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Background: Tacrolimus (FK506) use has been suggested as a risk factor for post-transplantation diabetes mellitus (PTDM) because it can impair insulin secretion. This association warrants further investigation. This study aimed to examine the prevalence of PTDM and its association with FK506 use in kidney transplant recipients. The study also aimed to examine the relationship of FK506 use and diabetes-related biologic markers., Methods: A retrospective chart review was used to collect data at a medical center in northern Taiwan from September 2003 to February 2012. PTDM was defined with the use of the criteria of the American Diabetes Association., Results: Among 166 patients included in the analysis, PTDM was reported in 49 patients (29.5%). A total of 93 patients used the FK506 regimen, of whom 34 (36.6%) were PTDM cases. Logistic regression showed that FK506 use (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.20-6.11; P = .016) and older age (OR,1.08; 95% CI, 1.03-1.13; P = .001) were significant risk factors for PTDM. In addition, FK506 use in PTDM cases was associated with a significantly higher hemoglobin A1c level (7.55 vs 5.81; P = .01) and a borderline significantly higher insulin resistance index (3.24 vs 1.92; P = .053) than was FK506 use without the presence of PTDM., Conclusions: Older age and an FK506 regimen were important predictors of the prevalence of PTDM. Greater early detection and prevention efforts for PTDM are needed for older transplant recipients. PTDM patients with an FK506 regimen had higher hemoglobin A1c levels and insulin resistance index than did patients who did not use FK506. The association of serum indicators with FK506 use in the prevalence of PTDM warrants further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: One major cause of graft loss is chronic allograft nephropathy (CAN), which may relate to calcineurin inhibitors (CNIs). We converted CAN cases from CNIs to sirolimus and observed the outcomes., Method: From January 2004 to August 2007, there were 28 kidney recipients in our center with creeping creatinine levels compatible with CAN. We started sirolimus at 2 mg/d and reduced the CNIs gradually. Sirolimus trough levels were kept between 5 and 8 ng/mL. Mycophenolic acid was cut in half; there was no adjustment on prednisolone dose., Results: The mean switch time was 47.3 months after transplantation. One case discontinued sirolimus due to severe drug-induced pneumonitis. Twelve of the 27 (45%) patients showed improvements in graft function. The most frequent complications were anemia (13/28), hyperlipidemia (13/28), and pneumonitis (4/28). A baseline serum creatinine level less than 2.2 mg/dL seemed to forecast a response to sirolimus conversion. Most of the graft functional improvement occurred within 6 months after the switch. No graft or patient loss was encountered., Conclusion: Our experience suggested that 45% of patients with sirolimus conversion showed improved graft function. Among patients within 1 year after transplantation, those with a creatinine level less than 2.2 mg/dL, no proteinuria, and no hyperlipidemia seemed to be better candidates for Sirolimus conversion.

Objectives: The majority of pregnancies after transplantation reported in the literature occurred in patients treated with a combination of calcineurin inhibitors, prednisolone, and azathioprine. There is little experience with newer drugs. We report a successful pregnancy in a kidney recipient with exposure to sirolimus-based immunosuppression., Methods: We describe a case of successful delivery in a 30-year-old woman who became pregnant 1 year and 8 months after a living related renal transplantation. She received sirolimus, cyclosporine, and prednisolone before conception and during the first and second trimesters of gestation., Results: The female recipient received sirolimus in combination with cyclosporine and prednisolone. During follow-up, her serum creatinine values were stable with pregnancy occurring at 1 year and 8 months after transplantation. At 27 gestational weeks, sirolimus was discontinued and she was maintained on cyclosporine and prednisolone. There were no signs or symptoms of graft rejection. A Cesarean section was performed at 39 weeks of gestation to deliver a healthy, 2994-g, Apgar 10, male infant. The renal function of the female recipient continued to be stable after delivery., Conclusion: To date, pregnancies in renal transplant recipients are still considered high risk. The U.S. National Transplantation Pregnancy Registry (NTPR) has reported increased rates of maternal and fetal complications. There have been no live births reported to the NTPR about female recipients exposed to sirolimus throughout gestation. We report a live birth without a structural defects with successful delivery after sirolimus use during the first and second trimesters of gestation.

