A Survival Analysis of Living Donor Kidney Transplant.

BACKGROUND: Superior patient and graft survival rates have been attributed to living donor kidney transplant (LDKT) when compared to deceased donor transplantation. The aim of this study was to assess graft survival in a population of LDKT in the last 14 years and the potential impact of some clinical features. METHODS: A retrospective observational study was conducted, reviewing the records of all patients undergoing LDKT in one center from January 1, 2004, to December 31, 2017. Survival data were evaluated by Kaplan-Meier, log rank test, and Cox regression. RESULTS: Two hundred seventy-seven LDKT were performed. The median follow-up time was 4 (0-13) years. Graft loss was observed in 9% of patients; 4 patients died. The overall survival was 97% at year 1, 94% at year 5, and 83% at years 10 and 13. We found a significantly worse graft survival in patients with early vascular complications that required surgical intervention (P = .00) ≥3 HLA MM (P = .01), ≥1 HLA-DR MM (P = .04) and female recipients (P = .01). The negative impact of ≥1 HLA-B MM on survival was borderline (P = .05). After excluding early graft losses secondary to vascular events, ≥1 HLA-A MM and rejection have also implicated a negative impact on survival (P = .04 and .01, respectively). In the multivariate analysis, these variables were still related to inferior survival. CONCLUSIONS: We observed a good overall graft survival (>80% after 13 years). Possible factors related to poor outcomes suggested by this study were early vascular complications; HLA mismatches; rejection; and, with less certainty, female recipients.

Nitrogen isotopic fractionation as a biomarker for nitrogen use efficiency in ruminants: a meta-analysis.

Animal proteins are naturally 15N enriched relative to the diet and the extent of this difference (Δ15Nanimal-diet or N isotopic fractionation) has been correlated to N use efficiency (NUE; N gain or milk N yield/N intake) in some recent ruminant studies. The present study used meta-analysis to investigate whether Δ15Nanimal-diet can be used as a predictor of NUE across a range of dietary conditions, particularly at the level of between-animal variation. An additional objective was to identify variables related to N partitioning explaining the link between NUE and Δ15Nanimal-diet. Individual values from eight publications reporting both NUE and Δ15Nanimal-diet for domestic ruminants were used to create a database comprising 11 experimental studies, 41 treatments and individual animal values for NUE (n=226) and Δ15Nanimal-diet (n=291). Data were analyzed by mixed-effect regression analysis taking into account experimental factors as random effects on both the intercept and slope of the model. Diets were characterized according to the INRA feeding system in terms of N utilization at the rumen, digestive and metabolic levels. These variables were used in a partial least squares regression analysis to predict separately NUE and Δ15Nanimal-diet variation, with the objective of identifying common variables linking NUE and Δ15Nanimal-diet. For individuals reared under similar conditions (within-study) and at the same time (within-period), the variance of NUE and Δ15Nanimal-diet not explained by dietary treatments (i.e. between-animal variation plus experimental error) was 35% and 55%, respectively. Mixed-effect regression analysis conducted with treatment means showed that Δ15Nanimal-diet was significantly and negatively correlated to NUE variation across diets (NUE=0.415 -0.055×Δ15Nanimal-diet). When using individual values and taking into account the random effects of study, period and diet, the relationship was also significant (NUE=0.358 -0.035×Δ15Nanimal-diet). However, there may be a biased prediction for animals close to zero, or in negative, N balance. When using a novel statistical approach, attempting to regress between-animal variation in NUE on between-animal variation in Δ15Nanimal-diet (without the influence of experimental factors), the negative relationship was still significant, highlighting the ability of Δ15Nanimal-diet to capture individual variability. Among the studied variables related to N utilization, those concerning N efficiency use at the metabolic level contributed most to predict both Δ15Nanimal-diet and NUE variation, with rumen fermentation and digestion contributing to a lesser extent. This study confirmed that on average Δ15Nanimal-diet can predict NUE variation across diets and across individuals reared under similar conditions.

Role of de novo donor-specific anti-HLA antibodies in kidney graft failure: A case-control study.

