Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients.

Background: The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive.

Methods: This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls.

Pretransplantation GAD-autoantibody status to guide prophylactic antibody induction therapy in simultaneous pancreas and kidney transplantation.

Background: Daclizumab and antithymocyte globulin (ATG) have been shown to reduce allograft rejection. We assessed the safety and efficacy of daclizumab or ATG prophylaxis in combination with triple immunotherapy in simultaneous pancreas-kidney transplant (SPKT) recipients.

Methods: Thirty-nine type 1 diabetic patients scheduled for primary SPKT were randomized to receive prophylactic therapy with either daclizumab or ATG.

Late calcineurin inhibitor withdrawal prevents progressive left ventricular diastolic dysfunction in renal transplant recipients.

Background: Calcineurin inhibitor (CNI)-based therapy is associated with adverse cardiovascular effects. We examined the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on echocardiographic parameters.

Methods: This study was conducted as a substudy of a randomized trial in stable renal transplant recipients who were on a triple CNI-based regimen with prednisone and MMF that evaluated late concentration-controlled withdrawal of CNI or MMF on renal function.

Quantitative polymerase chain reaction profiling of immunomarkers in rejecting kidney allografts for predicting response to steroid treatment.

Background: Steroid-resistant acute rejection is a risk factor for inferior renal allograft outcome.

Methods: From 873 kidney transplant recipients (1995-2005), 108 patients with a first rejection episode were selected for study using strict inclusion criteria and clinical endpoint definition. We aimed to predict response to corticosteroid treatment using gene expression of 65 transcripts.

The functional polymorphism Ala258Ser in the innate receptor gene ficolin-2 in the donor predicts improved renal transplant outcome.

Background: Innate immunity plays a role in controlling adaptive immune responses.

Methods: We investigated the clinical relevance of single nucleotide polymorphisms in 22 genes encoding innate, secreted, and signaling pattern recognition receptors in a total of 520 donor-recipient pairs of postmortem, human leukocyte antigen-DR-compatible kidney transplantations. Associations with rejection incidence were tested in an a priori randomized training set and validation set.

Randomized trial comparing late concentration-controlled calcineurin inhibitor or mycophenolate mofetil withdrawal.

Background: Early calcineurin inhibitor (CNI) withdrawal with mycophenolate mofetil (MMF) has not become routine practice, due to concerns about excess acute rejection. Therapeutic drug monitoring may be advantageous when the CNI or MMF is withdrawn.

Methods: This prospective, randomized, concentration-controlled withdrawal study enrolled 177 stable renal transplant recipients on maintenance CNI-based immunosuppression, combined with steroids and MMF.

Increased influx of myeloid dendritic cells during acute rejection is associated with interstitial fibrosis and tubular atrophy and predicts poor outcome.

Dendritic cells are key players in renal allograft rejection and have been identified as an intrinsic part of the kidney. Here we quantified and phenotyped the dendritic cell populations in well-defined biopsies of 102 patients with acute renal allograft rejection in comparison with 78 available pretransplant biopsies. There was a strong increase in BDCA-1(+) and DC-SIGN(+) myeloid, BDCA-2(+) plasmacytoid, and DC-LAMP(+) mature dendritic cells in rejection biopsies compared with the corresponding pretransplant tissue.

C4d staining in renal allograft biopsies with early acute rejection and subsequent clinical outcome.

Background And Objectives: Diffuse C4d staining in peritubular capillaries (PTCs) during an acute rejection episode (ARE) is the footprint of antibody-mediated rejection. In current clinical practice, diffuse C4d+ staining during acute rejection is regarded as an inferior prognostic sign. This case-control study investigated the prognostic role of mere C4d staining for graft outcome during an ARE in a well defined cohort of similarly ARE-treated patients.

Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up.

Background: Cardiovascular disease is both a major threat to the life expectancy of kidney transplant recipients and an important determinant of late allograft loss. Obesity is an important risk factor for cardiovascular disease.

Methods: We investigated the relation between both pretransplant and 1-year posttransplant body mass index (BMI) with patient and renal graft survival in a cohort of 1810 adult patients.

Urinary properdin excretion is associated with intrarenal complement activation and poor renal function.