Background: A drug regimen including a calcineurin inhibitor (cyclosporine or tacrolimus) and prednisone has been the mainstay of maintenance immunosuppression in our renal transplant recipients for more than 10 years. After the introduction of mycophenolate mofetil (MMF), a new, potent immunosuppressant that may reduce the incidence of late rejection in renal transplant recipients, the immunosuppressive protocol in some recipients was changed to an MMF-based regimen. We sought to ascertain whether the addition of MMF lead to greater susceptibility to infectious complications., Patients and Methods: Between May 1991 and November 2002, all renal transplant recipients who received a two-drug regimen initially for more than 6 months were changed to an MMF-based regimen. The study includes patients with functional grafts for more than 6 months thereafter. Differences in the incidence, etiology, and outcome of infections were compared during the non-MMF versus the MMF periods., Results: Eighty patients of mean age of 38.6 years (range 13 to 69) included 43 men and 37 women. The mean daily MMF dose was 663 mg/patient (range 250 to 1500 mg). The mean follow-up time of non-MMF period and MMF periods were 3.4 and 2.1 years, respectively. The overall incidence of infections in the two periods was similar (0.2 infections/patient in the non-MMF period and 0.25 infections/patient in the MMF period, P = .57). No mortality was associated with these infectious complications. In conclusion, addition of MMF, a more potent immunosuppressive protocol, did not increase the incidence of infections in stable renal transplant recipients initially treated with a two-drug regimen.

Background: Acute rejection is a major cause of graft loss in renal transplantation. Because the highest risk for acute rejection is in the first month posttransplantation, improved prophylaxis could be most beneficial in this period. Simulect administration provides 30 to 45 days of immunoprophylaxis against acute rejection during the critical period after transplantation., Objectives: We sought to assess the incidence of acute rejection episodes and the safety and tolerability of Simulect plus Neoral immunosuppression. Patient and graft survival rates up to 3 years posttransplantation were evaluated., Method: Forty-one transplant recipients received Simulect by intravenous infusion of an initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on day 4 posttransplant. All renal recipients received immunosuppression with Neoral and steroid., Results: There were eight cases (19.5%) of acute rejection within 1 year. The rejection episodes were easily reversed with steroid pulse therapy in seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate was 100%., Conclusions: Simulect in combination with Neoral and steroid-reduced the incidence of acute rejection without an increase in adverse events. The low incidence and severity of acute rejection may have led to the superior 3-year patient and graft survival rates in renal transplantation.

Background: Acute rejection is the major cause of graft loss in renal transplantation. Sirolimus (rapamycin) inhibits the effects of cytokines on T and B cells; therefore, it provides prophylaxis against acute renal rejection. This open-label trial assessed the incidence of biopsy-confirmed acute rejection episodes, variation in renal function, as well as graft and patient survival rates up to 12 months posttransplantation when using sirolimus in combination with cyclosporine and prednisolone as immunosuppressants., Methods: Ten kidney transplant recipients received sirolimus 2 mg daily after a 6-mg loading dose. Doses were then adjusted to keep the whole-blood trough level between 5 and 20 mg/mL. All patients received sirolimus in combination with cyclosporine and prednisolone., Results: At 12 months after renal transplantation, the graft and patient survival rates were 90% and 90%, respectively. One patient died at 2 months due to sepsis with a functioning graft. The mean serum creatinine levels at 1, 3, and 6 months were 1.59 mg/dL, 1.71 mg/dL, and 1.65 ml/dL, respectively. There was no biopsy-confirmed acute rejection episode within 12 months., Conclusions: Sirolimus in combination with cyclosporine and prednisolone significantly protected kidney transplant recipients from acute rejection for up to 1 year of follow-up.

