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Background: Wound healing problems and lymphoceles have been reported with greater frequency in kidney recipients given de novo sirolimus. This problem has led to increased patient morbidity and cost; and has been an impediment to the completion of randomized controlled trials in which wound problems have necessitated premature discontinuation of mammalian target of rapamycin inhibitors., Methods: We developed a systematic program to reduce these problems based on patient selection (body mass index [BMI] <32 kg/m2), the use of closed suction drains, modifications of surgical technique, and avoidance of a loading dose of sirolimus. Consecutive series of adult kidney-only recipients given antibody induction followed by de novo sirolimus, mycophenolate mofetil, and steroids were compared; group 1: 204 patients transplanted with few restrictions and group 2: 103 patients transplanted using the above program., Results: This approach resulted in a significant reduction (group 2 vs. group 1) in cumulative wound complications (7.8% vs. 19.6%, P=0.007), and nonoperative wound complications (2.9% vs. 14.2%, P=0.001). In addition, the incidence of lymphoceles detected (22.3% vs. 47.1%, P<0.0001), treated (4.8% vs. 24.5%, P<0.0001), or needing surgical intervention (1.9% vs. 14.2%, P=0.001) was significantly reduced. Multivariate analysis demonstrated that a BMI more than 30 to 32 kg/m2 was the most significant variable related to delayed wound healing (odds ratio [OR] 3.01, 0.02) or surgical repair (OR 8.05, P=0.0001), whereas BMI (OR 1.54, P=0.038) and acute rejections (OR 1.34, P=0.03) were most associated with lymphocele treatment., Conclusions: A systematic program of wound care using de novo sirolimus can produce wound healing complications comparable with that reported with other agents.

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

Background: The aim of this study was to evaluate the incidence and risk factors for posttransplant diabetes mellitus (PTDM; defined as new insulin use and/or new hyperglycemia) in 528 kidney recipients using different immunosuppressive agents., Methods: Maintenance therapy included mycophenolate mofetil or azathioprine plus glucocorticoids in combination with Group I cyclosporine (263); Group II tacrolimus (60); or Group III sirolimus (205)., Results: The mean follow-up was 39.2 (range 9.0-103.8) months. Overall, the number of patients needing insulin was 7.4% (39/528). The incidences for Groups I, II, and III of 7.6%, 11.7%, and 5.9%, respectively, were not statistically different. Characteristics of patients with PTDM included older age (P=0.007); greater body weight (kg) at transplant, 6 months, and 12 months, respectively (P<0.001); greater BMI (kg/m2) at transplant, 6 months, and 12 months, respectively (P<0.001); more acute rejection episodes 28.2% vs. 13.5% (P=0.012); and increased incidence in African Americans (P=0.03). Multivariable analysis demonstrated increased risk for PTDM (defined as new insulin use) for tacrolimus, (hazard ratio [HR] 3.794, P=0.007); treated rejections (HR 2.491, P=0.0115); age (HR 1.407, P=0.0116); and BMI (HR 1.153, P<0.0001). New insulin use occurred sooner and with less total glucocorticoid dose for tacrolimus patients. If PTDM is defined as all cases of new hyperglycemia, then no immunosuppressive drug group demonstrated an increased risk. CONCLUSION.: The risk for developing PTDM is greatest among older recipients, and those obese at the time of transplant; those given steroid pulse therapy were at exceptionally high-risk. PTDM risk reduction should focus on weight loss in the obese end-stage renal disease population prior to transplant.

Background: We performed a sequential study to determine the efficacy and side effects of low-dose (1 g) mycophenolate mofetil (MMF) in a CNI drug avoidance regimen including sirolimus/steroids., Methods: A total of 260 kidney-only recipients were given basiliximab (232) or thymoglobulin (28) induction, and sirolimus/steroids. In addition, 160 recipients were begun on standard MMF 1 g twice daily (2-g group), while 100 recipients were begun on low-dose MMF 500 mg twice daily (1-g group). The 1-g recipients were concentration controlled to keep mycophenolic acid (MPA) C0 levels at 1.8-4 microg/ml., Results: There were no statistically significant differences in demographics between the groups. At 6 months there were no significant differences between the 2-g and 1-g MMF groups in patient survival (96.8% vs. 96%), graft survival (92.5% vs. 95%), biopsy-confirmed and treated acute rejection (8.8% vs. 13%), or mean creatinine mg/dL (1.41+/-0.52 vs. 1.47+/-0.67), respectively. Mean MPA C0 levels microg/ml were (4.7 vs. 2.3) at 1 month, (4.1 vs. 3.1) at 3 months, and (3.9 vs. 2.4) at 6 months. There were no significant differences at 1, 3, or 6 months in mean WBC, HgB, or platelets, or wound complications. There were significant reductions in the number of patients reporting nausea-vomiting-dyspepsia (20.6% vs. 8%, P=0.007), diarrhea (34.3% vs. 20%, P=0.01), and abdominal pains (10.6% vs. 4%, P=0.05), between the 2-g and 1-g MMF groups, respectively., Conclusions: The use of concentration-controlled 1-g MMF results in comparable transplant outcomes with less GI toxicity during the first 6 months posttransplant in a CNI drug-free sirolimus based immunosuppressive regimen.