The role of de novo donor-specific anti-human leukocyte antigen (anti-HLA) antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002 and 2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy. All patients had at least one serum collected 1 year before failure (in cases) or end of follow-up (in controls). Cases and controls were very well-matched in several baseline characteristics. Post-transplant anti-HLA antibodies were found in 84% of cases and only 36% of controls (P < .001), with 54% of cases and 16% of controls (P < .001) having dnDSA at time of detection. Chronic active antibody-mediated rejection was significantly more common (P < .001) in patients with dnDSA (61% vs 12%), in 53 (47%) patients that had at least one graft biopsy performed during follow-up. dnDSA was a significant risk factor (odds ratio [OR] = 6.06; P = .003) for graft failure in a multivariable conditional logistic regression model. dnDSA as a time-dependent variable, was also an independent predictor [hazard ratio (HR) = 2.46; P = .002] of graft failure in a multivariable Cox regression analysis. In both statistical approaches, only dnDSA-II (OR = 11.90; P = .006) (HR = 2.30; P = .014) was significantly associated with graft failure. Post-transplant dnDSA was clearly associated with graft loss, particularly if against HLA class II antigens. dnDSA detection should be a tool for post-transplant monitoring of kidney graft recipients, allowing for the identification of those with a higher risk of graft failure.

HPLC-DAD-ESI/MS(n) profiling of phenolic compounds from Lathyrus cicera L. seeds.

Lathyrus cicera L. seeds are of interest for food and feed purposes. Despite the recognized antioxidant activity of the seeds, arising from the phenolic fraction, their phenolic compounds have not been studied in depth yet. Therefore, to determine the phenolics profile of these seeds, a target analysis was performed using high-performance liquid chromatography coupled to photodiode-array detection and electrospray ionization/ion trap mass spectrometry (HPLC-DAD-ESI/MS(n)). Thirty-seven glycosylated flavonoids were identified for the first time in the seeds of this species and, according to their MS fragmentation, clustered in flavonol-3-O-di-/tri-glycosides-7-O-rhamnosides and other flavonol-glycosides, and flavonol-3-O-(cinnamoyl)glycoside-7-O-rhamnosides, flavonol-3-O-(dihydrophaseoyl, cinnamoyl)glycoside-7-O-rhamnosides and flavonol-3-O-(malonyl)glycoside-7-O-rhamnosides. Glycosides of kaempferol were the main flavonoids found (10 non-acylated and 21 acylated), followed by those of quercetin (3) and those of isorhamnetin, apigenin and luteolin (1). The most abundant flavonols were identified as kaempferol-3-O-(2-hexosyl)hexoside-7-O-rhamnosides. The methodology used allowed to increase the knowledge on a relevant phytochemical class of seeds from L. cicera.

Conversion From Twice-Daily to Once-Daily Tacrolimus in Stable Kidney Graft Recipients.

INTRODUCTION: Immunosuppression has a pivotal role in kidney transplantation. The new prolonged-release formulation of tacrolimus was developed to provide a more convenient once-daily dosing to improve patient adherence. METHODS: We selected 60 stable kidney transplant recipients who underwent tacrolimus conversion in our unit. Conversion was made on a 1 mg:1 mg basis in 66.7% of patients (n = 40) and on a 1 mg:1.1 mg basis in the remaining 33.3% (n = 20). Clinical and analytical data at conversion and postconversion was analyzed retrospectively to evaluate the efficacy and safety of conversion from tacrolimus twice-daily to once-daily formulation. RESULTS: A significant reduction in tacrolimus blood levels requiring an increase in tacrolimus daily dose was observed postconversion. Postconversion tacrolimus blood level reduction >25% was significantly higher in the conversion group 1 mg:1 mg basis (P = .004). In patients converted 1 mg:1 mg, female sex and higher tacrolimus level at conversion were significant risk factors for a reduction >25% in tacrolimus blood levels after conversion. No significant change was detected between mean glomerular filtration rate at conversion (57 mL/min) and at 3, 6, and 9 months postconversion. CONCLUSIONS: Once-daily tacrolimus at similar doses to the twice-daily formulation is an efficient and safe treatment option. Conversion made on 1 mg:1.1 mg basis seems advantageous at least in some patients.

Effect of Different Sensitization Events on HLA Alloimmunization in Kidney Transplantation Candidates.

