immunosuppression in 42 patients. Their maintenance immunosuppressive treatment included triple (n = 44) or double (n = 79) regimens, including a calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]), methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%) patients had a rejection episode within 1 year after transplantation and 22 (17.9%) had infections. Within the first year after transplantation the patients who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%) than the patients without this therapy (n = 20, 24.7%), which was not statistically significant (P = .245). However, basiliximab significantly affected the occurrence of rejection episodes among the double immunosuppressive regimen group (P = .006), but not the triple regimen group (P = .098) without an impact on infection episodes (P value of double, triple = .291, .414) within 1 year after transplantation. We concluded that basiliximab was more useful for the recipients treated with double immunosuppression with a calcineurin inhibitor and steroid than for those on a triple regimen including mycophenolate mofetil.     

Randomized trial of conversion from mycophenolate mofetil to azathioprine 6 months after renal allograft transplantation.

BACKGROUND: In the first year after renal allograft transplantation, triple therapy immunosuppression with cyclosporin (CsA), prednisone (P), and mycophenolate mofetil (MMF) is superior to a triple therapy treatment that includes azathioprine (AZA) instead of MMF. Whether long-term treatment with CsA-P-MMF is better than treatment with CsA-P-AZA is a matter of debate, as 3-year graft survival is similar in MMF- and AZA-treated patients. The purpose of the present study was to examine the short-term effect of changing MMF to AZA in low-risk renal allograft recipients 6 months after transplantation. METHOD: This was a randomized, open-label single-centre study, recruiting 48 low risk renal allograft recipients on CsA-P-MMF therapy 6 months after transplantation, comparing the outcome with continued MMF treatment (2 g b.i.d.) (group A, n=22) or switching MMF to AZA (1 mg/kg) treatment (group B, n=26). RESULTS: The outcome after a 6-months follow-up of patients in group A and group B was similar. Treatment failure rates (defined as clinically diagnosed acute rejection episodes) were 4.5% in group A and 3.8% in group B. There were no patient deaths and no graft failures during the 6-months observation period. Graft function was excellent and similar in both groups. CONCLUSION: Replacing MMF with AZA 6 months after transplantation in low-risk renal allograft recipients is safe and is not associated with altered graft function in the short term.