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Stuart M Flechner

Publications and source records attributed to Stuart M Flechner.

18 recordsLinked to original sources
PubMed2006

Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation.

BACKGROUND: Calcineurin inhibitor(CNI)-free protocols using sirolimus (SRL) in kidney transplantation have proven effective, although reports have linked SRL to proteinuria. We sought to investigate this link and its impact on graft function. METHODS: We retrospectively analyzed 184 live donor kidney transplant recipients who exclusively received de novo CNI-based (n = 106) or SRL-based (n = 78) regimens. Estimated glomerular filtration rate (GFR) and semi-quantitative dipstick proteinuria measurements were obtained at one, six, 12, and 24 months and six and 12 months, respectively. RESULTS: SRL-treated patients had higher frequencies of proteinuria (> or =1+) at 6 months (40.8% vs. 21.4%, P = 0.006) and 12 months (37.8% vs. 18.4%, P = 0.004) than those treated with CNI. Independent predictors of proteinuria at 12 months were GFR at one month (OR 0.62 per 10 ml/min/1.73 m, P<0.001), delayed graft function (OR 11.5, P = 0.02), and a SRL-based regimen (OR 4.18, P=0.002). By univariable analysis, SRL vs. CNI patients had higher GFR at each point. SRL-treated patients without proteinuria had higher GFR at 12 months compared to CNI-treated patients with and without proteinuria (66 vs. 50 or 56 ml/min/1.73 m, P < 0.05). No difference in GFR was seen between SRL-treated patients with proteinuria vs. CNI-treated patients without proteinuria (57 vs. 56 ml/min/1.73 m, P > 0.05). Absence of proteinuria and a SRL-based regimen remained independently associated FS with higher GFR at 12 months by multivariable analyses. CONCLUSIONS: De novo SRL-based immunosuppression is associated with a higher frequency of semi-quantitative proteinuria, however, estimated graft function at 1 year posttransplant remains superior to that of CNI-treated patients. Nevertheless, the long-term implications of these findings need to be determined.

Adult↗
PubMed2006

Posttransplant diabetes mellitus in kidney transplant recipients receiving calcineurin or mTOR inhibitor drugs.

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.

Adult↗
PubMed2006

Post-transplant diabetes mellitus: risk reduction strategies in the elderly.

New-onset diabetes mellitus in a previously non-diabetic transplant recipient is a serious adverse event that confers significant morbidity and mortality. The most significant consequences of post-transplant diabetes mellitus (PTDM) in solid organ transplant recipients include decreased patient and graft survival, an increased risk of infectious complications, and morbid cardiovascular events. The development of PTDM in the elderly is of particular concern because this group is already at increased risk of progression of cardiovascular disease. Because the elderly, especially those aged >65 years, are the fastest-growing segment of the renal transplant population, attention needs to be given to PTDM risk reduction and post-transplant management. PTDM develops as a consequence of both impaired insulin production and enhanced peripheral insulin resistance. A number of non-modifiable factors such as age, race, family history, hepatitis C, polycystic kidney disease and emerging genetic causes have been identified as risk factors for PTDM. However, a number of modifiable factors can be targets for intervention in high-risk patients, including bodyweight (through dietary restriction and exercise), hypertension, hyperlipidaemia and the effects of certain immunosuppressive agents. The two agents most responsible for PTDM are tacrolimus and corticosteroids, especially when used in combination. Attempts to modify doses and regimens designed to eliminate or avoid these drugs should be considered. Use of HMG-CoA reductase inhibitors ('statins') and ACE inhibitors is particularly helpful in controlling hypertension and hyperlipidaemia in the elderly because these agents confer protection against future adverse cardiovascular events. Bisphosphonates are also advantageous in controlling the progression of osteoporosis and possible increased risk of bone fractures. Future trials in the elderly should focus on such endpoints as PTDM, post-transplant neoplasia, cardiovascular events and bone fracture events in order to identify the safest regimens that provide the optimal control of rejection while limiting the morbidity from these secondary events.

Aged↗
PubMed2005

Laparoscopic donor nephrectomy gene expression profiling reveals upregulation of stress and ischemia associated genes compared to control kidneys.