BACKGROUND: HLA alloimmunization is caused by sensitization events (SEs), such as transfusion, pregnancy, or previous organ transplantation, and the effects of particular SEs have not been thoroughly studied. Our aim was to evaluate how each SE affected HLA alloimmunization by considering Luminex assays. METHODS: Sera from 722 kidney transplantation candidates were screened per protocol by means of Luminex assays to determine the presence of anti-HLA class I/II antibodies; positive sera underwent single-antigen assay to determine the presence of specific antibodies against HLA A, B, C, DR, DQ, DP loci (positivity if median fluorescence intensity values were >1,000). The effect of each SE was analyzed considering only patients exposed to 1 kind of sensitization. RESULTS: In the 453 candidates with ≥1 SE, anti-HLA class I positivity rates were significantly higher in patients with previous transfusion (18.9%; P = .014), pregnancy (38.3%; P < .001) or transplant (75%; P < .001) compared with those with no SE (similar results for class II). The strength (median fluorescence intensity) of specific antibodies was significantly higher in patients with previous transplantation than in those with previous transfusion for HLA-A (8,017 vs 2,302; P = .02), HLA-B (7,765 vs 2,901; P = .018), and HLA-DR (9,835 vs 2,060; P = .003). Other anti-HLA antibody strengths were similar between patients with previous pregnancy or transplantation. CONCLUSIONS: Presence of any SE analyzed was associated with a higher prevalence of anti-HLA antibodies for class I ± II compared with nonsensitized patients. Transplantation had the strongest immunization effect on both classes, followed by pregnancy and then transfusion.

Allograft nephrectomy: a single-institution, 10-year experience.

INTRODUCTION: Allograft nephrectomy (AN) is associated with a high number of surgical complications. Some authors advocate that early nephrectomy (<1 year) is associated with fewer complications. Intracapsular (ICAN) and extracapsular AN (ECAN) might have a different impact on allosensitization and surgical outcomes. Our goal was to compare surgical outcomes between early and late AN in our institution and to compare ICAN and ECAN in terms of surgical outcomes and panel reactive antibodies (PRA) variation. MATERIALS AND METHODS: Between January 2000 and October 2012, we performed 104 AN at our institution (32 early and 72 late). Comparisons between early and late AN, and, within the latter, between the 2 different techniques were sought. Statistical analysis was performed for sample description, group comparison and %PRA variation. RESULTS: Among the 104 patients with a mean age of 47.9 ± 14.2 years, 54 were men. Age, gender, body mass index, and number of previous transplants were similar between early and late AN and between ICAN and ECAN patients. Late AN was associated with less blood loss (293.4 ± 229.0 vs 414.3 ± 349.5 mL; P = .03), shorter hospital stay (12.8 ± 14.5 vs 26.8 ± 26.5; P < .05), and fewer complications (22.2% vs 59.3%; P < .05). The chance of being relisted for transplantation was similar (50.0% in early vs 59.7% in late AN; P = .7). When comparing ICAN and ECAN, there was no difference in surgical outcomes. The %PRA variation between the 2 techniques was comparable (-1.2 ± 10.6 ICAN vs -0.5 ± 15.9 ECAN; P = .8), as was the chance of being relisted for transplantation (60.5% ICAN vs 58.6% ECAN; P = .8). CONCLUSIONS: Early AN was associated with a greater number of surgical complications. Nevertheless, the number of AN patients returning to the active waiting list was similar between early and late AN groups. ICAN and ECAN had similar surgical and postoperative outcomes, although a bias may be present because some conversions from ECAN to ICAN occurred owing to technical issues. As in other studies, ICAN did not seem to affect allosensitization or jeopardize the chance of being relisted for transplant when compared with ECAN.

Short communication: Relationship between the efficiency of utilization of feed nitrogen and 15N enrichment in casein from lactating dairy cows.

