tacrolimus and Cadaver

1. Although the number of cadaver donor transplants did not increase substantially over the past 10 years, unrelated living donor grafts increased from 153 in 1991 to 1,661 through 2000. Use of spousal and other unrelated donor organs contributed to this increase. There was a modest increase in living-related donor transplants from 2,328 in 1991 to 3,451 in 2000. 2. Cadaver donor graft survival at one year improved from 84% in 1991 to 90% in 2000. In contrast, one-year graft survival of living donor transplants only improved from 93% in 1991 to 95% in 2000. 3. Throughout the 10-year period, approximately 13% of transplants were repeat transplants from cadaver donors and roughly 8% were regrafts from live donors. 4. Cadaver donor transplants into White recipients declined from 68% in 1991 to 60% in 2000. For living donors, the percentage of White patients remained constant at about 70%. 5. Graft survival in patients of all races was about equal at one year but diverged at 3 years, with Asians having the highest and Blacks having the lowest 3-year graft survival rates. 6. Average donor age increased from 31.7 in 1991 to 36 in 2000 for cadaveric donor transplants and 37.9 in 1991 to 40.4 in 2000 for living donor transplants. Cadaveric kidneys from donors older than 50 years of age yielded significantly lower 3-year graft survival. 7. Average recipient age for cadaveric donor transplants increased from 42.1 in 1991 to 46.8 in 2000. The average recipient age for living donor transplants also increased steadily from 33.7 in 1991 to 42.9 in 2000. There was relatively little effect on graft survival rates for advanced age recipients. 8. The percentage of sensitized recipients receiving cadaver donor grafts declined from 27% in 1991 to 21% in 2000. Similarly, sensitized recipients receiving living donor grafts decreased from 17% in 1991 to 13% in 2000. Graft survival in patients with more than 50% PRA was lower at 3 years for patients receiving cadaveric donor grafts. Highly sensitized patients receiving living donor grafts had graft survival rates similar to those who were not sensitized. 9. Cold ischemia times decreased from an average of 24.2 hours in 1991 to 18.9 hours in 2000. Improved graft survival rates over those 10 years were noted in all groups, and even cold ischemia times more than 36 hours yielded 3-year graft survivals comparable to those with lower cold ischemia times in 1998. 10. The need for dialysis has remained constant at about 23% over the la

Topics: Adolescent; Adult; Azathioprine; Cadaver; Child; Child, Preschool; Cyclosporine; Drug Therapy, Combination; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infant; Kidney Transplantation; Living Donors; Middle Aged; Tacrolimus

The availability of a number of new immunosuppressive drugs has resulted in significant improvements in the outcome of kidney transplantation. Currently 1-year graft survival rate for cadaver kidney transplants is approximately 85%. A number of new agents are presently in clinical studies. This article reviews the currently available agents and examines various aspects of induction and maintenance immunosuppressive therapy, and the treatment of acute rejection episodes. In addition, the agents currently in clinical trials and future directions in immunosuppressive therapy are discussed.

Topics: Acute Disease; Cadaver; Cyclosporine; Forecasting; Graft Rejection; Graft Survival; HLA Antigens; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tacrolimus; Tissue Donors; Treatment Outcome

Human parvovirus B19 disease is an infrequent but recognized rare cause of anemia in immunocompromised patients. A few cases of parvovirus B19 infections have been reported in transplant recipients, of those only four patients underwent renal transplantation. The primary immunosuppressive therapy in these patients included prednisone with either cyclosporine or tacrolimus. In one patient the disease was self-limiting, while in three others the hematocrit improved following 10-15 d of treatment with commercial intravenous immunoglobulin (IVIG). Herein, we report the fifth case of pure red cell aplasia due to parvovirus B19 infection in a renal transplant recipient who responded to a 5-d course of IVIG. To our knowledge, this is the first case of parvovirus B19 infection in a patient with solid-organ transplantation whose immunosuppressive regimen included both mycophenolate mofetil and tacrolimus and in whom an excellent clinical response was achieved with a short course of IVIG infusion.

Topics: Adult; Anti-Inflammatory Agents; Cadaver; Cyclosporine; DNA, Viral; Hematocrit; Humans; Immunoblotting; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infusions, Intravenous; Kidney Transplantation; Male; Mycophenolic Acid; Parvoviridae Infections; Parvovirus B19, Human; Polymerase Chain Reaction; Prednisone; Red-Cell Aplasia, Pure; Remission Induction; Tacrolimus

Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes. We report that brief perioperative desensitization using either intravenous immunoglobulin (IVIG) or plasmapheresis/IVIG (PP/IVIG) treatment improves clinical outcomes among patients with positive crossmatches.. Immediately following deceased donor transplantation, 235 renal recipients were assigned points for PRA and flow crossmatches (FCXM): delayed graft function (DGF) ≤ 1 point received standard therapy; 2 points received high-dose IVIG; and ≥3 points received PP/IVIG. The DSAs were serially monitored by single antigen bead luminex for 1 year. Five-year clinical outcomes were determined from the chart review.. All desensitized patients had preoperatively positive FCXM with DSA. Rejection was more common (P < .05) among desensitized than nonsensitized groups. However, overall graft survivals were similar between the groups (P = not significant) and superior to historic untreated patients (P < .05). Treatment with PP/IVIG more effectively eliminated preexisting DSAs (67% vs 33%, P < 0.05) than IVIG, but neither regimen prevented de novo formation of DSA (20%, P = not significant). Graft survival was >90% in all desensitizated patients with DSA elimination as well as PP/IVIG patients with residual DSA. In contrast, IVIG patients with persistent DSA had poorer graft survival (45%, P < .05).. Preemptive perioperative desensitization improved overall graft survival of sensitized patients compared to historic untreated patients. Plasmapheresis/IVIG had greater impact on DSA eradication and graft survival than IVIG alone.

Topics: Adult; Antibodies; Antilymphocyte Serum; Cadaver; Cohort Studies; Delayed Graft Function; Desensitization, Immunologic; Female; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Methylprednisolone Hemisuccinate; Middle Aged; Mycophenolic Acid; Perioperative Care; Plasmapheresis; Tacrolimus

In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial.. For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B.. With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9±4.2 vs. 83.6±6.9 and 79.8±5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group.. Long-term results clearly indicate inferior clinical outcomes in group B.

Topics: Adrenal Cortex Hormones; Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Cadaver; Creatinine; Daclizumab; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Treatment Outcome

Everolimus (Evl) plus tacrolimus (Tac) in de novo renal transplantation is effective and safe. Whether the concentration of Evl affects efficacy and safety in a Tac-based regimen has not been previously reported.. To evaluate whether the concentration of Evl affects biopsy-proven acute rejection (BPAR), renal function, adverse events (AEs); and to assess for pharmacokinetic (PK) interactions.. Data were from a prospective, multicenter, open-label, randomized, exploratory 6-month study of 92 renal transplant patients treated de novo with concentration-controlled Evl (target trough levels > or =3 ng/mL) plus low-dose Tac or Evl plus standard-dose Tac; both groups received basiliximab and corticosteroids. Data were pooled across study arms to examine BPAR rates in patients with Evl trough levels less than 3 (n=26), 3 to 8 (n=62), or more than 8 ng/mL (n=4). Groups were stratified by both Evl and Tac trough levels to evaluate glomerular filtration rate and AEs. Evl and Tac PK interactions were evaluated in a subset of 14 patients.. Evl trough level of more than or equal to 3 ng/mL was associated with significantly lower rates of BPAR as compared with a trough level of less than 3 ng/mL. Glomerular filtration rate was similar at 6 months for both the low and standard Tac groups. No apparent PK interactions were observed between Evl and Tac. AEs were infrequent and did not seem to be associated with the Evl or Tac level.. Evl trough levels > or =3 ng/mL plus Tac are associated with low rates of BPAR without adversely affecting renal function. No evident PK interaction exists between Evl and Tac.

Topics: Adult; Biopsy; Cadaver; Drug Therapy, Combination; Everolimus; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Middle Aged; Sirolimus; Tacrolimus; Tissue Donors

We recently reported a randomized study in renal transplant patients (RTP) receiving tacrolimus, mycophenolate mofetil, and prednisone in which patients who had early protocol biopsies (PBx) derived no benefit compared with controls (no PBx) at 6 months, likely due to the low prevalence of subclinical rejection. We report on the follow-up of these patients to 24 months at which time a repeat PBx and tests of renal function were performed.. Of the 240 RTP randomized, 22 were excluded for a protocol violation. Approximately 75% of the remaining 218 (111 PBx and 107 controls) completed the study.. At 24 months, graft function was excellent with a mean creatinine clearance of approximately 74 mL/min and negligible proteinuria; however, the prevalence of interstitial fibrosis and tubular atrophy (IF/TA)-ci + ct more than or equal to 2-increased from approximately 3% at baseline to up to 40% to 50%. By logistic regression analysis, the only independent positive correlate of IF/TA was transplantation with a deceased donor. However, by post hoc analysis, use of angiotensin-II-converting enzyme inhibitors or angiotensin II receptor blockers was negatively correlated with both the prevalence of IF/TA at 24 months and its progression between 6 and 24 months in RTP that had paired biopsies.. A regimen of tacrolimus, mycophenolate mofetil, and prednisone results in excellent renal function at 24 months posttransplant but with a progressive increase in IF/TA. A potential inhibitory effect of angiotensin-II-converting enzyme inhibitor/angiotensin II receptor blockers on IF/TA is suggested that requires confirmation in a randomized study.

Topics: Adult; Biopsy; Cadaver; Disease Progression; Female; Fibrosis; Graft Rejection; HLA Antigens; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Prednisone; Regression Analysis; Tacrolimus; Tissue Donors

Chronic allograft nephropathy is the most frequent cause of long-term kidney allograft loss. Studies are desperately needed to improve long-term survival. Tacrolimus has been associated with less rejection and better kidney function compared with cyclosporine in clinical trials. This study tested the hypothesis that conversion from cyclosporine to tacrolimus might improve long-term outcomes in patients with chronic allograft damage.. In this multicenter Canadian clinical trial, cyclosporine-treated patients with biopsy-proven chronic allograft nephropathy and impaired renal function were randomly assigned (2:1) to convert to tacrolimus or continue on cyclosporine therapy. A total of 106 (70 tacrolimus and 36 cyclosporine treated) patients were followed-up for up to 5 years. The primary outcome was graft survival.. In an intention to treat analysis, subsequent graft (73% vs. 81%, P=0.2835, log-rank test) and patient survival (91% vs. 92%, P=0.8668, log-rank test) were not different between the tacrolimus and cyclosporine groups, respectively. Changes in Chronic Allograft Damage Index scores on protocol biopsies from baseline to 3 years were not different (+0.4+/-1.8 vs. +1.3+/-3.2, P=0.5910, cyclosporine vs. tacrolimus, respectively). There were no significant differences in biopsy-proven acute rejection (6 [8.6%] vs. 2 [5.6%], tacrolimus vs. cyclosporine, respectively, P=0.5906).. In this study, patients with chronic allograft damage converted from cyclosporine to tacrolimus demonstrated no apparent benefit.

Topics: Adult; Cadaver; Cyclosporine; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Middle Aged; Survival Analysis; Survivors; Tacrolimus; Telephone; Time Factors; Tissue Donors; Treatment Failure; Treatment Outcome

In liver transplantation, mycophenolate mofetil (MMF) is habitually administered using fixed doses. We assessed whether mycophenolic acid (MPA) monitoring could be advisable in liver transplant patients.. In 15 liver transplant patients receiving tacrolimus, daclizumab and MMF (1 g bid, orally), we determined the 12-hour plasma MPA pharmacokinetic profile after one dose of MMF at days 6, 10, and 16, and months 3 and 6. The inhibitory capacity of serum MPA on proliferation of CEM cells, a cell line insensitive to other immunosuppressants, was also determined.. A large interindividual variability in MPA profiles was observed at any time. Regardless of a gradual increase in individual MPA AUC and C(0) over time following transplantation, a substantial proportion of patients had these parameters below the ranges recommended in other organ transplantations throughout the study. When MPA AUC and C(0) were within the recommended ranges, CEM proliferation was inhibited by almost all serum samples, but when these pharmacokinetic parameters were below the recommended ranges, CEM proliferation was very variable and, therefore, unpredictable. No relationship between MPA pharmacokinetics and the efficacy of MMF could be established (only one patient developed rejection), probably due to the concomitant administration of tacrolimus and daclizumab. Gastrointestinal symptoms were the only adverse events with a significant relationship with MPA levels.. During the first postoperative months, exposure to MPA is low in a considerable proportion of liver transplant patients receiving MMF at a fixed dose of 1 g bid. MPA monitoring appears necessary in these patients.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cadaver; Cell Division; Daclizumab; Drug Therapy, Combination; Humans; Immunoglobulin G; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus; Tissue Donors

This study compared early postoperative complications in kidney transplant recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free regimen or a tacrolimus-based steroid-free regimen. We used a single-center, prospective, sequential but nonrandomized study design. Consecutive recipients of primary cadaveric or non-HLA identical kidney transplant recipients received either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning postoperative day 3, mycophenolate mofetil 1 gm twice a day, and methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome measures were patient and graft survival, BPAR, surgical and wound complications, viral infections and posttransplant diabetes mellitus (PTDM). Both groups had excellent early outcomes with no significant difference in patient or graft survival, early renal function, BPAR, surgical or wound complications, or viral infections between the two groups. Patients in the sirolimus-based CNI-free group had a significantly higher incidence of PTDM and a trend toward more discontinuation due to drug toxicity. Whether either regimen improves long-term outcomes awaits longer follow-up.

Topics: Adrenal Cortex Hormones; Adult; Cadaver; Calcineurin Inhibitors; Drug Therapy, Combination; Female; Graft Survival; Histocompatibility Testing; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Patient Selection; Postoperative Complications; Racial Groups; Survival Analysis; Tacrolimus; Tissue Donors; Treatment Outcome

This study presents the first prospective multicenter study assessing sirolimus-based immunosuppression with early (4-day) corticosteroid withdrawal (CSWD) in renal transplantation. Immunosuppression included: anti-IL-2 receptor antibody and tacrolimus/sirolimus. Inclusion criteria included adult primary recipients. Exclusion criteria included: (i) African Americans, (ii) current PRA >50%, (iii) multiple organ transplants, (iv) WBC < 3000 cells/microL and (v) fasting hypercholesterolemia/hypertriglyceridemia. The primary endpoints were acute rejection and the proportion of patients off corticosteroids. Seventy-seven patients were enrolled: mean age of 49.7 +/- 12 years. Transplants included: cadaveric (26%) and living donor (74%). Patient and graft survival were 100%. Biopsy proven acute rejection occurred in 13%; presumptive rejection in 10.5%. Banff grades included: IA (seven patients), IB (one patient), IIA (one patient) and IIB (one patient). Renal function at 1 year: serum creatinine (1.18 +/- 0.06 mg/dL). Mean weight gain was minimal at 1 year: 3 +/- 2 kg/patient. Mild increases in total, LDL and HDL cholesterol were observed and new antilipid agent use occurred in 26 patients. In conclusion, early CSWD under tacrolimus/sirolimus-based immunosuppression in selected, low-risk renal transplant recipients provides: (i) excellent patient and graft survival, (ii) good renal function, (iii) reduced hyperlipidemia and antilipid agent use and (iv) low acute rejection rates.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal; Basiliximab; Biopsy; Blood Pressure; Body Weight; Cadaver; Cardiovascular System; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Living Donors; Male; Middle Aged; Pilot Projects; Recombinant Fusion Proteins; Risk Factors; Sirolimus; Steroids; Tacrolimus; Time Factors; Treatment Outcome

Basiliximab (BX) induction, tacrolimus (TAC), and steroids have sharply reduced acute cellular rejection at our institution. However, late graft loss has continued, for which sirolimus (SL) was introduced into the protocol.. From July 1, 2001 to December 31, 2003, 152 live donor (LD) renal transplant recipients received TAC (level 15 to 20 ng/mL) and steroids, with BX induction. One hundred twenty-two patients (Group 1) received SL (3 mg/d African-americans; 2 mg/d for others) starting on days 2 and 3. The SL level was adjusted to 8 to 10 ng/d, usually by weeks 3 to 4 posttransplant. The TAC doses were then progressively reduced. Records were reviewed for demographics, immunosuppressive drug levels, serum cholesterol and blood pressure, and complications. Graft and patient survival rates were calculated. Comparison was made to 53 LD recipients transplanted from July 1, 1998, to June 30, 2001 (Group 2) receiving BX, steroids and TAC, without SL. Recipients of deceased donor kidneys were excluded because of variability in kidney quality, ischemic time, and patient management.. Demographics were similar between groups: African Americans, 25% to 35%; mean age 36 years; mean HLA mismatch 3.7. Wound problems and infection were minimal in both groups. Mean serum creatinine and cholesterol and systolic and diastolic blood pressure measured periodically up to 1 year were similar, as was the incidence of rejection. In 25% of patients, SL was discontinued.. Gradual introduction of SL appears to be associated with minimal wound problems. With more aggressive reduction in TAC, better renal function, and better long-term graft survival may be attainable. We currently lower TAC levels to 5 ng/mL by 3 months.

