Delayed Graft Function Under the Microscope: Surveillance Biopsies in Kidney Transplantation.

Delayed graft function (DGF) is a common complication of kidney transplantation and frequently leads to the necessity of surveillance biopsies. The purpose of this study is to describe the histological findings in surveillance biopsies of deceased donor kidney transplant recipients and evaluate the risk factors for graft outcomes. This is a monocentric, retrospective study including kidney transplant recipients that underwent a graft biopsy during the DGF period between January 2006 and July 2019. 356 biopsies were performed in 335 deceased donor transplant recipients. Biopsies were analyzed according to the Banff classification. The main histological findings were: acute tubular necrosis in 150 biopsies (42.1%), acute rejection in 96 biopsies (26.9%), and borderline findings in 91 biopsies (25.5%). In the multivariate analysis, recipient age (p = 0.028) and DGF duration (p = 0.005) were associated with rejection, antibody-induction with anti-thymocyte globulin (ATG) was protective (p = 0.001). The occurrence of rejection was associated with lower death-censored graft survival (log-rank; p = 0.009). Surveillance biopsies of kidney grafts experiencing DGF remain an essential tool for the care of kidney transplant recipients. The recipient's age and duration of DGF are independent risk factors for acute rejection, while antibody-induction therapy with ATG is associated with protection from its occurrence.

Oral and systemic factors in xerostomia / Relação de xerostomia com fatores bucais e sistêmicos

ABSTRACT Objective: The aim of this study was to evaluate the relationship among the following features: hyposalivation, systemic diseases and drug use, oral symptoms, dental condition, salivary flow and salivary pH, as well. Methods: A cross-sectional study was performed with 50 participants diagnosed with xerostomia, randomly selected and distributed in two groups: 25 with hyposalivation and 25 without hyposalivation, paired in age and sex. Unstimulated Salivary Flow Rate (USFR), Decayed, Missing, Filled, Teeth (DMFT) index and salivary pH were determined. The Mann-Whitney test and chi-square test were applied, considering significant for p-values <0.05. Results: Among the participants with hyposalivation, 88% used drugs and 96% presented systemic disease. And among those without hyposalivation, 48% used drugs and 64% presented systemic disease. The ones with hyposalivation showed the highest levels of dysgeusia (60%) and burn mouth (36%). There were statistically significant differences for the medians of USFR (0.08ml/minute / 0.2ml/minute) (p = 0.000), pH (6/7) (p = 0.000) and DMFT (22/17) (p = 0.004) obtained from participants with hyposalivation and without hyposalivation, respectively. Only in the group with hyposalivation there was a statistically significant association of unstimulated salivary flow rate with age (p = 0.035), type of systemic disease (p = 0.049) and pH (p=0.032) and DMFT demonstrated an association with systemic diseases (p = 0.015). Conclusion: The research results have suggested that hyposalivation worsens dental status triggering oral symptoms, and that salivary flow is influenced by the type of systemic disease and age group.

RESUMO Objetivos: Avaliar a relação entre hipossalivação, doenças sistêmicas e uso de medicamentos, sintomas bucais, experiência com cárie, fluxo e pH salivar. Métodos: Realizou-se estudo transversal com 50 participantes com xerostomia, selecionados e distribuídos aleatoriamente em dois grupos: 25 com hipossalivação e 25 sem hipossalivação, pareados em idade e sexo. Determinou-se o fluxo salivar em repouso (FSR), índice de dentes cariados, perdidos e obturados (CPO-D) e pH salivar. Aplicou-se teste de Mann-Whitney e teste qui-quadrado, considerando significantes valores de p<0,05. Resultados: No grupo de participantes com hipossalivação 88% usavam medicamentos e 96% tinham doença sistêmica e, entre os sem hipossalivação, 48% usavam medicamentos e 64% tinham doenças sistêmicas. Aqueles com hipossalivação tiveram os maiores percentuais de disgeusia (60%) e ardor bucal (36%). Houve diferenças estatisticamente significantes para as medianas de FSR (0,08 ml/minuto / 0,2 ml/minuto) (p=0,000), pH (6/7) (p=0,000) e CPO-D (22/17) (p=0,004) obtidas dos participantes com hipossalivação e sem hipossalivação, respectivamente. Apenas no grupo com hipossalivação houve associação estatisticamente significante do fluxo salivar em repouso com faixa etária (p=0,035), tipo de doença sistêmica (p=0,049) e pH (p=0,032) e, o CPO-D teve associação com doenças sistêmicas (p=0,015). Conclusão: Os resultados sugerem que a hipossalivação piora a condição dental, favorece a presença de sintomas bucais e, o fluxo salivar em repouso sofre influência de doenças sistêmicas e faixa etária.

Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

BACKGROUND: The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. OBJECTIVE: To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. METHODS: Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. RESULTS: Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01) and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months), remaining significantly lower than before transplantation (p<0.01) (pover time<0.01). At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. CONCLUSION: Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

Different Dietary Patterns and New-Onset Diabetes Mellitus After Kidney Transplantation: A Cross-Sectional Study.

OBJECTIVE: To verify the association of dietary patterns and dietary components with new-onset diabetes mellitus after transplantation (NODAT). DESIGN: Cross-sectional study. SUBJECTS: Adult kidney transplant recipients, without history of diabetes before transplantation, who received a kidney transplant and were followed up for at least 1 year. One hundred and sixteen subjects recruited between January 2013 and August 2014. Diagnosis of NODAT was established according to the American Diabetes Association criteria for type 2 diabetes. METHODS: Demographic, clinical, and anthropometric data were collected. Dietary intake was assessed by food frequency questionnaire, administered by a registered dietitian. Dietary patterns were identified by cluster analysis. Chi-square test was used to verify the association between dietary patterns and NODAT. Total energy, fiber, and cholesterol intake were calculated. Consumption of macronutrients, carbohydrates, proteins, and fats (total fats and saturated, monounsaturated, polyunsaturated and trans fatty acids), were expressed in percentage of total energy intake. RESULTS: Twenty-eight patients developed NODAT in the follow-up period. They presented higher body mass index and body fat percentage, as well as higher levels of triglycerides and urinary protein/creatinine ratio than the non-NODAT group. Two dietary patterns, I and II, were identified. Pattern II was characterized by higher intake of total, saturated, monounsaturated, and trans fats than pattern I. No association between the dietary patterns and NODAT was identified (P = .905), and there was no difference in the distribution of macronutrients, dietary fiber, and dietary cholesterol between the groups with and without NODAT. CONCLUSION: Posttransplant dietary patterns were not different between patients with and without NODAT. Further larger and prospective studies are needed to evaluate a possible relationship between dietary components and NODAT incidence in kidney transplant recipients.

Effects of metabolic syndrome on kidney transplantation outcomes: a systematic review and meta-analysis.

Metabolic syndrome (MS) has been associated with proteinuria and reduced glomerular filtration rate. Immunosuppressive agents increase the incidence of traditional risk factors for cardiovascular disease (CVD) and have known effects on MS components after kidney transplantation. The purpose of this meta-analysis was to evaluate the impact of MS on relevant outcomes after kidney transplantation. MEDLINE, EMBASE, and Cochrane Library were searched up to November 7, 2015. Papers that compared patients with and without MS and assessed one of the following outcomes, graft loss, death by cardiovascular disease, and all-cause mortality, were included. Of 585 studies identified, five studies including 1269 patients were evaluated. MS was identified as a risk factor for graft loss [relative risk, 3.06; 95% confidence interval (CI), 2.17, 4.32; I² = 0%; P heterogeneity = 0.72] and death by CVD (relative risk, 3.53; 95% CI, 1.27, 9.85; I² = 0%; P heterogeneity = 0.40). Results on the association between MS and all-cause mortality were inconclusive (relative risk, 2.61; 95% CI, 0.70, 9.81; I² = 58%; P heterogeneity = 0.09). Graft loss and death by CVD were associated with the presence of MS after transplantation. Randomized clinical trials should be conducted to define whether interventions on each MS component would result in better outcomes after transplantation.

Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is expressed in tubular epithelial cells after injury and may have a role in the development of renal graft fibrosis. In this study we evaluated the molecular and protein expressions of KIM-1 in dysfunctional allografts and also mRNA KIM-1 expression in urine as potential biomarkers of graft fibrosis. METHODS: Protein and mRNA levels in renal tissue and urinary sediment cells of 69 kidney transplant recipients that undertook for-cause graft biopsies were evaluated by immunohistochemistry and real-time polymerase chain reaction. The histopathology was classified according to the 2007 Banff schema. RESULTS: KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubular atrophy (IF/TA) compared with biopsies showing acute calcineurin inhibitor nephrotoxicity (CIN) (P <0.05). Kidney tissue KIM-1 mRNA signaling (in) was increased in biopsies with IF/TA compared with all other groups (P <0.05). In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05). Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine. CONCLUSIONS: KIM-1 seems to be a marker of kidney graft fibrosis. Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.

