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Background: Chronic kidney disease is common after heart or liver transplantation, with calcineurin inhibitors (CNI) considered the key contributor. A possible influence of posttransplant blood pressure has not been extensively examined., Methods: Data from adult recipients of a first heart or liver transplant were analyzed regarding the relationship between blood pressure at year 1, renal function at year 5, and CNI therapy., Results: Although we confirmed the well-known detrimental effect of increased 1-year systolic blood pressure on 5-year kidney graft survival, heart or liver graft survival was not affected. However, among 2534 heart transplant recipients with good renal function at year 1, increasing systolic blood pressure at year 1 was associated with higher rates of poor renal function at year 5 posttransplant. This association was confirmed on multivariate analysis overall (odds ratio, 1.25 per 20 mm Hg increment; P < 0.001) and within subgroups. Similar results were observed in 1822 liver transplant recipients (odds ratio, 1.35; P < 0.001). Neither the type of CNI nor CNI dose or trough level at year 1 showed a significant association with kidney function at year 5., Conclusions: One-year blood pressure was identified as the major modifiable risk factor associated with deteriorating kidney function between years 1 and 5 after heart or liver transplantation.

Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial. Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564). Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p = 0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines. Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.

Background: There have been striking changes during the last 10 years concerning the choice of calcineurin inhibitor and antimetabolite agent prescribed after kidney transplantation., Methods: A retrospective analysis of 51,303 patients undergoing deceased-donor kidney transplantation during 1998 to 2007 was performed using multivariate regression analysis. All patients received cyclosporine A (CsA) or tacrolimus (Tac) with azathioprine (AZA) or mycophenolic acid (MPA) on an intention-to-treat basis with corticosteroids plus/minus antibody induction. Graft survival rates and secondary outcomes were analyzed. A subanalysis was performed for transplants undertaken during 2002 to 2007, in which all patients were treated with MPA plus corticosteroids and CsA or Tac., Results: All-cause graft failure and death-censored graft failure to 5 years posttransplant did not differ significantly between Tac and CsA. We found no evidence in support of previous claims that MPA results in superior long-term graft survival compared with AZA treatment. At the end of year 1, Tac was associated with a lower risk for serum creatinine more than or equal to 130 mumol/L (P<0.001) and hypercholesterolemia (P<0.001) versus CsA, but a higher risk for de novo posttransplant diabetes (P<0.001). MPA treatment was associated with a lower risk of acute rejection (P<0.001) but a higher risk of hospitalization because of infection (P<0.001) versus AZA., Conclusions: Five-year graft survival in deceased-donor kidney transplant recipients is equivalent in patients receiving CsA- or Tac-based immunosuppression, and in those receiving MPA or AZA. The absence of a survival benefit with modern agents is relevant in the current cost-conscious era of prescribing.

Background: Data are scarce concerning the impact of maintenance immunosuppression dose reductions posttransplant., Methods: Graft survival according to dose reduction or discontinuation of calcineurin inhibitors or mycophenolate mofetil (MMF) after the first year posttransplant was evaluated in 25,045 patients undergoing kidney transplantation during 1996 to 2005. No patient in this analysis had experienced a rejection and all had good graft function before dose reduction., Results: Reduction of cyclosporine (CsA) dose to less than or equal to 150 mg/day, tacrolimus to less than or equal to 2 mg/day, or MMF to less than or equal to 1.0 g/day in patients on CsA or less than or equal to 0.5 g/day in patients on tacrolimus during the second year posttransplant was associated with a statistically significant reduction in graft survival (hazard ratios between 1.37 and 1.65). Withdrawal of CsA, tacrolimus, or MMF during year 2 was also associated with an increase in the risk of graft loss compared with continuing treatment (hazard ratio 1.52-1.73)., Conclusions: This observational analysis indicates that in kidney transplant patients with good graft function, withdrawing maintenance CsA, tacrolimus or MMF, or reducing the dose of these agents below certain thresholds after the first year posttransplant is associated with a significant risk of graft loss.

