Donor organ intervention before kidney transplantation: Head-to-head comparison of therapeutic hypothermia, machine perfusion, and donor dopamine pretreatment. What is the evidence?

Therapeutic hypothermia, hypothermic pulsatile machine perfusion (MP), and renal-dose dopamine administered to stable brain-dead donors have shown efficacy to reduce the dialysis requirement after kidney transplantation. In a head-to-head comparison of the three major randomized controlled trials in this field, we estimated the number-needed-to-treat for each method, evaluated costs and inquired into special features regarding long-term outcomes. The MP and hypothermia trials used any dialysis requirement during the first postoperative week, whereas the dopamine trial assessed >1 dialysis session as primary endpoint.

Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial.

Background And Objectives: Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 g/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exposure-response relationship with treatment duration.

Design, Setting, Participants, & Measurements: Five-year follow-up of 487 renal transplant patients from 60 European centers who had participated in the randomized, multicenter trial of dopamine donor pretreatment between 2004 and 2007 (ClinicalTrials.

Chorea in a patient with cryopyrin-associated periodic syndrome.

Objective: To describe a patient with cryopyrin-associated periodic syndrome (CAPS) with an uncommon neurologic phenotype and a rare underlying genetic mutation.

Results: Our patient had CAPS with a rare NLPR3 missense mutation (p.Tyr859Cys) in exon 6 with chorea as the major symptom.

Excellent graft and patient survival after renal transplantation from donors after brain death with acute kidney injury: a case-control study.

Background: Whether organs from donors after brain death (DBD) with acute kidney injury (AKI) should be accepted for transplantation is still a matter of debate.

Methods: This was a retrospective, center-based, matched cohort study of 33 renal transplant patients who received a renal allograft from a DBD with AKI. Sixty-five kidney transplants without donor AKI transplanted directly before and after the index transplantation served as controls.

High interpatient variability in response to mycophenolic acid maintenance therapy in patients with ANCA-associated vasculitis.

Background: Mycophenolic acid (MPA) is used in the maintenance therapy of antineutrophil cytoplasm antibody-associated systemic vasculitis (AASV). MPA exerts its immunosuppression by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH), depleting activated lymphocytes of guanine nucleotides and retarding their proliferation. The purpose of our study was to examine the correlation between clinical outcome and pharmacokinetic-pharmacodynamic (PD) relationships of MPA in patients with AASV.

Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study.

Introduction: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN).

Methods: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week.

Differentiation between Wegener's granulomatosis and microscopic polyangiitis by an artificial neural network and by traditional methods.

Objective: To investigate the operating characteristics of the American College of Rheumatology (ACR) traditional format criteria for Wegener's granulomatosis (WG), the Sørensen criteria for WG and microscopic polyangiitis (MPA), and the Chapel Hill nomenclature for WG and MPA. Further, to develop and validate improved criteria for distinguishing WG from MPA by an artificial neural network (ANN) and by traditional approaches [classification tree (CT), logistic regression (LR)].

Methods: All criteria were applied to 240 patients with WG and 78 patients with MPA recruited by a multicenter study.

Use of highly sensitive C-reactive protein for followup of Wegener's granulomatosis.

Objective: Since Wegener's granulomatosis (WG) represents a relapsing disease, efforts have been made to reliably predict relapses using blood tests. Followup measures such as conventionally determined C-reactive protein (CRP), antineutrophil cytoplasmic antibody (C-ANCA) titer, and proteinase-3 (PR3) ELISA are applied. We evaluated whether during remission elevated highly sensitive CRP (hsCRP) precedes relapse as a marker of subclinical inflammation and thus might improve clinical assessment.

Proton pump inhibitors interfere with the immunosuppressive potency of mycophenolate mofetil.

Objectives: MMF is cleaved in the acidic milieu of the gastric compartment. However, its absorption might be impeded by proton pump inhibitors (PPIs), which suppress acid production and thus increase stomach pH. Since PPIs are widely used, it is useful to clarify whether the total drug amount of MMF is available in patients undergoing PPI treatment.

Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients.

It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFalpha and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67).

Persistent T-cell activation and clinical correlations in patients with ANCA-associated systemic vasculitis.