Topics: Adult; Blood Pressure; Cadaver; Creatinine; Drug Therapy, Combination; Female; Histocompatibility Testing; HLA Antigens; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Safety; Sirolimus; Tacrolimus; Tissue Donors

Renal transplants from elderly donors have a high incidence of delayed graft function, which can be increased by the initial use of calcineurin inhibitors. Our purpose was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed introduction of low-dose tacrolimus using elderly donors to elderly recipients.. This observational study involved 13 transplant centers. In total there were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses; preoperatively and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8 ng/mL. The mean follow-up was 8 months.. Two grafts were lost due to primary nonfunction and acute rejection and 48 patients (40%) required dialysis due to delayed graft function, although it was generally of short duration (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II). Three patients withdrew from the study, and three died (sepsis, accident, and cardiovascular event). The remaining 111 patients continued follow-up, with a median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients had at least one episode of infection, half of which were urinary tract infections. There were 16 cases of CMV infection.. Based on the initial results, our immunosuppressive regimen seems to offer good short-term renal function while maintaining an acceptable rejection rate and a low incidence of serious infections.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cadaver; Creatinine; Daclizumab; Drug Therapy, Combination; Graft Rejection; Humans; Immunoglobulin G; Kidney Transplantation; Middle Aged; Tacrolimus; Tissue Donors

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.

Topics: Adult; Cadaver; Cyclosporins; Emulsions; Fasting; Female; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Kidney Transplantation; Length of Stay; Living Donors; Male; Tacrolimus; Tissue Donors

To reduce long-term nephrotoxic calcineurin inhibitor dosage, adjunctive sirolimus or mycophenolate mofetil (MMF) was used in a 150-patient, randomized, three-armed trial in cadaveric or human leukocyte antigen non-identical living-donor first renal transplant recipients (n=50/group).. Group A received tacrolimus and sirolimus. Target tacrolimus trough levels postoperatively were 10, 8, and 6 ng/mL at 1 month, 6 months, and 1 year, respectively. Group B received tacrolimus and MMF. Target tacrolimus trough levels were 10 and 8 ng/mL at 1 month and 1 year, with a targeted dose of MMF of 1 g twice daily. Group C received cyclosporine A (CsA) (Neoral, Novartis, Basel, Switzerland) and sirolimus with target CsA trough levels of 225 and 175 ng/mL at 1 month and 1 year. Maintenance sirolimus target trough levels were 8 ng/mL in groups A and C. Each group received daclizumab induction and methylprednisolone maintenance. This first of two companion 1-year reports details demographics, drug-dosing interactions, and rejection.. There were no notable differences in group demographics, but a somewhat less favorable course occurred in group C, despite higher bioavailability of sirolimus in group C versus group A (P<0.001). Acute rejection rates were lower in groups A (4%) and B (4%) combined versus group C (14%) (P=0.03). Histopathologic findings were supported by comparing perioperative with 1-year postoperative protocol biopsies.. This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus.

Topics: Adult; Area Under Curve; Biological Availability; Cadaver; Cyclosporine; Drug Interactions; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Tacrolimus; Time Factors; Tissue Donors

Previous investigations have shown that plasma selenium concentrations are significantly lower in patients with established chronic graft nephropathy (CGN) than in healthy transplant controls. The aims of this study were to determine when in the transplant process low selenium concentrations become apparent and to explore the relationship between selenium levels and risk factors for CGN.. Plasma selenium concentrations were measured in 40 patients (20 receiving cyclosporin, 20 receiving tacrolimus) undergoing transplantation. Samples were obtained immediately before transplantation and at 3, 6 and 12 months after transplantation.. A low plasma selenium concentration was found in 30 patients at the time of transplantation but this had normalized in the majority of patients by 3 months. Plasma selenium concentrations at 3, 6 and 12 months were significantly higher than baseline values for both treatment arms, but were significantly lower at 3 months in patients who experienced either clinical acute rejection (CAR) or cytomegalovirus (CMV) infection during the preceding months.. Low plasma selenium concentrations are common at the time of transplantation but appear to normalize thereafter. The identification of low selenium levels in patients who experience CAR or CMV (two important risk factors for clinically apparent CGN) suggests that the relationship between selenium and CGN warrants further investigation.

Topics: Adolescent; Adult; Aged; Cadaver; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Peripheral Nervous System Diseases; Selenium; Tacrolimus

Balancing the risk of acute rejection (AR) with drug-induced toxicities complicates the selection of the optimal immunosuppressive regimen, especially in the high-risk renal transplant recipient. This study was designed to determine the optimal dosage combinations of tacrolimus and sirolimus in a high-risk cadaveric renal transplant population.. Primary cadaveric renal transplant recipients were randomly assigned to receive either standard tacrolimus (trough levels of 10-15 ng/mL) plus reduced sirolimus (trough levels of 5-10 ng,mL) (Group I) or to receive reduced tacrolimus (trough levels of 5-10 ng,mL) plus standard sirolimus (trough levels of 10-15 ng/mL) (Group II). All patients received Thymoglobulin induction and steroids.. Thirty-nine (16 in Group I and 23 in Group II) high-risk renal transplant recipients (100% cadaveric donors, 79% African-American recipients, and 59% delayed graft function) are the subjects of this report. At 6 months, the patient survival rate was 94 and 100% and the graft survival rate was 94 and 83% in Groups I and II, respectively. The incidence of biopsy-proven AR was 6 and 5% in Groups I and II, respectively. Eight patients (50%) in Group I required discontinuation of tacrolimus, seven because of biopsy-proven tacrolimus nephrotoxicity and one secondarily to interstitial pneumonitis. Wound complications were the most frequent adverse event reported in both groups.. The combination of tacrolimus and sirolimus was associated with a low risk of AR in this cohort of high-risk renal transplant recipients. However, 50% of patients who received standard tacrolimus and reduced sirolimus combination had to be discontinued from the regimen because of biopsy-proven nephrotoxicity. These preliminary results provide evidence that sirolimus should not be added to tacrolimus without dosage adjustments. We have discontinued recruitment of patients to the standard tacrolimus and reduced sirolimus combination and we have tightened our criteria for selection of marginal donor kidneys with our high-risk renal transplant recipients.

Topics: Cadaver; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Risk; Sirolimus; Survival Rate; Tacrolimus

This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation.. Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared.. The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4 +/-20.0 mL/min vs. 50.5 +/-20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications).. Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Topics: Adult; Cadaver; Calcineurin Inhibitors; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Safety; Sirolimus; Tacrolimus

In an attempt to reduce both initial and long-term (nephrotoxic) calcineurin inhibitor maintenance dosage and totally eliminate maintenance corticosteroids, alemtuzumab (Campath-1H) was used as induction therapy in first cadaver and non-HLA-identical living donor renal transplantation.. Forty-four de novo renal allograft recipients were treated with Campath-1H (0.3 mg/kg) on days 0 and 4 postoperatively, preceded by methylprednisolone boluses. Maintenance target 12-hr tacrolimus trough levels of 5 to 7 ng/mL were operational from the outset as well as (reduced) mycophenolate mofetil dosage of 500 mg twice daily. No corticosteroids were planned to be given after the first week postoperatively.. With a median follow-up of 9 (range, 1-19) months, patient and graft survival rates are each at 100%. Biopsy-proven acute rejection was diagnosed in four patients. Infections requiring hospitalization developed in four patients. Thirty-eight recipients remain without the need for long-term corticosteroid therapy.. In an early assessment, the combination of Campath-1H, low dosing of tacrolimus and mycophenolate mofetil, and avoidance of maintenance corticosteroid use seems to be safe and effective for kidney transplant recipients. Long-term outcomes will be reported in the future.

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Cadaver; Creatinine; Drug Therapy, Combination; Ethnicity; Female; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Injections, Intravenous; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Tissue Donors

Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), or cyclosporine (Neoral; CsA) + MMF. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function (DGF). Patients were followed-up for 3 years.. The results at 3 years corroborate and extend the findings of the 2-year results. Patients with DGF treated with TAC+MMF experienced an increase in 3-year allograft survival compared with patients receiving CsA+MMF (84.1% vs. 49.9%, P=0.02). Patients randomized to either treatment arm containing TAC exhibited numerically superior kidney function when compared with CsA. During the 3 years, new-onset insulin dependence occurred in 6, 3, and 11 patients in the TAC+MMF, CsA+MMF, and TAC+AZA treatment arms, respectively. Furthermore, patients randomized to TAC+MMF received significantly lower doses of MMF as compared with those who received CsA+MMF.. All three immunosuppressive regimens provided excellent safety and efficacy. However, the best results overall were achieved with TAC+MMF. The combination may provide particular benefit to kidney allograft recipients with DGF. In patients who experienced DGF, graft survival was better at 3 years in those patients receiving TAC in combination with either MMF or AZA as compared with the patients receiving CsA with MMF.

Topics: Acute Disease; Azathioprine; Cadaver; Creatinine; Cyclosporine; Drug Therapy, Combination; Florida; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Hyperglycemia; Kidney Transplantation; Mycophenolic Acid; Postoperative Complications; Probability; Racial Groups; Survival Analysis; Tacrolimus; Time Factors; Tissue Donors

The aim of the study was to elucidate whether cyclosporine- and tacrolimus-based immunosuppression impairs tubular reabsorption of phosphate after kidney transplantation. Sixty cadaveric allograft recipients were included in the study. Forty patients receiving triple immunosupression with cyclosporine, azathioprine, and prednisone were studied for 1, 6, 12 months (groups A1 and A2, 20 patients) and for 24, 30, and 36 months (groups B1 and B2, 20 patients) after transplantation. Twenty patients who received tacrolimus with steroid withdrawal after 3 months were included in the study (group C). Recipients from groups A2 and B2 were treated additionally with vitamin D and calcium carbonate. Serum iPTH, 25-OHD, 1.25(OH)(2)D concentrations were determined, and TRP (mmol/L) and TmP/GFR (mmol/L) were calculated using Walton-Bijvoet nomogram. Higher values of total calcium serum concentration in group A were detected. Lower inorganic phosphate serum concentrations were detected in groups A and C, in contrast to group B where they remained within normal values. TmP/GFR values were significantly higher in group C in the first and third examination in comparison with patients of group A. Moreover, TRP index values were significantly higher than analogous values of groups A and B. Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared to cyclosporine-treated recipients. No correlation between iPTH, 25-OHD, 1,25(OH)(2)D concentration, and tubular dysfunction parameters was observed. Amelioration of phosphate handling, in spite of hyperparathyroidism intensity, can follow early steroid avoidance.

Topics: Adolescent; Adult; Cadaver; Calcium Carbonate; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney Tubules; Male; Middle Aged; Phosphates; Retrospective Studies; Tacrolimus; Vitamin D

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Blood Glucose; Cadaver; Cyclosporine; Daclizumab; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Histocompatibility Testing; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Lipids; Living Donors; Male; Middle Aged; Tacrolimus; Tissue Donors

Topics: Adrenal Cortex Hormones; Cadaver; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Mycophenolic Acid; Prospective Studies; Tacrolimus; Time Factors; Tissue Donors

Topics: Adrenal Cortex Hormones; Azathioprine; Cadaver; Cholesterol; Creatinine; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Kidney Transplantation; Postoperative Complications; Spain; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients.. Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months.. At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05).. Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significant improvement in efficacy.

Topics: Adrenal Cortex Hormones; Adult; Cadaver; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Survival Analysis; Tacrolimus; Time Factors; Treatment Outcome

A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years.. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years.. The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF.. All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Topics: Administration, Oral; Adolescent; Adult; Antilymphocyte Serum; Azathioprine; Black People; Cadaver; Child; Cross-Over Studies; Cyclosporine; Diabetes Mellitus; Drug Monitoring; Drug Therapy, Combination; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Insulin; Kidney Function Tests; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Mycophenolic Acid; Postoperative Complications; Survival Rate; Tacrolimus; Time Factors; Tissue Donors; United States; White People

Topics: Cadaver; Cohort Studies; Cyclosporine; Graft Survival; Heart Arrest; Humans; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Retrospective Studies; Tacrolimus; Tissue Donors

Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation.. A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year.. There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups.. All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

Topics: Adult; Azathioprine; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Prospective Studies; Tacrolimus

Tacrolimus (FK506) is a safe and effective treatment for the prevention of rejection of renal allografts. Mycophenolate mofetil (MMF) has been used as adjunct immunosuppressive therapy with cyclosporine and corticosteroids for the same purpose. The objective of this study was to investigate the safety and efficacy of FK506 and MMF in renal transplant recipients.. After cadaveric renal transplant, patients were randomized to receive tacrolimus in combination with either azathioprine (AZA, n=59), MMF 1 g/day (n=59), or MMF 2 g/day group (n=58). Patients were followed for 1 yr posttransplant for the incidence of biopsy-confirmed acute rejection, patient and graft survival, and adverse events.. Tacrolimus doses and trough concentrations were similar between treatment groups at all time points; 80% of patients were maintained within a range of 5.0-13.9 ng/ml at 12 months posttransplant. The mean dose of MMF decreased in the 2 g/day group to 1.5 g/day by 6 months posttransplant, primarily due to gastrointestinal GI-related disorders. The incidence of biopsy-confirmed acute rejection at 1 year was 32.2%, 32.2%, and 8.6% in the AZA, MMF 1 g/day, and MMF 2 g/day groups, respectively (P<0.01). The use of antilymphocyte antibodies for the treatment of rejection was comparable across treatment groups. The incidence of most adverse events was similar across treatment groups and comparable with previous reports. The overall incidence of posttransplant diabetes mellitus was 11.9%, with the lowest rate observed in the MMF 2 g/day group (4.7%), and was reversible in 40% of patients. The incidence of malignancies and opportunistic infections was low and not different across treatment groups.. Tacrolimus in combination with an initial dose of MMF 2 g/day is a very effective and safe regimen in cadaveric kidney transplant recipients.