The objective of the present study was to evaluate the relationship between the efficiency of conversion of feed N into milk N [N-use efficiency (NUE)] and (15)N enrichment of milk casein from lactating cows fed corn silage-based diets. Samples of feeds and milk were obtained from 3 experiments with lactating dairy cows. All diets were based on corn silage and were designed to evaluate the effects of (1) diets with different ratios of effective rumen-degradable protein to fermentable metabolizable energy (experiment 1), (2) different proportions of quickly and slowly rumen-degradable protein (experiment 2), and (3) synchronizing the availability of fermentable metabolizable energy and effective rumen-degradable protein in the rumen (experiment 3). Although no significant effect of diet on casein δ(15)N values was detected, casein was more enriched than the diet in each of the experiments. Nitrogen-use efficiency was negatively related to adjusted Δ(15)N (casein δ(15)N--diet δ(15)N) for experiments 1 and 2 individually and when combining data from all 3 experiments. The relatively low values for Δ(15)N suggest that these productive animals were using dietary N efficiently, with a high proportion of N going to milk protein and less to urea. The weak, although significant, relationship between NUE and adjusted Δ(15)N, is consistent with relatively little variation in hepatic deamination and transamination, with variation in rumen efficiency having the predominant effect on NUE. The present study confirms the lower (15)N enrichment in protein when NUE is high and the potential to use N-isotope fractionation as a marker of NUE.

Kidney transplantation across a positive crossmatch: a single-center experience.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal disease, with improved mortality and quality of life compared with dialysis. Desensitization protocols have allowed kidney transplantation of highly sensitized patients, who have a lower probability to receive a matching kidney from a deceased or living donor. The aim of this work was to analyze the post-transplantation period of highly HLA-sensitized patients with positive flow cytometry crossmatch against donor cells. METHODS: Following an observational, retrospective design, we investigated 16 highly sensitized patients who underwent kidney or kidney-pancreas transplantation, assessing the impact of desensitization protocols and investigating treatment-related complications, graft function, antibody-mediated rejection (AMR) rate, and graft and patient survivals. RESULTS: We studied 16 patients with positive flow cytometry crossmatch, who were divided into 2 groups based on whether they were submitted to a desensitization protocol or not. Patients who were desensitized underwent transplantation in later years, had higher immunologic risk (panel reactive antibody peak 62% vs 33%; P = .038), higher percentage of 2nd kidney transplant (75% vs 25%; P = .066), and higher percentage of donor-specific anti-HLA antibodies identified (P = .028). A majority of patients were desensitized with high-dose intravenous immunoglobulin and plasmapheresis, and 5 patients received rituximab. Acute AMR rate was of 38%, and rituximab was associated with fewer episodes of AMR. Only 1 patient had graft failure, due to chronic humoral rejection, and the remaining maintained good graft function (mean serum creatinine value of 1.33 mg/dL). No patient died and few complications related to immunossupression were observed. CONCLUSIONS: Desensitization protocols were safe and allowed kidney transplantation in highly sensitized patients that probably would never undergo transplantation and gave the opportunity of living-donor transplant to patients with anti-HLA antibodies against the donor.

Better outcomes of peritoneal dialysis in diabetic patients in spite of risk of loss of autonomy for home dialysis.

INTRODUCTION: Diabetes mellitus is a leading cause of chronic renal failure, challenging therapy strategies. Patients with diabetes may benefit from peritoneal dialysis (PD) but higher technique failure is feared. Our purpose was to critically evaluate clinical outcomes of this modality in diabetics, in order to find quality improvement strategies in these risk patients. METHODS: A registry-based study of 432 incident patients, 23% with diabetes, from a university hospital PD program was performed. Traditional methods (Kaplan-Meier, Cox models) and innovative survival analysis, taking competing risks into account, were performed, as well as exploring the trends in cohorts according to the decade of PD start. RESULTS: In spite of the detrimental effect of diabetes in patient survival compared to non-diabetics (77%, 52% vs 86%, 71%, at 2 and 4 years, respectively; p < 0.0001) the hazard ratio (HR) for death decreased in the more contemporary cohort (0.303, 95% confidence interval (CI) 0.150 - 0.614, p < 0.001). It is noteworthy that diabetes was not associated with lower technique survival: 74%, 51% vs 79%, 57%, at 2 and 4 years, respectively (p = not significant (NS)). On multivariate analysis, diabetes was an independent predictor for mortality, but not for technique failure. The hazard ratio (HR) for technique failure also decreased in the more recent cohort (0.566, 95% CI 0.348 - 0.919, p = 0.021). Among reasons for transfer to hemodialysis, proportion of ultrafiltration failure was similar between groups (26% vs 22%, p = NS), but drop-out due to loss of autonomy occurred more in the group with diabetes (23% vs 5%, p = 0.004), mainly due to ischemic stroke. The hospitalization rate was also higher in diabetic patients (1.39 vs 0.84 episodes per patient-year (E/PY), p = 0.004) but the peritonitis rate was not increased (0.53 vs 0.61 E/PY, p = NS). CONCLUSION: PD was an effective long-term renal replacement therapy in diabetics, without higher rates of technique failure, ultrafiltration failure or peritonitis. Better outcomes were achieved in the contemporary cohort. The menace of autonomy loss due to stroke and higher hospitalization rates enhance the need for assisted PD strategies and better control of comorbidities.