Expression patterns of B cells in acute kidney transplant rejection.

OBJECTIVES: To evaluate B-cell expression patterns and association with function and survival in dysfunctional kidney allografts. MATERIALS AND METHODS: There were 110 kidney transplant recipients included who had for-cause biopsies. Demographic and transplant data were collected. Immunostaining for B cells, plasma cells, and C4d was performed by the immunoperoxidase technique in paraffin-embedded samples. Circulating antihuman leukocyte antigen donor-specific antibodies were detected in a single-antigen assay at biopsy. The main outcomes were kidney graft survival and function. The patients were evaluated in 3 groups according to the Banff classification: no rejection (40 patients), T-cell-mediated rejection (50 patients), and antibody-mediated rejection (20 patients). RESULTS: The CD138-positive plasma cell-rich infiltrates predominated in antibody-mediated rejection and were associated with stronger reactivity against panel antibodies (r = 0.41; P ≤ .001) and positive donor-specific antibodies (r = 0.32; P ≤ .006). The CD20-positive lymphocytes were associated with T-cell-mediated rejection, increased human leukocyte antigen mismatch, and frequency of retransplant. The CD138-positive cell infiltrates also were significantly greater in patients who had late than early rejection. There was no correlation between cellular CD20 and CD138 expression, and neither CD20 nor CD138 predicted worse graft function or survival. Other markers of antibody-mediated rejection such as C4d and donor-specific antibodies were associated with worse graft function and survival at 4 years after transplant. In multivariate analysis, C4d was the only risk factor associated with graft loss. CONCLUSIONS: After kidney transplant, CD20-positive B-cell infiltrates were associated with T-cell-mediated rejection, and CD138-positive plasma cells were associated with antibody-mediated rejection. Graft loss was associated with the presence of C4d.

Prevalência de Fatores de Risco Cardiovascular em Pacientes em Hemodiálise - O Estudo CORDIAL / Prevalence of Cardiovascular Risk Factors in Hemodialysis Patients - The CORDIAL Study

Fundamentos: Há uma carência de dados epidemiológicos sobre o perfil de risco cardiovascular nos pacientes renais crônicos em hemodiálise no Brasil. Objetivo: O estudo CORDIAL foi planejado para avaliar fatores de risco cardiovascular e acompanhar a evolução de uma população em programa de hemodiálise numa cidade metropolitana do Brasil. Métodos: Todos os pacientes em hemodiálise por doença renal crônica nos quinze centros de nefrologia de Porto Alegre foram considerados para inclusão na fase inicial do estudo CORDIAL. Dados clínicos, laboratoriais e demográficos foram obtidos nos registros médicos, e em entrevistas individuais estruturadas realizadas com todos os pacientes por pesquisadores treinados. Resultados: Foram incluídos 1215 pacientes (97,3% de todos os que estavam em hemodiálise na cidade de Porto Alegre). A média de idade era 58,3 anos, 59,5% eram homens e 62,8% eram brancos. A prevalência de fatores de risco cardiovascular encontrada foi 87,5% para hipertensão, 84,7% para dislipidemia, 73,1% para sedentarismo, 53,7% para tabagismo e 35,8% para diabetes. Em uma análise multivariada ajustada, sedentarismo (p = 0,032; RP 1,08 - IC95%: 1,01-1,15), dislipidemia (p = 0,019; RP 1,08 - IC95%: 1,01-1,14), e obesidade (p < 0,001; RP 1,96 - IC95%: 1,45-2,63) foram mais frequentes em mulheres; e hipertensão (p = 0,018; PR 1,06 - IC95%: 1,01-1,11) e tabagismo (p = 0,006; RP 2,7 - IC95%: 1,79-4,17) foram mais frequentes naqueles com menos de 65 anos. Sedentarismo apresentou uma associação independente com tempo em diálise inferior a 12 meses (p < 0,001; RP 1,23 - IC95%: 1,14-1,33). Conclusão: Pacientes em hemodiálise nesta metrópole do sul do Brasil apresentaram uma prevalência elevada de fatores de risco cardiovascular similar a diversos países do hemisfério norte. .

