Significant Increase in Cytomegalovirus (CMV) Infection in Solid Organ Transplants Associated With Increased Use of Thymoglobulin as Induction Therapy?

BACKGROUND: Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). METHODS: This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. RESULTS: Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. CONCLUSIONS: The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.

Effects of recipient education disparity on living donor kidney transplant outcomes across different ethnic groups: a retrospective study in the United States.

Background: Previous studies have shown that education level is associated with the prognosis of cadaveric kidney transplant recipients. However, it is unclear whether education affects the prognosis of living kidney transplant (LDKT) recipients. In addition, it remains to be determined whether the uneven distribution of educational levels consistently affects the prognosis of LDKT recipients across ethnic groups (White, Black, Hispanic and Asian). Methods: After establishing inclusion and exclusion criteria, we conducted a retrospective study of LDKT recipients who received their first single LDKT between 2005 and 2020. The LDKT recipients were divided into lower- and higher-education groups according to categorize the educational level of recipients, and transplant outcomes, including graft survival, patient survival, and death-censored graft survival (DCGS), were analyzed and compared. Results: Graft survival, DCGS and patient mortality were significantly better in the higher-education group compared with those in the lower-education group (P<0.001), with the risk of graft failure, death censored graft failure (DCGF) and patient mortality increasing by 11%, 15% and 7% in the lower-education group, respectively. Furthermore, compared with the higher-education group, the risk of graft failure in Black recipients increased by 18% [adjusted hazard ratio (aHR), 1.18; 95% confidence interval (CI): 1.07 to 1.30], and the risk of patient mortality among White recipients decreased by 7% (aHR, 0.93; 95% CI: 0.87 to 0.99). However, there were no significant differences in graft failure and patient mortality among Hispanic and Asian recipients, respectively. Conclusions: This study revealed that LDKT recipients with a higher education level had better transplant outcomes. However, these transplant outcome differences were mainly found in White and Black recipients. These data confirm the significant effect of different levels of education on the prognosis of LDKT recipients.

Reflexões sobre a utilização do Teste de Progresso na avaliação programática do estudante / Reflections on the use of the Progress Test in the programmatic student assessment

Resumo: Introdução: O Teste de Progresso (TP) constitui modalidade estabelecida e bem-sucedida de avaliação de conhecimentos do estudante das profissões da saúde, principalmente os de Medicina, com potencial de contribuir substancialmente para as finalidades formativa e informativa (controle de qualidade e indicação de melhoria nos processos de ensino e aprendizagem). Adicionalmente, o TP apresenta características adequadas à sua inclusão em sistemas institucionais de avaliação que privilegiem a finalidade formativa, como a avaliação programática (AP), mas que cumprem também a somativa. Nas escolas que vêm definindo ações visando à introdução da AP em seus cursos de graduação, é necessária a reflexão sobre as fortalezas e limitações da utilização do TP no sistema de avaliação. Desenvolvimento: A partir das considerações de um grupo de trabalho representativo de toda a instituição, incumbido de propor meios de introdução da AP em um novo currículo para o curso de Medicina, contando com assessoria internacional com experiência tanto no TP como na AP, elaborou-se reflexão sobre esse tema, baseada na experiência dos autores e em dados da literatura. Propõe-se que, dentro da perspectiva longitudinal da AP, o TP constitua um dos pilares na avaliação de conhecimentos. O TP pode servir de base para acompanhamento do estudante, no contexto da sua turma (coorte), e seus resultados devem ser discutidos com o mentor que o acompanha e lhe dá suporte. O TP deve ter também papel central na gestão, como fonte de informações para eventual revisão e qualificação do currículo e das suas atividades de ensino e aprendizagem. É previsível que a utilização do TP na AP traga diferentes desafios e barreiras, que serão mais facilmente superados se houver na instituição experiências já consolidadas de aplicação de exames institucionais e de desenvolvimento docente para a elaboração de questões objetivas de boa qualidade. Conclusão: A efetividade do TP dentro do sistema institucional de AP vai depender de medidas que visem aumentar a sua efetividade na avaliação e que estimulem a participação ativa do estudante, refletindo sobre seu desempenho no TP, com o apoio do seu mentor, de modo a se engajar em ações que fomentem a autorregulação da aprendizagem.

