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.

N-glycosylation of carnosinase influences protein secretion and enzyme activity: implications for hyperglycemia.

Objective: The (CTG)(n) polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion. Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1 secretion is changed under hyperglycemic conditions.

Hypothermic injury: the mitochondrial calcium, ATP and ROS love-hate triangle out of balance.

Background/aims: Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine.

Methods: Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species and reduced thio-group measurement, intracellular calcium measurement and mitochondrial calcium staining were performed in the study.

Rosiglitazone reduces angiotensin II and advanced glycation end product-dependent sustained nuclear factor-kappaB activation in cultured human proximal tubular epithelial cells.

Tubular damage is a major feature in the development of diabetic nephropathy. This study investigates the effects of the thiazolidindione rosiglitazone on angiotensin II and advanced glycation end product-induced tubular activation in human proximal tubular epithelial cells IN VITRO. Angiotensin II and advanced glycation end products, both induced a dose-dependent sustained activation of the redox-sensitive transcription factor, Nuclear Factor KAPPA B (NF-kappaB).

Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?

Persistent T cell activation is a common finding in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AAV) patients. Because imatinib, a selective inhibitor of the ABL, ARG, PDGFR and c-KIT tyrosine kinases, inhibits T cell activation, this study was conducted to evaluate the potential use of imatinib for the treatment AAV patients refractory to conventional therapy. In particular, we investigated the inhibition of T cell activation by this drug and its efficacy on activated T cells from anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitides (AASV) patients.

Analgesics use and ESRD in younger age: a case-control study.

Background: An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design.

Methods: We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004.

Efficacy and tolerability of conversion from cyclosporin to azathioprine after kidney transplantation: a review of the evidence.

After the introduction of cyclosporin as an immunosuppressive drug for organ transplantation at the beginning of the 1980s, concern arose about adverse effects of this new drug. Nephrotoxicity, fear of progressive loss of renal function with long term use of cyclosporin, a higher incidence of lymphomas in the first studies with cyclosporin and the high costs of the new drug led to the modification of immunosuppressive regimens so that cyclosporin was replaced by azathioprine several months after renal transplantation. Short and long term follow-up of elective conversion studies demonstrated equal patient and graft survival in the azathioprine (conversion) and cyclosporin (control) groups.

Atorvastatin donor pretreatment prevents ischemia/reperfusion injury in renal transplantation in rats: possible role for aldose-reductase inhibition.

Background: The aim of the present study was to evaluate the effect of donor pretreatment with atorvastatin on ischemia/reperfusion (I/R) injury in renal transplantation in rats.

Methods: Donor rats were pretreated orally with atorvastatin or vehicle 2 days prior to explantation. Kidneys were stored for 24 hr at 4 degrees C in University of Wisconsin solution and transplanted into isogeneic or allogeneic recipients.

Proteinuria-lowering effect of heparin therapy in diabetic nephropathy without affecting the renin-angiotensin-aldosterone system.

Angiotensin-converting enzyme inhibitors and angiotensin II (AngII) type 1 receptor blockers lower proteinuria and preserve renal function in diabetic nephropathy (DN). The antiproteinuric effects are greater than their blood pressure reduction, involving the sieving properties of the glomerular filter. In DN, glomerular staining for heparan sulfate proteoglycans is decreased.

L-carnosine, a substrate of carnosinase-1, influences glucose metabolism.

Objective: Carnosinase 1 (CN1) is a secreted dipeptidase that hydrolyzes L-carnosine. Recently, we have identified an allelic variant of human CN1 (hCN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in human diabetic patients. We therefore hypothesized that L-carnosine in the serum represents a critical protective factor in diabetic patients.

A CTG polymorphism in the CNDP1 gene determines the secretion of serum carnosinase in Cos-7 transfected cells.

Recently, we demonstrated that a polymorphism in exon 2 of the serum carnosinase (CNDP1) gene is associated with susceptibility to developing diabetic nephropathy. Based on the number of CTG repeats in the signal peptide, five different alleles coding for 4, 5, 6, 7, or 8 leucines (4L-8L) are known. Diabetic patients without nephropathy are homozygous for the 5L allele more frequently than those with nephropathy.

Dopamine treatment in brain-dead rats mediates anti-inflammatory effects: the role of hemodynamic stabilization and D-receptor stimulation.

Brain death (BD) is associated with profound inflammation in end-organs. Dopamine (DA) treatment reduces this inflammatory response, but the underlying mechanisms remain thus far largely unknown. In this study, we investigated if the anti-inflammatory effect of DA was related to hemodynamic stabilization and by which receptors it was mediated.

Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis.

Systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of renal recovery in those who presented with a serum creatinine >500 micromol/L (5.

Increased circulating endothelial progenitor cells in septic patients: correlation with survival.

Objective: Endothelial damage and detachment of endothelial cells are known to occur in septic patients. Thus, recruitment of circulating endothelial progenitor cells (cEPCs) to these lesions might have a beneficial effect on the clinical course in septic patients. Therefore, we were interested in whether EPCs, detected by flow cytometry, are increasingly mobilized during sepsis and if this mobilization is associated with clinical outcome.

Influence of hypersulfated and low molecular weight heparins on ischemia/reperfusion: injury and allograft rejection in rat kidneys.

The aim of the study was to evaluate the effect of the hypersulfated nonanticoagulant heparin derivative LU 51198 (LU) and of the low molecular weight heparin reviparin (REVI) on ischemia/reperfusion (I/R) injury, acute rejection (AR) and chronic allograft nephropathy (CAN) in rats. Organs were harvested 5 days after 60 min of renal I/R injury. For investigation of AR and CAN we used the allogeneic Fisher-Lewis model.

Donor dopamine pretreatment inhibits tubulitis in renal allografts subjected to prolonged cold preservation.

Background: In the present study, we used the Brown-Norway (BN) to Lewis model as a model for acute rejection, to test the hypothesis that dopamine (DA) treatment of BN donors significantly reduces the inflammatory response after renal transplantation.

Methods: BN and Lewis rats (isograft controls) were treated for 24 hr with DA (5 microg/kg/min) or NaCl (0.9%), respectively.

Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss.

Micro-vascular and renal complications in diabetic patients are a considerable clinical challenge. In a previous study, we found a significant decrease in vascular endothelial growth factor A (VEGF-A) mRNA levels in glomeruli from patients with diabetic nephropathy (DN). We now set out to investigate the relationship between reduced VEGF-A and connective tissue growth factor (CTGF) expression levels, the number of podocytes, and the extent of interstitial fibrosis.

A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans.

Background: Four linkage analyses have identified a region on chromosome 18q22-23 that appears to harbour a diabetic nephropathy (DN) susceptibility locus. A trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs.

Atorvastatin interferes with activation of human CD4(+) T cells via inhibition of small guanosine triphosphatase (GTPase) activity and caspase-independent apoptosis.

Although a beneficial effect of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, i.e. statins, on cell-mediated immunity has been suggested in vivo and in vitro, little is known about the molecular and biochemical events by which statins inhibit T cell proliferation.

In vivo effects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis.

15-Deoxyspergualin (DSG) is an alternative treatment modality for Wegener's granulomatosis (WG) patients refractory to conventional treatment. Nevertheless, it is unclear how DSG modulates disease activity in these patients. This study was conducted to investigate which parameters of adaptive and acquired immunity were influenced during two subsequent cycles of DSG treatment.

Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.

Background: Early graft function (EGF) has an enduring effect on the subsequent course after kidney transplantation. This study compares quantitative parameters of EGF for the prediction of graft survival.

Methods: We involved 300 consecutive transplant recipients from deceased donors from 1989 to 2005.

Allelic variation in the CNDP1 gene and its lack of association with longevity and coronary heart disease.

Carnosine, a cytoprotective dipeptide found at very high concentrations in skeletal muscle, heart and brain, is cleaved in blood by serum carnosinase which is encoded by the CNDP1 gene. We recently found that homozygosity of a 5-leucine variant in the leader peptide of this enzyme protects diabetes mellitus patients against nephropathy. Hypothesising that the same allele could also be associated with longevity or a reduced incidence of cardiovascular problems, we examined the frequency of CNDP1 alleles in German centenarians, patients with premature coronary heart disease, and matched controls.

Hypothermia-induced loss of endothelial barrier function is restored after dopamine pretreatment: role of p42/p44 activation.

Background: Donor dopamine usage is associated with improved immediate graft function after renal transplantation. Although prolonged cold preservation results in an increased vascular permeability, the present study was conducted to examine in vitro and in vivo if dopamine pretreatment influences endothelial barrier function under such conditions.

Methods: To assess cold preservation injury in vitro and in vivo, cultured human umbilical vein endothelial cells (HUVEC) and Lewis donor rats were pretreated with dopamine or isotonic saline prior to cold storage.

Effect of pre-treatment with catecholamines on cold preservation and ischemia/reperfusion-injury in rats.

Treatment of organ donors with catecholamines reduces acute rejection episodes and improves long-term graft survival after renal transplantation. The aim of this study was to investigate the effect of catecholamine pre-treatment on ischemia/reperfusion (I/R)- and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral nephrectomy.