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.

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.

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.

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.

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.

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.

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.

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.

[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.

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.

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients / Correlações clinico-patológicas da marcação de C4d e sua influência na evolução de receptores de transplante renal

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 percent) biopsies, of which 23 (14.7 percent) had diffuse and 25 (16 percent) focal distribution. Pre-transplantation panel reactive antibodies ( percentPRA) 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 percentPRA 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.

INTRODUÇÃO: A fração do complemento C4d é um marcador de rejeição mediada por anticorpos (RMA) em aloenxertos renais, embora na rejeição celular também se observem depósitos de C4d. OBJETIVOS: Correlacionar a expressão de C4d com parâmetros clínicopatológicos e a evolução do enxerto renal em três anos. MÉTODOS: Foram incluídos 146 receptores de transplante renal com biópsias por indicação. A marcação de C4d foi feita por imuno-histoquímica em parafina. Foram medidas a função e a sobrevida do enxerto e determinadas as variáveis preditivas de sua evolução por meio de modelo de regressão de Cox. RESULTADOS: A marcação positiva para C4d foi detectada em 48 (31 por cento) biópsias, das quais 23 (14,7 por cento) tinham marcação difusa e 25 (16 por cento), focal. A reatividade contra painel ( por centoPRA) de classe I e II pré-transplante foi significativamente maior nos pacientes C4d+ quando comparada aos C4d-. Tanto glomerulite quanto pericapilarite foram associadas com C4d (p = 0,002 e p < 0,001, respectivamente). A presença de C4d em biópsias sem rejeição (SR), rejeição celular aguda (RCA) ou fibrose intersticial/atrofia tubular (FI/AT) não teve impacto na função ou na sobrevida do enxerto. Comparados a indivíduos com SR, RCA e FI/AT C4d-, pacientes com RMA C4d+ tiveram pior sobrevida do enxerto em 3 anos (p = 0,034), mas não houve diferença entre RMA versus SR, RCA e FI/AT C4d+ (p = 0,10). Na regressão de Cox, função do enxerto no momento da biópsia e por centoPRA alto foram preditores de perda do enxerto. CONCLUSÕES: A pesquisa de C4d em biópsias do enxerto renal é útil para identificar RMA, com correlações clínicopatológicas bem definidas. O impacto do C4d em outros diagnósticos histológicos necessita de investigação adicional.

Perfil socioeconômico dos pacientes com doença renal crônica em diálise na região noroeste do Rio Grande do Sul / Socioeconomic profile of patients with chronic kidney disease on dialysis in the northwestern region of Rio Grande do Sul

O baixo nivel socioeconômico é um fator de risco para doenças crônicas e tem sido demonstrada uma relação inversa da renda com a incidência de Doença Renal Crônica (DRC). Além disso, vários estudos têm descrito associação de características étnicas com a maior prevalência da doença. Neste estudo, foram analisadas as características demográficas e socioeconômicas de pacientes com DRC em hemodiálise na Região Noroeste do Estado do Rio Grande do Sul. Métodos: Foram avaliados 260 pacientes em hemodiálise no ano de 2004. O instrumento empregado na coleta de dados foi o questionário utilizado pelo Instituto Brasileiro de Geografia e Estatística (IBGE) no censo demográfico 2000. Os dados obtidos foram comparados com a população da região. Adicionalmente, foram coletados dados referentes à doença, posse de plano de saúde e data de encaminhamento ao nefrologista. Avaliou-se o desfecho da mortalidade após dois anos da coleta inicial dos dados. Resultados: A prevalência em hemodiálise observada foi de 368 por milhão de população (pmp). Foram encontradas diferenças estatisticamente significativas entre os pacientes em hemodiálise e a população da região, com maior prevalência de pacientes do gênero masculino, faixas etárias mais elevadas, etnia não caucasóide, proveniência do meio urbano e estado civil casado. Em relação aos dados socioeconômicos, os pacientes em hemodiálise participantes do estudo têm significativamente menor escolaridade, menor renda familiar e menor nível de classificação econômica. A mortalidade em dois anos foi significativamente maior em pacientes com idade superior a 50 anos, com menor escolaridade e ausência de plano de saúde privado. Entre os pacientes das classes econômicas A e B, a mortalidade foi significativamente menor. Conclusão: Em relação à população da região, os pacientes em hemodiálise são mais idosos, mais frequentemente do gênero masculino e de etnia afrodescendente, com menor escolaridade e renda.

