[Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile]. / Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia.

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). AIM: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. CONCLUSION: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

In vitro and in vivo studies of the ALS-FTLD protein CHCHD10 reveal novel mitochondrial topology and protein interactions.

Mutations in coiled-coil-helix-coiled-coil-helix-domain containing 10 (CHCHD10), a mitochondrial twin CX9C protein whose function is still unknown, cause myopathy, motor neuron disease, frontotemporal dementia, and Parkinson's disease. Here, we investigate CHCHD10 topology and its protein interactome, as well as the effects of CHCHD10 depletion or expression of disease-associated mutations in wild-type cells. We find that CHCHD10 associates with membranes in the mitochondrial intermembrane space, where it interacts with a closely related protein, CHCHD2. Furthermore, both CHCHD10 and CHCHD2 interact with p32/GC1QR, a protein with various intra and extra-mitochondrial functions. CHCHD10 and CHCHD2 have short half-lives, suggesting regulatory rather than structural functions. Cell lines with CHCHD10 knockdown do not display bioenergetic defects, but, unexpectedly, accumulate excessive intramitochondrial iron. In mice, CHCHD10 is expressed in many tissues, most abundantly in heart, skeletal muscle, liver, and in specific CNS regions, notably the dopaminergic neurons of the substantia nigra and spinal cord neurons, which is consistent with the pathology associated with CHCHD10 mutations. Homozygote CHCHD10 knockout mice are viable, have no gross phenotypes, no bioenergetic defects or ultrastructural mitochondrial abnormalities in brain, heart or skeletal muscle, indicating that functional redundancy or compensatory mechanisms for CHCHD10 loss occur in vivo. Instead, cells expressing S59L or R15L mutant versions of CHCHD10, but not WT, have impaired mitochondrial energy metabolism. Taken together, the evidence obtained from our in vitro and in vivo studies suggest that CHCHD10 mutants cause disease through a gain of toxic function mechanism, rather than a loss of function.

Bladder cancer in Spain 2011: population based study.

PURPOSE: We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. MATERIALS AND METHODS: Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. RESULTS: A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean ± SD age of 70.5 ± 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. CONCLUSIONS: The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ.

Isolation of cholesterol- and deoxycholate-degrading bacteria from soil samples: evidence of a common pathway.

Nineteen different steroid-degrading bacteria were isolated from soil samples by using selective media containing either cholesterol or deoxycholate as sole carbon source. Strains that assimilated cholesterol (17 COL strains) were gram-positive, belonging to the genera Gordonia, Tsukamurella, and Rhodococcus, and grew on media containing other steroids but were unable to use deoxycholate as sole carbon source. Surprisingly, some of the COL strains unable to grow using deoxycholate as sole carbon source were able to catabolize other bile salts (e.g., cholate). Conversely, strains able to grow using deoxycholate as the sole carbon source (two DOC isolates) were gram-negative, belonging to the genus Pseudomonas, and were unable to catabolize cholesterol and other sterols. COL and DOC were included into the corresponding taxonomic groups based on their morphology (cells and colonies), metabolic properties (kind of substrates that support bacterial growth), and genetic sequences (16S rDNA and rpoB). Additionally, different DOC21 Tn5 insertion mutants have been obtained. These mutants have been classified into two different groups: (1) those affected in the catabolism of bile salts but that, as wild type, can grow in other steroids and (2) those unable to grow in media containing any of the steroids tested. The identification of the insertion point of Tn5 in one of the mutants belonging to the second group (DOC21 Mut1) revealed that the gene knocked-out encodes an A-ring meta-cleavage dioxygenase needed for steroid catabolism.

Herd-level risk factors for lameness in freestall farms in the northeastern United States and California.