Topics: Acute Disease; Adult; Azathioprine; Cadaver; Diabetes Mellitus; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Treatment Failure; Treatment Outcome

Topics: Adult; Cadaver; Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Tacrolimus; Tissue Donors

Topics: Acute Disease; Adult; Aged; Cadaver; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Risk Assessment; Risk Factors; Survival Rate; Tacrolimus; Tissue Donors; Treatment Outcome

Topics: Adolescent; Adult; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Survival Rate; Tacrolimus; Tissue Donors

Topics: Adult; Aged; Azathioprine; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Prednisone; Tacrolimus; Time Factors; Tissue Donors

Topics: Adult; Azathioprine; Cadaver; Cause of Death; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Prednisolone; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

Topics: Adult; Age Factors; Aged; Cadaver; Female; Follow-Up Studies; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Survival Rate; Tacrolimus; Time Factors; Tissue Donors; Treatment Outcome

Topics: Adolescent; Adult; Antilymphocyte Serum; Azathioprine; Cadaver; Child; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Heart Arrest; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Methylprednisolone; Middle Aged; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

We performed a prospective randomized trial to compare the efficacy and safety of tacrolimus (FK506) versus cyclosporine (CSA) in black primary cadaveric renal transplant (CRT) recipients.. Between December 1994 and February 1997, 35 black primary CRT recipients were enrolled in this trial. All patients received 7 days of induction therapy with OKT3. Fourteen patients received FK506 and prednisone only. Twenty-one patients received CSA, azathioprine, and prednisone. The two groups were comparable in terms of age, gender, plasma renin activity, human leukocyte antigen mismatches, and cause of renal failure.. Patient and graft survival were 12 of 14 (86%) for the FK506 group and 20 of 21 (95%) for the CSA group (P = 0.71). Three patients died owing to cardiac events with functioning grafts. Acute rejection was 2 of 14 (14%) for the FK506 and 8 of 21 (38%) for the CSA group (P = 0.25). Two other patients on CSA were converted to FK506 as rescue for OKT3-resistant rejection. Mean serum cholesterol at 1 year was 198 +/- 45 mg/dL for the FK506 group and 244 +/- 49 mg/dL for the CSA group (P = 0.03). Mean serum creatinine at 1 year was 1.39 +/- 0.38 mg/dL for the FK506 group and 1.94 +/- 0.64 mg/dL for the CSA group (P = 0.02).. Patient and graft survival were similar in both groups at 1 year posttransplant. Although statistically not significant, the incidence of acute rejection was lower in the FK506 group. Furthermore, FK506-treated patients had significantly lower serum creatinine and cholesterol levels at 1 year posttransplant.

Topics: Adult; Azathioprine; Black People; Cadaver; Cyclosporine; Female; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Prednisone; Prospective Studies; Tacrolimus; Transplantation Immunology; Treatment Outcome

Topics: Adrenal Cortex Hormones; Antilymphocyte Serum; Cadaver; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Hyperglycemia; Immunosuppressive Agents; Incidence; Kidney Transplantation; Mycophenolic Acid; Postoperative Complications; Tacrolimus; Tissue Donors

Topics: Adolescent; Adult; Aged; Cadaver; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Risk Factors; Tacrolimus; Time Factors; Tissue Donors

Topics: Adult; Azathioprine; Cadaver; Dopamine; Drug Administration Schedule; Furosemide; Humans; Immunosuppressive Agents; Kidney Transplantation; Mannitol; Methylprednisolone; Prospective Studies; Tacrolimus; Tissue Donors

Topics: Adolescent; Adult; Blood Transfusion; Cadaver; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Methylprednisolone; Middle Aged; Postoperative Complications; Prednisolone; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

Topics: Adult; Cadaver; Cyclosporine; Drug Therapy, Combination; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Prospective Studies; Tacrolimus; Time Factors; Tissue Donors

Topics: Bias; Black People; Cadaver; Cross-Over Studies; Cyclosporine; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Follow-Up Studies; Graft Survival; Humans; Hypoglycemic Agents; Immunosuppression Therapy; Immunosuppressive Agents; Insulin; Kidney Transplantation; Postoperative Complications; Survival Rate; Tacrolimus; Time Factors; Tissue Donors; United States; White People

We assessed the frequency and costs of hospitalizations in patients receiving tacrolimus (FK506) compared with patients receiving cyclosporine A for immunosuppression during 1 year after kidney transplantation. Four hundred twelve cadaveric kidney transplant recipients were randomized onto a phase III, prospective, multicenter, clinical trial. Hospital billing data were collected for 1 year posttransplantation. Total inpatient costs were calculated from billed charges and standardized to 1995 US dollars. Medical resource utilization rates and inpatient costs were compared between treatment groups using unpaired Student's t-tests. Complete billing data (transplantation and all posttransplantation hospitalizations) were available for 65% (268 of 412) of the study patients. Among tacrolimus and cyclosporine patients with complete billing data, the rates of allograft rejection were 32% and 47%, respectively (P=0.009), and the rates of rehospitalization during the year after transplantation were 53% and 63%, respectively (P=0.080). The mean per-episode rehospitalization costs were significantly lower among tacrolimus-treated patients compared with cyclosporine-treated patients ($7,495 v $11,497; P=0.031), and the mean total rehospitalization costs were significantly lower in the tacrolimus group compared with the cyclosporine group ($8,550 v $14,869; P=0.029). In addition, the total 1-year hospitalization costs (including transplantation and posttransplantation hospitalizations) were significantly lower in the tacrolimus group compared with the cyclosporine group ($53,435 v $61,191; P=0.046). Compared with cyclosporine-based immunosuppression, tacrolimus-based immunosuppression for kidney transplant recipients was associated with a significantly lower rate of rejection, which was associated with significantly lower per-episode rehospitalization costs, lower total 1-year rehospitalization costs, and lower total 1-year hospitalization costs.

Topics: Adult; Cadaver; Cyclosporine; Female; Georgia; Graft Rejection; Health Resources; Hospital Charges; Hospitalization; Humans; Immunosuppressive Agents; Kidney Transplantation; Length of Stay; Male; Middle Aged; Patient Readmission; Prospective Studies; Tacrolimus; Transplantation, Homologous

Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants.. A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection.. One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients.. Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.

Topics: Acute Disease; Adult; Antilymphocyte Serum; Cadaver; Cause of Death; Clinical Protocols; Creatinine; Cross-Over Studies; Cyclosporine; Diabetes Mellitus; Female; Graft Rejection; Humans; Immunosuppressive Agents; Insulin; Kidney Transplantation; Male; Patient Selection; Regression Analysis; Tacrolimus

Topics: Antibodies, Monoclonal; Azathioprine; Cadaver; Cyclosporine; Cytomegalovirus Infections; Drug Therapy, Combination; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Methylprednisolone; Patient Readmission; Survival Rate; Tacrolimus; Tissue Donors

Since November 1982, 276 primary cadaveric kidney transplants have been performed using kidneys from non-heart beating donors. Between November 1982 and December 1986, 49 transplant patients were treated with cyclosporine and steroid immunosuppressive therapy (CSA regimen). Twenty-seven patients were treated with low dose cyclosporine (initial dosage, 4 mg/kg/day), steroid therapy, and a 21-day course of 500 mg/day antilymphocyte globulin (ALG 1 regimen) between January 1987 and December 1987. Seventy-nine patients were treated with low dose cyclosporine (initial dosage, 6 mg/ kg/day), steroid therapy, and a 14-day course of 1,000 mg/day antilymphocyte globulin (ALG 2 regimen) between January 1988 and June 1990, and 85 patients were treated with low dose cyclosporine (initial dosage, 6 mg/ kg/day), steroid therapy, and a 14-day course of 1,000 mg/day antilymphocyte globulin followed by 2 mg/kg/day mizoribine (ALG 3 regimen) between July 1990 and May 1995. Ten patients, who showed hypersensitivity to antilymphocyte globulin therapy, were treated with low dose cyclosporine, steroid therapy, and mizoribine. Finally, 26 patients were treated with FK506 and steroid therapy (FK506 regimen) between June 1990 and February 1992. Graft survival was 78% at 1 year, 69% at 3 years, 63% at 5 years, and 51% at 10 years in the CSA regimen group and 67% at 1 year, 52% at 3 years, and 48% at 5 years in the ALG 1 regimen group. It was 85% at 1 year, 70% at 3 years, and 62% at 5 years in the ALG 2 regimen group and 87% at 1 year and 67% at 3 years in the ALG 3 regimen group. In the FK506 regimen group, graft survival was 92% at 1 year and 80% at 3-5 years. Never-functioning grafts were observed in 3 CSA patients (6%), 1 ALG 1 patient (4%), 3 ALG 2 patients (4%), 3 ALG 3 patients (4%), and 1 FK506 patient (4%). These results indicate that low dose cyclosporine (initial dosage, 6 mg/kg/day), steroid therapy, and a 14 day course of antilymphocyte globulin therapy is beneficial for cadaveric renal transplant patients receiving kidneys from non-heart beating donors; FK506 and steroid therapy might be more effective than cyclosporine based immunosuppressive therapies even in such patients.

Topics: Adolescent; Adult; Antilymphocyte Serum; Cadaver; Cyclosporine; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Steroids; Tacrolimus; Tissue Donors

Topics: Adult; Amylases; Biomarkers; Blood Glucose; Cadaver; Creatinine; Cyclosporine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Pancreas Transplantation; Recurrence; Tacrolimus; Time Factors; Tissue Donors; Urine

Topics: Bacterial Infections; Blood Pressure; Cadaver; Cyclosporine; Drug Monitoring; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Kidney Transplantation; Male; Mycoses; Patient Selection; Postoperative Complications; Prednisolone; Tacrolimus; Time Factors; Tissue Donors; Virus Diseases

Previous clinical evaluation of FK506 in renal transplantation has demonstrated equivalent patient and graft survival when compared with cyclosporine-based regimens. However, lower steroid and anti-hypertensive mediation requirements and lower serum cholesterol levels have been seen in patients receiving FK506. In August, 1991, a prospective, randomized trial was begun, comparing FK506/prednisone with FK506/azathioprine/prednisone. Two-hundred-and-four adults were entered into this trial between August 1, 1991, and October 11, 1992. The mean recipient age was 43.8 +/- 13.7 years, with a range of 17.6-78.0 years. Sixty-one (30%) recipients received a 2nd, 3rd or 4th transplant, while 35 (17%) had a PRA greater than 40% at the time of transplant. Thirty-three (16%) of the transplants were in recipients over 60 years of age, Thirteen percent of the kidneys were from living donors; 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hours, and the mean donor age was 34 +/- 2.10 years, with a range from 4 months to 75 years. With a mean follow-up of 9 +/- 4 months, the 1-year actuarial patient survival is 93%; for the two-drug group it is 95%, and for the three-drug group it is 91% (p = NS). One-year actuarial graft survival is 86%; in the two-drug group it is 90%, while in the three-drug group it is 82% (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actuarial Analysis; Adult; Azathioprine; Cadaver; Drug Therapy, Combination; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Postoperative Complications; Prednisone; Prospective Studies; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

For a 4-month period from July to October 1990, 37 primary renal transplant patients were enrolled in the early phase II study of FK 506. An i.v. dose of FK 506 0.075 mg/kg twice a day was administered initially, and then in oral dose of 0.15 mg/kg twice a day followed. Prednisolone was started at 1 mg/kg daily as an additioned drug. Some 32 live related donors with one-mismatched haplotype of HLA and 5 cadaveric donors underwent transplantation. All patients are alive, and all kidney allografts are functioning. A correlation between the trough level of FK 506 in whole blood and acute rejection or adverse events was retrospectively investigated. There was a significant correlation between the trough level in whole blood and acute rejection or renal impairment. In conclusion, the therapeutic dose of FK 506 should be adjusted by monitoring the trough level in whole blood, the range of which might be recommended to be 15-20 ng/ml during the early phase after transplantation.

Topics: Adolescent; Adult; Cadaver; Graft Rejection; Histocompatibility Testing; Humans; Immunosuppressive Agents; Japan; Kidney Transplantation; Living Donors; Methylprednisolone; Middle Aged; Patient Selection; Tacrolimus; Tissue Donors

In kidney transplantation, immunotherapy with thymoglobulin (rATG) has been used to down-regulate the patient immune system. rATG is a powerful immunobiologic drug used to deplete lymphocytes to prevent early acute rejection. The aim of this research was to evaluate the effects of immunotherapy by rATG on graft suvival during a 9-year period in kidney-transplanted patients with different immunological profiles.. A sample of 469 patients were allocated into four groups (G) based on immunological risk of rejection: G1, low risk, not sensitized recipients, solid-phase immunoassay with single antigen beads (SPI-SAB) < 10%; G2, medium risk I, sensitized recipients, SPI-SAB ≥ 10 < 50%; G3, medium risk II sensitized (SPI-SAB ≥50%); and G4, high risk, sensitized recipients, SPI-SAB- donor-specific antibody positive (DSA+). Only patients from G3 and G4 received immunotherapy.. Of 255 patients who received a kidney from a living donor (LD), 42 (16.47%) from all groups (G) had T-cell-mediated rejection (TCMR) and four (G1) lost their grafts, 8 (3.14%) had antibody-mediated rejection (AMR), and two lost their graft in G1 and G4. Of 214 patients who received a kidney from deceased donors (DD), 37 (17.29%) had TCMR with one lost graft in G1. AMR was shown in 13 (6.07%) patients, with three losses observed in G2. Statistical differences between the groups in the 9-year graft survival rate were found only in the comparison of G1 versus G2 (P = 0.005) and G2 versus G4 (P = 0.047) for DD. For LD, no statistical differences were found.. This clinical retrospective study shows that immunotherapy induction was associated with improvement of outcomes, graft function, and survival in patients treated with immunotherapy in comparison with patients who did not received induction therapy. These findings strongly suggest that immunotherapy should be used for all patients transplanted with kidneys from deceased donors.

Topics: Adult; Age Factors; Antilymphocyte Serum; Cadaver; Cyclosporine; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Immunotherapy; Kidney Transplantation; Living Donors; Maintenance Chemotherapy; Male; Methylprednisolone; Mycophenolic Acid; Retrospective Studies; Risk; Sex Factors; Sirolimus; Survival Rate; T-Lymphocytes; Tacrolimus; Time Factors; Treatment Outcome

Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center.. 246 KT were performed at our center between 01/2012 and 12/2015 and 100 KTR obtained from a DD were analyzed; 24% harbored DSA by SAB assay, MFI values >500 were considered positive. All recipients received thymoglobulin induction and generic tacrolimus-based maintenance therapy. Graft biopsies were performed by protocol on months 3 and 12 as well as per indication. The incidence of AMR and ACR was correlated with the existence of pretransplant DSA.. Overall, 34% of patients developed an acute rejection episode, 54.2% in the DSA group versus 27.6% in the non-DSA group (p=0.032), and most of these events were detected as subclinical conditions in protocol biopsies. AMR events developed in 33.3% and 19.7% (p=0.176) in the DSA and the non-DSA groups, respectively. ACR events were found in 16.6% and 6.6% (p=0.127) in the DSA and non-DSA groups, respectively. Graft function was similar between groups at the end of the 1st year posttransplant and no immunological graft loss occurred.. Despite the use of depleting induction therapy and adequate tacrolimus trough levels along with MMF and steroids, a high rate of rejection events was observed during the first year post-transplantation.

Topics: Acute Disease; Adult; Aged; Antibody-Dependent Cell Cytotoxicity; Antilymphocyte Serum; Blood Grouping and Crossmatching; Cadaver; Cohort Studies; Female; Follow-Up Studies; Graft Rejection; HLA Antigens; Humans; Immunosuppressive Agents; Incidence; Isoantibodies; Kidney Transplantation; Male; Middle Aged; Tacrolimus

To study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors.. The clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors.. Sixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05).. The pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy.

Topics: Adult; Age Factors; Biopsy; Cadaver; Child; Graft Rejection; Humans; Immunohistochemistry; Immunosuppressive Agents; Infarction; Kidney; Kidney Transplantation; Kidney Tubules; Necrosis; Tacrolimus; Transplantation, Homologous; Treatment Outcome

ABO-incompatible liver transplantation (ILT) was formerly contraindicated because of the increased risk of antibody-mediated humoral graft rejection due to preformed anti-A/-B antibodies on recipient endothelial cells. A 2.5-year-old girl with end-stage liver disease underwent cadaveric donation ILT because of acute liver failure and esophageal variceal bleeding before transplantation. The patient's blood type was A Rh (-) and the donor's blood type B Rh (+). The operation and postoperative course were uneventful. The immunosuppression consisted of steroids, and tacrolimus was initiated on the day of the surgery. The patient's hemoglobin level did not change, and direct Coombs test performed daily was consistently negative. Anti-B titer was observed at a maximum of 1/8. The patient was followed up during the first year. This case of ILT from a cadaveric donor is significant because the 2.5-year-old recipient did not experience any complications after undergoing routine immunosuppressive treatment.

