Simultaneous pancreas-kidney transplant versus kidney transplant alone in diabetic patients.

The decision for simultaneous pancreas-kidney (SPK) versus kidney transplant alone (KTA) in diabetic patients with renal failure depends on the potential risks and benefits for each procedure. The purpose of this study was to compare the morbidity, mortality, and renal allograft survival in diabetic patients who underwent SPK versus KTA, and to discern the added risks associated with pancreas transplantation. Between 7/1/86 and 9/30/90, 69 primary cadaver SPK and 59 primary cadaver KTA were performed in type I diabetic patients with chronic renal failure. Antilymphocyte globulin or OKT3 was used for induction therapy, followed by standard triple therapy (prednisone, azathioprine, and cyclosporine). Patient and graft survivals were retrospectively analyzed. In addition, a detailed comparison of morbidity in those patients treated after 7/1/87 was performed (53 SPK, 49 KTA). For those less than 45 years of age (65 SPK, 42 KTA), there were no significant differences (P greater than 0.6) in the actuarial patient survival at one year (SPK 92%, KTA 95%), or two years (SPK 89%, KTA 92%), or actuarial renal allograft survival at one year (SPK 82%, KTA 83%) or two years (SPK 77%, KTA 83%). However, for those greater than 45 years old, actuarial renal allograft survival was significantly higher (P less than 0.03) in the KTA group. The mean serum creatinine levels were similar at one year (SPK 1.8, KTA 1.9 mg/d).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gallstone formation after pancreas and/or kidney transplantation: an analysis of risk factors

Pancreas and kidney transplantation (SPK) is the treatment of choice for patients with type 1 diabetes mellitus and end-stage renal failure. Gallstones are common after SPK transplantation but little is known about the true incidence and etiology of gallstones in this group. We therefore evaluated the incidence of gallstones and the presence of transplant-related risk factors in patients after SPK and kidney transplantation alone (KTA). Data were evaluated of 56 consecutive patients who underwent SPK transplantation and compared the results with those of 91 consecutive nondiabetic patients who underwent KTA transplantation at the Leiden University Medical Center between 1987 and 1994. Of the 58 evaluable KTA patients, 20.7% developed gallstones during 7.7 yr of follow-up and in the SPK group 43.9% of the 41 evaluable patients developed gallstones during 7.1 yr of follow-up. Postoperative weight loss and cyclosporin A-related hepatotoxicity correlated with gallstone formation both in SPK and KTA patients. In addition, the duration of postoperative fasting and autonomic neuropathy correlated with gallstones in SPK patients. It is concluded that both in patients after SPK transplantation and in patients after KTA transplantation, the risk to develop gallstones is significantly increased. Physicians should be aware of the high incidence of gallstones in SPK recipients.     

Charcot neuroarthropathy after simultaneous pancreas–kidney transplantation: risk factors,prevalence, and outcome

We retrospectively analyzed outcome and risk factors of developing Charcot foot (CF) in 100 patients with type 1 diabetes mellitus who underwent a simultaneous pancreas–kidney (SPK) transplantation. Patients who developed CF after SPK transplantation had significantly higher mortality (56% vs. 18%) and more frequently graft failure (44% vs. 13%). Recipients with CF also experienced acute rejections more frequently (78% vs. 41%). They furthermore had higher pre‐transplant values of HbA_1c, received cyclosporine and azathioprine more often, and had significantly higher cumulative corticosteroid use. Patients transplanted in an earlier era (1992–1998) received cyclosporine and azathioprine more often and had a significantly higher cumulative corticosteroid use with the higher prevalence of CF. Conversely, patients with diabetes transplanted more recently (1999–2012) received lower doses of corticosteroids as part of their tacrolimus‐based immunosuppressive therapy, resulting in fewer CF attacks. In conclusion, development of CF after SPK is associated with poor patient and graft outcome. Poor pre‐transplant diabetic control and the use of high‐dose corticosteroids are risk factors for the development of CF. We recommend reduction in or even total avoidance of corticosteroids after SPK transplantation. Given the importance of the diagnosis of CF on outcome, a systematic examination of SPK patients' feet is recommended.     