The objective was to investigate the association between herd-level management and facility design factors and the prevalence of lameness in high-producing dairy cows in freestall herds in the northeastern United States (NE; Vermont, New York, Pennsylvania) and California (CA). Housing and management measures such as pen space, stall design, bedding type, and milking routine were collected for the high-producing pen in 40 farms in NE and 39 farms in CA. All cows in the pen were gait scored using a 1-to-5 scale and classified as clinically lame (score ≥3) or severely lame (score ≥4). Measures associated with the (logit-transformed) proportion of clinically or severely lame cows at the univariable level were submitted to multivariable general linear models. In NE, lameness increased on farms that used sawdust bedding [odds ratio (OR)=1.71; 95% confidence interval (CI)=1.06-2.76] and decreased with herd size (OR=0.94; CI=0.90-0.97, for a 100-cow increase), use of deep bedding (OR=0.48; CI=0.29-0.79), and access to pasture (OR=0.52; CI=0.32-0.85). The multivariable model included herd size, access to pasture, and provision of deep bedding, and explained 50% of the variation in clinical lameness. Severe lameness increased with the percentage of stalls with fecal contamination (OR=1.15; CI=1.06-1.25, for a 10% increase) and with use of sawdust bedding (OR=2.13; CI=1.31-3.47), and decreased with use of deep bedding (OR=0.31; CI=0.19-0.50), sand bedding (OR=0.32; CI=0.19-0.53), herd size (OR=0.93; CI=-0.89-0.97, for a 100-cow increase), and rearing replacement heifers on site (OR=0.57; CI=0.32-0.99). The multivariable model included deep bedding and herd size, and explained 59% of the variation of severe lameness. In CA, clinical lameness increased with the percentage of stalls containing fecal contamination (OR=1.15; CI=1.05-1.26, for a 10% increase), and decreased with herd size (OR=0.96; CI=0.94-0.99, for a 100-cow increase), presence of rubber in the alley to the milking parlor (OR=0.46; CI=0.28-0.76), distance of the neck rail from the rear curb (OR=0.97; CI=0.95-0.99, for a 1-cm increase), water space per cow (OR=0.92; CI=0.85-0.99, for a 1-cm increase), and increased frequency of footbaths per week (OR=0.90; CI=081-0.99, for a 1-unit increase). The multivariable model included herd size, percentage of stalls containing fecal contamination, and presence of rubber in the alley to the milking parlor, and explained 44% of the variation of clinical lameness. Severe lameness increased with the percentage of stalls containing fecal contamination (OR=1.23; CI=1.06-1.42, for a 10% increase) and decreased with frequency of manure removal in the pen per day (OR=0.72; CI=0.53-0.97, for a 1-unit increase). The final model included both variables and explained 28% of the variation in severe lameness. In conclusion, changes in housing and management may help decrease the prevalence of lameness on dairy farms, but key risk factors vary across regions.

Herd-level risk factors for hock injuries in freestall-housed dairy cows in the northeastern United States and California.

The aim of this study was to investigate the associations between management and facility design factors and the prevalence of hock injuries in high-producing dairy cows in 76 freestall herds in the northeastern United States (NE-US; Vermont, New York, Pennsylvania) and California (CA). One group of high-production multiparous cows was monitored on each farm, and data on management, facility and stall design, and the conditions of the hocks were collected. Focal cows [n=38 ± 3 (mean ± standard deviation)] were evaluated for hock injuries using a 3-point scale (where 1=healthy and 3=evidently swollen or severe injury). Measures associated with the proportion (logit-transformed) of cows having injuries (score ≥ 2) or severe injuries (score=3) at the univariable level were submitted to multivariable general linear models. In NE-US, overall hock injuries increased with the percentage of stalls with fecal contamination [odds ratio (OR)=1.26; 95% confidence interval (CI)=1.02-1.54, for a 10% increase], and with the use of sawdust as bedding (OR=3.47; CI=1.14-10.62), and decreased with deep bedding (i.e., at least 10 cm depth of any type of bedding; OR=0.05; CI=0.02-0.14), use of sand as bedding (OR=0.06; CI=0.02-0.15), bedding dry matter (DM) ≥ 83.9% (OR=0.08; CI=0.03-0.20), and access to pasture during the dry period (OR=0.17; CI=0.05-0.53). When these variables were submitted to a multivariable model, the presence of deep bedding was the only factor that remained significant, explaining 54% of the variation in overall injuries. Severe hock injuries increased with the use of automatic scrapers (OR=2.29; CI=1.11-4.71) and the percentage of stalls with fecal contamination (OR=1.14; CI=1.00-1.31, for a 10% increase), and decreased with sand bedding (OR=0.22; CI=0.10-0.49), deep bedding (OR=0.24; CI=0.11-0.52), bedding DM ≥ 83.9% (OR=0.28; CI=0.14-0.58), and access to pasture during the dry period (OR=0.42; CI=0.18-0.97). The final multivariable model, which explained 36% of the variation in severe hock injuries, included the use of automatic scrapers and deep bedding. In CA, stall stocking density (OR=1.41; CI=1.00-2.01, for a 10% increase) and poor bedding maintenance (OR=1.08; CI=1.01-1.16, for a 2.5-cm decrease in depth of deep-bedded stalls) were associated with an increase of overall and severe hock injuries, respectively. Deep-bedded and well-maintained stalls reduce the risk of hock injuries. Regional variation in risk factors for these injuries should be considered when formulating on-farm recommendations.