Background: It is widely assumed that the graft-enhancing properties of antilymphocyte induction agents and their lymphoma-inducing potential are intimately related., Methods: The Collaborative Transplant Study (CTS) database was used to evaluate graft survival and non-Hodgkin lymphoma at 3 years according to type of induction in 112,122 patients receiving a deceased-donor renal transplant during 1985 to 2004., Results: The relative risk of 3-year graft loss versus no induction was 1.07 (95% confidence interval [CI], 1.01-1.13; P=0.016) with murine anti-CD3 monoclonal antibody (OKT3), 1.03 (95% CI, 0.95-1.11; NS) with antithymocyte globulin (ATG)-Fresenius, 1.18 (95% CI, 1.02-1.35; P=0.021) with ATGAM, 0.74 (95% CI, 0.68-0.81; P<0.001) with Thymoglobulin, and 0.78 (95% CI, 0.72-0.84; P<0.001) with interleukin (IL)-2RA induction. The standardized incidence ratio of lymphoma compared with a similar nontransplant population was 21.5 (95% CI, 15.7-28.8; P<0.001) with OKT3, 4.9 (95% CI, 1.6-11.5; P=0.008) with ATG-Fresenius, 29.0 (95% CI, 12.5-57.1; P<0.001) with ATGAM, 21.6 (95% CI, 14.3-31.2; P<0.001) with Thymoglobulin, 7.8 (95% CI, 4.4-12.9; P<0.001) with IL-2RAs, and 9.4 (95% CI, 8.3-10.6 P<0.001) with no induction., Conclusions: Those agents that offered the highest rates of graft survival were not necessarily associated with the highest risk of lymphoma. Graft survival was significantly improved with Thymoglobulin and IL-2RA induction, whereas lymphoma rates were highest with ATGAM, OKT3, and Thymoglobulin. IL-2RA agents seem to offer the best risk-to-benefit ratio for this patient population overall in terms of graft survival and lymphoma.

A patient undergoing allogeneic hand transplantation needs lifelong immunosuppression with the risk of serious side effects, including life-threatening disease. The question remains: does the eventual improvement in function justify the risk? To answer this question, we try to assess the risks based on a large body of cumulative data derived from more 200,000 kidney transplants using the Collaborative Transplantation Study (CTS). Only selective data which apply to a patient population aged between 15-40 years were used (n = 58,310). Data are compared to the literature references and show superiority with respect to patient numbers, statistics, actuality, and methodology. The CTS data show that the incidence of de novo malignancies is lower than previously reported. The risk of developing any form of cancer is approximately 3%, of developing a skin cancer 1.1%, and of developing a lymphoma 0.58% within 5 years after transplantation. The risk of suffering from a cataract is 11% after 5 years, which is also lower than previously reported. Although the incidence of side effects (particularly malignant disease) is likely to be lower than previously thought, the risk-benefit question must be answered by each hand surgeon for each individual patient., (Copyright 2004 Wiley-Liss, Inc.)

Background: Previous analysis of kidney transplant data from the Collaborative Transplant Study database showed that patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 7 years posttransplantation. Longer-term and additional analyses have now been performed., Methods: Data from cadaver kidney transplants performed between 1985 and 1998 were analyzed retrospectively. Patients were included if they had a functioning graft 1 year posttransplantation, and the daily cyclosporine dose administered 1 year posttransplantation was reported. Data on cyclosporine dose, serum creatinine concentration, and systolic blood pressure were recorded 1 and 5 years after transplantation; information on graft survival was documented at yearly intervals., Results: Patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 10 years posttransplantation. Cyclosporine <2 mg/kg/day was least beneficial overall and in subanalyses based on age, risk level, and 1-year serum creatinine concentration. The microemulsion cyclosporine formulation (Neoral) was associated with a significantly higher 4-year graft survival rate than the conventional formulation (Sandimmune; P=0.0001). Median systolic blood pressure 5 years posttransplantation was similar in each 1-year cyclosporine dose category (range of medians 139.0-140.0 mmHg). The percentages of patients with serum creatinine concentrations of <130, 130-260, 260-400, or >400 micromol/L 1 and 5 years posttransplantation were similar across 1-year cyclosporine dose categories, with the exception of >6 mg/kg/day, where there was a shift toward a less favorable serum creatinine concentration over time., Conclusions: The 1-year cyclosporine dose was significantly associated with long-term graft survival, with evidence of underimmunosuppression at doses <3 mg/kg/day and overimmunosuppression at doses >6 mg/kg/day, but had little influence on systolic blood pressure or serum creatinine concentration at doses up to 6 mg/kg/day.

Background: There are conflicting reports in the literature concerning the efficacy of maintenance immunosuppression in renal transplantation with a regimen of azathioprine and steroids., Methods: The daily dosage (mg/kg) of azathioprine administered 1 year after transplantation was analyzed in relation to subsequent long-term graft outcome. Transplants performed from 1985 to 1996 and reported to the Collaborative Transplant Study were analyzed., Results: In patients on maintenance immunosuppression without cyclosporine, the daily dosage of azathioprine had a highly significant influence on long-term graft outcome. Patients who received > 1.5 mg/kg/ day of azathioprine had a 69% graft survival rate at 7 years, compared with a 55% rate in patients receiving 1.01-1.5 mg/kg/day (P<0.0001) and a 45% rate in patients receiving < or = 1.00 mg/kg/day (P<0.0001). This observation was valid for patients who were taken off cyclosporine during the first year as well as for patients who were treated with azathioprine and steroids (without cyclosporine) from the beginning., Conclusion: Maintenance immunosuppression with azathioprine and steroids results in good long-term kidney graft survival, provided azathioprine is administered at a daily dose of >1.5 mg/kg.