Being Overweight Is Related to Faster Decline in Annual Glomerular Filtration Rate in Kidney Transplant.

Few studies have examined the relationship between non-immunological factors and glomerular filtration rate (GFR) decline in kidney transplant. Correcting these factors in native kidneys slows the progression of chronic kidney disease. The aim of this study was to analyze the association between the control of non-immunological factors and the annual decline of GFR. METHODS: A single-center, retrospective study was performed. We included 128 patients who received kidney transplants between 2000 and 2015, with at least 1-year post-transplant follow-up. Clinical records were reviewed. GFR was estimated by CKD-EPI. Three groups were defined according to the annual change in eGFR (ΔGFR 2016-1015): non-progressors (> -1 mL/min/1.73 m2), slow progressors (> -1 and < -5 mL/min/1.73 m2), and fast progressors (< -5 mL/min/1.73 m2). Percentage of achievement of KDIGO target was also analyzed. RESULTS: The mean GFR was 62.5 mL/min/1.73 m2. Glomerulonephritis was the most common cause of kidney failure (36%). When the fast progressor group was compared with the non-progressor group, they differed significantly in age-patients were younger (40 ± 12.3 vs 45 ± 13.1 years)-post-transplant body mass index (27.4 ± 5.6 vs 25.2 x ± 5.9 kg/m2), and serum uric acid, which was significantly higher (6.4 ± 1.7 vs 5.5 ± 1.58 mg/dL). There were no differences between the groups with regard to blood pressure, dyslipidemia, proteinuria, or venous bicarbonate. Target systolic blood pressure was achieved by 45% of patients. Biopsy-proven acute rejection was higher in the fast progression group, although this was not statistically significant (13 [24.5%] vs 8 [13.1%]). CONCLUSIONS: High body mass index was associated with a faster decline in glomerular filtration rate in this study. Target blood pressure <140/90 mm Hg was achieved in less than 50% of cases.

Acute Antibody-Mediated Rejection in Kidney Transplant Based on the 2013 Banff Criteria: Single-Center Experience in Uruguay.

BACKGROUND: Acute antibody-mediated rejection (AMR) diagnosis criteria have changed in recent consensus of Banff, with current evidence of C4d-negative AMR. Our objective was to evaluate incidence of AMR in renal transplantation according to Banff 2013 criteria and to examine the histological features and outcome. METHODS: This retrospective study involved all kidney transplants with histological diagnosis of acute rejection (AR) at our center between 2000 and 2014. All the biopsies with AR were re-assessed by a nephro-pathologist and classified by use of the Banff 2013 criteria. RESULTS: Of 205 kidney transplants, biopsy-proven AR was diagnosed in 25 cases (12%). Re-assessing them according to Banff 2013 criteria, AMR was diagnosed in 17 (8.3%) and represented 68% of the confirmed rejections. AMR diagnosis was performed on day 23 ± 26, with median of 11 days. From the 17 cases, 7 had concomitant T-cell-mediated rejection. All cases presented endothelial edema and acute tubular necrosis. Glomerulitis was found in 12 cases and capillaritis in 14. In 3, associated thrombotic micro-angiopathy (TMA) was found. Intimal and transmural arteritis was evidenced in 5 and 1 patient. In 2, transplant glomerulopathy was present. Seven of the 10 biopsies with C4d staining in the peri-tubular capillaries were positive. Twelve cases received plasmapheresis, 6 received gamma-globulin, and 6 received rituximab. After administration of anti-AMR therapy, 16 cases recovered renal function, reaching a serum creatinine level of 1.5 ± 0.6 mg %. Graft survival at 1 year was lower in the AMR group versus patients without AMR (81.9% vs 98.9%, log-rank test, P < .001). Risk factors for AMR were re-transplant (30% vs 7%, P = .02), HLA-DR mismatch (1.06 ± 0.65 vs 0.7 ± 0.6, P = .03), panel-reactive antibody (28% ± 33 vs 6.2 ± 13, P = .00), and delayed graft function (82% vs 30%, P = .00). CONCLUSIONS: Adapting the new Banff 2013 criteria increased the sensitivity of the diagnosis of ARM. Regarding our data, despite an adequate response to the therapy, it resulted in a worse graft survival by the first year of renal transplant.