Cardiovascular risk factors and events in pancreas-kidney transplants.

Cardiovascular and cerebrovascular disease (CCVD) are major causes of morbidity and mortality among patients with diabetes. Strict control of treatable risk factors that contribute to atherosclerosis is important to reduce the risk of stroke, myocardial infarction, and peripheral arterial disease. Simultaneous pancreas-kidney transplantation (SPKT) may significantly improve these risk factors in patients with type 1 diabetes. We studied 103 SPKT from our center with both organs functioning for metabolic and hypertensive control; body mass index (BMI); immunosuppression; and CCVD events. The 53 females/50 males showed a mean age of 35 ± 6 years, diabetes for 24 ± 6 years, and on dialysis for 31 ± 23 months. The follow-up ranged from 6-142 months. Mean value of last creatinine clearance was 76 ± 24 mL/min, all 103 SPKT were insulin-independent with mean glycemia = 81 ± 10 mg/dL and hemoglobin A1c (HbA1c) = 5.3% ± 0.4%. All of them were under tacrolimus treatment; 9.7% also with sirolimus but 67% steroid-free. According to the National Cholesterol Education Program Adult Treatment Panel 3 criteria, 4 patients showed a fasting glucose > 100 mg/dL; only one, HbA1c > 5.6%. Hypertension was recorded in 38.5%; low high-density lipoprotein cholesterol in 19.4%; hypertriglyceridemia in 7.8%; BMI > 30% in only 2 patients; 21.4% were prescribed statins. We registered cardiovascular events in 7 patients (6.8%). Patients with steroid treatment showed higher triglycerides (122 ± 53 vs 90 ± 36 mg/dL; P = .001) and more often tended to be hypertensive (41.2% vs 37.7%, P = .073) compared with those free of these drugs. Hypertension was associated with an higher BMI (24.1 ± 2.8 vs 22.3 ± 2.9 kg/m(2), P = .002). BMI > 25% was associated with higher total cholesterol (195 ± 47 vs 169 ± 28 mg/dL, P = .015) and low-density lipoprotein cholesterol (116 ± 40 vs 96 ± 27 mg/dL, P = .003). Among our SPKT the prevalences of CCVD and metabolic syndrome were low. Hypertension was the most frequent single factor. Obesity was rare. In patients on steroids, hypertriglyceridemia was more prevalent and hypertension tended to be more frequent. Hypertensive patients showed a higher BMI, which correlated with a worse lipid profile. Steroid withdrawal, whenever possible, may be important to achieve metabolic goals and minimize cardiovascular risk.

A case series of de novo inflammatory bowel disease after kidney transplantation.

Diarrhea, which is common after transplantation, may be due to infections and immunosuppressive therapy. Inflammatory bowel disease (IBD) de novo or as an exacerbation of pre-existent disease is a rare complication after kidney transplantation with pre-existing disease having a less aggressive clinical course than the de novo disease. Cytomegalovirus mismatch, prescription of tacrolimus instead of cyclosporine or mycophenolate mofetil rather than azathioprine as well as low-dose corticosteroid treatments have been linked to an increased incidence of IBD. This series of renal transplant recipients with de novo IBD showed a higher incidence and more aggressive course than that previously described, possibly related to increased use of tacrolimus with minimization of steroids.