We compared gene expression profiles from six donor kidneys prior to surgical manipulation to six kidneys removed after laparoscopic donor nephrectomy (LDN) and several hours of CO2 pneumoperitoneum. Biopsies were obtained from renal cortex and hybridized to Affymetrix HG-U133A GeneChips. For control kidneys, we identified 1380 genes present on all six samples that had a signal intensity >1,000. Functional classification of these revealed genes for cellular signaling (201; 15%), regulation of transcription (156; 11%), cellular transport (144; 10%) and cellular metabolism (111; 8%). A class comparison between the controls and LDN kidneys yielded 865 differentially expressed genes. Functional classification of the 502 genes differentially upregulated in LDN kidneys identified associations with apoptosis, cell adhesion, cell signaling, regulation of cell growth/proliferation, immune/inflammation, ischemia/stress response and proteolysis/peptidolysis. These data demonstrate an altered renal transcriptome induced by several hours of CO2 pneumoperitoneum and laparoscopic surgery characterized by upregulation of ischemia and injury associated genes.

Adult↗
PubMed2005

Simultaneous vs. sequential laparoscopic bilateral native nephrectomy and renal transplantation.

We reviewed our experience with simultaneous single incision bilateral native nephrectomy and renal transplantation in 11 patients (Group 1), compared to seven recipients who underwent staged laparoscopic bilateral nephrectomy followed by kidney transplantation (Group 2). Mean age, donor source, sex, cause of ESRD, and specimen size were similar in both groups (P=0.1). All Group 2 patients and 9 of 11 Group 1 patients had autosomal-dominant polycystic kidney disease. Perioperative Group 1 complications included: bowel injury, transplant urine leak, necrotic pancreatitis, delayed bowel movement, and severe shoulder pain secondary to diaphragmatic irritation. Seven (63.6%) Group 1 patients required an additional surgical procedure: midline incisional hernia, repair ureteral fistula, and repair enterocutaneous fistula. One Group 1 patient lost his graft secondary to bowel injury and intra-abdominal sepsis. No major complications, reoperations, or graft loss occurred in Group 2. For simultaneous bilateral native nephrectomy and kidney transplantation, over 60% of patients required an additional surgical procedure. Laparoscopic bilateral nephrectomy followed by kidney transplantation is a safe and feasible alternative.

Adult↗
PubMed2005

The effect of 2-gram versus 1-gram concentration controlled mycophenolate mofetil on renal transplant outcomes using sirolimus-based calcineurin inhibitor drug-free immunosuppression.

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.

Adolescent↗
PubMed2005

Laparoscopic live donor nephrectomy has equivalent early and late renal function outcomes compared with open donor nephrectomy.

OBJECTIVES: To assess the patterns of early functional recovery and long-term function in laparoscopic and open procured live donor nephrectomy (LDN) kidneys, highlighting the radionuclide scan as an additional tool for assessment, because of concerns regarding renal functional recovery after laparoscopic LDN. METHODS: We reviewed the donor and recipient records of 101 laparoscopic and 35 open LDNs performed between August 1997 and September 2001. Data were collected on demographic, immunologic, and intraoperative variables and ureteral/vascular complications. Delayed renal function recovery in recipients was evaluated by serum creatinine greater than 2.5 mg/dL on postoperative day 5, dialysis in first postoperative week, and two renographic criteria--the time to peak activity and the time to one-half peak activity on postoperative day 5. Long-term outcomes were evaluated by serum creatinine at 1, 3, 6, and 12 months and 2 and 3 years, creatinine clearance at 1 year, and patient and allograft survival. RESULTS: Donor and recipient age, sex, body mass index, and number of HLA mismatches did not differ between the two groups. The mean operating room time and blood loss were comparable. No differences were found in the early functional parameters (renography, creatinine at postoperative day 1 and 5, or dialysis in week 1) or long-term outcome (patient and graft survival, creatinine, and rejection at 1 year and patient and graft survival at 1, 2, and 3 years). CONCLUSIONS: Early recovery of graft function, longer term renal function, and 3-year patient and allograft survival are similar for live donor kidneys obtained by either a laparoscopic or an open surgical technique.