Topics: ABO Blood-Group System; Blood Group Incompatibility; Cadaver; Child, Preschool; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Tacrolimus

The success of an immunosuppressive drug therapy depends on the extent of exposure to the drugs (the blood levels and duration), which is measured as the area under the curve (AUC). Tacrolimus shows considerable variability in its pharmacokinetics, with poor correlation between the tacrolimus trough level and systemic exposure, as measured by the AUC of concentration time. Monitoring trough levels helps not only in reducing nephrotoxiicity but also in reducing the chances of acute rejection; although there is no international consensus, the trough concentration is used to determine dosing and the AUC for calculating the exposure of the patient to the drug. The major objective of this study was to find the best sampling time for an abbreviated AUC0-6 (area under the concentration time curve) to predict the total body exposure to tacrolimus in adult renal transplantation recipients.. The study involved retrospective analysis of 14 renal transplant patients (2 female and 12 male) that were on triple immunosuppressive therapy, methyl prednisolone, mycophenolate mofetil and tacrolimus. To determine trough concentrations, blood samples were collected before administration of tacrolimus (0 h) and at fixed time points of 2 h, 4 h and 6 h after administration of oral tacrolimus and analyzed in duplicate by microparticle enzyme immunoassay. AUC0-6 was determined using the linear trapezoidal rule. The association between the blood concentration and AUC6 were evaluated by the Pearson correlation coefficient. All statistical analyses were performed using the SPSS software (IBM Corp., NY, USA) program.. Trough levels were fairly consistent at 7.9-18 ng·h/mL in all the patients included in this study, and this did not show variation with age or sex. The AUC0-6 was higher [202-290 ng/mL at 3-8 mg bis-daily (b.d.) dosage] in patients who received kidneys from cadavers compared to recipients from live donors (60.5-171 ng/mL at 3-8 mg b.d. dosage), but the clinical significance of this is not known. The highest AUC0-6 was 246 ng/mL, observed at 4.5 mg b.d. dosage. Dosages higher than 2 mg b.d. did not result in a noticeable increase in AUC0-6. Peak blood levels of tacrolimus were obtained 4 h after administration.. Trough level determination and a C2, C4 two-point limited sampling strategy may be useful to plan the dosing strategy and estimate the exposure of renal transplant patients to tacrolimus.

Topics: Administration, Oral; Adult; Area Under Curve; Cadaver; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Immunoenzyme Techniques; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors

In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Cadaver; Combined Modality Therapy; Female; Graft Rejection; Histocompatibility; HLA Antigens; Humans; Immunization; Immunoglobulins, Intravenous; Immunosuppressive Agents; Isoantibodies; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Plasmapheresis; Prednisone; Premedication; Reoperation; Rituximab; Tacrolimus; Tissue Donors

Between August 2006 and August 2009, 33 patients with end-stage renal disease were the recipients of kidney transplantations. The donors were living related 29 operations with 4 recipients of 2 deceased donors following accidents with cardiac arrest controlled after permission by the next of kin. We used standard techniques for the donor and recipient operations. All recipients were prescribed 1 dose of alemtuzumab (Campath 1 H 20-30 mg), peroperatively preceded by 500 mg methylprednisolone. In 2 recipients, a second infusion of Campath 1 was administered on postoperative day 2. On postoperative day 3, we prescribed monotherapy with either cyclosporine (n=29) at a starting dose of 7 mg/kg body weight or tacrolimus (n=6) at a starting dose of 0.7 mg/kg body weight. With the exception of patients treated for an acute rejection episode, no patient received steroid therapy. There were 7 acute rejection episodes, which were treated with 3 consecutive daily doses of methylprednisolone (250 mg). The 1-year patient survival was 94% and 2-year graft survival, 84.8%. We concluded that the use of Campath 1 together with a non-steroid maintenance immunosuppressive regimen provided acceptable graft and patient survival in our developing country.

Topics: Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Cadaver; Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Middle Aged; Mongolia; Siblings; Tacrolimus; Tissue Donors; Young Adult

Mycophenolate mofetil (MMF) is routinely used at a fixed dose, but several factors interact to alter the blood level of mycophenolic acid (MPA), resulting in toxicity or treatment failure.. From January 2007 to December 2008, 85 kidney transplantation patients were given a fixed dose of 1.5 g/d of MMF in 12-hour intervals. MPA trough levels were measured on postoperative 1 week, 1 month, 3 months, 6 months, and 12 months.. Mean age of patients was 41 years. Thirty five cases were deceased donor kidney transplantations and 50 were living donor kidney transplantations. Mean trough levels of MPA were 1.04 microg/mL, 1.09 microg/mL, 1.28 microg/mL, 1.83 microg/mL, and 1.69 microg/mL at postoperative 1 week, 1 month, 3 months, 6 months, and 12 months, respectively. Mean trough levels of the subgroup of patients taking cyclosporine were 0.82 microg/mL, 0.94 microg/mL, 1.01 microg/mL, 1.56 microg/mL, and 1.46 microg/mL (n=36). Mean trough levels of the subgroup of patients taking tacrolimus were 1.19 microg/mL, 1.21 microg/mL, 1.56 microg/mL, 2.13 microg/mL, and 2.20 microg/mL (n=49). At 12 months, 31% of all patients experienced one or more opportunistic infections. Eight patients (9.4%) had cytomegalovirus infections, 14 patients (16.5%) had polyomavirus infections, and four patients (4.7%) had parvovirus infections. Ten patients (11.8%) experienced biopsy-proven acute rejection during the follow-up period.. Mean MPA trough levels of patients on 1.5 g/d of MMF reached 1.0 microg/mL within 1 week. Thirty one percent of patients experienced opportunistic infections, and 11.8% of patients had biopsy-proven acute rejections.

Topics: Adult; Cadaver; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors

Cytomegalovirus (CMV) infection is not only a common complication after liver transplantation but also a significant contributing factor to morbidity and mortality. We investigated whether preemptive therapy can prevent CMV syndrome or tissue-invasive CMV disease in an endemic area. Preemptive therapy was initiated when more than 10 positive CMV pp65 antigen-positive cells per 400,000 white blood cells were detected, regardless of clinical manifestations. Intravenous ganciclovir as preemptive therapy was administered daily for 10 to 14 days until negative results were achieved. The incidence of initial CMV antigenemia and CMV syndrome during the posttransplantation period was 49.7% (353/710) and 5.2% (37/710), respectively. One hundred eight-two patients (51.6%) received ganciclovir as preemptive therapy. Patients with CMV antigenemia who received preemptive therapy had high Model for End-Stage Liver Disease score, repeat operation, renal dysfunction, infection, low hemoglobin concentration, low platelet count, low albumin concentration, high international normalized ratio, high total bilirubin value, high aspartate transaminase concentration, and high CMV peak titer. Cytomegalovirus syndrome and tissue-invasive CMV disease were more common in these patients. The survival curve in patients without CMV syndrome was better than that in those with CMV syndrome (P=.000). Patients with more than 10 pp65 antigen-positive cells per 400,000 white blood cells should be treated aggressively with an antiviral agent as preemptive therapy because CMV infection is common in CMV-endemic areas and patients with CMV syndrome demonstrate poor survival rates.

Topics: Adult; Cadaver; Cyclosporine; Cytomegalovirus; Cytomegalovirus Infections; Endemic Diseases; Female; Graft Rejection; Hepatitis B; Hepatitis C; Humans; Immunosuppressive Agents; Korea; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Tacrolimus; Tissue Donors

Advagraf, an extended release formulation of tacrolimus, is administered once daily during the morning fast. Tacrolimus can be safely converted from the twice daily formulation (Prograf) to the same dose (1 mg:1 mg) of once daily dosing tacrolimus (m-Tac). The adverse effects of tacrolimus play important roles in posttransplant cardiovascular risk factors (CVR): hyperglycemia, posttransplant diabetes mellitus, dyslipidemia and hypertension. It has been suggested that avoiding high tacrolimus peak levels minimizes its diabetogenic effects leading to better glycemic control. The aim of our study was to observe the effects of conversion to m-Tac therapy on graft function and CVR among stable transplant kidney recipients.. We selected 2 groups of 20 patients with stable kidney transplantation, who had been treated with Prograf for >6 months with a triple regimen. Group 1 were converted to once daily tacrolimus at the same dose (1 mg:1 mg); whereas in group 2, the therapy was maintained as a twice daily regimen. Blood pressure, creatinine and glomerular filtration rate levels evaluated by the Modification of Diet in Renal Disease formula, as well as urea, total, high- and low-density lipoprotein remained stable between the 2 groups as well as inside group 1 before and after conversion.. After conversion, glycemia and triglyceride values showed significant reductions in group 1 and between the 2 groups. These results were significant, as they may be associated with better long-term graft and patient survivals.

Topics: Adult; Blood Glucose; Cadaver; Cardiovascular Diseases; Cholesterol; Creatinine; Drug Administration Schedule; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney Transplantation; Lipoproteins, HDL; Lipoproteins, LDL; Living Donors; Male; Middle Aged; Risk Factors; Tacrolimus; Tissue Donors; Triglycerides

IL2 receptor antagonist (IL2ra) induction therapy has gained favor due to an excellent safety profile and improved outcomes in randomized trials using cyclosporine-based immunosuppression. However, there have been no large randomized trials or retrospective analyses examining the effect of IL2ra versus no induction using tacrolimus and mycophenolate (TAC/MPA)-based therapy.. A retrospective analysis from the Scientific Renal Transplant Registry of adult, primary kidney transplant recipients from 2000 to 2008 with initial immunosuppression of TAC/MPA and prednisone, who received IL2ra induction therapy or no induction therapy (n=28,686) was performed. The primary outcome was acute rejection at 1 year, and secondary outcomes were graft and patient survival at 1 and 3 years. Multivariable analysis was used to control for factors shown to influence the incidence of acute rejection, and separate analyses were performed for deceased versus living donors.. Acute rejection at 1 year was significantly lower with IL2ra (11.6%) versus no induction therapy (13.0%; P=0.001). One-year (95.7% vs. 95.8%) and 3-year (87.5% vs. 87.8%) graft survival, and 1-year (97.4% vs. 97.5%) and 3-year (92.8% vs. 93.2%) patient survival, was not different between those receiving IL2ra and no induction therapy. On multivariable analysis, the relative risk of acute rejection with IL2ra was 0.90 (95% CI, 0.85-0.96; P=0.001), and the effect was greater in living donors (relative risk, 0.82; P<0.001) than deceased donors (relative risk, 0.95; P=0.23).. The benefit of IL2ra induction with TAC/MPA/prednisone maintenance immunosuppression is less than previously reported due to a low baseline incidence of acute rejection.

Topics: Adult; Cadaver; Cohort Studies; Female; Graft Rejection; Humans; Immunosuppressive Agents; Interleukin-2 Receptor alpha Subunit; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Prednisone; Registries; Retrospective Studies; Tacrolimus; Tissue Donors

Liver transplantation (OLT) in children has seen significant improvements in recent years. Long-term immunosuppressive strategies have focused on avoiding the risks of long-term immunosuppression, particularly nephrotoxicity, de novo malignancy and late infections. Since its introduction in renal transplantation in 1999, sirolimus (SRL) has been used by an increasing number of liver transplant centers. The aim of this study was to review the experience using SRL in pediatric liver transplant recipients at a single center.. Between 1989 and 2006, 318 children underwent OLT including 13 who were converted to SRL therapy because of tacrolimus-related side effects. The indications were posttransplant lymphoproliferative disease (PTLD; n = 11), nephrotoxicity (n = 1), and de novo autoimmune hepatitis (n = 1). One patient with PTLD previously concurrently displayed chronic rejection. SRL dosages ranged between 0.4 and 5 mg/d. The median duration of follow-up was 18 months.. PTLD recurred in 1 patient. There were no episodes of acute rejection. One child developed hyperlipidemia that resolved with diet and medication.. Conversion from tacrolimus to SRL in selected pediatric liver transplant recipients is safe. Children with PTLD may benefit from immunosuppression with SRL after liver transplantation.

Topics: Adolescent; Cadaver; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Infant; Liver Failure; Liver Transplantation; Living Donors; Lymphoproliferative Disorders; Male; Postoperative Complications; Retrospective Studies; Sirolimus; Tacrolimus; Tissue Donors

Obesity is a common problem following renal transplantation. Rimonabant, a cannabinoid-1 receptor blocker, offers a new approach for reducing obesity.. The potential pharmacokinetic interaction between rimonabant and cyclosporine A (CsA, n=10) and tacrolimus (Tac, n=8) was assessed in stable renal transplant recipients 6.2 (0.9-21.7) years posttransplant. A 12-hour pharmacokinetic profile was obtained before and after two months of concomitant treatment with 20 mg rimonabant each morning.. Rimonabant treatment induced a moderate, but significant increase in CsA AUC0-12 (19.8+/-16.1 %, P=0.005). Cmax and C2 values tended to increase whereas C0 remained unaffected. Tac pharmacokinetics was not significantly affected by rimonabant treatment. Eleven of 18 patients experienced adverse events. Two patients reported depressions and one reported severe nightmares.. The effect on CsA pharmacokinetics is probably of marginal clinical relevance since trough concentrations were unaltered, but CsA concentrations should probably be more closely monitored if rimonabant treatment is initiated, preferably by C2 monitoring.

Topics: Adult; Anti-Obesity Agents; Area Under Curve; Cadaver; Cannabinoids; Cyclosporine; Drug Interactions; Female; Humans; Kidney Transplantation; Kinetics; Living Donors; Male; Middle Aged; Piperidines; Pyrazoles; Rimonabant; Tacrolimus; Tissue Donors

The Symphony study compared four immunosuppressant regimens, defined by protocol-specified target drug concentrations. This subanalysis examines actual drug levels and the implications on the interpretation of results.. De novo renal transplant patients (n=1645) were randomized to receive mycophenolate mofetil (2 g/day) and corticosteroids in combination with standard-dose cyclosporine A (CsA; 150-300 ng/mL for 3 months then 100-200 ng/mL), or daclizumab induction and low-dose CsA (50-100 ng/mL), low-dose tacrolimus (Tac; 3-7 ng/mL), or low-dose sirolimus (SRL; 4-8 ng/mL).. Low-dose Tac was significantly superior for renal function, acute rejection, and graft survival at 12 months. Median trough levels of CsA, Tac, or SRL were toward the high end of target ranges in all groups, and 50% to 60% were within target. During weeks 1 to 8, only 6.5% to 11.0% of patients were consistently within target. At week 8, the range of concentrations encompassing 75% of patients on standard-dose CsA was 141 to 321 ng/mL; for low-dose CsA, 62 to 159 ng/mL; for low-dose Tac, 4.3 to 10.0 ng/mL, and for low-dose SRL, 4.4 to 11.2 ng/mL. The protocol-defined target levels were approximately, but not fully achieved.. To replicate the Symphony study results in clinical practice, the protocol-defined drug concentration targets should be aimed for, but the concentrations actually achieved may be regarded as acceptable. Future clinical studies should include measures of how well target drug levels were achieved to better guide further attempts to develop new regimens designed to reduce or eliminate calcineurin inhibitors.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cadaver; Clinical Trials as Topic; Cyclosporine; Daclizumab; Dose-Response Relationship, Drug; Drug Therapy; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Research Design; Sirolimus; Tacrolimus; Tissue Donors

Registry analyses suggest that tacrolimus (TAC)/mycophenolate (MPA) immunosuppression is associated with superior kidney graft survival versus TAC/sirolimus (SRL). Large single-center experience can assist in clarifying these findings, by examining outcomes related to specific utilization practice.. We retrospectively examined the outcomes of 518 consecutive first renal transplants at a single center treated with TAC/SRL (n=307) or TAC/MPA (n=211) with prednisone. Graft and patient survival, acute rejection, and 1-year glomerular filtration rate (GFR) were analyzed by era of transplant (2000-2002 vs. 2003-2006). Changes in TAC/SRL utilization between eras included elimination of the SRL loading dose and a reduction in TAC target trough concentrations.. Three-year graft survival with TAC/SRL was lower when first used (2000-2002) because of a higher incidence of patient death, primarily due to cardiovascular causes. Survival improved from 85.3% to 95.9% between 2000 to 2002 and 2003 to 2006 (P=0.001), with comparable graft and patient survival between TAC/SRL and TAC/MPA cohorts, confirmed following multivariable analysis controlling for donor and recipient factors. Rates of BK virus and acute rejection were comparable, but a higher incidence of hyperlipidemia, anemia, posttransplant diabetes, and a lower 1-year GFR (57.6 vs. 63.1 mL/min, P=0.008) was noted in the TAC/SRL cohort.. These data, as the largest long-term single-center report comparing TAC/SRL with TAC/MPA in kidney transplantation, demonstrate worse patient survival initially with TAC/SRL, with improved outcomes in a later era that were temporally associated with reduced TAC exposure. Differences in cardiovascular risk factors and 1-year GFR highlight the need for further investigation of the optimal utilization of SRL in kidney transplantation.