Low socioeconomic status is a risk factor for chronic diseases and has been demonstrated an inverse relationship of income to the incidence of Chronic Kidney Disease (CKD). In addition, several studies have described the association of ethnicity with the highest prevalence of the disease. In this study, we analyzed the demographic and socioeconomic characteristics of patients with CKD on hemodialysis in the northwest region of Rio Grande do Sul Methods: We studied 260 hemodialysis patients in 2004. The instrument used in data collection was the questionnaire used by the Brazilian Institute of Geography and Statistics (IBGE) in 2000 census. The data obtained were compared with the population of the region. Additionally, data were collected regarding the disease, possession of health insurance and date of referral to the nephrologist. We evaluated the outcome of mortality two years after the initial collection of data. Results: The prevalence observed in hemodialysis was 368 per million population (pmp). Statistically significant differences were found between hemodialysis patients and the population of the region, with higher prevalence of male patients, older age groups, non-Caucasian ethnicity, origin of the urban environment and being married. In relation to socioeconomic data, the hemodialysis patients in the study have significantly less education, lower family income and lower-economic classification. Mortality at two years was significantly higher in patients older than 50 years, with less education and no private health insurance. Among patients of lower socioeconomic classes A and B, the mortality was significantly lower. Conclusion: In relation to the region's population, hemodialysis patients are older, more often than males of African descent and ethnicity, with lower education and income.

Individualização da imunossupressão em pacientes transplantados renais / Individualization of immunosuppressive therapy in renal transplantation

Atualmente, os avanços na terapia imunossupressora em transplantes renais permitemque se individualize o regime de imunossupressão de acordo com as características dospacientes. A avaliação individualizada do risco leva em conta características do receptor, taiscomo idade, raça, compatibilidade HLA (antígenos leucocitários humanos), co-morbidades, riscoimunológico (sensibilização para antígenos do sistema HLA e retransplantes) e transplantes deórgãos duplos. São também consideradas as características do doador, sendo as principaisidade, função renal, co-morbidades e ser doador de critérios expandidos. De uma maneirageral, regimes imunossupressores mais potentes são utilizados em receptores de alto riscoimunológico, e regimes menos nefrotóxicos, nos receptores de baixo risco imunológico ou nosque recebem rins de doadores não-ideais.

The advances in immunosuppressive therapy currently allow the individualization ofimmunosuppressive regimens according to the characteristics of kidney transplant recipients.Age, race, HLA (human leukocyte antigens) matching, comorbid conditions, immunological risk(HLA sensitization and retransplantation) and double organ transplants are the main recipientrisk factors. Donor characteristics such as age, renal function, comorbid conditions and expandedcriteria donors are also considered. More intensive immunosuppressive regimens are usuallyused for recipients with high immunological risk and less nephrotoxic regimens are offered tolower immunological risk patients and for expanded criteria donor recipients.

Interpretação e uso clínico da pesquisa de dismorfismo eritrocitário no sedimento urinário / Clinical utility and interpretation of screening for urinary erythrocyte dysmorphism

Introdução: O dismorfismo eritrocitário urinário foi descrito há vários anos e tem sidousado para identificar os sangramentos glomerulares e para orientar a investigação subseqüente.Este estudo avalia a variabilidade na análise do dismorfismo eritrocitário por diferentesobservadores, verificando a correlação entre as observações e sua associação com o diagnósticoetiológico das hematúrias.Métodos: Foram selecionadas 18 amostras de sedimento urinário de pacientes comhematúria glomerular e não-glomerular, cujas imagens foram capturadas por um programa deanálise de imagens e gravadas em meio magnético. Essas imagens foram analisadas por dozeobservadores treinados na análise de dismorfismo eritrocitário que atuam em laboratórios deanálises clínicas de Porto Alegre. Os observadores, cegos em relação ao diagnóstico etiológicoda hematúria, classificaram as amostras pela presença ou ausência de dismorfismo e estimarama porcentagem de hemácias dismórficas em relação ao seu número total.Resultados: Utilizando o ponto de corte de 75% de hemácias dismórficas como diagnósticode hematúria glomerular, o diagnóstico correto foi obtido em 79% das observações. Asensibilidade foi de 76%, e a especificidade de 82%, com valores preditivos positivo e negativode 80% e 78% respectivamente. A correlação entre as observações foi calculada com o uso decoeficiente kappa, observando-se uma concordância moderada (kappa = 0,58).Conclusões: Este estudo demonstrou que, a despeito da ausência de critérios rígidos deavaliação e classificação do dismorfismo, sua realização por profissionais capacitados apresentaum nível aceitável de acurácia e concordância, justificando seu uso na avaliação de pacientescom hematúria.