Tacrolimus-induced alopecia in female kidney-pancreas transplant recipients

BACKGROUND: Immunosuppressive drugs given to solid organ transplant recipients may be responsible for cosmetic side effects which can endanger patient compliance. Cyclosporine is associated with hirsutism whereas tacrolimus has been associated with rare cases of alopecia. Since 1998, we have included tacrolimus within the immunosuppressive regimen following kidney-pancreas transplantation. The aim of this study was to evaluate the incidence of alopecia in this population and possible risk factors. METHODS: Between January 1, 1995 and October 31, 2003, 59 consecutive simultaneous kidney-pancreas (SPK) transplants were performed in 58 recipients (27 females and 31 males). The immunosuppressive regimen comprised corticosteroids, calcineurin inhibitor (cyclosporine, n=11; or tacrolimus, n=40) and a purine inhibitor (azathioprine or mycophenolate mofetil). RESULTS: Clinically significant alopecia occurred in 13 patients (28.9%) receiving tacrolimus versus none receiving cyclosporine (P<0.001). Of those who experienced alopecia, 11 were female and two were male (P=0.02). The mean delay between transplantation and alopecia was 422 days (range 100-1,567). Other causes of alopecia were excluded. Treatment of alopecia with topic minoxidil was successful in all cases but one, which required conversion from tacrolimus to cyclosporine. CONCLUSIONS: Alopecia is a frequent complication in women receiving tacrolimus therapy following SPK transplantation. Its pathogenesis is unknown. This cosmetic complication must be discussed with patients before transplantation to minimize the risk of noncompliance.     

The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients

Cyclosporin and tacrolimus remain the cornerstone immunosuppressive drugs in organ transplantation. Dosing and monitoring these drugs is based on pharmacokinetic protocols, but measuring a pharmacodynamic parameter, calcineurin phosphatase (CaN) activity, could be a valuable supplement in determining optimal doses. Forty stable renal transplant patients were investigated three times in a 6-month period. Blood samples were drawn at 0, 1, 2, 3 and 4 h after oral intake of tacrolimus (FK) or cyclosporin at days 1 and 180. At day 90, one blood sample at trough level (FK) or C2 level (cyclosporin A, CsA) was drawn. CaN activity was determined in whole blood as the release of 32P from a phosphorylated peptide. Activity of the 32P was quantitated by liquid scintillation and results converted to Units CaN, utilizing a calibration curve with CaN. We demonstrated that calcineurin activity profiles at days 1 and 180 were the same for both drugs. Furthermore, we found that patients treated with tacrolimus or cyclosporin displayed different calcineurin activity profiles. We found that cyclosporin displayed greater calcineurin inhibition than tacrolimus. We have demonstrated that the two drugs exert significantly different effects on calcineurin activity in renal transplant patients with stable, well-functioning grafts and that tacrolimus-treated patients can maintain good, stable graft function with minimal CaN inhibition.     

Impact of transplantation on quality of life in patients with diabetes and renal dysfunction

BACKGROUND: Simultaneous pancreas/kidney transplant (SPK) is an effective therapy that enables people with insulin-dependent diabetes mellitus (IDDM) and renal failure to maintain a more normal lifestyle, without the burdens of dialysis and insulin therapy. However, SPK has been viewed as a higher cost and higher risk procedure than kidney transplant, and it is unclear if SPK offers better health and quality of life (QOL) outcomes than insulin therapy plus kidney transplant alone (KTA). The purpose of this study is to determine which procedure affords better health and QOL outcomes. METHODS: This is a prospective observational study with assessments at pretransplant and 1 and 3 years posttransplant. Patients with IDDM and renal dysfunction who received either SPK or KTA from August 1990 to September 1993 at a university transplant center were enrolled. A convenience sample of patients with IDDM and complications not seeking transplants were enrolled during the same time interval. The main outcome measures were the SF-36 Short Form Health Survey and a Satisfaction with Diabetes Therapy Scale. RESULTS: Most health status and QOL measures improved from baseline values within each transplant group. After adjustment for diabetes severity and other baseline variables, year 3 follow-up scores of the SPK cohort were better than those of the KTA cohort for several SF-36 scales: physical functioning (P=0.038); bodily pain (P=0.047), general health (P=0.014), and the physical component summary (P=0.003). SPK recipients also reported greater satisfaction with diabetes therapy (P=0.014) and perceived more benefits to secondary complications. The KTA patients, however, had higher adjusted scores for the role-emotional subscale (P=.037) and the mental component summary (P=.037). By year 3, the SPK cohort is at the 30th and 51st percentiles of the general adult US population in self-reported physical and mental health; the KTA cohort is at the 10th and 73rd percentile. CONCLUSIONS: At follow-up, both SPK and KTA patients report better health and quality of life but SPK patients report greater improvements than KTA patients in physical health and in areas that are diabetes specific. Although the improved physical outcomes of SPK patients are consistent with perceived benefits to secondary complications, the mental health differences cannot be explained by the study data and warrant further study.     

Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients.

BACKGROUND: Refractory acute cellular rejection may occur despite triple-drug immunosuppression (cyclosporine A, steroids, azathioprine/mycophenolate mofetil). The purpose of this study was to determine the efficacy of tacrolimus rescue therapy in patients maintained on cyclosporine-based immunosuppression (CBI). METHODS: Between December 1993 and October 1996, 208 patients underwent thoracic organ transplantation at the Hospital of the University of Wisconsin at Madison. One hundred forty-nine patients underwent heart replacement; 59 underwent lung transplantation. One hundred thirty-nine of the heart transplant cohort received CBI preceded by induction therapy with OKT3. Forty-six of the lung transplant cohort received CBI without induction cytolytic therapy. Refractory rejection was defined as failure to respond to high-dose steroids (500 mg to 1 g IV methylprednisolone for 3 days) and/or monoclonal antibody therapy (OKT3, 5 to 10 mg IV/day for 7 to 14 days). In patients with refractory rejection, cyclosporine was replaced with tacrolimus. RESULTS: Overall, 16% (30/185) of patients receiving CBI experienced refractory rejection. Thirty-one episodes of grade IIIa or greater rejection occurred in 11% (15/139) of heart transplant recipients. Twenty episodes of grade II to IV rejection occurred in 33% (15/46) of lung transplant recipients. After tacrolimus rescue therapy, 93% (14/15) of patients in the heart transplant group converted to grade II or less rejection. Refractory rejection was reversed in 73% (11/15) of the lung transplant group. Reversal was documented at biopsy in all (8/8) lung recipients in whom it had been histologically identified. FEV1 values of 3 additional patients stabilized. CONCLUSIONS: The incidence of refractory rejection in thoracic organ transplant recipients on CBI is significant. Reversal of refractory rejection follows rescue immunotherapy with tacrolimus.     

De novo immunosuppression with sirolimus and tacrolimus in heart transplant recipients compared with cyclosporine and mycophenolate mofetil: a one-year follow-up analysis

BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in combination with a calcineurin inhibitor in heart transplant recipients. METHODS: From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment group) received a combination of sirolimus, tacrolimus, low-dose rabbit antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial survival, rate of rejection, incidence of infection, probability of developing diabetes mellitus, renal function, platelet and white blood cell counts, and incidence of coronary artery disease at 1 year, were compared with a cohort of 25 patients (control group) who underwent transplantation primarily in 2000 and in early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids. All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier actuarial 1-year survival rates were equivalent between groups (97% for the treatment group and 88% for the control group), as was freedom from allograft rejection (48% and 42% for treatment and control groups, respectively). No cases of transplant arteriopathy were noted within the first posttransplantation year. Renal function was not significantly affected in either group. There was a striking increased incidence of mediastinitis in the treatment group (19%) versus 0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose rabbit antithymocyte globulin) were associated with an increased incidence of mediastinitis and posttransplantation diabetes mellitus. No obvious long-term benefit on survival, arteriopathy, or renal function was noted.     