Topics: Adult; Cadaver; Drug Therapy, Combination; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Factors; Sirolimus; Survival Rate; Tacrolimus; Tissue Donors

Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months.. Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy.. There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group.. CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.

Topics: Adolescent; Adult; Cadaver; Child; Creatinine; Cytochrome P-450 CYP3A; Drug Therapy, Combination; Female; Genotype; Humans; Immunosuppressive Agents; Kidney Transplantation; Kidney Tubules; Male; Middle Aged; Polymorphism, Genetic; Tacrolimus; Tissue Donors; Transplantation, Homologous; Young Adult

Data on free water excretion capacity of renal transplant recipients are scant. The aim of this study was to evaluate the ability of electrolyte free water clearance (E-CH(2)O) by the allograft in renal transplant patients and the effects of various immunosuppressive drugs. Renal transplant recipients with good graft function (creatinine < 1.5 mg/dL) as well as controls were divided into five groups according to their immunosuppressive regimen: group I, azathioprine (n = 15); group II, cyclosporine (n = 28); group III, tacrolimus (n = 28); group IV healthy controls (n = 20); and group V renal transplant donors (n = 16). Following a 12-hour fast, we administered oral water loading (20 mL/kg) with urine collection for 3 hours. We calculated creatinine clearance for 3 hours and E-CH(2)O. No matter which immunosuppressive drug, the E-CH(2)O of recipients (groups I, II, and III) was lower than that of donors or healthy controls. The creatinine clearance of the cyclosporine arm was significantly lower than all of the other groups. Decreased E-CH(2)O in renal transplant patients might be due to diminished water input to the loop of Henle related to subclinical allograft insufficiency as a result of posttransplantation pathology and/or immunosuppressive drug therapy or the transport of water into the extrarenal interstitium as a result of vascular endothelial dysfunction due to the pretransplant uremic milleu.

Topics: Adult; Azathioprine; Cadaver; Creatinine; Cyclosporine; Drinking; Electrolytes; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Metabolic Clearance Rate; Middle Aged; Serum Albumin; Tacrolimus; Tissue Donors; Water

After decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for selected patients with type 1 diabetes mellitus. Between January 2001 and January 2008, 100 patients underwent pancreatic transplantation at our center: 88 simultaneous pancreas-kidney transplantation and 12 pancreas transplantations alone. Pancreas graft management of the exocrine drainage technique involved enteric drainage in 8 (all simultaneous pancreas-kidney) and the bladder in 92 cases. The recipient systemic venous system was used for the pancreas graft venous effluent in all cases. Our overall results have shown that the number of functioning pancreatic grafts was 64 of 100. Graft losses were: rejection (n = 8), venous thrombosis (n = 9), arterial thrombosis (n = 1), or surgical complications such as anastomotic leak (n = 3), perigraft infection (n = 10), pancreatitis of the graft (n = 5). Most cases of pancreatitis (80%) had preservation times exceeding 18 hours. Despite surgical and immunosuppressive complications, our impression was that pancreas transplantation was a highly effective therapy for diabetes mellitus. After 7 years of the program and 100 transplantations, we believe that there is a major role for transplantation in diabetes management.

Topics: Adolescent; Adult; Brazil; Cadaver; Child; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Pancreas Transplantation; Registries; Retrospective Studies; Tacrolimus; Tissue Donors; Treatment Outcome; United States

To clarify the demographic data, outcomes and complications of renal transplantation in children at Srinagarind (university) Hospital.. The authors reviewed the medical records of children with end-stage renal disease (ESRD) who received renal transplantation at Srinagarind Hospital, Khon Kaen, between August 2001 and July 2008.. Eight male and seven female patients were identified Their mean age was 12.8 +/- 3.2 years (range, 5.0-17.6). The major cause of ESRD was a congenital anomaly of the kidneys (53%). All of the children received cadaveric transplantations and none received induction therapy. Triple immunosuppressive drugs comprising cyclosporine, prednisolone and mycophenolate mofetil were administered to 12 patients. Tacrolimus, instead of cyclosporine, was given to three patients who had received a renal transplant since January 2008. The median follow-up time was 15 months (3 to 82 months). The most frequent complication was urinary tract infection (40%). Acute graft loss was found in one patient (6.7%) due to graft infarction. Other complications included herpes viral infection, chronic rejection, acute rejection, severe gingival hyperplasia, myopathy, lymphocele and transitional cell carcinoma of the bladder. Two patients returned to dialysis due to graft infarction and chronic rejection, respectively. The mean serum creatinine at the last follow-up of the remaining cases was 1.2 +/- 0.5 mg/dL (range, 0.6-2.3). All of the patients survived. The 1- and 5-year graft survival rates were 93.3% and 86.7%, respectively.. The present study demonstrates the potential for successful outcomes of pediatric renal transplantation in this resource-limited area.

Topics: Adolescent; Age Factors; Cadaver; Child; Child, Preschool; Cyclosporine; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Intensive Care Units, Pediatric; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Mycophenolic Acid; Postoperative Complications; Prednisolone; Retrospective Studies; Tacrolimus; Thailand

Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Chronic nephrotoxicity due to TAC has been reported to be similar to that of cyclosporine in kidney transplant patients. Since, the severity and influence of chronic TAC nephrotoxicity are not fully elucidated, we studied the clinicohistological characteristics of chronic TAC nephrotoxicity in kidney transplants.. We retrospectively studied the clinicohistological profiles of 15 transplant patients under TAC-based immunosuppression, who were diagnosed as chronic TAC nephrotoxicity by allograft biopsies, showing characteristic arteriolopathy--periodic acid-Schiff PAS--positive hyaline thickening in small arteries--between January 2004 and December 2005. The mean recipient age was 37.3 years and they consisted of 11 men and 4 women. The mean age of their donors was 59.4 years.. The diagnoses of chronic TAC nephrotoxicities were established at an average of 54.7 months postoperatively. The severities of arteriolopathy were moderate in eight cases and severe in eight cases. The mean dosage of TAC at the time of diagnoses was 0.054 mg/kg with mean whole blood trough levels of 5.09 ng/mL, which is recognized to be within the so-called recommended level. Moderate to severe arteriosclerosis of medium-sized arteries were observed in 12 cases (80.0%).. The existence of moderate to severe arteriosclerosis in medium-sized arteries would have the potential of causing chronic TAC nephrotoxicities, rather than the dosage or whole blood trough level of TAC.

Topics: ABO Blood-Group System; Adolescent; Adult; Arteries; Arterioles; Biopsy; Cadaver; Child; Female; Graft Rejection; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Retrospective Studies; Tacrolimus; Tissue Donors; Transplantation, Homologous; Treatment Failure

To assess the significance of antibodies detected by complement-dependent cytotoxicity (CDC), solid phase (SPA) and flow cytometry (FC) assays we compared their predictive value in 354 consecutive cases of deceased-donor kidney transplantation. Pre-transplantation screening of anti-HLA class I and class II antibodies was performed by CDC and SPA. The direct crossmatch between recipients' sera and donors' T and B cells was performed by CDC followed by FC and SPA ("virtual cross-match"). The past history of antibodies displayed by the recipient was not considered a contraindication for transplantation even when it showed DSA. A side-by-side comparison of the correlation between graft loss, history of DSA and cross-match results indicated that sensitivity was 5%, 16% and 17% while specificity was 99%, 93% and 86% in CDC, SPA, FC crossmatches respectively. There was no significant difference between the 3 year survival of primary and secondary kidney allografts. We conclude that screening and cross-matching the sera by CDC provides reliable results and optimizes the patient's chances to receive a transplant. SPA and FC, however, are of great importance for identifying patients which require close monitoring by biopsy and serology for early diagnosis and treatment of acute antibody mediated rejection (AAMR).

Topics: Adrenal Cortex Hormones; Adult; Aged; Cadaver; Cytotoxicity Tests, Immunologic; Female; Flow Cytometry; Graft Rejection; Graft Survival; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Histocompatibility Testing; Humans; Immunosuppression Therapy; Isoantibodies; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Predictive Value of Tests; Sensitivity and Specificity; Tacrolimus

Preoperative reduction of isoagglutinins leads to successful ABO-incompatible (ABOi) renal transplantation. The strategy includes pretransplantation plasmapheresis, more potent immunosuppressive drugs, splenectomy, and anti-CD20 antibody. It has been reported that low isoagglutinin antibody titers posttransplant were observed among ABOi renal transplants with favorable outcome. The isoagglutinin titers may increase slightly when plasmapheresis is discontinued; however, it never returns to the pretreatment level under immunosuppressive therapy. This raises the question of what occurs to the isoagglutinin titer in ABO-compatible renal transplants under maintenance immunosuppressive pharmacotherapy.. We analyzed 10 renal transplant recipients, including seven living and three cadaveric donors. Patients were treated with basiliximab (20 mg) intravenously on day 0 and day 4. Maintenance immunosuppressive therapy involved a calcineurin inhibitor, mycophenolate mofetil, and steroid. Anti-human globulin isoagglutinin titers were routinely examined 1 day before and day 0 and 1, 2, 3, 4, 8, 12, and 24 weeks posttransplant. No ALG or intravenous immunoglobulin or plasmapheresis treatment was provided in the follow-up period.. Our preliminary data showed nearly no influence on isoagglutinin titer levels in 6-month follow-up under maintenance immunosuppressive therapy. In addition, no significant difference in isoagglutinin titer was observed between tacrolimus and cyclosporine groups.. Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.

Topics: ABO Blood-Group System; Agglutinins; Antibodies, Monoclonal; Basiliximab; Cadaver; Creatinine; Follow-Up Studies; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Recombinant Fusion Proteins; Tacrolimus; Time Factors; Tissue Donors

Hepatic dysfunction is an important determinant of the clearance of tacrolimus; however, the impact of reduced hepatic mass in living donor liver transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is not known. AIM.: The aim of the present study is to compare the dosage, concentration and pharmacokinetics parameters of tacrolimus between LDLT and deceased donor liver transplant (DDLT) recipients.. Daily doses used and trough concentrations measured were compared in 12 LDLT and 12 DDLT patients. Multiple blood samples were taken over one dosing interval after oral tacrolimus administration, and pharmacokinetics differences were compared.. The mean tacrolimus dosage in first 14 postoperative days was (0.06 mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower doses used, mean trough concentration was significantly greater in LDLT as compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013). On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr postdose concentration (Clast), and average concentration (Cavg) were significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/-1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4 ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7% greater and clearance, 47.5% lower in LDLT as compared with DDLT.. Although not statistically significant, the dose normalized AUC was 37.7% greater and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus dose reduction of about 30-40% may be prudent in LDLT compared with DDLT recipients.

Topics: Adult; Area Under Curve; Blood Urea Nitrogen; Cadaver; Creatinine; Female; Humans; Immunosuppressive Agents; Liver Diseases; Liver Transplantation; Living Donors; Male; Middle Aged; Tacrolimus; Tissue Donors

The association of tacrolimus (TAC) and mycophenolate mofetil (MMF) in renal transplant patients has diminished the incidence of acute rejection. We evaluated the use of generic TAC and MMF as primary immunosuppression in 6 living related (LR) and 11 cadaveric (C) donor renal transplant recipients (9 men, 8 women) of mean age 37 +/- 12 years (range, 17-56 years) between May 2006 and June 2007. From day 0 all patients received TAC, MMF, and prednisone without antibody induction. They were followed for the development of acute rejection, graft loss, side effects, and mortality. Mean follow-up was 7.6 months (range, 2-15 months). No biopsy-proven acute rejection episodes, graft loss, or recipient deaths were observed. Creatinine levels at the end of the study were 1.90 +/- 1.0 mg/dL (range, 0.62-4.25 mg/dL for C recipients and 1.19 +/- 0.15 mg/dL (range, 0.91-1.35 mg/dL) for LR recipients. Mean systolic and diastolic blood pressures were 130/73 mm Hg with 12 patients (70.5%) on antihypertensive therapy with calcium antagonists and beta-blockers. Mean (range) of total cholesterol, triglycerides, and glucose were 172 (110-244) mg/dL, 139 (69-277) mg/dL, and 89 (63-129) mg/dL, respectively. MMF was suspended in 1 patient due to diarrhea and 1 other because of leukopenia. We observed that generic TAC and MMF yielded effective and safe immunosuppression in terms of mortality, biopsy-proven acute rejection, and graft loss with a low incidence of adverse effects during the study period.

Topics: Adult; Cadaver; China; Drug Administration Schedule; Drug Therapy, Combination; Drugs, Generic; Female; Follow-Up Studies; Humans; Immunosuppression Therapy; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Mycophenolic Acid; Prednisone; Survival Analysis; Tacrolimus; Tissue Donors

Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone.. We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results.. At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001.. Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.

Topics: Adult; Aged; Cadaver; Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Tacrolimus; Tissue Donors

Tacrolimus (Tac) is mainly metabolized in the liver. The aim of this trial was to analyze Tac bioavailability after partial liver transplantation.. A total of 33 patients after right split liver grafting (n=8 living related, LRLT; n=8 cadaver split, CS) or full-size liver transplantation (n=17, FS) were included in this trial. All of them received Tac perorally with an initial dose of 2x5 mg/d. Dose adjustment was performed according to the Tac trough level (T0) with an initial target T0 levels of 12 to 15 ng/mL.. The time to reach target T0 levels tended to be lower (P=.05) in the split liver groups (LRLT: 2.8+/-1.6 days; CS: 2.1+/-0.9 days; FS: 4.5+/-3.2 days). In addition, mean Tac dose to maintain the target T0 level was significantly decreased (P=.01) in the split liver cohorts (LRLT: 5.8+/-1.1 mg/d; CS: 5.5+/-2.5 mg/d; FS: 9.8+/-3.9 mg/d). Only graft weight/standard liver volume ratio (r=.566, P=.02) and graft weight/body weight ratio (r=.709, P=.002) showed significant correlations with Tac maintenance doses in the split liver group.. Peroral Tac bioavailability was significantly higher after partial liver transplantation using the right hepatic lobe compared with full-size transplants. The volume of the split liver graft highly correlated with Tac maintenance therapy and should be used to calculate the most appropriate initial posttransplantation Tac dose.

Topics: Adult; Biological Availability; Body Weight; Cadaver; Female; Hepatectomy; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Male; Middle Aged; Organ Size; Tacrolimus; Tissue and Organ Harvesting; Tissue Donors

We report three pediatric liver transplant recipients receiving tacrolimus immunosuppression presented with vomiting, heme-positive stools and failure to thrive, who had subtotal villous atrophy in their histology because of food protein sensitivity. Case findings and current literature of the casual relationship between tacrolimus and food allergies briefly reviewed.