Introduction: Urinary erythrocyte dysmorphism was described long ago and has beenused to identify glomerular bleeding and to guide subsequent investigation. The aim of this studywas to analyze the variability of erythrocyte dysmorphism observation performed by severalobservers, evaluating the correlation between the observations and their association with etiologicdiagnosis of hematuria.Methods: Eighteen urinary sediment samples from patients with glomerular and nonglomerularhematuria were studied. Their images were captured by phase-contrast microscopyand saved for later analysis. These images were analyzed by 12 observers experienced in erythrocyte dysmorphism evaluation who work in clinical laboratories in Porto Alegre, Brazil. Theobservers, who were blinded to the etiologic diagnosis of hematuria, classified the samplesaccording to the presence or absence of erythrocyte dysmorphism and estimated the percentageof dysmorphic erythrocytes in relation to total number.Results: Correct diagnoses were obtained in 79% of the observations, considering 75%as the cut-off point of dysmorphic erythrocytes for the diagnosis of glomerular hematuria.Sensitivity and specificity were 76 and 82%, respectively; positive predictive value was 80% andnegative predictive value was 78%. Agreement among observers was calculated using the kappacoefficient, which showed a moderate agreement (kappa = 0.58).Conclusions: Our study demonstrated that, despite the absence of strict criteria forassessing and classifying dysmorphism, the performance of urinary erythrocyte dysmorphismtest by skilled professionals presents an acceptable level of accuracy and agreement, whichsupports its use in the evaluation of patients with hematuria.

[Elevated cyclosporine A trough levels in HCV positive kidney transplant recipients]. / Níveis de vale de ciclosporina elevados em transplantados renais anti-HCV positivos.

OBJECTIVE: Compare the CsA trough levels of HCV+ kidney transplant recipients to a control group METHODS: All anti-HCV positive patients that received a renal allograft between January 1992 and April 1996 were initially included as cases. Patients with diabetes mellitus, HBsAg+, who were taking medication that could modify CsA pharmacokinetics and those with elevated aminotransferases were excluded. For each anti-HCV positive index case the following transplanted anti-HCV negative patient was included as a control. Third generation ELISA was used for determination of the anti-HCV status and CsA dosages were performed by polarized fluorometry with polyclonal antibodies. RESULTS: No differences in the demographic variables were found. The average CsA through levels in the first month were higher (551 +/- 280 ng/ml) in the 23 cases as compared to the 31 controls (418 +/- 228 ng/ml; p< 0.05). The differences became apparent at the end of the first week (528 +/- 275 versus 344 +/- 283 ng/ml; p<0.01) and persisted at discharge (582 +/-284 versus 457 +/- 229; p=0,08). CONCLUSION: We concluded that anti-HCV positive patients have higher blood levels of CsA for a particular dosage, than anti-HCV negative controls. Prospective studies with a more appropriate pharmacokinetic approach are needed to confirm the present findings.

Níveis de vale de ciclosporina elevados em transplantados renais anti-HCV positivos / Elevated cyclosporine A trough levels in HCV positive kidney transplant recipients

OBJETIVO: Comparar os níveis de vale de CsA de transplantados renais anti-HCV+ com um grupo controle. MÉTODOS: Incluímos como casos todos os pacientes anti-HCV+ transplantados entre janeiro de 1992 e abril de 1996, e os anti-HCV- transplantados a seguir do caso como controles. Excluímos pacientes diabéticos, HbsAg+, os que recebiam fármacos com interaçäo com a CsA e aqueles com transaminases elevadas. A sorologia para HCV foi testada pelo método ELISA de 3ª geraçäo, e as dosagens de ciclosporina através de fluorimetria polarizada com anticorpo policlonal. RESULTADOS: As principais variáveis demográficas näo diferiram entre os grupos. O nível de vale médio de CsA do primeiro mês pós-transplante foi maior nos 23 pacientes anti-HCV+ (551 ± 280 ng/ml) do que nos 31 controles (418 ± 228 ng/ml, p<0,05). As diferenças tornaram-se aparentes ao final da primeira semana (528 ± 275 versus 344 ± 283 ng/ml; p<0,01) e persistiam no momento da alta (582 ± 284 ng/ml versus 457 ± 229 ng/ml; p=0,08). CONCLUSÄO: Os pacientes anti-HCV+ apresentam níveis de vale de CsA elevados em relaçäo à populaçäo controle, o que indica a realizaçäo de estudo farmacocinético da droga neste prevalente grupo de transplantados renais