Adult↗
PubMed2005

Current management of transplant renal artery stenosis: clinical utility of duplex Doppler ultrasonography.

OBJECTIVES: To perform a retrospective study to determine the clinical utility of Doppler ultrasonography (DUS) and to determine its role in the management of transplant renal artery stenosis (TRAS). METHODS: Patients undergoing DUS between January 1998 and January 2001 for clinical suspicion of TRAS were included in the study. A total of 51 patients were divided into two groups according to the peak systolic velocity. Additional management was based on the clinical and DUS findings and their congruence. Patients were followed up and their outcome was analyzed. RESULTS: Of the 51 patients who entered the study, 26 were in the low probability group (LPG) and 25 in the high probability group (HPG). Nine patients in the LPG underwent additional investigations; eight underwent magnetic resonance angiography and one angiography. Of these 9 patients, 6 had stenosis, 4 of whom required angiography. In total, 5 patients from the LPG underwent angioplasty, and 4 of them had stenosis (1 with TRAS, 2 with common iliac artery stenosis, and 1 with renal artery ostial stenosis). Three patients underwent angioplasty and 2 of them improved. In the HPG, 20 of 25 patients underwent additional investigations, including magnetic resonance angiography in 12 and angiography in 8, with stenosis in 15 patients. Of the HPG, 13 of 25 patients underwent angiography, with 10 requiring angioplasty--8 for TRAS and 2 for adjacent renal artery stenosis, with improvement in 8 patients. Congruent clinical and DUS findings were highly predictive of significant stenosis more amenable to improvement. CONCLUSIONS: The results of our study have shown that high-probability DUS and congruent clinical findings are likely to identify a significant stenosis that is amenable to treatment. Low-probability DUS findings do not eliminate the possibility of stenosis, but intervention in this group is less likely to result in improvement.

Female↗
PubMed2004

Salvage of compromised renal vessels in kidney transplantation using third-party cadaveric extenders: impact on posttransplant anti-HLA antibody formation.

Kidney transplant surgery can be complicated by short, attenuated, or injured renal vessels which are now more frequently encountered with laparoscopic right donor nephrectomy. We describe a technique to overcome this problem in seven recipients (2 cadaveric and 5 living donors) by constructing third-party "vascular extenders" using cadaveric iliac vessels retrieved previously and preserved at 4 degrees C in University of Wisconsin solution. Mean vessel cold storage time was 25.7 days (range, 2-56 days). Immunosuppression consisted of sirolimus, mycophenolate mofetil, and steroids. Prompt reperfusion of all allografts was observed, and there were no surgical complications. Integrity of the extenders was confirmed using serial MAG3 renal scans and magnetic resonance angiography. Mean serum creatinine was 1.44 mg/dl at 19.2 months (range, 0.7-2 mg/dl at 3-31 months). Each recipient had a negative posttransplant kidney donor specific flow cytometry crossmatch. Two recipients developed HLA antibodies, one to DR7 and another DR13 (mismatched to the vessel donor) at 4 and 11 months posttransplant, respectively.

Adenosine↗
PubMed2004

BK nephropathy in kidney transplant recipients treated with a calcineurin inhibitor-free immunosuppression regimen.

Recently, polyomavirus-associated nephropathy (PVAN) has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. Susceptibility appears to be related to the type and intensity of pharmacologic immunosuppression but some reports have suggested a link among the development of PVAN, the treatment of rejection or maintenance with a tacrolimus-based immunosuppressive regimen. We report three cases of PVAN in patients who never received immunosuppression with calcineurin inhibitors (CNIs). Two patients received induction immunosuppression consisting of an IL-2 receptor antagonist while 1 received thymoglobulin. These 3 patients were maintained on prednisone, sirolimus and mycophenolate mofetil (MMF) and none was treated for rejection. All three patients presented with an elevated serum creatinine and demonstrated polyomavirus infection on biopsy and by blood PCR. These cases demonstrate that, unlike reports linking tacrolimus and PVAN, polyomavirus infection may develop in patients maintained on CNI-free immunosuppressive regimens and have not had episodes of rejection.