1型糖尿病肾病尿毒症期患者胰肾联合移植与单独肾移植远期疗效观察

目的研究1型糖尿病肾病尿毒症期患者胰肾联合移植（simultaneouspancreas—kidneytransplantation,SPK）与单独肾移植（kidneytransplantationalone,KTA）的长期临床效果。方法选取2001年10月至2004年7月在南方医科大学南方医院接受SPK和KTA的1型糖尿病肾病尿毒症期患者共16例,其中SPK组6例,KTA组10例。回顾性分析和比较两组5年人／移植物存活率、急性排斥反应和蛋白尿的发生率及空腹血糖、血肌酐、血脂（甘油三酯、胆固醇）、血压水平。结果16例受者至今存活。SPK组移植胰腺功能正常,1例于移植后第5年血肌酐升至450μmol／L左右,尿蛋白阳性,其余受者血肌酐均不超过130μmol／L,尿蛋白阴性,5年人／移植物存活率均为100％。KTA组3例血肌酐浓度为150～180μmol／L,尿蛋白阳性,1例于移植后第4年因血肌酐升至700μmol／L以上开始规律血液透析治疗,5年人／移植物存活率为100％和90％。两组急性排斥反应的发生率差异无统计学意义（P〉0．05）。移植后5年SPK组和KTA组血肌酐平均浓度为（166．3±139．3）μmol／L和（209．8±188．6）μmoL／L,蛋白尿、高血脂、高血压的发生率分别为16．7％、33．3％、50％和40％、60％、80％,SPK组均低于KTA组,但差别无统计学意义（均P〉0．05）;而血糖水平、胆固醇浓度、收缩压水平SPK组均低于KTA组,差别有统计学意义（均P〈0．05）。结论SPK是1型糖尿病肾病尿毒症期患者的有效治疗方法,与KTA比较,其移植后5年的移植肾功能较好,高血脂、高血压的发生率较低。     

Randomized clinical trial of the effect of microemulsion cyclosporin and tacrolimus on renal allograft fibrosis

BACKGROUND: The aim of this study was to compare the effect of Neoral cyclosporin- and tacrolimus-based therapy on the development of renal allograft fibrosis (chronic allograft nephropathy; CAN) in a prospective randomized trial. METHODS: A total of 102 patients undergoing renal transplantation were randomized to immunosuppression with either microemulsion cyclosporin (Neoral; 15 mg per kg per day adjusted to whole-blood trough concentrations of 200-300 ng/ml) or tacrolimus (0.2 mg per kg per day adjusted to whole-blood trough levels of 8-15 ng/ml) in conjunction with steroids, or at a lower dose (7 mg per kg per day and 0.1 mg per kg per day respectively) with the addition of azathioprine for non-heart-beating renal transplant recipients. Renal transplant interstitial fibrosis was quantified using computerized histomorphometric measurement of picrosirius red-stained 1-year protocol renal transplant biopsies. Levels of interstitial fibrosis were compared in relation to observed efficacy and toxicity profiles of the two drugs. RESULTS: There was a significant increase in allograft interstitial fibrosis in the patients treated with Neoral compared with those given tacrolimus. There was no significant difference in the demographic characteristics between the patient groups or in the incidence of acute rejection (Neoral 36 per cent versus tacrolimus 35 per cent) or steroid-resistant rejection (both 10 per cent) between the two drugs. There was a higher incidence of insulin resistance in the tacrolimus group (post-transplant diabetes mellitus, glucose tolerance testing) but this was not statistically significant. Neoral was associated with a significant increase in total cholesterol (P = 0.030) and low-density lipoprotein (P = 0.021) levels, which persisted throughout the study period. CONCLUSION: Despite equivalent efficacy and pretransplantation risk factors for CAN, Neoral was associated with increased allograft fibrosis and significantly higher serum low-density lipoprotein cholesterol levels compared with tacrolimus.     