Abstract: Introduction: The Progress Test (PT) is a well-established and mostly successful modality of student knowledge assessment in the health professions, mainly those in the medical area, with the potential to contribute substantially to the formative and informative purposes (quality control and indication of improvement in the teaching-learning processes). Additionally, the PT has characteristics that are adequate for its inclusion in institutional evaluation systems that facilitate the formative purpose, such as programmatic assessment (PA), but that also meet the summative purpose. In schools that have defined actions aimed at introducing PA in their undergraduate courses, it is necessary to reflect on the strengths and limitations of using PT in the evaluation system. Development: based on the considerations of a working group representative of the entire institution, tasked with proposing means of introducing PA in a new curriculum for the medical course, with international advice with experience in both PT and PA, we generated a reflection on this topic, based on the authors' experience and data from the literature. It is proposed that, within the longitudinal perspective of the PA, the PT constitutes one of the pillars in the assessment of knowledge. The PT can be used as a basis for monitoring the students, in the context of their class (cohort), and its results should be discussed with the mentors who accompanies and supports them. The PT must also play a central role in management, as a source of information for eventual review and qualification of the curriculum and its teaching-learning activities. It is predictable that the use of the PT in PA will bring different challenges and barriers, which will be more easily overcome if the institution has already consolidated experiences in the application of institutional exams and in faculty development for the production of good quality objective questions. Conclusion: the effectiveness of the PT within the institutional PA system will depend on measures aimed at increasing its effectiveness in the assessment and that encourage the student's active participation, reflecting on their performance in the PT, with the support of their mentor, aiming to engage in actions that encourage learning self-regulation.

Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients.

This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698-0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.

Prevalence of latent tuberculosis and associated factors in patients with chronic kidney disease on hemodialysis.

OBJECTIVE: to identify the prevalence of latent tuberculosis in patients with chronic kidney disease on hemodialysis and associated factors. METHOD: a cross-sectional study conducted with 176 patients with chronic kidney disease on hemodialysis. The tuberculin test was performed with the standardized antigen, distributed by the Brazilian Ministry of Health, and the reading occurred after 72 to 96 hours of the application. An association test (Chi-square, Fisher's exact), prevalence ratio, and multivariate regression tests were performed. RESULTS: the prevalence of latent tuberculosis diagnosed through Tuberculosis Skin Test was 8.5% (15/176). The "has/has had diabetes" (aOR: 0.117; 95%CI: 0.015-0.92) and "having regular garbage collection (aOR: 0.076; 95%CI: 0.008-0.702) factors were associated with a lower probability of having a Positive skin test. CONCLUSION: the low prevalence of latent tuberculosis identified and the factors associated with it reinforce the need for screening for latent tuberculosis infection for diabetics combined with an analysis of previous risk factors and comorbidities.

Bone loss in hepatitis B virus-infected patients can be associated with greater osteoclastic activity independently of the retroviral use.

Nucleoside/nucleotide analogs such as tenofovir, have been used as long-term therapy for the treatment of hepatitis B and side effects such as the reduction in bone mineral density have been associated with their use. To determine the relationships between bone, hormonal, biochemical, and mineral parameters in patients with hepatitis B treated with nucleoside/nucleotide antiviral. A cross-sectional study was conducted with 81 adult patients with chronic hepatitis B infection. Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analyses were performed for osteocalcin, deoxypyridinoline, parathyroid hormone, vitamin D, IGF-1, TSH, testosterone, estradiol, FSH, transaminases, urea, creatinine, calcium, serum and urinary phosphorus, magnesium, and FGF-23, body composition was performed by DXA. Participants, both gender, were divided according to the use of antiretrovirals: Group1: 27 inactive virus carriers without medication; Group2: 27 patients using tenofovir; and Group3: 27 patients using lamivudine or entecavir. DXA readings diagnosed osteopenia in the lumbar spine for 7.4% of individuals in Group1, 15% in Group2, and 3.7% in Group3. For all groups, we observed normal values in bone formation markers, osteocalcin levels as well as parathyroid hormone, insulin growth factor 1, and FGF-23. In all groups, we found increased levels of urinary deoxypyridinoline, a bone resorption marker. Increased levels in the bone resorption markers indicated a high resorptive activity of bone tissue. These data suggested high resorption activity of bone tissue in hepatitis B virus-infected patients independent of the use of antiretrovirals.

Association of dietary acid load with serum bicarbonate in chronic kidney disease (CKD) patients.