Background: There are scarce epidemiological data on cardiovascular risk profile of chronic hemodialysis patients in Brazil. Objective: The CORDIAL study was designed to evaluate cardiovascular risk factors and follow up a hemodialysis population in a Brazilian metropolitan city. Methods: All patients undergoing regular hemodialysis for chronic renal failure in all fifteen nephrology centers of Porto Alegre were considered for inclusion in the baseline phase of the CORDIAL study. Clinical, laboratory and demographic data were obtained in medical records and in structured individual interviews performed in all patients by trained researchers. Results: A total of 1215 patients were included (97.3% of all hemodialysis patients in the city of Porto Alegre). Their average age was 58.3 years old, 59.5% were male and 62.8% were white. The prevalence of cardiovascular risk factors observed was 87.5% for hypertension, 84.7% for dyslipidemia, 73.1% for sedentary lifestyle, 53.7% for tobacco use, and 35.8% for diabetes. In a multivariate adjusted analysis, we found that sedentary lifestyle (p = 0.032, PR 1.08 - 95%CI: 1.01-1.15), dyslipidemia (p = 0.019, PR 1.08 - 95%CI: 1.01-1.14), and obesity (p < 0.001, PR 1.96 - 95%CI: 1.45-2.63) were more frequent in women; and hypertension (p = 0.018, PR 1.06 - 95%CI: 1.01-1.11) and tobacco use (p = 0.006, PR 2.7 - 95%CI: 1.79-4.17) were more often found among patients under 65 years old. Sedentary lifestyle was independently associated with time in dialysis less than 12 months (p < 0.001, PR 1.23 - 95% CI: 1.14-1.33). Conclusion: Hemodialysis patients in this southern metropolitan Brazilian city have a high prevalence of cardiovascular risk factors resembling many northern countries. .

Prevalence of cardiovascular risk factors in hemodialysis patients - The CORDIAL study.

BACKGROUND: There are scarce epidemiological data on cardiovascular risk profile of chronic hemodialysis patients in Brazil. OBJECTIVE: The CORDIAL study was designed to evaluate cardiovascular risk factors and follow up a hemodialysis population in a Brazilian metropolitan city. METHODS: All patients undergoing regular hemodialysis for chronic renal failure in all fifteen nephrology centers of Porto Alegre were considered for inclusion in the baseline phase of the CORDIAL study. Clinical, laboratory and demographic data were obtained in medical records and in structured individual interviews performed in all patients by trained researchers. RESULTS: A total of 1215 patients were included (97.3% of all hemodialysis patients in the city of Porto Alegre). Their average age was 58.3 years old, 59.5% were male and 62.8% were white. The prevalence of cardiovascular risk factors observed was 87.5% for hypertension, 84.7% for dyslipidemia, 73.1% for sedentary lifestyle, 53.7% for tobacco use, and 35.8% for diabetes. In a multivariate adjusted analysis, we found that sedentary lifestyle (p = 0.032, PR 1.08 - 95%CI: 1.01-1.15), dyslipidemia (p = 0.019, PR 1.08 - 95%CI: 1.01-1.14), and obesity (p < 0.001, PR 1.96 - 95%CI: 1.45-2.63) were more frequent in women; and hypertension (p = 0.018, PR 1.06 - 95%CI: 1.01-1.11) and tobacco use (p = 0.006, PR 2.7 - 95%CI: 1.79-4.17) were more often found among patients under 65 years old. Sedentary lifestyle was independently associated with time in dialysis less than 12 months (p < 0.001, PR 1.23 - 95% CI: 1.14-1.33). CONCLUSION: Hemodialysis patients in this southern metropolitan Brazilian city have a high prevalence of cardiovascular risk factors resembling many northern countries.

Evaluation of metabolic syndrome and associations with inflammation and graft function in renal transplant recipients / Avaliação da síndrome metabólica e suas associações com inflamação e função do enxerto em pacientes receptores de transplante renal