Background: Although in antineutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AASV) patients, activation of T-cells has been described, persistence of these alterations has not been well characterized. This study was conducted to define persistent T-cell activation (PTA) in AASV patients and to assess whether this correlates with disease activity, disease severity, age or therapy.

Methods: The expression of CD4, CD45RO, CD25, CD26, CD28, CCR7 and HLA-DR was examined longitudinally in 38 consecutive AASV patients.

Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is typically characterized by episodic fever, myalgia, skin rash, conjunctivitis, and abdominal cramps. Recently, mutations in the TNFRSF1A gene on chromosome 12p13 encoding tumor necrosis factor receptor type 1 have been linked to this autoinflammatory syndrome. We report the case of a 29-year-old white woman who experienced periodic inflammatory manifestations with fever up to 40 degrees C, leukocytosis, and elevation of C-reactive protein level (>100 mg/L) in conjunction with acute peritonitis of unknown origin since the age of 19 years.

Serial ANCA determinations for monitoring disease activity in patients with ANCA-associated vasculitis: systematic review.

Background: Antineutrophil cytoplasmic antibodies (ANCAs) are considered by some investigators to be sensitive markers of disease activity and have been suggested to predict relapse and guide therapeutic decisions. Studies using serial ANCA monitoring in patients with ANCA-associated vasculitis (AASV) have yielded controversial results during the last 15 years. To assess the diagnostic value of serial ANCA testing in the follow-up of patients with AASV, we conducted a systematic review of the available literature.

Prolonged treatment of refractory Wegener's granulomatosis with 15-deoxyspergualin: an open study in seven patients.

Background: A subset of patients with Wegener's granulomatosis does not respond to daily oral cyclophosphamide (CYC) plus corticosteroids or suffers from intolerable side effects. A 6 month course of the immunosuppressant 15-deoxyspergualin (DSG) has previously been employed successfully in these refractory cases. However, there are no reports on long-term treatment with DSG.

Newer insights into the aetiology and pathogenesis of myeloperoxidase associated autoimmunity.

In recent years there have been substantial developments in the understanding of the aetiology and pathogenesis of ANCA-associated vasculitides, including myeloperoxidase (MPO) associated autoimmunity. This review will describe genetic and environmental factors that may increase the risk for the disease and will summarise findings demonstrating that T-cells, B-cells and ANCA themselves are of pathogenetic significance. Leukocyte gene expression profiles indicate that the reactivation of granule protein genes contributes to the pathogenesis of AASV.

Treatment of refractory Wegener's granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients.

Background: A subset of patients with Wegener's granulomatosis does not respond sufficiently to cyclophosphamide and glucocorticosteroids or suffers of intolerable side effects. Anecdotal data suggest that antithymocyte globulin (ATG) may be a treatment option for these patients. We now describe 15 patients treated with ATG for refractory Wegener's granulomatosis.

Clinical applications of antineutrophil cytoplasmic antibody testing.

Purpose Of Review: Antineutrophil cytoplasmic antibodies are closely associated with Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome and have contributed to new pathogenetic concepts and improved nomenclature of systemic vasculitides (antineutrophil cytoplasmic antibody-associated vasculitides). However, the application of antineutrophil cytoplasmic antibody testing as a clinical diagnostic tool is still regarded as controversial. This review summarizes the most recent developments in the field, identifies areas of uncertainty, and gives practical guidelines.

Organ transplantation in the vasculitides.

Despite important therapeutic improvements, permanent organ failure may develop in primary systemic vasculitides and affect the heart, the lungs, and especially the kidneys. In systemic vasculitides associated with antineutrophil cytoplasmic antibodies (AASV), end-stage renal failure develops in 20% of cases. Renal transplantation became a beneficial option in these patients, with a graft and patient survival comparable to that in nondiabetic patients.

Vitronectin- and fibronectin-containing immune complexes in primary systemic vasculitis.

In primary systemic vasculitis anti endothelial cell autoantibodies (AECA) have been described frequently. They represent a heterogeneous group of autoantibodies whose target antigens are mostly unknown. We tried to find AECA-antigens by a co-operative binding assay with a panel of monoclonal antibodies (mAb) directed to human umbilical vein endothelial cells (HUVEC) and extracellular matrix proteins.