Topics: Cadaver; Child; Child, Preschool; Duodenitis; Endoscopy; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Tacrolimus; Treatment Outcome

Tacrolimus (Tac), developed in 1990, has been applied as an immunosuppressive agent for liver, heart, and kidney transplantation and is known to have more powerful immunosuppressive effects than cyclosporine (CyA). To evaluate the efficacy of Tac in cadaveric kidney transplants from non-heart beating donors, we present the long-term outcome of patients receiving kidneys with ischemic damage, and compared it with that of CyA. Between July 1990 and December 2000, 55 patients with end-stage renal disease received kidneys from non-heart beating donors (Maastrichy category 3) and were treated with Tac and steroid immunosuppressive therapy. During the same period, we also performed 137 non-heart beating cadaveric renal transplants treated with CyA-based immunosuppressive therapy. The patient survival rate was 98% at 1 yr and 96% at 3-10 yr in the Tac group, and 97% at 1-3 yr, 93% at 5 yr and 85% at 10 yr in the CyA group. The graft survival rate was 91% at 1 yr, 80% at 3 yr, 63% at 5 yr and 34% at 10 yr in the Tac group, and 88% at 1 yr, 75% at 3 yr, 63% at 5 yr and 49% at 10 yr in the CyA group. There was no significant difference in either patient or graft survival rates between the two groups. Acute early rejection in the Tac group was less than that in the CyA group but acute tubular necrosis was the same in both groups. This indicates that Tac is available for cadaveric kidney transplants from non-heart beating donors. In conclusion, Tac is available as an immunosuppressive agent even for kidney transplants from non-heart beating donors.

Topics: Adult; Cadaver; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Ischemia; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Longitudinal Studies; Male; Methylprednisolone; Survival Rate; Tacrolimus; Tissue and Organ Harvesting; Tissue Donors; Treatment Outcome

Acute rejection is a major problem in kidney transplantation. To reduce its likelihood, we investigated the efficacy and safety of an immunosuppressive regimen including tacrolimus, basiliximab, mycophenolate mofetil, and low-dose steroids.. Fifty-seven patients, including 14 pediatric patients, were enrolled in this study. The mean age at the time of transplantation was 33.5 years, and the mean observation period was 8.2 months. The mean trough concentrations of FK at 1, 6, and 12 months posttransplant were 10.2, 6.6, and 6.0 ng/mL, respectively.. All recipients survived without graft loss. The cumulative incidence of acute rejection in adults was 2.3% and 8.4% at 6 and 12 months posttransplant, respectively. Of the adverse events, 11 recipients (19.3%) were positive for CMV antigenemia or had CMV infections. Four recipients (7.0%) exhibited mild hyperglycemia.. Our immunosuppressive regimen demonstrated favorable results, reducing the incidence of acute rejection without causing severe adverse events, especially in adults.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Basiliximab; Cadaver; Child; Child, Preschool; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Living Donors; Male; Middle Aged; Mycophenolic Acid; Recombinant Fusion Proteins; Tacrolimus; Tissue Donors

Acute rejection remains an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may play a predictive role in identifying individuals who are at higher risk of acute rejection with a view to individualizing their immunosuppression. The aim of this study was to investigate any possible associations between acute rejection and certain cytokine polymorphisms.. We genotyped 91 cadaveric renal transplant recipients on tacrolimus-based immunosuppression and 84 of their donors. The cytokine polymorphisms studied were the following: tumor necrosis factor (TNF)-alpha-1032 T/C, TNF-alpha-865 C/A, TNF-alpha-859 G/A, interleukin (IL)1-R1-970 C/T, IL-10 haplotype [-1082, -819, -592], and IL-6-174 C/G.. We found no association between any polymorphism and the incidence of acute rejection. This was true for both the recipient and donor population.. Cytokine polymorphisms did not influence acute rejection in our study. We conclude that in the modern era of immunosuppression cytokine genotyping is not a significant predictor of acute rejection in renal transplantation.

Topics: Adult; Cadaver; Cytokines; Genotype; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Polymorphism, Genetic; Risk Factors; Tacrolimus

The safety and efficacy of tacrolimus (Tac)-based immunosuppressive treatments were studied in 115 pediatric renal transplant recipients (mean follow-up period, approximately 20 months). The acute rejection rate was 22.7% 6 months after transplantation and the steroid-resistant acute rejection rate was 6.4%. The 5-year patient and graft survival rates were 98.6% and 95.9%, respectively. Major adverse effects included infection, ie, cytomegalovirus (CMV) antigenemia (41.7%), renal dysfunction (29.6%), and impaired glucose tolerance (20.9%). The incidences of these adverse events were significantly decreased among patients who had undergone transplantation after March 2000 (n = 43), namely, 30.2%, 18.6%, and 11.6%, respectively.

Topics: Adult; Cadaver; Female; Follow-Up Studies; Glucose Intolerance; Graft Rejection; Humans; Immunosuppressive Agents; Infections; Japan; Kidney Transplantation; Living Donors; Male; Nervous System Diseases; Postoperative Complications; Retrospective Studies; Survival Analysis; Tacrolimus; Time Factors; Tissue Donors

We evaluated the influence of different immunosuppressive regimens on delayed renal graft function and progression of renal function in the first year after transplantation.. Patients were divided into four groups according to the immunosuppressive regimen received: (1) rapamycin (Rap) + mycophenolate mofetil (MMF) + methylprednisolone (MP) + daclizumab (Dmab); (n = 44); (2) tacrolimus (Tac) + MMF + MP + Dmab (n = 39); (3) cyclosporine (CsA) + MMF + MP + basiliximab (Bmab); (n = 30); (4) antithymocyte globulin (ATG) + MMF + MP and CsA after ATG withdrawal (n = 40). Data were analyzed using ANOVA and linear regression. Delayed graft function was defined as the need for hemodialysis posttransplantation.. There were no statistically significant differences between the four groups in terms of gender, time on dialysis before transplantation, histocompatibility, donor age, and cold ischemia time. However, age (49.8, 50.4, 49.8, and 43.5 years, P < .05), panel reactive antibodies (22%, 39%, 27%, 34%, P < .05) and time of delayed graft function (12, 7, 3, 6 days, P < .05) were significantly different between the four groups. The time of delayed graft function depended on the immunosuppressive regimen, as well as donor and recipient age (P < .05). The creatinine clearance demonstrated a statistically significant difference between the four groups in the first month after transplantation (45, 46, 61, 53 mL/min, P < .05), though no further difference was observed at the month 12th.. The type of immunosuppressive therapy seems to substantially influence the time of recovery from delayed renal graft function, even though it does not seem to affect future graft function. Especially Rap, probably due to its potent antiproliferative effects, seems to prolong the length of graft recovery after renal transplantation.

Topics: Adolescent; Adult; Analysis of Variance; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Cadaver; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Regression Analysis; Retrospective Studies; Sirolimus; Tacrolimus; Tissue Donors

Living donors represent 30% of our kidneys for renal transplantation. Laparoscopic nephrectomy is the best surgical procedure to obtain them due to its clear advantages such as low morbidity, less blood supply and donor time in hospital. From March 2002 to August 2004 we performed 50 laparoscopic nephrectomies for renal transplantation. Kidneys were transplanted to recipients receiving tacrolimus 0.1 mg/kg/bid, mycophenolate mofetil 1 g/bid and prednisone 0.5-1 mg/kg/day p.o 48 hours before transplantation. Mean time for surgery was 170 minutes (120-260), warm ischaemia time 3.1 minutes (1.5-10) and cold ischaemia time 1.27 hours (0.85-4). Mean bleeding was 270 cc (100-900) and donor time in hospital 5.5 days (3-9). Four cases required conversion of the laparoscopic procedure to open surgery because of bleeding. 72 hours post-transplant mean plasmatic creatinine was 170 micromol/l. None of the patients suffered delayed graft function. 18% presented acute rejection. Survival of donor and recipient was 100% at 1 year and graft survival was 94% at 1 year (kidney losses were due to acute rejection, severe acute pancreatitis and surgical problem).

Topics: Anti-Inflammatory Agents; Cadaver; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Laparoscopy; Length of Stay; Living Donors; Middle Aged; Mycophenolic Acid; Nephrectomy; Prednisone; Survival Analysis; Tacrolimus; Time Factors; Treatment Outcome

Cyclosporine (CsA) nephrotoxicity is enhanced by sirolimus (SRL). Tacrolimus is perceived to be less nephrotoxic than CsA, and therefore, CsA has been largely replaced by tacrolimus (TAC) when calcineurin inhibitors are used with SRL. We analyzed 44 915 adult renal transplants in the Scientific Renal Transplant Registry (SRTR) from 2000 to 2004. Three thousand five hundred twenty-four (7.8%) patients received a baseline immunosuppressive regimen of TAC/SRL, with an inferior overall (log-rank p<0.001) and death-censored graft survival (p<0.001) as compared to TAC/MMF (N=27 007). This effect was confirmed in multivariate Cox models; the adjusted hazard ratio (AHR) for overall graft loss with TAC/SRL was 1.47 (95% CI=1.32, 1.63) and for CsA/SRL 1.38 (95% CI=1.20, 1.59) relative to TAC/MMF. These effects were most apparent in high-risk transplants. Six-month acute rejection rates were low (11.5-12.6%) and not different between groups. In summary, national data indicate that TAC/SRL as compared to TAC/MMF is associated with significantly worse renal allograft survival in all subgroups of patients and, in particular, higher-risk transplants. These results have to be interpreted in the context of the inherent limitations of any retrospective database analysis and evaluated in context with data from prospective clinical trials.

Topics: Adolescent; Adult; Aged; Cadaver; Child; Child, Preschool; Clinical Trials as Topic; Cohort Studies; Databases as Topic; Drug Therapy, Combination; Graft Survival; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Living Donors; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Proportional Hazards Models; Retrospective Studies; Sirolimus; Tacrolimus; Time Factors; Transplantation Conditioning; Treatment Outcome

New onset diabetes mellitus (NODM) affects kidney transplantation outcome. Several risk factors, including immunosuppressive drug levels, are related with NODM development. This analysis evaluates the incidence and risk factors of NODM in kidney transplant patients receiving tacrolimus, taking into account 6-month blood levels and concentration-dose ratios (CDRs). Seventy-six patients under tacrolimus therapy who received a cadaveric renal transplant in our centre and with graft survival higher than 1 year were included in the study. NODM was defined as two fasting plasma glucose values > or =126 mg/dl or symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dl throughout the first year. We examined previously reported variables related with NODM development. The incidence of NODM at 12 months was 27.6%. Risk factors for NODM included older age, higher first tacrolimus level, higher body mass index and lower first year weight gain. In multivariate analysis, the first year occurrence of NODM was significantly determined by the first tacrolimus blood level >20 ng/ml and age older than 50 years. CDR remains significantly higher in NODM throughout the 6 months. Older age and a high first tacrolimus blood level are associated with the development of NODM during the first year after kidney transplantation. NODM patients show higher CDR during the first 6 months.

Topics: Adult; Aged; Blood Glucose; Cadaver; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Humans; Immunoassay; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome

We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 +/- 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology.

Topics: Analysis of Variance; Antilymphocyte Serum; Cadaver; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Hepatitis C, Chronic; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Function Tests; Liver Transplantation; Male; Middle Aged; Prednisone; Probability; Proportional Hazards Models; Retrospective Studies; Severity of Illness Index; Survival Rate; Tacrolimus; Transplantation Immunology

The aim of this study was to determine the tacrolimus blood levels in recipients of living donor liver transplants (LDLT) compared with recipients who undergo whole cadaveric liver grafts and to correlate the tacrolimus trough levels with the 12-hour area under the concentration (AUC) curve. From June 2002 to June 2003, the 10 LDLT were prospectively compared with 11 cadaveric transplants. The main immunosuppression was tacrolimus plus steroids. Intraoperative methylprednisolone was administered to all cadaveric organ recipients and only 6 of the 10 LDLT. Median tacrolimus trough levels at day 10 were 14.1 ng/mL for the LDLT group and 9.1 ng/mL for the CLT group (P = NS). The median tacrolimus AUC at day 10 were 185.2 ngxh/mL and 148.1 ngxh/mL for the LDLT group and the cadaveric group, respectively (P = NS). Median tacrolimus trough levels at day 2 were 24.3 ng/mL versus 9.9 ng/mL in the LDLT recipients with and without steroids, respectively (P < .05). Also, median tacrolimus AUC at day 2 were 239 ngxh/mL and 179.7 ngxh/mL when we compared LDLT recipients with and without steroids (P = NS). A significant correlation was observed between tacrolimus trough levels and AUC in the LDLT group (C.C. = 0.936; P < .0001). In conclusion, LDLT recipients display higher tacrolimus blood levels in comparison with cadaveric liver recipients, with a good correlation between tacrolimus trough levels and AUC. Intraoperative steroid administration induces higher tacrolimus levels in LDLT recipients.

Topics: Adrenal Cortex Hormones; Cadaver; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Tacrolimus; Tissue Donors

Safety and tolerability of basiliximab in renal transplantation have been proven in different immunosuppressive regimens. Few informations are available about the association of basiliximab with tacrolimus and steroids. We present a retrospective analysis performed in Caucasian cadaveric renal transplant recipients, comparing a basiliximab, tacrolimus and steroids induction protocol (GrA: 51 patients) with a tacrolimus and steroids protocol (GrB: 46 patients). A significant decrease in acute rejection rate in the first 3 months (2.0% vs. 17.4%; p < 0.01) was noted. Interestingly, the recipients in GrA were at major immunologic risk for the younger age of recipients, the greater number of mismatches and the higher rate of second transplants. The hospitalization times resulted reduced of 5.3 d in GrA vs. GrB (20.8 d vs. 26.1 d; p < 0.05). The adverse events patterns and profiles were similar in the two treatments groups. One patient in each group had a post-transplant lymphoprolipherative disorder. No significant difference was found in patient and graft survival. According to the results of this study, in a Caucasian adult population, basiliximab in association with tacrolimus and steroids is a safe and efficacious tool for acute rejection prevention and it is cost saving by reducing the hospitalization times.

Topics: Acute Disease; Adolescent; Adult; Antibodies, Monoclonal; Basiliximab; Cadaver; Drug Therapy, Combination; Female; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Length of Stay; Male; Methylprednisolone; Recombinant Fusion Proteins; Retrospective Studies; Tacrolimus; White People

Clinical data on the potential immunologic impact of portal (PD) vs. systemic (SD) venous pancreas graft drainage on outcome remains controversial. We reviewed the UNOS database to study the effect of PD vs. SD on the incidence of kidney graft rejection and survival in first cadaveric simultaneous pancreas-kidney (SPK) recipients transplanted 1994-2001. We studied three groups: all SPK (n=6629, 13% PD) (group I), SPK on tacrolimus (n=3563, 17% PD) (group II), and SPK on tacrolimus performed at centers with significant PD experience (n=948, 46% PD) (group III). The cumulative kidney graft rejection incidence for PD vs. SD was only significantly different in group I (for PD vs. SD, respectively: at 6 months, 31% vs. 36% [p=0.015]; at 1 year, 37% vs. 43% [p=0.006]). Kidney graft survival was similar in all groups for PD vs. SD. Multivariate analysis of group III showed only transplantation during the earlier era (1994-96), but not SD, to be an independent risk factor for kidney graft rejection. Portal venous pancreas graft drainage does not affect kidney graft rejection and survival in SPK recipients on tacrolimus. Our data suggests that the efficacy of current immunosuppressive protocols and increasing center experience are clinically much more relevant than any potential immunologic advantage of portal venous drainage in SPK recipients.