A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.

Complex III (CIII; ubiquinol cytochrome c reductase of the mitochondrial respiratory chain) catalyzes electron transfer from succinate and nicotinamide adenine dinucleotide-linked dehydrogenases to cytochrome c. CIII is made up of 11 subunits, of which all but one (cytochrome b) are encoded by nuclear DNA. CIII deficiencies are rare and manifest heterogeneous clinical presentations. Although pathogenic mutations in the gene encoding mitochondrial cytochrome b have been described, mutations in the nuclear-DNA-encoded subunits have not been reported. Involvement of various genes has been indicated in assembly of yeast CIII (refs. 8-11). So far only one such gene, BCS1L, has been identified in human. BCS1L represents, therefore, an obvious candidate gene in CIII deficiency. Here, we report BCS1L mutations in six patients, from four unrelated families and presenting neonatal proximal tubulopathy, hepatic involvement and encephalopathy. Complementation study in yeast confirmed the deleterious effect of these mutations. Mutation of BCS1L would seem to be a frequent cause of CIII deficiency, as one-third of our patients have BCS1L mutations.

Benchmarking cow comfort on North American freestall dairies: lameness, leg injuries, lying time, facility design, and management for high-producing Holstein dairy cows.

In this paper, we describe a novel approach to corporate involvement in on-farm assessment, driven by the desire to provide a service for dairy producers and to create a vehicle for engagement on issues of dairy cow welfare. This program provides producers with feedback on animal-based (including gait score, leg injuries, and lying time) and facility-based (including freestall design, bedding practices, feed bunk design and management, and stocking density) measures that can be used to better address their management goals. The aim of this paper is to describe variation in the prevalence of lameness and leg injuries, lying behavior, facility design, and management practices for high-producing cows on freestall dairy farms in 3 regions of North America: British Columbia (BC; n=42); California (CA; n=39); and the northeastern United States (NE-US; n=40). Prevalence of clinical lameness averaged (mean ± SD) 27.9±14.1% in BC, 30.8±15.5% in CA, and 54.8±16.7% in NE-US; prevalence of severe lameness averaged 7.1±5.4% in BC, 3.6±4.2% in CA, and 8.2±5.6% in NE-US. Overall prevalence of hock injuries was 42.3±26.2% in BC, 56.2±21.6% in CA, and 81.2±22.5% in NE-US; prevalence of severe injuries was 3.7±5.2% in BC, 1.8±3.1% in CA, 5.4±5.9% in NE-US. Prevalence of swollen knees was minimal in CA (0.3±0.6%) but high (23.1±16.3%) in NE-US (not scored in BC). Lying times were similar across regions (11.0±0.7h/d in BC, 10.4±0.8h/d in CA, 10.6±0.9h/d in NE-US), but individual lying times among cows assessed varied (4.2 to 19.5h/d, 3.7 to 17.5h/d, and 2.8 to 20.5h/d in BC, CA, and NE-US, respectively). These results showed considerable variation in lameness and leg injury prevalence as well as facility design and management among freestall farms in North America. Each of the 3 regions had farms with a very low prevalence of lameness and injuries, suggesting great opportunities for improvement on other farms within the region.

