A "weight-listing" paradox for candidates of renal transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality.

The association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use during postischemic acute transplant failure and renal allograft survival.

Background: Postischemic acute renal transplant failure occurs in approximately one fourth of all dead donor transplantations. Uncertainty exists regarding the putative association between the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) and kidney transplant graft survival in patients with delayed allograft function.

Methods: We conducted an open cohort study of all 436 patients who experienced an acute renal transplant failure out of all 2,031 subjects who received their first kidney transplant at the Medical University of Vienna between 1990 and 2003.

Age and sex are sufficient for predicting fractures occurring within 1 year of hemodialysis treatment.

Background: The incidence of fractures averages 20 per 1000 hemodialysis patient years at risk. This study sought to design and evaluate the utility of a simple prediction rule for fractures in dialysis patients using only standard demographical and biochemical information.

Methods: 1777 prevalent hemodialysis patients of the Austrian dialysis and transplant database who had an evaluation of fractures in 2004 and 2005 were included into analysis.

Protein biomarkers associated with acute renal failure and chronic kidney disease.

Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired.

Diagnosis of renal osteodystrophy.

The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different. Bone histology remains the gold standard for the exact classification of ROD.

Developments in clinical islet, liver thoracic, kidney and pancreas transplantation in the last 5 years.

Although organ transplantation has matured into a proven therapy for end-stage organ failure, the many notable developments of the past 5 years speak to the multitude of remaining challenges. Two new procedures, islet transplantation and adult-to-adult living donor liver transplantation, have emerged to enlarge our therapeutic armamentarium for Type 1 diabetes mellitus and end-stage liver disease, respectively. In cardiac transplantation, the acceptance of ventricular assist devices as destination therapy is a notable event in light of critical shortage of deceased donor organs.

Transforming omics data into context: bioinformatics on genomics and proteomics raw data.

Differential gene expression analysis and proteomics have exerted significant impact on the elucidation of concerted cellular processes, as simultaneous measurement of hundreds to thousands of individual objects on the level of RNA and protein ensembles became technically feasible. The availability of such data sets has promised a profound understanding of phenomena on an aggregate level, expressed as the phenotypic response (observables) of cells, e.g.

Complete renal tubular acidosis late after kidney transplantation.

Background: Neither the prevalence nor the associated risk factors of late post-transplant renal tubular acidosis (RTA) are known.

Methods: We conducted a cross-sectional study with 576 patients for more than 12 months after kidney transplantation, and a glomerular filtration rate (GFR) >40 ml/min. RTA was diagnosed by measurement of the urine anionic gap, urine pH and plasma potassium during acidosis, and fractional bicarbonate excretion after bicarbonate loading.

Effects of bisphosphonates on bone loss in the first year after renal transplantation--a meta-analysis of randomized controlled trials.

Background: Bone loss remains a serious problem after kidney transplantation and is most pronounced during the first months after engraftment. Bisphosphonates are frequently used to treat post-transplant osteodystrophy, but data of large randomized controlled trials (RCTs) are missing.

Methods: We, therefore, conducted this systematic review of the literature, searching electronic databases, reference lists and abstracts from scientific meetings to identify RCTs in all languages.

Autologous stem-cell transplantation in progressing amyloidosis is associated with severe transplant-related toxicity.

Background: Amyloid light-chain (AL) amyloidosis is a disorder of plasma cells in which depositions of immunoglobulin light-chain fragments cause progressive organ failure and death with a median survival of one year, but autologous stem-cell transplantation can induce high response rates, especially in isolated renal involvement.

Methods: Six patients aged between 43 and 59 years were diagnosed with AL-amyloidosis and had stem cells mobilized with either recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone (n = 2) or cyclophosphamide (2-4 g/m(2)) and rhG-CSF (n = 4). All six patients had kidney involvement and nephrotic syndrome, four had cardiac involvement and two involvement of the vascular, nervous and gastrointestinal systems.

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation.

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo.

Molecular signature of mice T lymphocytes following tolerance induction by allogeneic BMT and CD40-CD40L costimulation blockade.

Tolerance induction by mixed chimerism and costimulation blockade is a promising approach to avoid immunosuppression, but the molecular basis of tolerant T lymphocytes remains elusive. We investigated the genome-wide gene expression profile of murine T lymphocytes after tolerance induction by allogeneic bone marrow transplantation (BMT) and costimulatory blockade using the anti-CD40L antibody MR1. Molecular functions, biological processes, cellular locations, and coregulation of identified genes were determined.

Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation.

Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525 enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to first skin and nonskin malignancies were compared between treatments using a survival analysis.

Transcriptional response in the unaffected kidney after contralateral hydronephrosis or nephrectomy.

Background: Unilateral loss of kidney function is followed by compensatory contralateral growth. The early, genome-wide transcriptional response of the untouched kidney to unilateral ureteral obstruction (UUO) or unilateral nephrectomy is unknown.