Topics: Adult; Cadaver; Databases as Topic; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Multivariate Analysis; Pancreas Transplantation; Portal Vein; Proportional Hazards Models; Regression Analysis; Risk Factors; Tacrolimus; Time Factors

There has been concern that adult living-donor liver transplantation (LLTx) for hepatitis C virus (HCV) infection may lead to recurrent disease that is more severe compared with the results of cadaveric LTx (CLTx), because the smaller sized graft in LLTx regenerates and may increase viral replication. This study examines the survival outcome and HCV recurrence in CLTx versus LLTx performed at a single institution.. A total of 100 consecutive adult recipients (75 men and 25 women; mean age 49.9+/-8.4 years) of LTx (65 CLTxs and 35 LLTxs performed July 2000-July 2002) who tested positive for HCV by polymerase chain reaction were examined retrospectively until October 2003. All patients received tacrolimus-based immunosuppression with mycophenolate mofetil and steroids.. The overall actual patient survival was 85% (83.1% for CLTx vs. 88.6% for LLTx). The 39-month Kaplan-Meier actuarial patient survivals were 75.1% for CLTx and 88.6% for LLTx. Of 15 deaths, 6 were the result of recurrent HCV (five CLTxs and one LLTx), and of 10 retransplants, 2 were related to recurrent HCV (one CLTx and one LLTx). The rates of recurrence were 72.3% and 77.1%, the hepatitis activity indices were 5.4 + 2.4 and 6.2 + 2.8, the fibrosis scores were 1.4+/-1.4 and 1.5+/-1.3, and the times to recurrence were 318+/-269 days and 394+/-250 days for CLTx and LLTx, respectively. None of the differences between the two groups were significant.. No detrimental effect of HCV infection was found in LLTx recipients when compared with contemporaneous CLTx recipients. Patient survival, graft survival, rate of HCV recurrence, severity of HCV recurrence, graft loss from HCV, and interval for recurrence in CLTx and LLTx were similar.

Topics: Adult; Aged; Cadaver; Cause of Death; Graft Survival; Hepatitis C; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Middle Aged; Recurrence; Retrospective Studies; Tacrolimus; Transplantation, Homologous

We have proposed that the mechanisms of alloengraftment and variable acquired tolerance can be facilitated by minimum posttransplant immunosuppression. It was further suggested that the efficacy of minimalistic treatment could be enhanced by preoperative recipient conditioning with an antilymphoid antibody preparation. A total of 76 adults (38 hepatitis C virus [HCV], 38 HCV) were infused with 30 mg alemtuzumab before primary cadaveric liver transplantation and maintained afterward on daily monotherapy unless breakthrough rejection mandated additional agents. In stable patients, the intervals between tacrolimus doses were lengthened ("spaced weaning") after approximately 4 months. Eighty-four contemporaneous nonlymphoid-depleted liver recipients (58 HCV, 26 HCV) were treated with conventional postoperative immunosuppression. The overall incidence of rejection was similar with the two strategies of immunosuppression. With follow-ups of 14 to 22 months, patient and primary graft survival in HCV cases are 97% and 90%, respectively, with alemtuzumab depletion plus minimal immunosuppression versus 71% and 70%, respectively, under conventional immunosuppression. In HCV recipients, current patient and graft survival in the alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively, under conventional treatment. With both strategies of immunosuppression, the adverse effect of preexisting HCV on survival parameters and graft function already was significant at the 1-year milestone, but its extent was not evident until the second year. With or without HCV, 62% of the 64 surviving lymphoid-depleted patients are on spaced immunosuppression, and four patients receive no immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic maintenance immunosuppression is a practical strategy of liver transplantation in HCV recipients but not HCV recipients.

Topics: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Cadaver; Female; Graft Rejection; Graft Survival; Hepacivirus; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Tacrolimus; Transplantation Conditioning

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplan

Topics: Adolescent; Cadaver; Chi-Square Distribution; Child; Cyclosporine; Drug Therapy, Combination; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Mycophenolic Acid; Prednisone; Retrospective Studies; Survival Analysis; Tacrolimus; Treatment Outcome

The high cost of tacrolimus is a major problem in Mexico. Ketoconazole increases tacrolimus bioavailability by inhibiting cytochrome P450 3A4 and glycoprotein-p.. To demonstrate that the coadministration of tacrolimus and ketoconazole allows a significant dose and cost reduction.. This prospective study administered tacrolimus and ketoconazole to renal transplant recipients with dose adjustment according to tacrolimus blood levels. At 0-1, 1-6, 6-12, and 12-24 months posttransplant demographic, transplant type, immunosuppression, and clinical data were reviewed. The cost of tacrolimus treatment was calculated based on the dose used as compared to the recommended dose (0.15-0.20 mg/kg/d).. Eleven patients with an age of 40 years (range, 13-71) were studied from May 2000 to August 2002. Follow-up was 15 +/- 10 months. Graft source was living donor in six patients and cadaveric in five. All patients received tacrolimus + mycophenolate mofetil + prednisone. The mean ketoconazole dose was 87 mg/d. Since the dose of tacrolimus was 0.04 mg/kg/d versus the recommended dose of 0.15-0.20 mg/kg/d, there was a 78% cost reduction (P =.000). Tacrolimus blood levels remained in the therapeutic range. There were no drug-related side effects.. The co-administration of tacrolimus and ketoconazole results in a substantial dose and cost reduction while maintaining therapeutic levels. No adverse metabolic consequences were seen with this combination.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Cadaver; Costs and Cost Analysis; Demography; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Ketoconazole; Kidney Transplantation; Living Donors; Mexico; Middle Aged; Tacrolimus; Time Factors; Tissue Donors

Topics: Acute Disease; Cadaver; Fatal Outcome; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Pancreatitis; Tacrolimus

Finding the best combination of immunosuppression is an important challenge in kidney transplantation. Current short-term (1- and 3-year) allograft survival is quite good, making it difficult to determine differences in therapeutic regimens without large sample sizes. Using data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network database, the current study provides substantial statistical power to analyze the outcomes for different immunosuppressive regimens.. To compare the effects of four discharge regimens (cyclosporine and azathioprine [CYA+AZA], CYA and mycophenolate mofetil [MMF], tacrolimus [TAC]+AZA, and TAC+MMF) on long-term survival, a multivariate Cox regression analysis was conducted on 19246 primary cadaveric kidney transplants during 1995 to 1998.. Compared with CYA+AZA, the combination of CYA+MMF was associated with a 10% reduced risk of graft loss (relative risk [RR] 0.90, 95% confidence limit [CL] 0.84-0.96, P<0.001), whereas TAC+AZA was associated with an 18% reduced risk (RR 0.82, 95% CL 0.67-1.005, P=0.06) and TAC+MMF with a 20% reduced risk of graft loss (RR 0.80, 95% CL 0.71-0.89, P<0.001). All three regimens benefited patients regardless of delayed graft function (DGF) or early acute rejection status. In addition, in the absence of DGF, the combinations of CYA+MMF, TAC+AZA, and TAC+MMF were associated with a reduced risk of mortality compared with CYA+AZA.. The major finding of this study was improved graft and patient survival associated with TAC+MMF and CYA+MMF in patients with or without DGF or early acute rejection.

Topics: Adolescent; Azathioprine; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Tacrolimus; Treatment Outcome

Simultaneous pancreas and kidney transplantation (SPK) from cadaveric donors has become a widely accepted therapeutic option for insulin-dependent uremic patients. In 1996 the first SPK from a live donor was performed. This procedure offers the advantage of a better immunologic match, reduced cold ischemia injury, and decreased waiting time. As such, it is an attractive alternative treatment for diabetic patients with end-stage nephropathy with an available living donor.. We performed six SPKs from living-related donors. There were four men and two women among the recipients; median age was 34 (range, 29-39) years. All donors were recipients' siblings with excellent HLA matching. Donors underwent standardized metabolic workup, anti-insulin and anti-islet antibody assays, and computed tomography of the abdomen. Both donors and recipients were treated with octreotide for 5 days perioperatively. After transplantation, the patients were maintained on tacrolimus-based immunosuppression, with the exception of one recipient of SPK from an identical twin, who received cyclosporine monotherapy.. All the donors are doing well and have normal renal function and blood glucose levels. One-year patient, renal, and pancreatic graft survival rates were 100%, 100%, and 83%, respectively. Acute kidney rejection was documented in two patients, and both recovered completely after OKT3 therapy. No rejection of pancreatic graft has been documented. Except for one patient who lost the graft because of hemorrhagic pancreatitis, all recipients maintained serum glucose levels at less than 130 mg/dL without insulin therapy. No major surgical complications such as graft thrombosis, intra-abdominal infection, or abscess were reported.. Living donor SPK can represent a successful alternative to cadaveric donor SPK. The procedure can be performed safely in the donor and with low morbidity in the recipient.

Topics: Adult; Blood Glucose; Cadaver; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Muromonab-CD3; Pancreas Transplantation; Tacrolimus; Tissue Donors; Treatment Outcome; Uremia

Renal transplants (RTs) from elderly donors show a high incidence of delayed graft function, which may be increased by the initial use of calcineurin inhibitors.. The purpose of this study was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and mycophenolate mofetil (MMF) with delayed introduction of low-dose tacrolimus in RT from elderly donors to elderly recipients.. This observational study in 13 centers included 78 patients, aged 61+/-7 years (range, 50-77), who received a kidney from a donor with a mean age of 64+/-5 years (range, 55-76), 94% of whom had died from a cardiovascular accident (CVA). Immunosuppression consisted of 1 mg/kg daclizumab in two doses (pre-RT and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean, 5.5 days) and adjusted to a target level of 5 to 8 ng/ml. The mean follow up was 27 weeks.. One graft was lost due to primary renal failure and 28 patients (36.4%) required dialysis due to delayed graft function, although it was generally of short duration (median, 4 days; only 2 cases >2 weeks). Acute rejection was seen in 11 patients (14%), with 9 of these confirmed by biopsy (11%, Banff 1997 grade I or II). Three patients withdrew from the study and two patients died (sepsis and accident). The remaining 72 patients continued follow up with a median 6-month creatinine value of 1.6 mg/dL. Sixty-seven percent of patients had at least one episode of infection, half of which were of urinary tract infections. There were nine cases of CMV infection.. These initial results suggest that this immunosuppressive regimen offers good efficacy with regard to short-term renal function, while maintaining both an acceptable low rejection rate and incidence of serious infections.

Topics: Age Factors; Aged; Cadaver; Cause of Death; Creatinine; Drug Administration Schedule; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Safety; Stroke; Tacrolimus; Time Factors; Tissue Donors

Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation.. Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters.. LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01).. Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants.

Topics: Adult; Antilymphocyte Serum; Cadaver; Calcineurin Inhibitors; Cyclosporine; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Tacrolimus; Treatment Outcome

Registry data can provide valuable information about possible treatment effects; however, pretreatment differences in patient characteristics may influence treatment assignment. Careful analysis must therefore be undertaken when evaluating treatment differences in the context of nonrandomized studies so that the impact of treatment selection bias is minimized.. A multivariable risk factor analysis of adult patients registered in the US Renal Data System who received a primary renal allograft during 1995 to 1998 was undertaken to compare 3-year graft survival using tacrolimus or Neoral with mycophenolate mofetil (MMF) and steroids.. In total, 9,449 patients were included (cadaveric donor n=6,011; living donor n=3,438). Patients (2,130) received tacrolimus, and 7,319 received Neoral. At 3 years posttransplant, the proportion of cadaveric donor recipients experiencing all causes of graft loss was 10.0% for tacrolimus and 10.6% for Neoral; for living donor recipients these figures were 6.5% and 6.7%, respectively (unadjusted Kaplan-Meier analysis). The incidence of graft failure excluding death was also similar between the two groups. With Cox proportional hazards modeling, the adjusted relative hazard of 3-year graft failure for cadaveric donor patients taking tacrolimus versus Neoral was 1.02 (95% confidence interval [CI] 0.8-1.3), and for living-donor recipients it was 1.15 (95% CI 0.8-1.8).. These results indicate excellent 3-year graft survival for both cadaveric and living-donor renal-transplant patients receiving either Neoral or tacrolimus with MMF and steroids, with no significant differences between treatment groups. On the basis of these results, relative cost-effectiveness may become increasingly important in selection of tacrolimus or Neoral as primary immunosuppressant for renal-transplant patients.

Topics: Adult; Body Mass Index; Cadaver; Cost-Benefit Analysis; Cyclosporine; Drug Therapy, Combination; Emulsions; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Missouri; Proportional Hazards Models; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors; Treatment Failure

This multicenter study was retrospectively evaluated for the predictive factors affecting the long-term graft survival of a kidney transplant from a non-heart-beating donor (NHBD).. A total of 706 patients received transplants from NHBD in 11 centers between 1986 and 2000 and the results were entered into the analysis. The patients were treated with cyclosporine- or tacrolimus-based immunosuppressive therapy. Graft survival was calculated by the Kaplan-Meier method. Factors selected for univariate analysis were donor age, and acute early and acute late rejection. Hypertension (HT), hyperlipidemia (HL), and diabetes mellitus were also analyzed in 638 recipients whose graft survived for more than 1 yr.. In the cases using NHBD, graft survival for 1, 5, and 10 yr was 87, 69, and 53%, respectively. Donor age of over 55 yr, acute early and late rejection, post-transplant HT and diabetes at the first post-operative year were shown to be significantly harmful on long-term graft survival. For longer graft survival in NHBD kidney transplantations, reducing acute rejection, and controlling blood pressure and sugar are crucial.

Topics: Age Factors; Cadaver; Cyclosporine; Diabetes Mellitus; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Hyperlipidemias; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors; Tissue Donors

Topics: Adult; Antibodies, Monoclonal; Basiliximab; Cadaver; Drug Administration Schedule; Humans; Immunosuppressive Agents; Liver Transplantation; Methylprednisolone; Postoperative Period; Recombinant Fusion Proteins; Safety; Tacrolimus; Tissue Donors

Topics: Cadaver; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Heart Arrest; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Survival Rate; Tacrolimus; Time Factors; Tissue and Organ Harvesting; Tissue Donors; Treatment Outcome

Topics: Adult; Brain Death; Cadaver; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Heart Arrest; Humans; Japan; Kidney Transplantation; Living Donors; Male; Middle Aged; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Black People; Cadaver; Cause of Death; Daclizumab; Florida; Follow-Up Studies; Graft Rejection; Hispanic or Latino; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Middle Aged; Minority Groups; Mycophenolic Acid; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors; Tissue Donors; Treatment Failure; Treatment Outcome; White People

Topics: Adult; Azathioprine; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Heart Arrest; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Renal Replacement Therapy; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors; Waiting Lists

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Cadaver; Child; Drug Administration Schedule; Drug Monitoring; Female; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Retrospective Studies; Tacrolimus; Tissue Donors

Topics: Adolescent; Antilymphocyte Serum; Azathioprine; Body Weight; Cadaver; California; Child; Cyclosporine; Drug Therapy, Combination; Female; Humans; Kidney Transplantation; Living Donors; Male; Medical Records; Mycophenolic Acid; Racial Groups; Retrospective Studies; Tacrolimus; Tissue Donors

Topics: Acute Disease; Adult; Black People; Cadaver; Calcineurin Inhibitors; Cyclosporine; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Pennsylvania; Racial Groups; Reoperation; Retrospective Studies; Survival Analysis; Tacrolimus; Time Factors; Tissue Donors

Topics: Adolescent; Adult; Aged; Cadaver; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Nervous System Diseases; Postoperative Complications; Retrospective Studies; Seizures; Tacrolimus; Tissue Donors

Two recent brief reports suggest that recipients of living donor liver transplants achieve higher levels of immunosuppressive agents than cadaveric (CAD) liver transplant recipients administered the same dose. These results could have important implications regarding the dosing of immunosuppressives in living donor liver transplant recipients. We report our findings relative to immunosuppressive doses and levels in a cohort of 46 living donor liver transplant recipients. Immunosuppressive blood levels and doses were recorded weeks 1, 2, 3, and 4 and months 2, 3, 4, 5, and 6 for 46 living donor liver transplant recipients and 66 matched CAD liver transplant recipients who underwent transplantation between August 1997 and May 2001. The ratio of level to dose also was recorded at each interval. The mean overall cyclosporine A dose was similar in living donor liver transplant recipients (323 mg/d) compared with CAD recipients (344 mg/d; P = not significant [NS]). The mean overall tacrolimus dose was 15% lower in patients who underwent living donor liver transplantation (LDLT; 5.7 mg/d) than CAD transplantation (6.7 mg/d), although statistical significance was not achieved (P =.08). The mean overall cyclosporine A level was 18% higher in those undergoing LDLT (275 ng/mL) than CAD transplantation (234 ng/mL; P =.015). The mean overall tacrolimus level was the same in living donor liver transplant recipients (10.8 ng/mL) and CAD recipients (10.2 ng/mL; P = NS). The overall cyclosporine A level-dose ratio was 26% higher for those undergoing LDLT (0.83) than CAD transplantation (0.66; P =.01). The overall tacrolimus level-dose ratio was 26% higher for those undergoing LDLT (1.82) than CAD transplantation (1.44; P =.01). In conclusion, (1) living donor liver transplant recipients achieve higher blood levels of tacrolimus and cyclosporine A for a given dose compared with CAD recipients, and (2) this difference is observed up to 6 months after transplantation, when hepatic regeneration is completed.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Cadaver; Cohort Studies; Cyclosporine; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Male; Tacrolimus