Aged↗
PubMed2004

The influence of various maintenance immunosuppressive drugs on lymphocele formation and treatment after kidney transplantation.

PURPOSE: We compared the incidence of lymphocele formation and treatment in kidney transplant recipients given 3 immunosuppressive drug regimens. MATERIALS AND METHODS: Consecutive series of adult kidney only recipients, including group 1-152 who received sirolimus/mycophenolate mofetil (MMF)/prednisone (P), group 2-168 who received cyclosporine/MMF/P and group 3-193 who received cyclosporine/azathioprine/P, were analyzed for post-transplantation lymphocele formation. All available records and imaging studies were reviewed, such as ultrasound, computerized tomography, magnetic resonance imaging etc, for peritransplant fluid collections greater than 2.5 cm. Demographic characteristics and the risk factors for lymphocele were compared in these 513 recipients using univariate and multivariate analysis. RESULTS: The overall incidence of lymphocele formation was 174 of 513 cases (33.9%) and the incidence of treated lymphoceles was 81 of 513 (15.7%). In groups 1 to 3 the incidence was 45.5%, 33.9% and 24.7%, respectively. These differences were significantly higher in group 1 vs groups 2 or 3 (p = 0.014) but they were not significantly different between groups 2 and 3. Similarly the incidence of treated lymphoceles was 23%, 12.5% and 12.9%, respectively. Findings were again statistically higher in group 1 vs groups 2 and 3 (p = 0.003) but not statistically significant between groups 2 and 3. A greater number of group 1 patients required surgical interventions compared with those in groups 2 and 3 (13.8% vs 4.7% and 4.8%, respectively, p = 0.019). In addition, acute rejection (p = 0.001) and body mass index greater than 32 (p = 0.02) were significant risk factors on multivariate analysis. CONCLUSIONS: The combination of sirolimus/MMF/P, obesity with a body mass index of greater than 30 kg/m and acute rejection are independent risk factors for lymphocele formation and treatment after kidney transplantation. Patients should be counseled and consideration should be given to prophylactic measures in this higher risk renal transplant population.

Adult↗
PubMed2004

Fate of donor kidney: laparoscopic versus open technique.

PURPOSE: Laparoscopic donor nephrectomy (LDN) is an increasingly accepted modality for procuring donor kidneys for transplantation. We analyzed and compared the short and long-term outcomes of living transplant allografts from kidneys procured by laparoscopic or open donor (ODN) technique and managed with a single immunosuppression regimen in each group. MATERIALS AND METHODS: Records of recipients who underwent living (laparoscopic or open) donor nephrectomy were reviewed from August 1999 to July 2001 for LDN and from January 1994 to December 1999 for ODN. Patients included were on a single immunosuppression regimen particular to each group. Sirolimus, mycophenolate mofetil and prednisone were given to the LDN group, and calcineurin inhibitor (FK-506 or cyclosporine), mycophenolate mofetil and prednisone were given to the ODN group. Excluded from study were patients with prior kidney transplant or patients not receiving immunosuppression as previously described. Also excluded from study were patients lost to followup before 1 year. Data were retrieved retrospectively from case notes or from the transplant database and analyzed using SAS software (SAS Institute, Cary, North Carolina). RESULTS: A total of 71 patients from the LDN group and 60 patients from the ODN group qualified for the study. Demographic data are comparable in both groups except for the significantly longer followup in the ODN group. Serum creatinine was 2.2 and 1.8 mg/dl at postoperative day 4, 1.3 and 1.3 mg/dl at day 10, and 1.3 and 1.4 mg/dl at 1 month in the LDN and ODN groups, respectively. Time to achieve nadir serum creatinine was 8.7 versus 6.6 days for LDN and ODN groups, respectively (p = not significant). Delayed graft function was noted in 5 of 71 (7%) in the LDN group and 3 of 60 (5%) in the ODN group (p = 0.5). In the LDN group 13 (18%) patients had a serum creatinine of greater than 1.5 mg/dl at postoperative day 30 compared to 6 (10%) in the ODN group (p = 0.06). Mean serum creatinine at 1 year was lower for LDN recipients (p = not significant). But at last followup this difference became statistically significant in favor of LDN. Mean followup was 939 versus 2,046 days for LDN versus ODN, respectively (p <0.0001). Recipient mean hospital stay was 5.2 versus 6.7 days for LDN versus ODN, respectively (p = 0.08). There were 8 of 78 (10.2%) episodes of acute rejection in the LDN group compared to 22% in the ODN group (p = 0.08). The complication rate (ureteral vascular, lymphocele, acute rejection and wound) was 11% in LDN compared to 15% in the ODN group. Long-term graft function, graft survival and patient survival in the LDN group were comparable to the ODN group. CONCLUSIONS: Early graft recovery is slower in LDN allografts, although not statistically significant, but long-term function in the LDN group is significantly better compared to the ODN group. Laparoscopic donor kidneys take longer to achieve nadir serum creatinine, but this does not influence long-term outcome and results.