Methods: Twelve adult male Sprague-Dawley rats were subjected to UUO and twelve rats to unilateral nephrectomy.

Superior outcomes in renal transplantation after early cyclosporine withdrawal and sirolimus maintenance therapy, regardless of baseline renal function.

Background: It has become increasingly important to refine therapeutic strategies according to individual patient characteristics. We evaluated the long-term impact of renal function at the time of withdrawing cyclosporine (CsA) in renal allograft recipients receiving sirolimus (SRL), CsA, and steroids (ST).

Methods: At 3 months+/-2 weeks, 430 of 525 patients were eligible to be randomized to remain on triple-therapy (SRL-CsA-ST, n=215) or to have CsA withdrawn (SRL-ST, n=215).

Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing.

Expression of the small heat shock protein alphaB-crystallin in differentiated thyroid tumors has been described recently. In this study, we investigated the molecular mechanisms that affect the expression of alphaB-crystallin in benign goiters (n = 7) and highly malignant anaplastic thyroid carcinomas (ATCs) (n = 3). AlphaB-crystallin expression was compared with that of Hsp27-1.

Detection of coregulation in differential gene expression profiles.

Genomics and proteomics approaches generate distinct gene expression and protein profiles, listing individual genes embedded in broad functional terms as gene ontologies. However, interpretation of gene profiles in a regulatory and functional context remains a major issue. Elucidation of regulatory mechanisms at the gene expression level via analysis of promoter regions is a prominent procedure to decipher such gene regulatory networks.

Improved renal function in de novo renal transplant patients on sirolimus maintenance therapy following discontinuation of cyclosporine.

In the presirolimus era, cyclosporine withdrawal in de novo renal transplant patients was associated with increased rates of rejections; thus, no improvement in long-term graft survival was achieved. However, those patients who did not reject exhibited longer graft survival than did those on cyclosporine. In recent years sirolimus has been introduced into clinical practice and, so far, 4 randomized cyclosporine withdrawal trials in de novo patients after renal transplantation have been published, together with 3 smaller studies directly comparing cyclosporine with sirolimus.

Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation.

We report the 48-month results of a trial testing whether withdrawal of cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would impact renal allograft survival. Eligible patients receiving SRL-CsA-ST from transplantation were randomly assigned at 3 months to remain on triple therapy (SRL-CsA-ST, n = 215) or to have CsA withdrawn and SRL trough concentrations increased (SRL-ST, n = 215). SRL-ST therapy resulted in significantly better graft survival, either when including death with a functioning graft as an event (84.

Renal phosphate loss in hereditary and acquired disorders of bone mineralization.

Three metabolic bone diseases display similar characteristics such as hypophosphatemia due to chronically elevated renal phosphate clearance, inappropriately low 1,25 (OH)2 vitamin D serum levels, and variable bone disease (rickets and osteomalacia). X-linked dominant hypophosphatemic rickets (XLH), also called vitamin D-resistant rickets and autosomal dominant hypophosphatemic rickets (ADHR) represent two inherited diseases, whereas oncogenic hypophosphatemia (OHO), also known as tumor induced osteomalacia (TIO), is an acquired paraneoplastic syndrome that, in certain aspects, has much in common with XLH and ADHR. Although the primary causes for these disorders are distinct and well established, their similar features suggest a unifying pathophysiological basis.

Alterations in gene expression in cadaveric vs. live donor kidneys suggest impaired tubular counterbalance of oxidative stress at implantation.

Recipients of live donor transplant kidneys (LIV) exhibit a significantly longer allograft half-life compared with cadaveric donor organs (CADs). The reasons are incompletely understood. Therefore this study sought to elucidate the genome-wide gene expression profiles in microdissected transplant kidney biopsies obtained from five cadaveric and five matched live donors before transplantation.

The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function.

Background: It is unknown whether continuation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney transplantation has an influence on early kidney graft function.

Methods: We compared early postoperative graft function between 260 cadaveric kidney transplant recipients, either with or without peritransplantation ACE inhibitor/ATII blocker therapy. Regression analysis was used to show the influence of variables interfering with posttransplantation serum creatinine levels.

Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal.

Graft function at 6 or 12 mo is positively correlated with renal transplant survival. The 36-mo results of a study that tested whether withdrawing cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would affect renal graft survival are reported. Eligible patients (n = 430) who were receiving SRL-CsA-ST were randomly assigned at 3 mo to remain on SRL-CsA-ST or to have CsA withdrawn (SRL-ST group).

Health-related quality of life outcomes after kidney transplantation.

With the improvements in short and long term graft and patient survival after renal transplantation over the last two decades Health-Related Quality of Life (HRQL) is becoming an important additional outcome parameter. Global and disease specific instruments are available to evaluate objective and subjective QOL. Among the most popular global tools is the SF-36, examples of disease specific instruments are the Kidney Transplant Questionnaire (KTQ), the Kidney Disease Questionnaire (KDQ) and the Kidney Disease-Quality of Life (KDQOL).