Cardiac transplant vasculopathy treated by percutaneous coronary intervention

AIM: Cardiac transplant vasculopathy is a limit to long-term survival in heart transplantation (H-Tx) recipients. PTCA results in our H-Tx population were retrospectively analyzed. METHODS: From November 1985 to May 2004, 767 patients underwent heart transplantation. All patients received immunosuppressive therapy with cyclosporine or tacrolimus, azathioprine, steroids and mycophenolate mofetil. Lymphocyte was administrated by 3-7 days course of either rabbit antithymocyte globulins or anti-lymphocyte globulins or by a 14 days course of OKT3. Coronary angiograms were performed every year and more frequently if graft vasculopathy was already diagnosed or suspected. RESULTS: Fifty-two coronary artery lesions were treated during 42 percutaneous transluminal cardioangioplasty (PTCA)/stent procedures in 36 patients. Mean time since heart transplantation to PTCA was 80 +/- 27 months. Indication to PTCA was asymptomatic angiographic graft vasculopathy in 34 patients (94%) and acute myocardial infarction in 2 patients (6%). PTCA was performed on left anterior descending artery in 34 cases (65.4%), on circumflex artery in 10 cases (19.2%), on right coronary artery in 8 cases (15.4%). There were no procedure related deaths. None of the patients required emergency bypass surgery. Two patients had transient acute renal failure. Patient follow-up showed 10 deaths after 1 +/- 54 months from PTCA. Six died for progression of graft vasculopathy, three for cancer and one for gastrointestinal bleeding. Two patients underwent heart retransplantation after 20 and 107 months from the first procedure. Mean follow-up of the remaining patients is 78.3 +/- 50.3 months. CONCLUSION: PTCA may represent a reasonable treatment for graft vasculopathy in selected heart transplant recipients.     

The use of intravenous tacrolimus and mycophenolate mofetil as induction and maintenance immunosuppression in simultaneous pancreas--kidney recipients with previous transplants

Clinical trials using quadruple immunosuppression that include the combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas-kidney (SPK) transplantation. In attempting to obtain a low rejection rate without antibody induction therapy, we proceeded with the combination of TAC intravenous (i.v.), MMF, and steroids as induction therapy and as primary immunosuppression for recipients with previous transplants. In this study, we analyzed 10 patients who received previous transplants, treated with low-dose TAC i.v. as induction therapy. Group A consisted of 6 patients with previous transplants that underwent SPK and group B consisted of four recipients with previous SPK that underwent cadaveric kidney transplants. For group A, the previous transplants were: living related kidney (LRK) followed by islet cell (IC) transplant (n=2), LRK transplant (n=1), cadaver kidney (CAD) and IC transplant (n=1), SPK (n=1), and three previous CAD kidney transplants (n=1). In group A, all six kidneys were lost due to recurrent diabetic nephropathy, IC possibly to rejection, and the pancreas due to thrombosis. In group B with previous SPK transplants, three recipients lost their kidney to chronic rejection and one to long-term use of a nephrotoxic antibiotic. Currently, in all group A and B patients, the kidney and the pancreas are functioning, although 1 patient in group A developed type 2 diabetes (normal fasting C-peptide). Two patients in group A developed three rejection episodes that responded to steroid treatment. The results indicate the TAC i.v. in combination with oral TAC, MMF, and steroids offer effective induction therapy in patients with previous transplants.     

Very early steroid withdrawal in simultaneous pancreas-kidney transplants.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is an effective treatment for patients suffering from type 1 diabetes mellitus. Conventional immunosuppressive treatments include steroids that may induce insulin resistance and are responsible for many side effects. In de novo SPK, early withdrawal of corticosteroids may be an important issue. METHODS: A total of 24 consecutive patients with type 1 diabetes mellitus had been treated by SPK transplantation. All of them had a short induction therapy with anti-thymoglobulin (ATG) and steroids for only 4 days, association with CellCept and tacrolimus. The rate of acute rejection, graft and patient survival and side effects have been analysed. RESULTS: Patient and kidney survival was 100% and the pancreas survival was 95.6% at 1 year. The rate of acute rejection of kidney and pancreas was 4.2% and 8.3% at 6 months, respectively. The mean serum creatinine was 98.9+/-19.6 micromol/l and the mean HbA1c concentration was 5.1%+/-0.5% at 6 months. Only four patients developed a cytomegalovirus primo-infection, associated in one case with pneumonia, whereas 75% of patients developed a bacterial infection. Because of the occurrence of leucopenia and/or diarrhoea, CellCept has been dramatically decreased in 33% of cases and required the re-introduction of steroids. CONCLUSION: A short induction with ATG and steroids associated with a chronic therapy with CellCept and tacrolimus is safe and efficient in preventing acute renal rejection in SPK.     