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients.

UNLABELLED: BK virus (BKV) nephropathy is a common viral infection in renal transplant patients, with a prevalence of 1-9% at approximately 12 months after surgery. While it is widely agreed that reduction of immunosuppression should be the first intervention after diagnosis of BKV infection, there is no consensus on whether calcineurin inhibitors or antiproliferative drugs should be reduced first. Furthermore, target levels of immunosuppressive drugs are poorly defined, as are criteria for replacing one immunosuppressive agent with another. RESULTS: We report our series of 15 renal transplant patients who underwent surgery between September 2004 and March 2010 and who developed BKV infection. The first 8 patients were treated with reduction of immunosuppression; 7 of these patients received cidofovir and 6 received intravenous immunoglobulin. The remaining 7 renal transplant recipients received mammalian target of rapamycin inhibitors (imTOR). In this group, we observed faster and more efficacious BKV clearance in plasma and urine and a steady improvement in allograft function, with no episodes of acute allograft rejection during follow-up. The polymerase chain reaction assay for BKV in urine became positive in 2 patients in whom imTOR were stopped due to severe side effects. CONCLUSIONS: The use of imTOR should be considered a first step in the treatment of renal transplant recipients with BKV infection. In our experience, this change in treatment was safe and resulted in viral clearance.

Secondary amyloidosis associated with histiocytosis X.

We report a 34-year-old man diagnosed with Langerhans cell histiocytosis (LCH) or histiocytosis X in 1980. He had multiple focal osseous lesions, difficult control of the disease activity and was treated many times with chemo- and radiotherapy for symptomatic control. His kidney disease started 20 years after the diagnosis with progressive renal failure and increasing non-nephrotic proteinuria, coinciding with two flares of LCH. A percutaneous renal biopsy demonstrated amyloidosis. There is only one case described in the amyloidosis literature associated with LCH.

[Clinical and microbiological aspects of peritonitis associated with peritoneal dialysis in adult patients with chronic renal failure in the Emergency Department]. / Aspectos clínicos y microbiológicos de la peritonitis asociada a diálisis peritoneal en pacientes adultos con insuficiencia renal crónica en el Servicio de Urgencias.

BACKGROUND: Peritonitis is the most important and frequent complication of peritoneal dialysis (PD). Bacterial infections are responsible in most cases, with characteristic symptoms. AIM: To determine the most frequent pathogens in peritonitis associated with PD in patients with chronic renal failure (CRF). Methodos: Retrospective, descriptive, cross-sectional and observational study of patients with peritonitis in PD with CRF of the emergency department, between July 2012 and June 2013. Sociodemographic, diagnostic, clinical and microbiological and cellular data were evaluated from the patient's fluid. Dialysis. RESULTS: From 73 reviewed records, 52% were male. The primary cause of CRF was diabetes mellitus type 2 (67%). Symptoms presented: abdominal pain (86%), vomiting (42%) and nausea (34%), with anemia, azotemia, hyperglycemia, hypoalbuminemia and hyponatremia. The positive microbiological cultures were 59%; and the pathogens identified were Candida tropicalis (9.6%), Staphylococcus epidermidis (8.2%), Enterococcus faecalis and Staphylococcus haemolyticus (6.8% each one), associated with elevated leukocytes, azotemia and high cellularity in peritoneal fluid (p <0.05). CONCLUSIONS: The main microorganism determined was of fungal origin associated with leukocytes, azotemia and high cellularity.

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (P<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

Study of anemia after late introduction of everolimus in the immunosuppressive treatment of renal transplant patients.