Alterações histológicas dos rins e expressão das metalotioneínas e das proteínas de choque térmico em ratos Wistar após exposição ao fungicida tirame / Kidney histological alterations and metallothionein and heat shock protein expression in Wistar rats after fungicide thiram exposure

Avaliaram-se as alterações histológicas e a expressão das metalotioneínas (MTs) e das proteínas de choque térmico (Hsp70) nos rins de ratos Wistar após a exposição ao fungicida tirame. Os animais foram distribuídos em três grupos: grupo dieta-padrão; grupo dieta-padrão+óleo de milho; e grupo tirame. Foram encontradas diferenças significativas (P<0,05) na evolução do peso corporal entre os ratos do grupo tirame e os dos grupos controle e óleo de milho, e não foram verificadas lesões histológicas evidentes nos rins dos animais. Foram encontradas diferenças entre os animais do grupo exposto ao tirame e os dos grupos controle e óleo quanto às características histomorfométricas relativas ao corpúsculo renal - exceto para a proporção área da cápsula de Bowman:área do glomérulo - e relativas aos túbulos contorcidos proximal e distal - exceto para altura do epitélio dos túbulos distais. Nos ratos expostos ao tirame, foi observada imunomarcação positiva para as MTs, de moderada a forte, nos túbulos contorcidos da região cortical, diminuindo do córtex em direção à medula, e forte imunomarcação para as Hsp70 nas áreas do córtex e da medula, no glomérulo e nos túbulos contorcidos. Os resultados sugerem que o tirame pode ter toxicidade crônica nos mamíferos por afetar o seu crescimento e que a expressão das MTs e das Hsp70, provável resposta celular adaptativa ao estresse oxidativo causado pelo tirame, pode ser utilizada como biomarcador de exposição a este químico.

The histological alterations and the expression of metallothionein (MTs) and heat shock protein (Hsp70) in the kidney of Wistar rats after thiram fungicide exposure were evaluated. Animals were distributed into three groups: standard diet group, standard diet + corn oil group and thiram group. Significant differences were found (P<0,05) in the evolution of body weight between rats in the thiram group and those in the control and corn oil groups, and no histological lesions were evident in the animals' kidneys. Differences were found among animals in the group exposed to thiram and the control and oil groups regarding histomorphometric characteristics of the renal corpuscle - except for the proportion in the area of Bowman's capsule: glomerulus area - and regarding the height of the epitelium in the distal tubules. In rats exposed to thiram, a positive moderate to strong immunoexpression was observed for MTs, in the cortical convulated tubules decreasing the cortex towards the medulla, and a strong immunoexpression for Hsp70 in the cortex and medulla areas, in the glomerulus and convulated tubules. The results suggest that thiram may have chronic toxicity in mammals affecting their growth, and that the expression of MTs and Hsp70, a probable cellular adaptive response to the oxidative stress caused by thiram, may be used as a biomarker of exposure to this chemical.

Effects of protein sources on concentrations of hydrogen sulphide in the rumen headspace gas of dairy cows.

Two Latin square design experiments investigated the relationship between hydrogen sulphide concentration in the rumen headspace gas of dairy cows and the early stages of protein degradation in the rumen. In Expt 1, three protein sources differing in rumen N (nitrogen) degradability (maize gluten feed (MGF); sunflower meal (SFM); and soyabean meal (SBM)) were used, whereas in Expt 2 four different batches of the same feed (MGF) differing in colour (CIE L*, a*, b* (CIELAB) scale) were used. After allowing the concentration of hydrogen sulphide in rumen gas to decline close to zero, a fixed amount of protein sources was offered to cows and the concentrations of hydrogen sulphide were recorded in rumen headspace gas at 30-min intervals. In Expt 1, the concentration of hydrogen sulphide showed considerable variation between protein sources, with MGF having the highest concentration followed by SFM and SBM resulting in very low concentrations. The N wash losses (zero time measurements with nylon bags) ranked the feeds in the same way, from MGF (highest; 61%) to SBM (lowest; 26%). There were marked differences in the degradation of cystine and methionine between protein sources, although the degradation of cystine was always higher than for methionine. MGF (Expt 2) led to increased concentrations of hydrogen sulphide, with peak concentrations achieved between 1 and 2 h after feeding. The concentrations of hydrogen sulphide were higher for MGF1, intermediate for MGF2 and lower for MGF3 and MGF4, agreeing with colour scale. Differences in the early stages of dietary sulphur degradation corresponded with differences in hydrogen sulphide concentrations in rumen gas. The results suggest that hydrogen sulphide concentrations in the rumen headspace gas could be useful to evaluate nutritional parameters not measured by the in sacco technique, contributing to a better understanding of the response of dairy cows to different protein supplements.

