A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching.

Outcome Comparison of Acute Respiratory Distress Syndrome (ARDS) in Patients with Trauma-Associated and Non-Trauma-Associated ARDS: A Retrospective 11-Year Period Analysis.

(1) Background: Acute respiratory distress syndrome (ARDS) is a rare complication in multiply injured patients. Due to the rarity of ARDS development after trauma, little is known about outcomes of patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. (2) Methods: This retrospective analysis included = 1038 ARDS patients admitted to the ARDS center of Charité-Universitätsmedizin Berlin between 2007 and 2018.

The Impact of on Tacrolimus Pharmacokinetics and Outcome in Clinical Practice at a Single Kidney Transplant Center.

Although there is evidence that the variant should be considered in tacrolimus dosing in renal transplantation, its impact beyond tacrolimus dose requirements remains controversial. In a cohort of 121 kidney transplant recipients, we analyzed the , , and alleles and the variants , , and for their impact on exposure and dose requirement. Relevant clinical outcome measures such as acute rejection within the first year after transplantation, delayed graft function, and renal function at discharge (estimated glomerular filtration rate) were evaluated.

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.

Analytical evaluation of a real-time PCR-based DNA demethylation assay to assess the frequency of naturally occurring regulatory T cells in peripheral blood.

Objectives: Regulatory T cells (Tregs) which may indicate operational tolerance provide a promising biomarker for individualization of immunosuppression. Naturally thymus-derived Tregs (nTregs) represent the major suppressive phenotype and can be identified by their demethylation status in the Tregs Specific Demethylated Region (TSDR) of the Forkhead-Box-P3 (FOXP3) gene using quantitative PCR (qPCR).

Design And Methods: The analytical performance of a TSDR demethylation qPCR assay was assessed in whole blood of healthy individuals (HI) and kidney transplant recipients (KTR).

Efficacy and safety of tacrolimus compared with ciclosporin-A in renal transplantation: 7-year observational results.

The European Tacrolimus versus Ciclosporin-A Microemulsion (CsA-ME) Renal Transplantation Study demonstrated that tacrolimus decreased acute rejection rates at 6 months. Primary endpoints of this investigator-initiated, observational 7-year follow-up study were acute rejection rates, patient and graft survival rates, and a composite endpoint (BPAR, graft loss, and patient death). We analyzed data from the original intent-to-treat population (n = 557; 286 tacrolimus, 271 CsA-ME).

Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation.

Background: In solid organ transplantation, sensitive real-time biomarkers to assess the graft health are desirable to enable early intervention, for example, to avoid full-blown rejections. During rejection, high amounts of graft-derived cell-free DNA (GcfDNA) are shed into the blood stream. The quantification of this GcfDNA in allotransplantation is considered to fulfill this need, because it can be measured with great precision and at reasonable cost.

Total and free plasma concentrations of the active metabolite of leflunomide in relation to therapeutic outcome in kidney transplant recipients with BK-virus nephropathy.

Plasma concentrations of A771726, the active moiety of leflunomide, have been suggested to be associated with antiviral efficacy and/or an increased risk of toxicity. A771726 is >99% bound to serum albumin, which can be relevant in kidney transplant recipients (KTRs) displaying impaired function, which leads to increased pharmacologically active free drug concentrations. This study investigated the relationship of total (t-) and free (f-) A771726 concentrations with clinical outcomes.

CD26/dipeptidyl peptidase IV: a comparative study of healthy persons and kidney transplant recipients before and early after transplantation.

Objectives: Human CD26 is co-stimulatory for lymphocytes, circulates in a soluble form in blood (sCD26), and has intrinsic dipeptidyl peptidase IV (DPPIV) activity. Associations between CD26 expression on the surface of T cells (CD26+/CD3+) and acute rejection and between (CD26+/CD3+)/DPPIV and clinical immunosuppression have been reported. These results encouraged the investigation of CD26 as a potential biomarker to optimize immunosuppressive therapy.

Why do we need biomarkers in solid organ transplantation.

Immunosuppressive therapy is administered to all solid organ transplant recipients to help prevent acute rejection and the loss of allograft function. Adequate immunosuppression is a delicate balance between rejection rates and chronic allograft dysfunction on the one hand and immunological and nonimmunological side effects on the other hand. The general strategy is to minimize the toxicity associated with triple immunosuppressive regimens and possibly enhance long-term allograft survival without compromising short-term allograft survival.

Early type II fiber atrophy in intensive care unit patients with nonexcitable muscle membrane.

Objective: Intensive care unit-acquired weakness indicates increased morbidity and mortality. Nonexcitable muscle membrane after direct muscle stimulation develops early and predicts intensive care unit-acquired weakness in sedated, mechanically ventilated patients. A comparison of muscle histology at an early stage in intensive care unit-acquired weakness has not been done.