Living donor liver transplantation in adult recipients is becoming increasingly common. The liver metabolizes most drugs, including immunosuppressive agents. Right-lobe grafts used in adult living donor liver transplantation consist of only 50% to 60% of the total liver. The purpose of this study is to determine whether there is a difference between tacrolimus doses and concentrations in patients who received a partial liver transplant from a living donor (LRD) versus those who received a whole-liver transplant from a cadaveric donor (CAD). Thirteen LRD recipients and 13 CAD recipients who underwent transplantation between April 1998 and July 2000 were included in this analysis. A CAD control group matched for age, sex, and race was used for comparison. Tacrolimus doses and concentrations were analyzed weekly for the first 4 weeks, then monthly for 6 months posttransplantation. There was no difference in acute rejection rates, renal and liver function test results, or number of potentially interacting medications administered between groups. LRD recipients required significantly lower doses of tacrolimus compared with CAD recipients at 2 weeks (0.058 v 0.110 mg/kg/d; P <.01), 3 weeks (0.068 v 0.123 mg/kg/d; P <.02), 4 weeks (0.086 v 0.141 mg/kg/d; P <.02), 2 months (0.097 v 0.141 mg/kg/d; P <.03), and 3 months (0.099 v 0.138 mg/kg/d; P <.03). Tacrolimus 12-hour trough concentrations were similar between groups at all times except for 2 weeks posttransplantation, when LRD recipients' concentrations were significantly greater than those of CAD recipients (12.4 v 9.5 ng/mL; P <.03). In addition, in the first month posttransplantation, LRD recipients were more likely to have greater concentrations of tacrolimus (>15 ng/mL; 22.1% v 9.2%; P <.01). In conclusion, LRD recipients have significantly decreased tacrolimus dosing requirements compared with CAD recipients during the first 3 months posttransplantation despite having similar tacrolimus concentrations.

Topics: Adult; Cadaver; Dose-Response Relationship, Drug; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Osmolar Concentration; Retrospective Studies; Tacrolimus

Topics: Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Renal Replacement Therapy; Retrospective Studies; Tacrolimus; Time Factors; Tissue Donors; Treatment Failure

Patients who develop delayed graft function (DGF) following cadaveric renal transplantation have inferior survival to those who do not. Calcineurin inhibitors (CNI) may prolong recovery from DGF. Patients with DGF are therefore routinely treated with either polyclonal antilymphocyte preparations or monoclonal anti-CD3 monoclonal antibodies and delayed introduction of CNI. The purpose of this study was to evaluate the efficacy of the anti-CD25 monoclonal antibody basiliximab (BSLIX) started post-operatively in patients at high risk for DGF combined with low dose tacrolimus (TAC).. Patients who received a primary cadaveric renal transplant only after August 1998 were included in this retrospective study (n = 143). All patients received TAC and mycophenolate Mofetil (MMF) pre-operatively. At 6 h post-operatively, graft function was assessed clinically by urine output and serum creatinine. Those patients who had a urine output < 300 cc/6 h or a rising serum creatinine were presumed to be at risk for DGF (n = 46). These patients were treated with 20 mg BSLIX and had TAC dose reduced to maintain a trough blood level of < 5 ng/mL. Basiliximab was repeated at day 5. Patients not felt to be at risk for DGF were treated with standard TAC dose with trough level target of 9-12 ng/mL. Patients at risk were classified as DGF if they needed dialysis or as slow graft function (SGF) if they did not. The combined group (SGF/DGF) were analysed together. Patients with SGF/DGF had their TAC dose increased to achieve trough levels of 9-12 ng/mL when renal function improved. Patient groups were compared for demographics, need for dialysis, serum creatinine, glomerular filtration rate (GFR), TAC trough levels, MMF dosage, complications and 1- and 2-yr actuarial graft survival.. Patients with SGF/DGF had a longer length of stay (8 vs. 5.7 d), were more likely to be black (41.3 vs. 25.7%), and required more post-operative haemodialysis (HD) (52.2 vs. 4.1%). SGF/DGF and non-SGF/DGF patients had similar rates of rejection (28.2 vs. 19.6%, p = 0.28) and steroid resistant rejection (SRR) (6.5 vs. 2.1%, p = 0.32). There were no differences in the rate of cytomegalovirus (CMV) infection (4.3 vs. 6.1%). Serum creatinine was higher and GFR lower at all time points in the SGF/DGF patients. The 1 and 2 yr actuarial survival in the non-SGF/DGF patients was 97.6 and 97.6% compared with 1 and 2 yrs actuarial survival of 94.1% and 80.0% in the SGF/DGF patients, p = 0.04. There were no differences in patient survival. There were no differences in actuarial survival for the SGF/DGF patients who received dialysis compared with those who did not receive dialysis. Comparison of patients who received HD (n = 28) to those who did not (n = 115), regardless of group demonstrated no difference in 1 and 2 yrs actuarial survival, 100 and 94.1% in HD patients vs. 98.2 and 92.5% in non-HD patients.. The clinical diagnosis of SGF/DGF can be made 6 h post-operatively based on urine output and serum creatinine. Basiliximab can be started post-operatively in these patients and decreased levels of TAC can be used to achieve acceptably low rates of rejection in these patients. However, SGF/DGF patients, regardless of their need for dialysis, have worse function at 1 yr and lower 2-yr actuarial graft survival compared with non-SGF/DGF patients. Most of the poor survival can be attributed to the SGF group. Further strategies to either prevent SGF/DGF or to optimize treatment in these patients are needed.

Topics: Antibodies, Monoclonal; Basiliximab; Cadaver; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Middle Aged; Receptors, Interleukin-2; Recombinant Fusion Proteins; Retrospective Studies; Risk Factors; Tacrolimus

Renal transplant recipients with positive flow cytometric crossmatches (FCXM) face greater risk of early rejection and graft failure. It is clear that the pharmacologic needs of this high risk group have not been identified. We retrospectively compared the impact of two drug regimens upon early rejection and 5 yr actuarial survival among 324 primary cadaveric transplant recipients with positive and negative FCXM. Patients received either Regimen I (OKT3 induction, cyclosporine and steroids) or Regimen II (mycophenolate mofetil with cyclosporine or Prograf). Recipient gender, age, disease etiology, ethnic distribution and cytotoxic panel reactive antibody (PRA) were equivalent between regimens (p=ns). With Regimen I, the incidence of rejection was greater for FCXM positive vs. FCXM negative patients (51 vs. 21%, p=0.001). In contrast, with Regimen II the incidence of rejection for FCXM positive and FCXM negative patients was equivalent (18 vs. 12%, p=ns) and lower than patients treated with Regimen I (p < 0.01). Ethnic variation was only observed with Regimen I in which African Americans with positive FCXM had more rejections than Caucasians (60 vs. 45%, p < 0.05). Five-year actuarial survival was lower for FCXM positive vs. FCXM negative patients treated with Regimen I (40 vs. 75%, p=0.0006) or Regimen 2 (60 vs. 90%, p=0.001). Allograft survival was equivalent (p=ns) among FCXM positive individuals receiving Regimen I or II. However, allograft survival among FCXM negative individuals improved with Regimen II (p < 0.05). Ethnic variation in survival was not observed with either regimen (p=ns).

Topics: Adult; Cadaver; Cyclosporine; Drug Therapy, Combination; Female; Flow Cytometry; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Prognosis; Retrospective Studies; Risk; Tacrolimus

Topics: Adult; Aged; Area Under Curve; Cadaver; Female; Follow-Up Studies; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Metabolic Clearance Rate; Middle Aged; Tacrolimus; Time Factors; Tissue Donors; Treatment Outcome

Topics: Administration, Oral; Adolescent; Adult; Aged; Cadaver; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Infant; Intestinal Absorption; Japan; Kidney Transplantation; Living Donors; Male; Middle Aged; Retrospective Studies; Tacrolimus; Tissue Donors

Topics: Adult; Aged; Cadaver; Family; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Risk Assessment; Survival Rate; Tacrolimus; Tissue Donors

Acute renal allograft rejection is usually seen within the first 3 months posttransplant, and is characterized by an intense infiltrate of T cells. Some acute rejections, however, contain many plasma cells and/or appear late posttransplant.. We have investigated 27 cases of intensely plasma cell-rich acute rejections (PCAR) from 1987 to 1997 and have compared them to 21 control cases (CAR) of typical acute rejection. Each group was divided into early (<6 months) and late (>6 months) subgroups. PCAR and CAR cases were matched for histological features of chronic allograft nephropathy. In all four groups, most cases had Banff '97 type IB and IIA acute rejection.. A significantly greater number of PCAR cases experienced graft failure due to chronic allograft nephropathy or complications of acute rejection (P<0.05). There was no significant difference between PCAR and CAR in HLA matching, occurrence of posttransplant acute tubular necrosis, presence versus absence of previous allografts, number of previous or subsequent acute rejection episodes, Banff '97 sum scores for acute rejection, cyclosporine A or FK506 levels, or percent change from baseline creatinine at time of biopsy. Plasma cells in PCAR cases showed IgG predominance whereas those in CAR had comparable staining for IgG and IgA. Kappa and lambda light chain immunostaining of all PCAR cases revealed polyclonality. Three of 18 PCAR cases studied for the presence of Epstein-Barr virus RNA showed scattered positivity in 2-7% of lymphoid cells, although the remainder was negative. None of the PCAR cases developed post-transpland lymphoproliferative disorder.. We conclude that PCAR can occur from 1 month to many years posttransplant, is associated with poor graft survival, and is not a manifestation of concomitant chronic allograft nephropathy or viral infection, including posttransplant lymphoproliferative disorder.

Topics: Acute Disease; Adolescent; Adult; Cadaver; Cyclosporine; Female; Graft Rejection; Humans; Immunohistochemistry; Immunosuppressive Agents; In Situ Hybridization; Kidney Transplantation; Male; Middle Aged; Plasma Cells; Tacrolimus; Time Factors; Treatment Outcome

Topics: Cadaver; Cost-Benefit Analysis; Cyclosporine; Humans; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Tacrolimus; Tissue Donors; United Kingdom

Topics: Adult; Aged; Antilymphocyte Serum; Cadaver; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors; Tissue Donors

Topics: ABO Blood-Group System; Adult; Blood Group Incompatibility; Cadaver; Cyclosporine; Female; Graft Survival; Heart Arrest; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Organ Preservation; Postoperative Complications; Retrospective Studies; Survival Rate; Tacrolimus; Tissue Donors

40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate (a) the stabilization of the donor CD3+ and CD34+ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; (b) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; (c) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; (d) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and (e) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls (P = 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively (P = < 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively ea

Topics: Adolescent; Adult; Aged; Antigens, CD34; Bone Marrow Transplantation; Cadaver; CD3 Complex; Child; Cytomegalovirus Infections; Flow Cytometry; Follow-Up Studies; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Polymerase Chain Reaction; T-Lymphocyte Subsets; Tacrolimus; Transplantation Chimera

Although FK 506 has been shown to effectively reverse refractory renal allograft rejection, its ability to reverse accelerated renal allograft rejection as a primary agent has not been specifically addressed. Herein evidence of the ability of FK 506 to reverse accelerated renal allograft rejection is presented. A 16-yr-old highly sensitized (PRA 75%) male underwent a second cadaveric renal transplant procedure. Despite induction immunosuppression with ATGAM, cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum creatinine (1.6-->2.1 ng/dl) and reduction in urine output (4000 ml/d-->1000 ml/d) were observed on the sixth post-transplant day. Renal allograft biopsy performed at that time revealed typical features of accelerated rejection including neutrophil margination in glomerular and interstitial capillaries, and C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by immunofluorescence). FK 506 therapy was promptly instituted and ATGAM therapy discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/dl) and subsequently progressively dropped to 1.2 mg/dl. Repeat biopsy on FK 506 treatment day 12 revealed marked histologic improvement. Renal function remains excellent (1.3 mg/dl) 18 months after initiation of FK 506 therapy, and recurrent rejection has not been observed. This experience provides evidence that FK 506 therapy may effectively reverse accelerated renal allograft rejection, and that it provides a means for treating antibody-mediated mechanisms of allograft rejection.

Topics: Adolescent; Anti-Inflammatory Agents; Antibodies; Antilymphocyte Serum; Azathioprine; Biopsy; Cadaver; Capillaries; Complement C3; Creatinine; Cyclosporine; Fibrin; Glucocorticoids; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Glomerulus; Kidney Transplantation; Male; Methylprednisolone Hemisuccinate; Neutrophils; Reoperation; Tacrolimus; Urinary Retention

Renal transplantation is a treatment option that should be considered for the elderly (> or = 60 years old) with end-stage renal disease. Little is known regarding the use of tacrolimus (as induction and maintenance immunosuppression) in this age group. We report the outcome of kidney transplantation in 21 patients aged 60 years or more with tacrolimus. During the past few years in kidney transplant maintenance immunosuppressive regimens, we have revised our standard general protocol from cyclosporine to tacrolimus-based therapy for maintenance immunosuppression and for rescue therapy. We also introduced mycophenolate (RS-61443) while we have continued to use ATGAM/OKT3 as induction regimen in the immediate postoperative period. We treated these renal recipients with tacrolimus and steroids in combination with azathioprine or mycophenolate mofetil without antibody induction. This was well tolerated and not associated with a higher rate of rejection (20%) whereas the potential toxicity of antilymphocyte preparations was avoided.

Topics: Administration, Oral; Age Factors; Aged; Azathioprine; Cadaver; Cyclosporine; Female; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Infusions, Intravenous; Kidney Failure, Chronic; Kidney Transplantation; Male; Methylprednisolone; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Tacrolimus; Treatment Outcome

Topics: Azathioprine; Black or African American; Black People; Cadaver; Cyclosporine; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Mycophenolic Acid; Philadelphia; Retrospective Studies; Tacrolimus; Tissue Donors; White People

Topics: Actuarial Analysis; Adult; Black or African American; Black People; Cadaver; Creatinine; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Pennsylvania; Reoperation; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors; Tissue Donors; Treatment Failure; Treatment Outcome

Topics: Basement Membrane; Biopsy; Cadaver; Capillaries; Creatinine; Cyclosporine; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Lymphocytes; Microscopy, Electron; Nephritis, Interstitial; Retrospective Studies; Tacrolimus; Tissue Donors

Thirty-seven primary renal transplant patients were enrolled in the early phase II study on kidney transplantation. All grafts survived during the follow-up period. However, 10 of the 37 patients were changed from FK 506 to conventional drugs, and 3 were treated concomitantly with azathioprine (AZA) or mizoribine (MZR) in the 3-month period of observation. After 3 months posttransplantation, an additional 10 patients were treated continuously with AZA or MZR. In addition, 3 were converted from FK 506 to conventional drugs. No additional conversion was observed after 4 months. Trough level monitoring was effective enough to regulate the FK 506 dosage. Nephrotoxicity and hyperglycemia were associated with a high trough level of FK 506 (whole blood, > 20 ng/ml).

Topics: Azathioprine; Cadaver; Creatinine; Drug Therapy, Combination; Follow-Up Studies; Histocompatibility Testing; Humans; Immunosuppressive Agents; Isoantibodies; Japan; Kidney Transplantation; Living Donors; Postoperative Complications; Prednisolone; Tacrolimus; Time Factors; Tissue Donors