INTRODUCTION: mTOR inhibitors (imTOR) are immunosuppressive drugs that have a concentration-related effects on hematopoiesis, potentially resulting in anemia. The reason is uncertain, but a pathogenic link between sirolimus-induced anemia and the appearance of an inflammatory state was recently suggested. Because inflammation-related anemia is characterized by a functional iron deficiency, we studied whether everolimus influenced iron homeostasis. METHODS: We studied iron homeostasis in 43 patients after late introduction of everolimus into the immunosuppressive treatment. Thirty-seven patients (86%) were receiving mycophenolate. Hemoglobin concentration, red blood cell count, mean corpuscular volume, serum iron, ferritin, C-reactive protein levels, and transferrin saturation were evaluated 3 months before and 1, 3, and 6 months after the switch. RESULTS: The percentage of anemic patients preconversion was 18.6% and it was 34.9% at 3 months and 18.6% at 6 months. We did not observe a significant reduction in hemoglobin, but there was increased red blood cell count after everolimus introduction, with a significant reduction in mean corpuscular volume. Serum iron and transferrin saturation levels were also markedly reduced after the switch, while ferritin serum concentrations remained stable. An improvement in renal function was observed. CONCLUSIONS: The anemia caused by everolimus--microcytosis, low serum iron, despite high ferritinemia, and elevated C-reactive protein levels--was consistent with the anemia of a chronic inflammatory state. This alteration occurred within the first months postconversion and disappeared at 6 months. The combination of mycophenolate and everolimus seemed to be useful without significant secondary effects.

Preemptive kidney transplant from deceased donors: an advantage in relation to reduced waiting list.

BACKGROUND: Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). AIM: We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. PATIENTS AND METHODS: Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 +/- 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. RESULTS: The types of donors in both groups were: non-heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 +/- 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 +/- 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 +/- 0.2 in the preemptive group versus 1.7 +/- 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. CONCLUSION: PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.

Better mycophenolic acid 12-hour trough level after enteric-coated mycophenolate sodium in patients with gastrointestinal intolerance to mycophenolate mofetil.

INTRODUCTION: Enteric-coated mycophenolate sodium (EC-MPS) is the enteric-coated salt form of mycophenolic acid (MPA), the active component of the prodrug mycophenolate mofetil. EC-MPS was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. There are no studies available comparing trough plasma levels in patients with GI intolerance to MMF when they are converted to EC-MPS. AIM: To compare the GI tolerance and the MPA levels in patients previously treated with MMF in whom this drug was replaced by EC-MPS. MATERIALS AND METHODS: A prospective study was conducted in 133 renal transplant patients after conversion from MMF to EC-MPS (median time posttransplant 42 months, range 1 to 240 months). The causes for EC-MPS switching were GI intolerance to MMF (51.9%; group A), low trough plasma levels with MMF (29.3%; group B), and others (18.8%; group C). These patients were converted to equipotent doses of EC-MPS. RESULTS: The trough plasma MPA levels increased from 1.5 +/- 1.1 microg/mL at baseline to 2.5 +/- 2.0 microg/mL at 1 month postconversion despite the equipotent EC-MPS doses not being increased. These higher plasma levels were maintained throughout the study. In group A, this increase was from 1.8 +/- 1.0 to 2.7 +/- 2.1 microg/mL (P = .01) and in group B from 0.8 +/- 0.4 to 2.4 +/- 1.4 microg/mL (P < .001). The doses and levels of calcineurin inhibitor decreased from baseline. Creatinine clearance improved from 56.5 +/- 24.7 mg/dL at baseline to 61.9 +/- 28.6 at 6 months postconversion (P = .02). There was a statistically significant increase in hemoglobin levels. In group A, the GI tolerance improved in 78% of the patients. CONCLUSIONS: At equipotent doses, patients converted to EC-MPS have higher and more adequate levels of MPA. At 6 months postconversion, we observed an improvement of the renal function, probably due to a reduction of calcineurin inhibitor drugs. However, the possibility that a better immunosuppressive efficacy as demonstrated by more suitable trough plasma levels may have been a contributing factor cannot be discarded.

Effect of the brain-death process on acute rejection in renal transplantation.