Advantages of kidney transplant precocity in graft long-term survival.

BACKGROUND: Preemptive kidney transplantation (KT) or KT after a brief period on dialysis (<6 months) has been associated with better graft survival. Our study aimed to analyze the effect of an early KT on graft survival censored for patient death with functioning graft. METHODS: A total of 1,373 kidney-only transplantations, from both living and deceased donors, performed from 1983 to 2010 were retrospectively studied. We defined 2 groups: those with early KT (preemptive or within 6 months after dialysis initiation; n = 131) and non-early KT (n = 1,242). Survival curves for each group were calculated by Kaplan-Meier analysis and compared by log-rank test. The independent effect of early KT on censored graft survival was analyzed by a multivariate-adjusted Cox proportional regression model. RESULTS: The 5-, 10-, 15-, and 20-year censored graft survival rates were, respectively, 96%, 89%, 79%, and 79% among the early KT group, and 91%, 81%, 68%, and 49% among the non-early KT group (P = .024). Multivariate analysis showed the following to be independent predictors for censored graft failure: non-early KT (hazard ratio [HR] 2.58; P = .028), recipient age (HR 0.97; P < .001), donor age (HR 1.03; P < .001), recipient negative status for cytomegalovirus IgG (HR 1.44; P = .032), delayed graft function (HR 1.48; P = .013), and acute rejection event (HR 1.68; P = .002). CONCLUSIONS: Our results show that early KT can be an approach for the improvement of long-term graft survival.

A comparison between serum creatinine and cystatin C-based equations for estimation of graft function.

BACKGROUND: Accurate monitoring of estimated glomerular filtration rate (GFR) is essential for an optimal management of kidney transplant (KT) patients. We aimed to compare the predictive performance of creatinine- and cystatin C-based GFR with creatinine clearance (CCr) in a 24-hour urine collection as the reference test. METHODS: GFR was calculated using cystatin C-based equations (Le Bricon, Stevens) and two creatinine-based equations [Cockcroft-Gault (CG), modification of diet in renal disease (MDRD)]. We enrolled 173 KT recipients. Bias, precision, and accuracy of each equation were determined. Kappa statistics evaluated the concordance between the reference test and GFR formulas in classifying patients according graft function (CCr <60 or ≥60 mL/min/1.73 m2). RESULTS: Patients (108 males) had a mean age of 48.6 ± 12.2 years and a median posttransplant time of 6.8 years. Mean CCr was 69.3 ± 19.9 (range: 32.1-105.2) mL/min/1.73 m2. The cystatin C-based equations estimates (Le Bricon, Stevens) had the highest accuracy (83.8% and 87.9% within 30% of CCr result, respectively). Precision of Le Bricon, Stevens, and MDRD was similar (around 13.5 mL/min/1.73 m2)) and much better than CG (22.5 mL/min/1.73 m2). The lowest bias was seen in Le Bricon (-1.2 mL/min/1.73 m2), followed by CG, Stevens, and MDRD (-2.6, -9.5, -16.5 mL/min/1.73 m(2), respectively). Kappa coefficient was higher in cystatin C-based equations (0.53) in contrast with CG (0.48) and MDRD (0.40). Stevens had a high sensitivity (90.8%) and low specificity (66.7%) and, conversely, Le Bricon had 64.6% sensitivity and 87.0% specificity. CONCLUSIONS: Cystatin C-based equations showed a better predictive performance of graft function than creatinine-based equations. The role of cystatin C in graft function monitoring deserves further investigation.

Hyperuricemia in adult renal allograft recipients: prevalence and predictors.