Association between pharmacodynamic biomarkers and clinical events in the early phase after kidney transplantation: a single-center pilot study.

Introduction: Strategies based on monitoring pharmacodynamic effects are increasingly evaluated to individualize immunosuppressive therapy. In the present investigation, both drug-specific and general pharmacodynamic biomarkers were assessed and their association with clinical events early after kidney transplantation was examined.

Methods: Thirty-five de novo kidney transplant patients receiving basiliximab, enteric-coated mycophenolate sodium (2×720 mg/day), steroids, and tacrolimus (target: 6-8 μg/L) were included.

Biomarkers as a tool for management of immunosuppression in transplant patients.

Therapeutic drug monitoring is a well-established approach in transplantation medicine to guide immunosuppressive therapy. However, it cannot always predict the effects of immunosuppressive drugs on immune cells, because it does not reflect any aspect of an individual patient's immune system. Pharmacodynamic monitoring is a more recent strategy to provide information about the biologic effect of a specific drug or drug combination on the individual transplant patient.

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results.

Background: The European tacrolimus versus ciclosporin A microemulsion (CsA-ME) renal transplantation study showed that tacrolimus was significantly more effective in preventing acute rejection and had a superior cardiovascular risk profile at 6 months.

Methods: The endpoints of this investigator-initiated, observational, 36-month follow-up were acute rejection incidence rates, rates of patient and graft survival and renal function. An additional analysis was performed using the combined endpoints BPAR, graft loss and patient death.

Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results.

Background: Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function.

Methods: The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids.

Contrast media nephropathy: intravenous CT angiography versus intraarterial digital subtraction angiography in renal artery stenosis: a prospective randomized trial.

Background: Spiral computed tomographic angiography (CTA) is a noninvasive method to diagnose renal artery stenosis (RAS). In digital subtraction angiography (DSA), contrast media (CM) is injected directly into the renal artery; in CTA, a greater amount of CM is injected intravenously, potentially leading to an increased incidence of CM nephropathy.

Methods: We investigated 80 patients with suspected RAS randomized to either CTA or DSA prospectively.

Angiography for renal artery stenosis: no additional impairment of renal function by angioplasty.

The aim of this study was to compare renal function between patients with renal angiography and patients with renal angiography and angioplasty (AP) for renal artery stenosis (RAS). Forty-seven patients with suspected RAS were prospectively investigated by digital subtraction angiography (DSA) using non-ionic low osmolar contrast media (CM). In 22 patients RAS was detected and in 16 cases an angioplasty was performed in the same session.

[Hypocomplementemic urticarial vasculitis syndrome].

History And Admission Findings: A 40-year-old woman was admitted with recurrent membranoproliferative glomerulonephritis. For many years she had been suffering from joint pains and attacks of angio-oedema of the upper and lower lip. Physical examination was unremarkable except for marked oedema and urticaria of the trunk and limbs.

[New kidney, but a sick heart. Why many patients with renal failure and kidney transplant patients die of cardiovascular disease].

Renal insufficiency and dialysis is associated with hypertriglyceridemia caused by a decreased activity of the enzyme lipoprotein lipase. Peritoneal dialysis is further complicated by hypercholesterolemia due to an increase in the synthesis of VLDL by the liver, stimulated by a rise in glucose absorption from the peritoneal dialysate. The treatment of choice is a lipid lowering diet.

Oxidant stress in hyperlipidemia-induced renal damage.

Hyperlipoproteinemia can aggravate glomerulosclerosis and chronic tubulointerstitial (ti) damage in kidneys without primary immunologic disease. We evaluated whether the effect of hyperlipidemia on progression of renal damage differed between kidneys without preexisting glomerular disease and kidneys with mesangioproliferative glomerulonephritis and whether the renal actions of hyperlipidemia were dependent on oxidant-antioxidant balance. Hyperlipidemia was induced by high-fat and high-cholesterol diet in uninephrectomized rats.

Simvastatin in nephrotic syndrome. Simvastatin in Nephrotic Syndrome Study Group.

Background: Hyperlipidemia of the nephrotic syndrome is a risk factor for the development of systemic atherosclerosis, but it also may aggravate glomerulosclerosis and enhance the progression of glomerular disease. HMG-CoA reductase inhibitors are effective in reducing cardiovascular morbidity and mortality. Whether they may influence the progression of glomerular disease is not clear.

Role of xanthine oxidase in passive Heymann nephritis in rats.

Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to proteinuria. This study examines the involvement of xanthine oxidase in this process.

Metabolic rates of 4-hydroxynonenal in tubular and mesangial cells of the kidney.

The degradation of the lipid peroxidation product 4-hydroxynonenal (HNE) in primary cultures of kidney tubular and mesangial cells was determined. Using various initial concentrations of the aldehyde a decline of cellular viability was found. Mesangial cells were more susceptible to the toxic effects of HNE.