Clinical spectrum of cutaneous manifestations in renal and renopancreatic recipients in two centers in Uruguay.

Uruguay, with a total population of 3,345,000 inhabitants, is the Latin American country with the second highest number of renal replacement therapies. Long-term immunosuppressant therapy is essential for graft survival but results in reduced immunosurveillance, leading to an increased risk of complications. A variety of dermatological manifestations and a large increase in nonmelanoma skin cancers have been reported in this population. The purpose of this study was to evaluate the frequency and clinical spectrum of cutaneous manifestations in renal and renopancreatic recipients in 2 reference centers in Uruguay. Two hundred and six renal or renopancreatic recipients between 21 and 77 years old were evaluated between September 2009 and September 2011. A total of 206 dermatoses were observed; 60% of the patients had at least 1 cutaneous manifestation. The most frequent dermatoses were cutaneous side effects due to immunosuppressive treatment (40.6%), followed by infections (26.1%), miscellaneous causes (18.9%), and malignant and premalignant lesions (14.4%). Transplant recipients represent a high-risk dermatological population. Physicians in transplant units should be aware of the importance of dermatological screening in order to promote early detection of skin cancer.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats.

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Increased plasma LIGHT levels in patients with atopic dermatitis.

LIGHT [the name of which is derived from 'homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes'], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP-1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP-1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin-1ß in THP-1 cells. Apoptosis was inhibited, the Bcl-2 level increased and the caspase-3 level decreased in THP-1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.

Cutaneous manifestations in 100 renal and reno-pancreatic recipients of Uruguay.

Uruguay is the second country of Latin America in prevalence of renal replacement therapies, including functioning kidney allografts. Long-term immunosuppressive therapy is essential for adequate graft function, but results in reduced immunosurveillance leading to an increased risk of complications such as infections and malignancies. A variety of cutaneous manifestations as well as an increase in non-melanoma skin cancers have been reported in this population. The objective of this study was to evaluate the frequency and clinical spectrum of cutaneous manifestations in renal and reno-pancreatic recipients in Uruguay. One hundred renal or reno-pancreatic recipients aged between 21- and 77-years-old were evaluated between September 2009 and September 2010. A total of 104 dermatoses were observed; 68% of the patients had at least one cutaneous manifestation. The most frequent dermatoses were cutaneous side effects due to immunosuppressive treatment (43.3%), followed by infections (27.9%), miscellaneous causes (22.1%), as well as malignant and premalignant lesions (6.7%). This is the first study evaluating dermatological complications in organ transplant recipients in our country. Most of the patients had at least one dermatological manifestation of immunosuppression, including a malignant or pre-malignant lesion, highlighting that this is a high-risk dermatological population. Cancer is one of the most important causes of death in recipients with functioning grafts. Its prevention is a major goal in the care of transplant recipients. Physicians in transplant units should be aware of the importance of dermatological screening and skin cancer surveillance.

Effect of serotonin on the differentiation of human monocytes into dendritic cells.

The local cytokine environment and presence of stimulatory signals determine whether monocytes acquire dendritic cell (DC) or macrophage characteristics and functions. Because enhanced platelet activation is reported in patients with many allergic disorders, such as atopic dermatitis, platelet-derived factors may influence monocytic differentiation into DC. In this study we examined the effect of serotonin, a prototypic mediator of allergic inflammation released mainly by activated platelets at the inflammatory site, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived DC. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of serotonin, and the phenotypes and function of these cells were analysed. In the presence of serotonin, monocytes differentiated into DC with reduced expression of co-stimulatory molecules and CD1a, whereas expression of CD14 was increased. These serotonin-treated DC exhibited significantly reduced stimulatory activity toward allogeneic T cells. However, these cells showed enhanced cytokine-producing capacity, including IL-10 but not IL-12. There was no significant difference between both types of DC in phagocytic activity. Experiments using agonists and antagonists indicated that serotonin 5-hydroxytryptamine (5-HT) induced the alteration of their phenotype and reduction in antigen-presenting capacity were mediated via 5-HTR(1/7). It is therefore suggested that serotonin-driven DC may have a regulatory function in the inflammatory process.