BACKGROUND: Hyperuricemia is a common complication after kidney transplantation that may adversely affect graft survival. OBJECTIVE: Our aim was to determine the prevalence of hyperuricemia in a sample of adult kidney graft recipients and to investigate its predictors. METHODS: A total of 302 patients were included in the study. We used univariate analyses to compare clinical characteristics between the hyper-and normouricemic groups. We used multivariate adjusted logistic regression to detect independent predictors of hyperuricemia. Hyperuricemia was defined as serum uric acid ≥6.5 mg/dL in women and ≥7.0 mg/dL in men or allopurinol use. RESULTS: The patients had a mean age of 49.6 ± 13.4 years, a median posttransplantation time of 7.6 years, and a mean estimated glomerular filtration rate (eGFR) of 51.9 ± 18.46 mL/min. The prevalence of hyperuricemia was 42.1% (n = 127). Hyperuricemic patients were predominately male (P = .004), older (P = .038), and with lower eGFR (P < .001). They also had a higher prevalence of hypertension (P = .001), dyslipidemia (P = .004) and proteinuria (P = .001). Multivariate adjusted regression model showed as significant predictors of hyperuricemia: male gender (odds ratio [OR], 2.46; P = .002); impaired renal function (OR 1.33 for every 10 mL/min reduction in eGFR; P < .001), higher body weight (OR 1.09 for every 1 kg/m(2) increase of body mass index; P = .044), prednisolone use (OR 2.12; P = .035), and cyclosporine versus tacrolimus use (OR 2.44; P = .039). CONCLUSIONS: The prevalence of posttransplant hyperuricemia was high, particularly in patients with classical cardiovascular risk factors and lower eGFR. However, our findings suggest that modifiable immunosuppression options could play a role in its management.

Effects of the food contaminant semicarbazide on testicular morphology of juvenile Wistar rats / Efeitos do contaminante alimentar semicarbazida na morfologia testicular de ratos Wistar jovens

O objectivo do presente trabalho foi avaliar os efeitos da semicarbazida na morfologia testicular de ratos Wistar jovens. Os animais foram tratados durante 30 dias com hidrocloreto de semicarbazida incorporado na dieta, nas concentrações de 0, 3 e 6g/kg. Os resultados obtidos revelaram uma diminuição estatisticamente significativa no diâmetro dos túbulos seminíferos, no diâmetro do lúmen dos túbulos seminíferos e na área ocupada pelo epitélio seminífero nos animais dos grupos experimentais em comparação com os animais do grupo controlo. Estes resultados evidenciam que a semicarbazida induz alterações importantes no desenvolvimento testicular e sugerem um estudo mais aprofundado sobre os mecanismos de acção, dos efeitos a longo prazo, da reversibilidade das lesões e nas capacidades reprodutivas. Estes aspectos são relevantes numa perspectiva de segurança alimentar, em particular para as crianças, as quais representam um grupo de maior exposição e susceptibilidade à semicarbazida.

Efeitos da semicarbazida no esqueleto de ratos Wistar em crescimento / Effects of semicarbazide on skeleton of growing Wistar rats

The effects of semicarbazide hydrochloride on skeletal tissues were evaluated using Wistar rats. In the animals submitted to the administration of semicarbazide, radiological examination showed bone and articular alterations with growth plates enlargement. Histological exams showed irregular patterns and proliferation of chondrocytes and excessive accumulation of extracellular matrix. Immunohistochemical exams showed PCNA positive reaction in pre- and hypertrofic chondrocytes. These results confirm that semicarbazide induces important changes in skeletal tissues and that has potential utility in experimental osteolathryrism.

Effect of dithiocarbamate thiram on Wistar rat growth plate and articular cartilage / Efeito do ditiocarbamato tirame sobre a placa de crescimento e cartilagem articular de ratos Wistar

Avaliou-se o efeito do tirame, ditiocarbamato largamente utilizado na agricultura como antifúngico e repelente de roedores, na ossificação endocondral de mamíferos, usando, como modelo, ratos Wistar. Não foram observadas lesões na cartilagem articular, nem nas placas de crescimento, o que pode ser atribuído à dose utilizada e à duração do ensaio. A diminuição da altura da placa de crescimento nos animais aos quais foi administrado o tirame parece traduzir o atraso verificado no crescimento em geral, e não um efeito específico na cartilagem, uma vez que as diferentes zonas da placa epifisária mantiveram as proporções dos animais do grupo-controle. Embora não tenham sido verificados, no presente trabalho, os efeitos registrados para outras espécies nos tecidos cartilaginosos, sugere-se a avaliação dos efeitos crónicos do tirame no crescimento e no desenvolvimento dos ossos longos em mamíferos.