INTRODUCTION: Cardiovascular disease (CVD) is a major determinant of mortality in renal transplant recipients (RTR). Metabolic syndrome (MS) and chronic inflammation are currently considered non traditional risk factors for cardiovascular disease. This study evaluates the frequency of these conditions their associations with graft function. OBJECTIVE: To evaluate the prevalence of metabolic syndrome (MS) and inflammation and their associations with graft function in renal transplant recipients. METHODS: A cross-sectional study was carried out with 200 RTR. MS was defined by the NCEP-ATP III criteria. Inflammation was assessed by CRP levels. Renal function was assessed by GFR estimation using the MDRD equation. RESULTS: MS occurred in 71 patients (35.5%). Patients with MS had higher CPR and decreased GFR levels. Inflammation was present in 99 patients (49.5%). Mean waist perimeter, body mass index, triglycerides and serum total cholesterol were significantly higher in inflamed patients. An association between MS and inflammation was demonstrated, 48 (67.6%) patients with MS were inflamed and among those without MS the rate of inflamed patients was 39.5% (51 patients) (p < 0.001). A significantly higher percentage of patients with MS in the group of patients in chronic renal disease stages III and IV was observed. CONCLUSION: In RTR there is a significant association among MS and inflammation. MS is negatively associated with graft function. The clinical implications of these findings must be evaluated in longitudinal studies.

INTRODUÇÃO: A doença cardiovascular (DCV) é um dos principais determinantes da mortalidade em receptores de transplante renal (RTR). A síndrome metabólica (SM) e a inflamação crônica atualmente são considerados fatores de risco não tradicionais para doença cardiovascular. OBJETIVO: Avaliar a frequência da SM e da inflamação e suas associações com a função do enxerto em receptores de transplante renal. MÉTODOS: Foi realizado um estudo transversal com 200 RTR. A SM foi definida pelos critérios do NCEP-ATP III. A inflamação foi avaliada por meio dos níveis de PCR. A função renal foi avaliada pela estimativa da TFG por meio da equação MDRD. RESULTADOS: A SM ocorreu em 71 pacientes (35,5%). Pacientes com SM apresentaram maior PCR e diminuição dos níveis de TFG. A inflamação esteve presente em 99 pacientes (49,5%). A circunferência abdominal, índice de massa corporal, triglicérides e colesterol total foram significativamente maiores em pacientes com inflamação. Foi demonstrada associação entre MS e inflamação, 48 (67,6%) pacientes com SM estavam inflamados e entre aqueles sem SM a taxa de inflamados foi de 39,5% (51 pacientes) (p < 0,001). Uma porcentagem significativamente maior de pacientes com SM foi observada no grupo de pacientes de doença renal crônica estágios III e IV. CONCLUSÃO: Em RTR há associação significativa entre MS e inflamação. A SM está negativamente associada com a função do enxerto. As implicações clínicas destes achados devem ser avaliadas em estudos longitudinais.

Association between 276G/T adiponectin gene polymorphism and new-onset diabetes after kidney transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a well-recognized complication of kidney transplantation and is associated with poor outcomes. Both adiponectin and chemokine ligand 5 (CCL5) proteins are related to glucose metabolism and genetic variations in their genes can lead to development of NODAT. The aim of this study was to investigate the association of adiponectin and CCL5 genes polymorphisms with NODAT in a population of Caucasian kidney transplant recipients. METHODS: Two hundred seventy Caucasian kidney transplant recipients (83 with NODAT and 187 without NODAT) were included in a nested case-control study. Patients with pretransplantation diabetes mellitus and multiorgan transplantation were excluded. NODAT diagnosis was determined by American Diabetes Association criteria. Subjects were genotyped for 276G/T adiponectin gene polymorphism (rs1501299) and rs2280789 and rs3817655 CCL5 gene polymorphisms by real-time polymerase chain reaction. RESULTS: The TT genotype of 276G/T adiponectin gene polymorphism was significantly more frequent in NODAT than non-NODAT patients compared with GG/GT genotypes (recessive model; P=0.031). TT genotype was identified as an independent risk factor for NODAT in Caucasian kidney transplant recipients after adjusting for age at transplantation, pretransplantation body mass index, and use of tacrolimus (TT vs. GG/GT, hazard ratio=1.88, 95% confidence interval=1.03-3.45, P=0.041). There were no differences in genotype distribution and allele frequency of rs2280789 and rs3817655 CCL5 gene polymorphisms between NODAT and non-NODAT groups. CONCLUSIONS: The 276G/T adiponectin gene polymorphism is associated with NODAT in Caucasian kidney transplant recipients.

Obesity in kidney transplant recipients: association with decline in glomerular filtration rate.

