Kathy Savas

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

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

The impact of sirolimus, mycophenolate mofetil, cyclosporine, azathioprine, and steroids on wound healing in 513 kidney-transplant recipients

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.

A systematic approach to minimizing wound problems for de novo sirolimus-treated kidney transplant recipients.

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.

Renal Transplantations in African Americans: A Single-center Experience of Outcomes and Innovations to Improve Access and Results

OBJECTIVE To report a single-center 10-year experience of outcomes of kidney transplantation in African Americans (AAs) vs Caucasian Americans (CA) and to propose ways in which to improve kidney transplant outcomes in AAs, increased access to kidney transplantation, prevention of kidney disease, and acceptance of organ donor registration rates in AAs. METHODS We compared outcomes of deceased donor (DD) and living donor (LD) renal transplantation in AAs vs CAs in 772 recipients of first allografts at our transplant center from January 1995 to March 2004. For DD and LD transplants, no significant differences in gender, age, body mass index, or transplant panel reactive antibody (PRA) existed between AA and CA recipients. RESULTS Primary diagnosis of hypertension was more common in AA, DD, and LD recipients. Significant differences for DD transplants included Medicaid insurance in 23% AA compared with 7.0% CA (P<.0001) and more frequent diabetes mellitus type 2 in AAs (15% vs 4.1%, P=.0009). Eighty-three percent of AAs had received hemodialysis compared with 72% of CAs (P=.02). AAs endured significantly longer pretransplant dialysis (911±618 vs 682±526 days CA, P=.0006) and greater time on the waiting list (972±575 vs 637±466 days CA, P<0001). In DD renal transplants, AAs had more human leukocyte antigen (HLA) mismatches than CAs (4.1±1.4 vs 2.7±2.1, P<.0001). Mean follow-up for survivors was 7.1±2.5 years. Among LD transplants, graft survival and graft function were comparable for AAs and CAs; however, among DD transplants, graft function and survival were substantially worse for AAs (P=.0003). In both LD and DD transplants, patient survival was similar for AAs and CAs. CONCLUSION Our data show that AAs receiving allografts from LDs have equivalent short- and long-term outcomes to CAs, but AAs have worse short- and long-term outcomes after DD transplantation. As such, we conclude that AAs should be educated about prevention of kidney disease, the importance of organ donor registration, the merits of LD over DD, and encouraged to seek LD options.

The effect of two different cyclosporine formulations on the long-term progression to chronic rejection in renal allograft recipients

Abstract: Introduction:  The introduction of the microemulsion formulation of cyclosporine (CsA) (Neoral – NEO) has been shown to provide improved absorption and less intrapatient variability than the previous formulation (Sandimmune – SIM) in kidney transplant recipients. It has been suggested that the use of the microemulsion formulation results in less acute rejection, and therefore permits better long‐term transplant outcomes. Our aim was to determine whether the microemulsion formulation of cyclosporine has reduced the long‐term (5 yr or more) rates of chronic rejection (allograft nephropathy) in a renal transplant population.