Background: The aim of this study was to determine whether there has been an increase in the incidence or severity of wound-healing complications that can be attributed to the introduction of newer immunosuppressive drugs., Methods: Consecutive series of adult kidney-only transplant recipients were selected from our Unified Transplant Database backward from September 2002. There were 513 patients divided into groups on the basis of their maintenance immunosuppression given for at least the first 30 days posttransplant. Group I (152) was given sirolimus, mycophenolate mofetil, and prednisone (SRL/MMF/P) between March 2000 and September 2002; group II (168) was given cyclosporine A (CsA)/MMF/P between January 1999 and July 2002; and group III (193) was given azathioprine (AzA)/CsA/P between January 1993 and December 1997. A classification system for wound-healing problems was developed, and each of the three groups was analyzed by univariate and multivariate analysis., Results: From groups III to II to I, there was a significant increase in mean age (42.4 vs. 49 years), percent of patients diabetic (17% vs. 29%), mean body mass index (BMI) (24.2 vs. 27.1 kg/m2), and percent BMI greater than 30 (13.5% vs. 27%). The cumulative percentage of all wound-healing problems between group I (19.7%) vs. group II (16.1%) and group III (15.6%) was not significantly different. The most significant risk factor was a recipient BMI greater than 30 (P=0.0012) and delayed graft function (P=0.0041)., Conclusions: During a 10-year period marked by changing recipient demographics, the introduction of MMF and SRL did not result in a significant increase in transplant wound-healing complications. The most significant risk factor associated with transplant wound-healing complications remains body weight, which was the major influence for each of the immunosuppressive drug combinations described.

Background: Progressive nephrotoxicity caused by calcineurin inhibitor drugs contributes to the long-term decline in renal function in kidney transplant patients., Methods: We conducted a randomized, prospective trial of calcineurin inhibitor drug avoidance in 61 adult primary kidney transplant recipients. Each patient received induction therapy with 20 mg basiliximab on days 0 and 4, and maintenance therapy with mycophenolate mofetil 1 g two times per day and steroids. Thirty-one patients received sirolimus, 5 mg daily after a 15-mg loading dose. Doses were then concentration-controlled to keep 24-hr trough levels at 10 to 12 ng/mL for 6 months and 5 to 10 ng/mL thereafter. Thirty patients began cyclosporine therapy at 6 to 8 mg/kg per day in divided doses and were then concentration-controlled to keep 12-hr troughs of 200 to 250 ng/mL., Results: Mean follow-up is 18.1 months (range, 12-26 months). The percentages of 1-year patient survival, graft survival, and biopsy-confirmed acute rejection rates were not significantly different between the sirolimus-treated patients (96.7%, 96.7%, and 6.4%, respectively) and the cyclosporine-treated patients (100%, 95.4%, and 16.6%, respectively). At 6 and 12 months, respectively, the sirolimus-treated patients enjoyed significantly better (P=0.008 and P=0.004) mean serum creatinine levels (1.29 and 1.32 mg/dL) and calculated creatinine clearances (77.8 and 81.1 mL/min) than cyclosporine-treated patients (1.74 and 1.78 mg/dL, and 64.1 and 61.1 mL/min, respectively). Sirolimus-treated recipients have significantly (P=0.001) higher 1-year trough levels of mycophenolic acid (4.16 ng/mL) than cyclosporine-treated patients (1.93 ng/mL). Sirolimus also delays the repopulation of basiliximab-depleted CD25 T cells compared with cyclosporine., Conclusions: Calcineurin inhibitor drug avoidance with basiliximab induction and sirolimus provides comparable 1-year transplant outcomes, with significantly better renal function in primary renal allograft recipients.

OBJECTIVE To investigate the effect of placing a prophylactic drain during renal transplantation on the incidence of lymphocele, wound complication and deep venous thrombosis (DVT) in renal transplant recipients induced with sirolimus vs calcineurin inhibitors (CNI), as sirolimus-based immunosuppression is a risk factor for the formation of fluid collections after transplantation. PATIENTS AND METHODS We analysed 165 consecutive adult renal transplant patients at our institution between January 2004 and February 2005. Group 1 (84) did not receive an intraoperative drain and group 2 (81) did. Recipients were analysed within each group based on immunosuppression (sirolimus or CNI) and whether they had wound complication, fluid collection, lymphocele treatment, or DVT. RESULTS In group 1 and 2, respectively, the wound complication rate was 22.6% vs 13.6% ( P = 0.134), the fluid collection rate 45.2% vs 16.% ( P < 0.001), the lymphocele treatment rate 19.0% vs 2.5% ( P = 0.001) the DVT rate 14.3% vs 4.9% ( P = 0.043) the fluid collection rate (for CNI) 26.5% vs 16.0% ( P = 0.246), the lymphocele treatment rate (for CNI) 5.9% vs 0% ( P = 0.084), the fluid collection rate (sirolimus) 58.0% vs 16.1% ( P < 0.001) and lymphocele treatment rate (sirolimus) 28% vs 6.5% ( P = 0.018). Multivariate analysis of risk factors for fluid collection showed significance for no drain (odds ratio 3.30, P = 0.002), associated wound complication (2.41, P = 0.041) and sirolimus (2.48, P = 0.015). CONCLUSIONS Placing a drain during transplantation decreased the incidence of fluid collection, lymphocele treatment and DVT. The reduction of fluid collection and lymphocele were significant for patients treated with sirolimus. We recommend placing a drain in patients undergoing induction with sirolimus-based immunosuppression. [ABSTRACT FROM AUTHOR]