Adult↗
PubMed2004

Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes.

A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients.

Adult↗
PubMed2004

De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years.

We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure and gene expression. Sixty-one kidney recipients treated with basiliximab mycophenolate mofetil (MMF) and prednisone (P) were randomly assigned to concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Comparing sirolimus/MMF/P to cyclosporine/MMF/P there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dL; p = 0.008), higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 mL/min; p = 0.008), iothalamate GFR (60.6 vs. 49.2 mL/min; p = 0.018) and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p = 0.013). Regression analysis of calculated GFRs from 1 to 36 months yielded a positive slope for sirolimus of 3.36 mL/min/year, and a negative slope for cyclosporine of -1.58 mL/min/year (p = 0.008). Gene expression profiles from kidneys with higher Banff chronic allograft nephropathy (CAN) scores confirmed significant up-regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. At 2 years the sirolimus-treated recipients have better renal function, a diminished prevalence of CAN and down-regulated expression of genes responsible for progression of CAN. All may provide for an alternative natural history with improved graft survival.

Adult↗
PubMed2003

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.

Adrenal Cortex Hormones↗
PubMed2002

Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine.

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.

Adolescent↗
PubMed2002

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

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. METHODS: The study population included 792 (508 cadaveric and 284 living donor) transplants performed in 786 patients at the Cleveland Clinic Foundation and its affiliate hospitals between July 1, 1987 and July 1, 1998. Patients who were less than 18-yr-old or had less than 12 months of graft function were excluded from the analysis. Over 90% of the cadaveric and 11% of the live donor recipients were given an induction antibody. A total of 591 patients were given the SIM formulation and 201 the NEO formulation of cyclosporine. Additional maintenance therapy included either azathioprine or mycophenolate mofetil, and steroids. All patients were followed to graft loss, death, or return to dialysis. The NEO group was followed until December 2001. The diagnosis of acute rejection was biopsy confirmed in >92% of cases. Chronic rejection was identified by clinical and biopsy criteria. Demographic and clinical data was collected from medical records, interviews, and phone contact with patients and treating physicians. RESULTS: The mean follow-up was 84 +/- 31 months for the SIM group, and 54 +/- 14 months for the NEO group. At 70 months there was no significant difference (p = 0.17) - actuarial patient survival between the SIM (90.7%) vs. the NEO (93%) treated patients. In addition, at 70 months there was no significant difference (p = 0.55) in death censored actuarial graft survival between the SIM (84.3%) and the NEO treated (85.7%) patients. The acute rejection-free rate was 10% higher for the NEO vs. the SIM patients (79 vs. 69%, p = 0.0004). Chronic rejection was diagnosed in 141 of 591 (24%) of the SIM patients and in 56 of 201 (28%) of the NEO patients (p = ns). At 5 yr the mean serum creatinine (mg/dL) was 2.07 +/- 1.69 for the SIM and 2.15 +/- 1.61 for the NEO patients (p = ns). CONCLUSIONS: The use of the microemulsion formulation of CsA has led to the improved delivery of the parent drug, and a decrease in the number of acute rejection episodes post-transplant. However, patient and graft survival, renal function, and progression to chronic allograft nephropathy at 5 yr were no different. The advantages of greater drug exposure from the microemulsion formulation may be counterbalanced by increased drug induced nephrotoxicity over time.

Adult↗