BACKGROUND/OBJECTIVES: Diet can affect the acid-base status depending on the balance between the intake of acid-inducing foods and base-inducing foods. The purpose of this study was to estimate the dietary acid load and evaluate its association with serum bicarbonate in patients with stages 3 and 4 chronic kidney disease. SUBJECTS/METHODS: One hundred adults (aged ≥ 20 years) with chronic kidney disease (CKD) stages 3 and 4 were enrolled in a cross-sectional study. A food diary was used to estimate the animal and plant protein intakes, which were used in the potential renal acid load (PRAL) formula described by Remer and Manz. PRAL was divided into quartiles. Regression models unadjusted and adjusted for age, gender, body mass index, diabetes, systolic and diastolic blood pressure, creatinine clearance were performed using the stepwise regression method. RESULTS: The median level (25th, 75th percentiles) of PRAL was 8.3 mEq/day (1.6, 15.6). The highest quartile of PRAL had a higher consumption of animal protein (77.8 ± 10.9%) and a reduced consumption of plant protein (22.2 ± 10.9%), compared to the lowest quartile (59.5 ± 18.6% animal protein, 40.5 ± 18.6% plant protein), p for trend <0.0001. In the adjusted analysis, a significant association was observed between the highest quartile of PRAL and serum bicarbonate in CKD patients compared to the lowest quartile (ß: 2.07, 95% CI: 0.21-3.92). According to the multiple linear regression, for each increase of 1 unit of PRAL there was a reduction of 0.25 mmol/L in serum bicarbonate (HCO3). Using the stepwise method, animal protein intake and PRAL were determinants of HCO3 (r = 0.49). CONCLUSIONS: In CKD patients of stages 3 and 4, the dietary acid load was associated with HCO3. Limiting dietary acid load could be a complementary approach in the dietary treatment of CKD. In addition, studies are needed to analyze the effect of replacing animal protein with plant protein.

Central venous catheter-related infections in patients receiving short-term hemodialysis therapy: incidence, associated factors, and microbiological aspects

Abstract INTRODUCTION: Bloodstream infections are the second most common cause of death among patients on hemodialysis. This study aimed to evaluate the incidence of and risk factors associated with central venous catheter-related infections in patients undergoing hemodialysis, and to identify and characterize the type and antimicrobial susceptibility profiles of the primary microorganisms isolated during one year of follow-up. METHODS: A prospective cohort study was conducted in 2014 in a hemodialysis referral center. We included 200 outpatients with acute kidney injury who had no permanent venous access. A nurse assessed the patients for signs of infection three times per week during dressing changes. The clinicopathologic characteristics of patients with and without local or systemic infection were compared. RESULTS: Fifty-five episodes of catheter-related infections occurred in 43 (22%) patients; 38 (69%) were bloodstream infections and 17 (31%) were local infections. Thirty-two (75%) patients with infection had femoral vein catheter placement. In total, 6,240 hemodialysis sessions were performed; the rates of primary bloodstream and local infection were 6.1 and 2.7 episodes per 1,000 patients on daily dialysis, respectively. In the univariate analysis, diabetes was significantly associated with the development of infection, while level of education, ethnicity, age, and sex were not. Gram-negative bacteria were primarily isolated from blood culture specimens (55% of samples). Of the Gram-negative isolates, 56% were resistant to the carbapenems. CONCLUSIONS: We identified a high incidence of catheter-related infections caused by resistant microorganisms in patients undergoing hemodialysis via central venous catheters.

Cutaneous and articular tuberculosis in a renal transplant recipient.

Seven months after undergoing kidney transplantation, a 56-year-old woman presented with papules and ulcers in her right forearm. The patient received antibiotics for 8 months with limited improvement. Eleven months after symptom onset, she presented with acute arthritis in her left knee. Asynovial fluid culture yielded Mycobacterium tuberculosis, and a forearm ulcer biopsy showed granulomatous inflammation. After surgical fistulectomy and 12 months of tuberculosis treatment, she was cured. Chronic cutaneous ulcers and articular manifestations in TB are rare, but they should always be considered in the differential diagnosis for immunosuppressed patients. Surgical intervention and prolonged treatment might be necessary.

