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Abstract: Cast nephropathy is a rare event among renal transplants, usually associated with multiple myleoma or light chain nephropathy. Herein we have reported primary graft dysfunction early posttransplantation due to cast nephropathy, associated with thrombotic microangiopathy. [Copyright &y& Elsevier]

Abstract: One of the major issues in contemporary kidney transplantation is prevention of acute allograft rejection episodes (AREs). Cytokines are crucial mediators of immune reactions leading to AREs. We correlated serum Th1/Th2 cytokine concentrations with AREs. The project included 44 patients undergoing kidney transplantation. During the 3-month period following the transplantation, ARE was diagnosed in 11 patients. Serum samples collected 1 day before and 2, 7, 14, and 30 days after transplantation were tested for interleukin (IL)-2, IL-4, IL-5, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α concentrations using flow cytometry. Nonrejection (NONAR) and rejection (ARE) groups of patients did not show significant differences in baseline demographic characteristics. We observed that higher pretransplantation serum levels of IFN-γ (P = .000003) and IL-10 (P = .000001) were associated with AREs. Our analysis also showed slightly higher IL-4 serum levels among NONAR patients up to 7 days posttransplantation, followed by a drop in concentrations in NONAR patients. In contrast, there was a continuous increase among ARE patients. No significant differences were observed in plasma levels of IL-2, IL-5, IL-10, or TNF-α between the two groups. Higher pretransplantation levels of IFN-γ and IL-10 observed in ARE patients indicated ongoing nondetected, probably nonspecific, inflammatory processes able to intensify an immune response directed against the transplanted organ leading to its acute rejection. Higher levels of IL-4 prior to and shortly after transplantation may have protective effects on graft survival. However, a prolonged, increased production of IL-4 after transplantation can also contribute to AREs. [Copyright &y& Elsevier]

Kidney transplantation is an optimal method of renal replacement therapy in patients with phase V chronic kidney disease. Elderly patients (older than 60 years) with a kidney transplant create a significant and constantly growing pool of patients with this type of organ transplantation. In this group of patients, long-term care should be particularly stringent and vigilant. Apart from typical conditions associated with chronic kidney disease and possible post-transplant complications as well as side effects of immunosuppressive treatment, the patient also experiences changes and limitations associated with the progress of age and diseases typical for old age, characterized by a higher risk of infection, and changed pharmacokinetics/pharmacodynamics. Undoubtedly, patients should remain under the medical care of qualified transplantologists, but constant cooperation with a general practitioner and geriatrician would be of added value. Study results show that although most of the elderly kidney recipients have constant contact with their general practitioners, and almost half of them use private care, contribution of the geriatrician to the transplant care system is unsatisfactory, and elderly kidney recipients would expect more extensive outpatient care. [ABSTRACT FROM AUTHOR]

Background Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). Methods Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin). Results Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5–15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%). Conclusions Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged-release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation. ClinicalTrials.gov NCT00189839 ; NCT00717470 . [ABSTRACT FROM AUTHOR]

Abstract: Cytokines are crucial inflammatory mediators involved in the development of immune response leading to allograft rejection. We investigated the cytokine patterns in patients sera from cases of acute rejection episodes (ARE), chronic rejection (CR), and long-term stable courses (STABLE). The project included 20 patients with ARE, 20 with CR, and 15 with at least a 5-year stable course. Serum samples collected at the time of rejection diagnosis were cytometrically tested for concentrations of interleukin (IL) 2, IL-4, IL-6, IL-10, interferon (IFN) γ, and tumor necrosis factor α. No significant differences between investigated groups were observed before transplantation (P > .05). Significant differences were observed among the groups in serum levels of IFN-γ, IL-4, IL-6, and IL-10. Our data suggested that distinct serum cytokine patterns were present among various states of kidney allograft function. ARE was characterized by a mixed cytokine pattern with elevated IL-10 and IFN-γ compared with the STABLE patients. The cytokine pattern in CR patients, in turn, was characterized by elevated levels of IL-4, IL-6, and IL-10 and decreased levels of IFN- γ compared with both STABLE and ARE subjects. Our results suggested that the TH2 response may contribute to the initiation and/or maintenance of CR, because IL-4, IL-6, and IL-10 serve as growth and differentiation factors for B cells to increase antibody production. We also observed up-regulated production of IFN-γ and down-regulation of TH2 cytokines among patients with stable long- term graft function. [Copyright &y& Elsevier]

Abstract: Our project aimed to investigate the relation between the level of pretransplantation and posttransplantation peripheral CD4+CD25+Foxp3+ T-regulatory lymphocytes (Tregs) and the development of acute rejection (AR) episodes in 44 patients after kidney transplantation. During the 6-month period following transplantation, AR was diagnosed in 11 patients. Peripheral blood samples were collected 1 day before and 10 days after transplantation and tested for concentrations of CD4+CD25+Foxp3+ cells by means of flow cytometry. The pretransplantation analysis showed significantly lower mean levels of peripheral Tregs in AR patients versus control group (P < .05). A lower level of Tregs was also observed in nonrejection (NONAR) patients versus control group (P < .05); however, it was still higher than in the AR group (P < .05). The 10-day posttransplantation analysis showed a similar pattern; however, a significant increase in the concentration of peripheral Tregs in NONAR patients was observed (P < .05), whereas no change was recorded in AR patients (P > .05). We found lower pretransplantation levels of peripheral Tregs in both AR and NONAR groups, versus control group. The deficiency of peripheral Tregs in patients with end-stage renal failure might be due to the long-term inflammatory processes adversely affecting the peripheral regulatory mechanisms. However, significantly lower levels of Tregs observed in AR patients might also be related to genetic predispositions. Our observation suggests that the size and possibly the functionality of Tregs in the AR group was not sufficient to successfully control the immune response after kidney transplantation, leading to acute rejection episodes. [Copyright &y& Elsevier]