Purpose: We evaluate whether cyclosporine (CsA) or tacrolimus (FK) could be reduced or eliminated after sirolimus was added in chronic allograft nephropathy (CAN). By reducing doses of CsA or FK, we expected that renal function would improve., Method and Material: Twenty-one patients with CAN had sirolimus added as an immunosuppressive agent. We evaluated the creatinine (Cr) level 3 months after addition. The doses of CsA and FK were decreased gradually and then eliminated over a course of 4 to 6 weeks. If the Cr level rose rapidly or other prominent signs of rejection occurred; low-dose CsA or FK would be added per protocol. We evaluated the duration of engraftment before sirolimus and the Cr level when it was added., Results: Renal function improved in 13 of 21 cases. The improvement in Cr ranged from 12.5% maximally to 1.84% minimally. Seven of 13 cases still required low-dose CsA. The average duration of engraftment before sirolimus was 13.66 +/- 10.80 months. The average Cr level before sirolimus was 1.65 +/- 0.56 mg/dL. In the other eight cases, the Cr level kept rising from 5.1% to 20.4%. The average duration of engraftment was 88.38 +/- 42.21 months. The average Cr level before sirolimus was 2.85 +/- 0.54 mg/dL. Hyperuricemia was noted in 31.3% and hyperlipidemia in 68.8%., Conclusion: Sirolimus is a safe alternative to reduce or eliminate CsA or FK in CAN. In cases with a long duration of engraftment and high Cr level, sirolimus might have some effect as a substitute for CNI and thus prevent further nephrotoxicity.

Lymphoproliferative disorder (LPD) is a well recognized complication of solid organ transplantation. It is associated with Epstein-Barr virus (EBV) infection and is often a fatal complication of immunosuppression. We report a 2.5-year-old boy who developed LPD presenting as small bowel lymphoma after liver transplantation. The patient had intermittent fever after transplantation and reactivation of latent EBV infection was documented by pre- and posttransplant serologic tests. About 5 months after his liver transplantation, the patient had sudden onset of abdominal pain and emergency laparotomy was performed for peritonitis. He proved to have multiple small bowel perforations caused by B cell lymphoma and died of multiple organ failure 9 days after operation, despite aggressive treatment and stopping immunosuppressive agents. We conclude that prevention of overimmunosuppression in pediatric recipients after liver transplantation and early detection and treatment of LPD are important to decrease this often-fatal complication.

"Haemophilus somnus" fractions which inhibited iodination of protein by bovine polymorphonuclear leukocytes were isolated by heat extracting a washed bacterial suspension at 60 degrees C or incubating the bacterial suspension at 37 degrees C and were partially purified by ultrafiltration. The components in each fraction were separated by reverse-phase high-performance liquid chromatography and identified as ribonucleotides, a ribonucleoside, and purine and pyrimidine bases. Most of the compounds were found to be inhibitory to iodination in a dose-dependent manner. When the effect of each component on iodination at the concentrations present in "H. somnus" fractions was determined, it was found that guanine and GMP were the components responsible for most of the suppression in the fraction isolated by heat extraction, whereas guanine and adenine were the major inhibitory components in the fraction isolated by incubation at 37 degrees C.

Abstract: Objective: BK virus infection after transplantation is known to cause graft failure but the association with malignancies is controversial. Methods: BK virus workup was performed for kidney recipients in our center under conditions of hematuria or acute deterioration of graft function. We reviewed the history and reported our treatment and the disease course of three patients with BK virus later diagnosed with urothelial carcinoma. Results: All three patients received kidneys from China with immunosuppression using a calcineurin inhibitor and monoclonal antibodies. Synchronous bladder and upper-tract tumors were treated with surgery followed by intravesical chemotherapies. We tapered the immunosuppressants and changed to a sirolimus-based regimen. Intravesical chemotherapy and concurrent chemoradiotherapy were performed to prevent recurrence. All three patients now have functional grafts. Conclusion: BK virus infection may lead to tumorigenesis. Besides decreasing immunosuppressants, we should be more alert to the detection of malignancies in BK virus-reactivated recipients. Early aggressive treatment may be curative, preserving functional grafts. [Copyright &y& Elsevier]