Cutaneous and articular tuberculosis in a renal transplant recipient

Abstract Seven months after undergoing kidney transplantation, a 56-year-old woman presented with papules and ulcers in her right forearm. The patient received antibiotics for 8 months with limited improvement. Eleven months after symptom onset, she presented with acute arthritis in her left knee. Asynovial fluid culture yielded Mycobacterium tuberculosis, and a forearm ulcer biopsy showed granulomatous inflammation. After surgical fistulectomy and 12 months of tuberculosis treatment, she was cured. Chronic cutaneous ulcers and articular manifestations in TB are rare, but they should always be considered in the differential diagnosis for immunosuppressed patients. Surgical intervention and prolonged treatment might be necessary.

Nutritional status, energy expenditure, and protein oxidative stress after kidney transplantation.

OBJECTIVES: To evaluate the association between nutritional status, resting energy expenditure (REE), and protein oxidative stress in patients after kidney transplantation (KT). METHODOLOGY: The study evaluated 35 patients transplanted at the time of hospital discharge and 3 months after regarding: body composition, REE (by indirect calorimetry), and injury factor (IF); serum urea, creatinine, glucose, albumin, total protein, advanced oxidation protein products (AOPP), vitamin C. RESULTS: Three months after discharge, there was an improvement in renal function, nutritional status, and oxidative stress, with a standardization in the REE/kg. There was an increase in body weight, mainly in fat mass. The correlations showed that a greater cold ischemia time resulted in a deeper decline in vitamin C; a longer hospital length stay resulted in a greater reduction in AOPP; the higher preoperative body weight showed greater increases in body fat and glucose after transplantation. For decreases in REE and IF, there were increases in total protein. Finally, at hospital discharge there was a greater gain in weight, lower albumin, and total protein among individuals who had rejection episodes. DISCUSSION: The KT improves many of metabolic abnormalities, with the improvement of nutritional status, oxidative stress, and normalization of REE.

Central venous catheter-related infections in patients receiving short-term hemodialysis therapy: incidence, associated factors, and microbiological aspects.

INTRODUCTION: Bloodstream infections are the second most common cause of death among patients on hemodialysis. This study aimed to evaluate the incidence of and risk factors associated with central venous catheter-related infections in patients undergoing hemodialysis, and to identify and characterize the type and antimicrobial susceptibility profiles of the primary microorganisms isolated during one year of follow-up. METHODS: A prospective cohort study was conducted in 2014 in a hemodialysis referral center. We included 200 outpatients with acute kidney injury who had no permanent venous access. A nurse assessed the patients for signs of infection three times per week during dressing changes. The clinicopathologic characteristics of patients with and without local or systemic infection were compared. RESULTS: Fifty-five episodes of catheter-related infections occurred in 43 (22%) patients; 38 (69%) were bloodstream infections and 17 (31%) were local infections. Thirty-two (75%) patients with infection had femoral vein catheter placement. In total, 6,240 hemodialysis sessions were performed; the rates of primary bloodstream and local infection were 6.1 and 2.7 episodes per 1,000 patients on daily dialysis, respectively. In the univariate analysis, diabetes was significantly associated with the development of infection, while level of education, ethnicity, age, and sex were not. Gram-negative bacteria were primarily isolated from blood culture specimens (55% of samples). Of the Gram-negative isolates, 56% were resistant to the carbapenems. CONCLUSIONS: We identified a high incidence of catheter-related infections caused by resistant microorganisms in patients undergoing hemodialysis via central venous catheters.

Study of the risk factors related to acquisition of urinary tract infections in patients submitted to renal transplant.

INTRODUCTION: Urinary tract infections (UTI) among transplant recipients are usually caused by gram-negative microorganisms and can provoke a high incidence of morbidity and mortality. The aim of this study was to evaluate the risk factors associated with the acquisition of UTIs during the first year after renal transplantation. METHODS: Here, we report a single-center retrospective cohort study of 99 renal transplant patients followed for the first year after surgery. The definition of a UTI episode was a urine culture showing bacterial growth and leucocyturia when patients presented with urinary symptoms. The absence of infection (asymptomatic bacteriuria) was defined as an absence of symptoms with negative urine culture or bacterial growth with any number of colonies. RESULTS: Ninety-nine patients were included in the study. During the study, 1,847 urine cultures were collected, and 320 (17.3%) tested positive for bacterial growth. Twenty-six (26.2%) patients developed a UTI. The most frequent microorganisms isolated from patients with UTIs were Klebsiella pneumoniae (36%), with 33% of the strains resistant to carbapenems, followed by Escherichia coli (20%). There were no deaths or graft losses associated with UTI episodes. CONCLUSIONS: Among the UTI risk factors studied, the only one that was associated with a higher incidence of infection was female sex. Moreover, the identification of drug-resistant strains is worrisome, as these infections have become widespread globally and represent a challenge in the control and management of infections, especially in solid organ transplantation.