INTRODUCTION: Growing experimental evidence suggests that the state of brain death (BD) activates surface molecules on peripheral organs by the massive release of macrophage- and T cell-associated cytokines as well as adhesion molecules into the circulation. The question is whether the sequelae of the BD process substantially influences the quality of the donor organ, the ensuing host response, or the ultimate transplant outcome. Our aim was to compare explosive BD with gradual-onset injury in terms of a trigger of the host immune mechanisms accelerating acute rejection processes. MATERIALS AND METHODS: This retrospective study included 149 cadaveric donors whose kidneys were transplanted in to 264 recipients. Exclusion criteria were previous transplants and hyperimmmunized patients. Donor variables were: sex, age, etiology of death, and hemodynamic conditions during the 24 hours prior to death. The recipient variables included, all possible conditions known to induce rejection. RESULTS: Cox analysis revealed the following factors to be predictive of acute vascular rejection: initial immunosuppression without induction (risk ratio [RR] 1.83; 95% confidence interval [CI] 1.02 to 3.25; P = .039) which there was a trend to an impact of a regimen without tacrolimus (RR 1.84; 95% CI 0.85 to 3.98; P = .099), or of recipient age < 30 years (RR 2.17; 95% CI 1.06 to 4.48); P = .053) or lower mean donor blood pressure during the 3 hours prior to death (RR 1.17; 95% CI 1.00 to 1.37; P = .054). CONCLUSIONS: Greater sympathetic activity during brain death produces nonspecific endothelial damage and increases organ immunogenicity, promoting rejection.

Histologic assessment of donor kidneys and graft outcome: multivariate analyses.

UNLABELLED: We performed a multivariate analysis to evaluate the importance of histologic parameters in donor kidney biopsies as predictors of graft outcome. METHODS: Wedge protocol biopsies from a single center were analyzed for glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), arteriosclerosis (AS), and arteriolar hyalinosis (AH). Alterations were quantified as percentage (GS, IF) or semiquantified according to Banff criteria (IF, TA, AS, AH). We calculated creatinine clearance (CrCl) at 1, 2, and 3 years posttransplant. Donor data included age, gender, and type: non-heart-beating donor or brain dead donors. Recipient data included age, gender, cold ischemia time, number of HLA mismatches, peak level of the panel reactive antibody (PRA), number of acute rejection episodes (ARE), and presence or absence of cytomegalovirus (CMV) disease. Univariate and multivariate analyses were performed. Follow-up range was 1 to 4.2 years. RESULTS: GS, IF, TA, and AH were associated with graft survival in the multivariate analysis. The histologic parameters were associated with CrCl at several posttransplant time intervals, but the significance of association was lost in the multivariate analysis. Donor age showed a better correlation with graft function. In the univariate analyses adjusting for donor age, only IF and AH were associated with graft function. CONCLUSIONS: Histologic parameters showed a modest association with graft function. In our study, donor age is the better predictor of graft function. IF and AH may be similar to or better than GS as predictors of graft outcome.

Evaluation of the efficacy and safety of the conversion from a calcineurin inhibitor to an everolimus-based therapy in maintenance renal transplant patients.

Everolimus has recently been introduced into clinical practice with promising perspectives due to its efficacy, lack of nephrotoxicity, and antitumor effects. Experience in clinical trials associated with low-dose cyclosporine showed good results, but there is almost no experience in calcineurin inhibitor (CNI) elimination learning it as the primary immunosuppressant. We describe our experience in a series of 78 stable renal transplant patients who were switched to Everolimus with complete and quick elimination of the CNI: the procedure of conversion, pharmacokinetic results after conversion, evolution of renal parameters (renal function, proteinuria, and others), and safety data (acute rejection and adverse events). An initial dose of 3 mg/d was adequate to obtain the recommended trough levels between 5 and 10 ng/mL. Our results demonstrated that conversion to Everolimus was a simple, safe procedure that must be considered in patients CNI toxicity, especially those with malignant neoplasms and progressive deterioration of renal function due to chronic allograft nephropathy.