In this study we aimed to evaluate the influence of obesity in kidney and patient survival and graft function. Retrospective cohort study of kidney transplant recipients performed between 2001 and 2009. The body mass index was calculated at time of transplantation, one and five years after. The main outcomes studied were incidence of delayed graft function, new onset diabetes after transplantation, patient and graft survival, and glomerular filtration rate. The prevalence of obesity and overweight patients were 10.7% and 26.8% respectively, with an increase to 16.9% and 32.5% one year after transplantation. Underweight and obese recipients presented a higher incidence of early graft loss. The incidence of new onset diabetes after transplantation was significantly higher at one and five years in overweight or obese recipients at baseline. Overweight and obese recipients presented significantly lower estimated glomerular filtration rate at five years posttransplantation (p = 0.002). In the Kaplan-Meier analyses no statistically significant differences in patients or grafts survivals were observed. Obese patients have a higher rate of early graft failure and a higher new onset diabetes after transplantation incidence. Also, the finding of decreased glomerular filtration rate is worrisome and perhaps longer follow-up will reveal more graft failures and patients deaths in the group of obese recipients.

Analysis of FOXP3 gene and protein expressions in renal allograft biopsies and their association with graft outcomes.

BACKGROUND: The transcription factor FOXP3 is increased in acute renal rejection, but its influence on graft outcomes is unclear. This study correlated FOXP3 with dendritic cells and graft outcomes. METHODS: We assessed 96 kidney transplants undergoing allograft biopsy for cause. FOXP3 mRNA was analyzed by real-time polymerase chain reaction (PCR) and FOXP3 protein and DCsCD83(+) by immunohistochemistry. Graft function and survival were assessed at 5 years post-transplantation, as well as by independent predictors of graft loss. RESULTS: Intragraft FOXP3 gene and protein expression were significantly correlated (r = 0.541, p < 0.001). Both FOXP3 mRNA and protein were increased in patients with acute rejection (AR). High expression of FOXP3 mRNA or protein in biopsies did not correlate with clinical variables, but there was a trend to higher positive variation in the glomerular filtration rate (GFR) from biopsy to last follow-up. Patients with FOXP3-mRNA(high) had more DCsCD83(+) in biopsy, but these cells did not associate with AR. Five-year graft survival was not influenced by either FOXP3 mRNA or protein expressions. CONCLUSIONS: FOXP3 mRNA and protein had a good correlation in archival renal graft tissue. Increased FOXP3 expression was found in AR and FOXP3 associated with high numbers of DCs. However, both FOXP3 mRNA and protein was not associated with better allograft outcomes.

Evaluation of metabolic syndrome and associations with inflammation and graft function in renal transplant recipients.

INTRODUCTION: Cardiovascular disease (CVD) is a major determinant of mortality in renal transplant recipients (RTR). Metabolic syndrome (MS) and chronic inflammation are currently considered non traditional risk factors for cardiovascular disease. This study evaluates the frequency of these conditions their associations with graft function. OBJECTIVE: To evaluate the prevalence of metabolic syndrome (MS) and inflammation and their associations with graft function in renal transplant recipients. METHODS: A cross-sectional study was carried out with 200 RTR. MS was defined by the NCEP-ATP III criteria. Inflammation was assessed by CRP levels. Renal function was assessed by GFR estimation using the MDRD equation. RESULTS: MS occurred in 71 patients (35.5%). Patients with MS had higher CPR and decreased GFR levels. Inflammation was present in 99 patients (49.5%). Mean waist perimeter, body mass index, triglycerides and serum total cholesterol were significantly higher in inflamed patients. An association between MS and inflammation was demonstrated, 48 (67.6%) patients with MS were inflamed and among those without MS the rate of inflamed patients was 39.5% (51 patients) (p < 0.001). A significantly higher percentage of patients with MS in the group of patients in chronic renal disease stages III and IV was observed. CONCLUSION: In RTR there is a significant association among MS and inflammation. MS is negatively associated with graft function. The clinical implications of these findings must be evaluated in longitudinal studies.

Transplante renal em pacientes HIV positivos: relato de dois casos da experiência inicial do Hospital de Clínicas de Porto Alegre / Kidney transplantation in HIV positive patients: two case reports from Hospital de Clínicas de Porto Alegre initial experience

Recentemente, o transplante renal passou a ser uma modalidade terapêutica aceita para o tratamento de pacientes renais crônicos terminais infectados pelo HIV. Para tal, há necessidade de estabilidade de parâmetros clínicos e laboratoriais relacionados à infecção pelo HIV e do uso de terapia antiretroviral de elevada eficiência. Neste relato, apresentamos os dois primeiros casos no Brasil de pacientes portadores de infecção pelo HIV transplantados com órgãos de doadores falecidos realizados com sucesso em nossa instituição. As interações entre os imunossupressores e as drogas antiretrovirais, as coinfecções, o perfil de risco cardiovascular e a elevada incidência de rejeição aguda permanecem os maiores problemas a serem equacionados nestes pacientes.