Background: Proteinuria predicts progressive renal failure. Next to being a progression marker, non-selective proteinuria itself is thought to be toxic to the tubulointerstitium. In proteinuric states, activation of filtered or locally produced complement is toxic for renal tubular cells and likely contributes to the progression of renal failure.

Urological complications and their impact on survival after kidney transplantation from deceased cardiac death donors.

Urological complications after kidney transplantation may result in significant morbidity and mortality. However, the incidence of such complications after deceased cardiac death (DCD) donor kidney transplantation and their effect on survival is unknown. Purpose of this study was to estimate the incidence of urological complications after DCD kidney transplantation, and to estimate their impact on survival.

Infectious complications after simultaneous pancreas-kidney transplantation: a role for the lectin pathway of complement activation.

Background: Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement activation, and its serum levels are largely determined by frequently occurring polymorphisms of the MBL gene. We questioned whether MBL deficiency influences infectious complications in patients after simultaneous pancreas-kidney transplantation (SPKT).

Methods: Infectious complications in the first year after transplantation were scored retrospectively in 152 consecutive SPKT patients who received their transplant at our center between 1990 and 2005.

Low pretransplantation mannose-binding lectin levels predict superior patient and graft survival after simultaneous pancreas-kidney transplantation.

Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and renal failure. However, this procedure is characterized by a high rate of postoperative infections, acute rejection episodes, and cardiovascular mortality. The lectin pathway of complement activation contributes to cardiovascular disease in diabetes and may play an important role in inflammatory damage after organ transplantation.

Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility.

Background: The introduction of human leukocyte antigen (HLA)-matching in nonliving kidney transplantation has resulted into a better graft outcome, but also in an increase of waiting time, especially for patients with rare HLA phenotypes. We addressed the question of the differential influence of HLA-DR-matching versus HLA-A,B in clinical kidney transplantation.

Methods: We used Kaplan-Meier product limit method to estimate survival rates, and Cox proportional hazard regression for the estimation of relative risks (Hazard-ratios) for different variables.

Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function.

Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most significant predictors of chronic allograft nephropathy. Protocol biopsies, both in deceased- and living-donor renal grafts, have shown that cortical tubulointerstitial fibrosis correlates with graft survival and function. The impact of not treating subclinical acute rejection (SAR) is less clear.

No difference in degree of interstitial Sirius red-stained area in serial biopsies from area under concentration-over-time curves-guided cyclosporine versus tacrolimus-treated renal transplant recipients at one year.

Interstitial fibrosis is the main characteristic of chronic allograft nephropathy and long-term graft failure. Cyclosporin (CsA) is thought to be more fibrogenic than tacrolimus. In a prospective, randomized, multicenter trial using a calcineurin-sparing regimen, renal interstitial volume was compared in CsA- and tacrolimus-treated renal transplant recipients by image analysis of Sirius red (SR)-stained cortical areas in protocol biopsies obtained at 6 mo (n = 94) and 12 mo (n = 97) after transplantation.

Association between mannose-binding lectin levels and graft survival in kidney transplantation.

The mannose-binding lectin (MBL) pathway of complement is activated by pattern recognition. Genetic MBL variants are frequent and associated with low MBL serum levels. Higher MBL levels may be associated with more complement-mediated damage resulting in inferior graft survival.

Calcium levels as a risk factor for delayed graft function.

Background: Delayed graft function (DGF) occurs in up to 50% of renal transplants. Hypercalcemia and hyperparathyroidism are associated with impaired renal function. Little is known on the effects of serum calcium levels on DGF.

Conversion from cyclosporine to azathioprine at three months reduces the incidence of chronic allograft nephropathy.

Background: Conversion from cyclosporine to azathioprine after renal transplantation has been shown to be beneficial in terms of allograft function, cardiovascular risk factor profile, and the incidence of gout. A higher incidence of acute rejection, however, has also been reported and uncertainty still exists about the long-term outcome after conversion. We report on the extended follow-up of an open-label, randomized trial that examined conversion to azathioprine as early as three months after transplantation.

Early versus late acute rejection episodes in renal transplantation.

Background: Acute rejection is a major complication after renal transplantation and the most important risk factor for chronic rejection. We investigated whether the timing of the last treated acute rejection episode (ARE) influences long-term outcome and compared the risk profiles of early versus late ARE.

Methods: A cohort of 654 patients who underwent cadaveric renal transplants (1983-1997) that functioned for more than 6 months was studied.