[Ischemic cadiopathy in patients undergoing chronic hemodialysis]. / Cardiopatía isquémica en pacientes en hemodiálisis crónica.

UNLABELLED: We report a retrospective study of patients on chronic hemodialysis in whom a diagnosis of ischemic heart disease had been established. We compared the findings on coronary cineangiography and the treatment (medical only, surgical revascularisation [CABG] and percutaneous transluminal coronary angioplasty [PTCA]) with the early and late evolution. From a population of 2,287 patients on chronic hemodialysis treatment during the 5 year period 1994-1999, 83 patients who underwent coronary cineangiography after starting dialysis were selected. Their mean age was 63 +/- 9.4 (39-80) and the mean time on hemodialysis was 6 years (6 months-19 years). RESULTS: 65 patients (78%) had severe coronary lesions, 40% of whom had three vessel disease. 14 patients had medical treatment only (group 1), 23 had CABG (group 2) and 28 PTCA (group 3). Mortality within 30 days of intervention was 13% in group 2 and 21.4% in group 3. Global survival at two years was 82% in group 2 and 69% in group 3. Survival without angina at 6 and 24 months were 69% and 46% in group 2 and 55% and 22% in group 3 respectively. Survival without acute myocardial infarction at 6 and 24 months was 95% and 95% in group 2 and 89% and 64% in group 3. Data analysis using Cox proportional risk model showed that PTCA posed a higher risk of angina and death than CABG. CONCLUSION: Surgery yielded better early and later results than angioplasty even in those patients with severe coronary artery disease.

Frequency, Type and Associated Diseases of Bacteria and Virus in The Oropharynx of Children Born to Human Immunodeficiency Virus-Infected Mothers.

HIV-infected children are more likely than other children to develop pneumonia, which in these children is often recurrent or persistent. The main reservoir of the major pathogens is the nasopharynx, but to date no data has been published on the frequency and biologic characteristics of S.pneumoniae, H.influenzae and respiratory viruses found in the upper respiratory tract of children born to human immunodeficiency virus-infected mothers. To document these aspects, 105 children was monitored by pharyngeal swab (PS) and nasopahryngeal aspirates (NPA) who attended an outpatient clinic for HIV-infection evaluation. Bacterial identification was performed by standard procedures. Serotype, biotype and beta-lactamase production was investigated in H.influenzae isolates. S.pneumoniae serotypes were recognized by "quellung" and the susceptibility to 4 antibiotics was assessed. Respiratory syncytial viruses, parainfluenza, influenza A and B, and adenoviruses were diagnosed by indirect immunofluorescence and/or viral isolation in cell cultures. Twenty-nine children were identified as infected by HIV as a result of maternal-child transmission. Seventy children born to HIV-positive mothers but who were not HIV-infected served as controls. Of 269 PS, 110 110 S. pneumoniae and 92 H.influenzae were identified. Also 31 viruses were detected in 188 NPA. After stratifying by age no differences were observed in the frequency of bacterial colonization or in the presence of viruses in the upper respiratory tract of the two groups. Some biologic characteristics of the agents were noteworthy such as the frequency of colonization by S.pneumoniae serotype 14, the predominance of H.influenzae biotype I and the high frequency of viruses in NPA of asymptomatic children. Of note, although colonization frequencies were similar, children presenting with acute respiratory illness (ARI) were more likely to have bacteria isolated if they also had HIV-infection than if they were HIV-negative. It is concluded that HIV-infection in infants as a result of maternal virus transmission have a similar frequency of bacteria and virus colonization of their respiratory tract, but a higher frequency of ARI and perhaps a higher frequency of types of bacteria with special characteristics.