Study of the risk factors related to acquisition of urinary tract infections in patients submitted to renal transplant

INTRODUCTION: Urinary tract infections (UTI) among transplant recipients are usually caused by gram-negative microorganisms and can provoke a high incidence of morbidity and mortality. The aim of this study was to evaluate the risk factors associated with the acquisition of UTIs during the first year after renal transplantation. METHODS: Here, we report a single-center retrospective cohort study of 99 renal transplant patients followed for the first year after surgery. The definition of a UTI episode was a urine culture showing bacterial growth and leucocyturia when patients presented with urinary symptoms. The absence of infection (asymptomatic bacteriuria) was defined as an absence of symptoms with negative urine culture or bacterial growth with any number of colonies. RESULTS: Ninety-nine patients were included in the study. During the study, 1,847 urine cultures were collected, and 320 (17.3%) tested positive for bacterial growth. Twenty-six (26.2%) patients developed a UTI. The most frequent microorganisms isolated from patients with UTIs were Klebsiella pneumoniae (36%), with 33% of the strains resistant to carbapenems, followed by Escherichia coli (20%). There were no deaths or graft losses associated with UTI episodes. CONCLUSIONS: Among the UTI risk factors studied, the only one that was associated with a higher incidence of infection was female sex. Moreover, the identification of drug-resistant strains is worrisome, as these infections have become widespread globally and represent a challenge in the control and management of infections, especially in solid organ transplantation. .

Vacinação contra Hepatite B em indivíduos renais crônicos em tratamento hemodialítico / Hepatitis B vaccination in chronic renal failure patients on hemodialysis / Vacunación contra Hepatitis B en individuos con insuficiencia renal crónica en hemodiálisis

Indivíduos em tratamento hemodialítico apresentam elevado risco de infecção pelo Vírus da Hepatite B, sendo, portanto, uma população alvo para vacinação contra Hepatite B. Este estudo de coorte retrospectivo objetivou avaliar o monitoramento da vacina contra Hepatite B em indivíduos que iniciaram hemodiálise em 2005 e permaneceram em seguimento por até quatro anos, em Ribeirão Preto-SP. A população foi constituída por 102 indivíduos. Somente 39,2% possuíam registro em prontuário de vacinação prévia contra Hepatite B, e 35,3% receberam o esquema vacinal completo. A maioria recebeu esquema de três doses (40 mcg) e 72,2% desenvolveram títulos protetores de anti-HBs. Dos 62 indivíduos sem registro de vacinação prévia em prontuário, 22,6% permaneceram em tratamento hemodialítico por mais de 42 meses. Os achados deste estudo evidenciam a necessidade urgente de mais esforços de gestores públicos e profissionais de saúde na vigilância da vacinação contra Hepatite B em centros de hemodiálise da região.

Individuals on hemodialysis are at high risk of infection by Hepatitis B Virus and are, therefore, a target population for vaccination against Hepatitis B. This retrospective cohort study aimed to evaluate Hepatitis B vaccination monitoring of patients who started hemodialysis in 2005 and continued in follow-up for up to four years in Ribeirão Preto, São Paulo State. Of the population of 102 individuals, only 39.2% were on record as previously vaccinated against Hepatitis B, while 35.3% received the full vaccination schedule. The majority received a three-dose regimen (40 mcg), and 72.2% developed protective titers of anti-HBs. Of the 62 individuals with no record of previous vaccination, 22.6% remained on hemodialysis for more than 42 months. Findings highlight the urgent need for more effort by policy managers and health professionals in surveillance of Hepatitis B vaccination at hemodialysis centers in the region.