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.

[Kidney transplantation in HIV positive patients: two case reports from Hospital de Clínicas de Porto Alegre initial experience]. / Transplante renal em pacientes HIV positivos: relato de dois casos da experiência inicial do Hospital de Clínicas de Porto Alegre.

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.

FOXP3+ regulatory T cells: from suppression of rejection to induction of renal allograft tolerance.

Naturally occurring and induced regulatory T cells (Tregs) can become hyporesponsive and anergic to antigen stimulation in autoimmune diseases and allograft rejection. The mechanisms of suppression of effector T cells by Tregs remain unclear, but there are in vitro and in vivo evidences showing that these cells are able to suppress antigen-specific responses via direct cell-to-cell contact, secrete anti-inflammatory cytokines such as TGF-ß and IL-10, and inhibit the generation of memory T cells, among others. The transcription factor FOXP3 is a specific marker of Tregs and its deficiency is associated with autoimmune diseases and inflammation. During acute rejection of kidney allografts, an augmented FOXP3 gene expression as well as increased CD4(+)CD25(+)FOXP3(+) and other cell populations are observed in graft biopsies. However, it is not clear whether Tregs migrate into the graft and are retained there to suppress the inflammatory process, or whether they are directly associated with more complex mechanisms to induce immune tolerance. FOXP3(+) Tregs may direct the immune response toward a graft acceptance program, potentially affecting the long-term survival of transplanted organs and tissues. Immunosuppressive drugs modulate the number and function of circulating Tregs and FOXP3 expression. Experimental and clinical studies have shown that mTOR inhibitors have positive and calcineurin inhibitors negative effects on Tregs, but it is difficult to set apart the effect of multiple other factors known to be associated with short- and long-term renal graft outcomes. This review aimed to describe the functions of Tregs and its transcription factor FOXP3 in suppression of immune response during rejection and in induction of kidney graft tolerance, as well as to review the individual effects of immunosuppressive drugs on Tregs.

Leptin, insulin resistance, and metabolic changes 5 years after renal transplantation.

OBJECTIVE: To evaluate leptin, insulin resistance (IR), and changes in body composition and lipid profile within 5 years after renal transplantation. DESIGN: Longitudinal study. SETTING: Hospital de Clínicas de Porto Alegre/RS, Brazil. SUBJECTS: Thirty-two renal transplant recipients were followed up for 5 years after transplantation. METHODS: Data were collected at transplantation time (T1) and after 3 months (T2), 1 year (T3), and 5 years (T4). Leptin serum levels, IR assessed by homeostasis model assessment (HOMA) index, lipid profile, and anthropometric measurements were analyzed. Data were compared with a control group at baseline. RESULTS: At T1, pretransplant patients had leptin levels (ng/mL) (11.9 [9.2 to 25.2]) higher than the control group (7.7 [5.2 to 9.9]; P < .0001). After transplantation, levels decreased at T2 and T3, but increased at T4 to values similar to those seen at T1 (T4: 9.2 [5.7 to 21]; P = 1). HOMA also decreased at T2, but increased at T4 to identical levels (T1: 2.1 [1.63 to 2.23], T4: 2.1 [1.6 to 2.85]; P = 1). No significant changes in body fat percentage (BF%) were observed; however, the arm muscle circumference increased significantly at T4 (P < .0001). At T2, total cholesterol, triglycerides, and low-density lipoprotein cholesterol increased, whereas at T4, lipid profile moved toward T1 levels. By linear regression analysis, gender, BF%, and HOMA were independent predictors of leptin levels. A trend toward higher body mass index was observed in woman who also presented higher leptin and lower HOMA levels. CONCLUSION: Leptin levels and HOMA decrease in the immediate posttransplant period and remain reduced for at least 1 year. Five years post transplantation, leptin, IR, BF%, and lipids have a profile similar to those in the pretransplant period. This metabolic profile is possibly associated with the elevated incidence of cardiovascular diseases observed in the late posttransplant period.

Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients.

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d⁻, patients with ABMR C4d⁺ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.