Steroid withdrawal in pancreas transplant recipients

BACKGROUND: Numerous studies of steroid withdrawal have been carried out in kidney and liver transplant recipients, but only a few in pancreas transplant recipients. Yet, pancreas transplant recipients could have significant long-term benefits from steroid withdrawal. METHODS: We performed a retrospective analysis to determine the feasibility of steroid withdrawal in pancreas transplant recipients. RESULTS: Of 360 recipients who underwent a pancreas transplant between January 1, 1994 and June 30, 1998, 14 attempted steroid withdrawal (12 simultaneous pancreas-kidney [SPK]; 2 pancreas transplant alone [PTA]). Reasons for steroid withdrawal were bone fractures (n = 3), psychiatric disorders (n = 2), severe acne (n = 1), recurrent infections (n = 4), and problems with hypercholesterolemia or hypertension (n = 4). All 14 were maintained on tacrolimus and mycophenolate mofetil (MMF) immunosuppression, except for 1 who was on tacrolimus and azathioprine (AZA). Of the 14 recipients, 11 had no episodes of acute rejection before steroid withdrawal. The remaining 3 had one or more acute rejection episodes. Of the 14 recipients, 10 (72%) currently remain off steroids (mean follow-up 18 months, range 5-51 months). However, 4 recipients have resumed steroids: 2 after an acute rejection episode (at 2 and 21 months post-withdrawal) and 2 because of leukopenia (WBC < 3000) and an inability to tolerate full-dose MMF. Steroid withdrawal was unsuccessful in both PTA recipients and in 2 of the 12 SPK recipients. All 14 recipients currently have a functioning pancreas graft. However, 1 of the SPK recipients, in whom steroid withdrawal failed, has developed chronic kidney rejection and is now back on hemodialysis awaiting a retransplant. CONCLUSION: Steroid withdrawal is possible in up to 70% of pancreas transplant recipients. Further studies are necessary to define ideal candidates for steroid withdrawal. Based on the results of this analysis, we have launched a prospective, randomized trial of steroid withdrawal in pancreas transplant recipients.     

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.     

Impact of simultaneous pancreas and kidney transplantation on cardiovascular risk factors in patients with type 1 diabetes mellitus

We retrospectively investigated the impact of pancreas transplantation on cardiovascular disease risk factors in patients with type 1 diabetic end-stage renal disease (ESRD). Two cohorts of patients, 44 simultaneous pancreas and kidney transplant patients (SPK) and 30 kidney transplant-alone patients (KTA), were included. Univariate and multivariate analyses were performed. Compared with KTA patients, SPK patients had significantly lower mean arterial pressure (88.5+/-12.7 vs. 98.2+/-13.0 mmHg, P=0.002), lower pulse pressure (51.6+/-15.1 vs. 61.4+/-15.6 mmHg, P=0.008), lower low-density lipoprotein cholesterol (83.5+/-20.6 vs. 99.2+/-32.5 mg/dl, P=0.02), and required fewer lipid-lowering medications (31.8% vs. 60.0%, P=0.02). Compared with pretransplant values, only SPK patients showed significant improvement in both blood pressure and total cholesterol. We conclude that SPK significantly improves blood pressure and dyslipidemia compared with KTA in type 1 diabetic ESRD patients.     

Prostate cancer in renal transplant recipients.

BACKGROUND: We conducted a retrospective multi-centre study to determine the characteristics of prostate cancer in renal transplant recipients (RTR) and to analyse the relation with immunosuppressive maintenance therapies. METHODS: Patients from 19 French transplant centres diagnosed with prostate cancer at least 1 year after kidney transplantation were included in this study. Data regarding demographics, kidney transplantation, prostate cancer and immunosuppressive treatment were analysed. RESULTS: Sixty-two patients met the eligibility criteria for this study. Thirty-eight patients (61.3%) received calcineurin inhibitors (CNI) and azathioprine (AZA) with or without steroids, twenty received CNI with or without steroids (32.2%) and four received CNI and mycophenolate mofetil (6.5%). Patients with CNI and AZA immunosuppressive therapy presented more high-stage cancer (T3 and T4) when compared to patients receiving CNI alone (47.5% versus 15%, respectively, P = 0.03). A non-significant increase in lymph node invasion was found in patients receiving CNI and AZA compared to patients receiving CNI alone (21% versus 5%, P = 0.16). In the multivariate analysis, the immunosuppressive regimen with CNI and AZA was the only independent risk factor for locally advanced disease (P = 0.007). CONCLUSION: Our results showed that RTR are at risk for early occurrence and for locally advanced prostate cancer, especially when they received a CNI and AZA maintenance immunosuppressive therapy.     