Individuos sometidos a hemodiálisis tienen un alto riesgo de infección por el Virus de Hepatitis B, siendo así una población objetivo para vacunación contra Hepatitis B. Este estudio de cohorte retrospectivo objetivó evaluar el monitoreo de la vacuna contra Hepatitis B en individuos que iniciaron hemodiálisis en 2005 y se mantuvieron en seguimiento hasta cuatro años en la ciudad de Ribeirão Preto, São Paulo – Brasil. Población fue constituida por 102 individuos. Sólo 39,2% tenían registro en prontuario de vacunación previa contra hepatitis B, y 35,3% recibieron vacunación completa. La mayoría recibió tres dosis (40 mcg) y 72,2% desarrollaron títulos protectores de anti-HBs. De los 62 individuos sin registro en prontuario de vacunación previa, 22,6% se mantuvieron en hemodiálisis por más de 42 meses. Hallazgos resaltan la urgente necesidad de más esfuerzos de gestores públicos y profesionales de salud en la vigilancia de vacunación contra Hepatitis B en centros de hemodiálisis de la región.

Corticotherapy response in primary IgA nephropathy.

INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group). The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles) at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h) and was 703 mg/24h (245; 983) and 684 mg/24h (266; 1023) at the 6th (p < 0.05 vs. baseline) and 12th months (p < 0.05 vs. baseline), respectively. In the control group the proteinuria was 1900 mg/24h (1620; 3197) at baseline and was 2290 mg/24h (1500; 2975) and 1600 mg/24h (1180; 2395) at the 6th and 12th months, respectively (not significant vs. baseline). When compared with the control group, the treated group showed lower proteinuria (p < 0.05) during the follow-up and a higher number of patients in remission (p < 0.05) at the 6th and 12th months. Renal function did not change during the follow-up and the adverse effects were mild in most of the patients. CONCLUSION: The 6-month course of steroid treatment was effective in reducing proteinuria during the 12 months of the follow-up, and was well-tolerated by most of the patients.

Corticotherapy response in primary IgA nephropathy / Resposta à corticoterapia na nefropatia da IgA primária

INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group). The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles) at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h) and was 703 mg/24h (245; 983) and 684 mg/24h (266; 1023) at the 6th (p < 0.05 vs. baseline) and 12th months (p < 0.05 vs. baseline), respectively. In the control group the proteinuria was 1900 mg/24h (1620; 3197) at baseline and was 2290 mg/24h (1500; 2975) and 1600 mg/24h (1180; 2395) at the 6th and 12th months, respectively (not significant vs. baseline). When compared with the control group, the treated group showed lower proteinuria (p < 0.05) during the follow-up and a higher number of patients in remission (p < 0.05) at the 6th and 12th months. Renal function did not change during the follow-up and the adverse effects were mild in most of the patients. CONCLUSION: The 6-month course of steroid treatment was effective in reducing proteinuria during the 12 months of the follow-up, and was well-tolerated by most of the patients.

INTRODUÇÃO: Tem sido sugerido que tratamento mais prolongado com corticosteroides pode ser benéfico em pacientes com nefropatia da IgA primária. OBJETIVO: Neste estudo retrospectivo avaliamos os efeitos na proteinúria e na função renal após 12 meses do protocolo baseado no uso por 6 meses de corticosteroides. MÉTODO: Doze pacientes receberam pulsos de 1 g/dia de metilprednisolona intravenosa por 3 dias consecutivos no início dos meses 1, 3 e 5, seguidos por prednisona (0,5 mg/kg) por via oral em dias alternados após cada pulso durante 6 meses (grupo tratado). O grupo controle foi composto por nove pacientes não tratados. RESULTADOS: A proteinúria (mg/24h; mediana; 25º; 75º percentis) no período basal no grupo tratado foi de 1861 (1518; 2417) e de 703 (245; 983) e de 684 (266; 1023) nos 6º (p < 0,05 vs. basal) e 12º (p < 0,05 vs. basal) meses, respectivamente. No grupo controle, a proteinúria foi de 1900 (1620; 3197) no período basal e de 2290 (1500; 2975) e de 1600 (1180; 2395) nos 6º e 12º meses, respectivamente (não significantes vs. basal). Comparado com o grupo controle, o grupo tratado teve menor proteinúria (p < 0,05) e número maior de pacientes em remissão (p < 0,05) nos 6º e 12º meses. A função renal não teve alteração significante e eventos adversos foram de pequena intensidade na maioria dos pacientes. CONCLUSÃO: O protocolo terapêutico base-ado no uso por 6 meses de corticosteroides foi efetivo em reduzir a proteinúria durante os 12 meses de seguimento e foi bem tolerado pela maioria dos pacientes.

Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy.

OBJECTIVES: The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-ß1, α-SMA and NF-kB. METHODS: We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-ß1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB. RESULTS: The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course. CONCLUSION: An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.