Metabolic outcomes and renal function after simultaneous kidney/pancreas transplantation compared with kidney transplantation alone for type 2 diabetes mellitus patients

In this study, we aimed to compare the metabolic outcomes, renal function, and survival outcomes of simultaneous pancreas and kidney transplantation (SPK) and kidney transplantation alone (KTA) among end-stage kidney disease (ESKD) patients with type II diabetes mellitus (T2DM). Patients with ESKD and T2DM who underwent KTA (n = 85) or SPK (n = 71) in a transplant center were retrospectively reviewed. Metabolic profiles, renal function, and survival outcomes were assessed repeatedly at different follow-up time points. Propensity score procedures were applied to enhance between-group comparability. The levels of renal and metabolic outcomes between SPK and KTA over time were examined and analyzed using mixed-model repeated-measures approaches. The median follow-up period was 1.8 years. Compared with KTA, SPK resulted in superior metabolic outcomes and renal function, with lower levels of glycated hemoglobin (HbA1c; P = 0.0055), fasting blood glucose (P < 0.001), triglyceride (P = 0.015), cholesterol (P = 0.0134), low-density lipoprotein (P = 0.0161), and higher estimated glomerular filtration rate (eGFR; P < 0.001). SPK provided better metabolic outcomes and renal function. The survival outcomes of the recipients and grafts were comparable between the two groups.     

Assessing the relative risk of cardiovascular disease among renal transplant patients receiving tacrolimus or cyclosporine

Calcineurin inhibitors potentially contribute to risk of cardiovascular events through the development of new-onset diabetes mellitus, hypertension and hyperlipidemia. The exact extent to which calcineurin inhibitors affect these risk factors is difficult to establish since pre-existing renal disease and concomitant immunosuppressive agents (such as steroids or TOR inhibitors) also exert an effect. Clinical trials have consistently shown a higher incidence of new-onset diabetes mellitus with tacrolimus, which has been borne out in large-scale registry analyses. However, the risk of hypertension is approximately 5% higher with cyclosporine than tacrolimus, as is the risk of hyperlipidemia. Statin therapy is effective in treating dyslipidemia and has significant benefits in renal transplant patients. An individualized approach to choice of calcineurin inhibitor, by which cyclosporine or tacrolimus are selected based on the patient's particular risk profile, may thus help to reduce the toll of cardiovascular mortality among renal transplant recipients in the future.     

Differences in gastric motor activity in renal transplant recipients treated with FK-506 versus cyclosporine

BACKGROUND: Little is known concerning gastric motility after renal transplantation and on the impact of immunosuppressants on gastric emptying. METHODS: Gastric emptying was measured in renal transplant recipients, taking different immunosuppressive therapy (steroids and cyclosporine/azathioprine/FK-506), and compared with normal volunteers. RESULTS: After renal transplantation, gastric emptying of liquids was normal, irrespective of the type of immunosuppression. However, solid gastric emptying was significantly faster in FK-506-treated patients compared with patients taking cyclosporine for all measured emptying parameters. Compared with normal volunteers solid gastric emptying was slower in patients taking cyclosporine, comparable in azathioprine treated patients, and characterized by an unusual short lag phase in patients taking FK-506. CONCLUSIONS: In stable renal transplant recipients gastric emptying of solids was significantly faster in patients on FK-506 compared with patients taking cyclosporine. Therefore, FK-506 may be the immunosuppressant of choice after solid organ transplantation in patients with problems related to gastroparesis.