Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Atypical hemolytic uremic syndrome in Brazil: clinical presentation, genetic findings and outcomes of a case series in adults and children treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and kidney injury caused by a dysregulation of the alternative complement pathway. METHODS: We conducted a multicenter nonregistry study aimed at collecting clinical, laboratory and genetic information of patients with aHUS in Brazil. Demographic data, genetic findings, treatments and outcomes are presented. RESULTS: Thirty-four patients were included, 62% were female and 67% were Caucasian. Half of the patients had the first manifestation of aHUS before the age of 18 years (pediatric group). Among the 17 patients who had the first manifestation after the age of 18 years (adult group), 6 were kidney transplant patients. Overall, 22 patients (65%) received plasma exchange/plasma infusion (PE/PI) and 31 patients (91%) received eculizumab. Eculizumab was started later in the adult group compared with the pediatric group. Two patients stopped dialysis after PE/PI and 19 patients stopped dialysis after eculizumab despite a late start. A pathogenic/likely pathogenic variant was found in 24.3% of patients. A coexisting condition or trigger was present in 59% of patients (infections, pregnancy, hypertension, autoimmune disease and transplant), especially in the adult group. There was a 30% relapse rate after stopping eculizumab, irrespective of genetic status. CONCLUSION: This is the largest case series of aHUS in Brazil involving a wide range of patients for which eculizumab was the main treatment. Although eculizumab was started later than advised in the guidelines, most patients were able to stop dialysis at variable intervals. Discontinuation of eculizumab was associated with a 30% relapse of aHUS.

Diacylglycerol kinase epsilon nephropathy: late diagnosis and therapeutic implications.

A 17-year-old male presented thrombotic microangiopathy (TMA) at 6 months of age with arterial hypertension, anemia, thrombocytopenia and kidney injury improving with plasma infusions. Fourteen years later, he was diagnosed with severe arterial hypertension, increase in serum creatinine and chronic TMA on kidney biopsy. Eculizumab was started and after 18 months of treatment, he persisted with hypertension, decline in renal function and proteinuria. Genetic analysis demonstrated mutation in diacylglycerol kinase epsilon (DGKe). Complement blockade was stopped. This case of late diagnosis of DGKe nephropathy highlights the importance of genetic testing in patients presenting TMA during the first year of life.

Reversal of pulmonary hypertension in children after adenoidectomy or adenotonsillectomy.

INTRODUCTION: Adenotonsillar hypertrophy is a common condition in pediatric patients with upper respiratory airways complaints, and pulmonary arterial hypertension (PAH) may be one complication of that condition. OBJECTIVES: To study the occurrence of PAH (mean pulmonary artery pressure higher than or equal to 25 mmHg) in a group of children with adenotonsillar hypertrophy and upper respiratory complaints (snoring or oral breathing), and to verify the pulmonary arterial pressure (PAP) changes after adenotonsillectomy. STUDY DESIGN: Case-control prospective study. SETTINGS: Study conducted at São Lucas Hospital, approaching both public and private sector. SUBJECT AND METHODS: Thirty-three pediatric patients with adenotonsillar hypertrophy and evidence of obstructive upper airways complaints were treated with adenotonsillectomy. All 33 patients underwent echocardiogram before and after the surgery with determination of the pulmonary arterial pressure (PAP), through either the tricuspid regurgitation or artery linear flow acceleration time estimation. Similar determinations were performed in 10 normal non operated controls. RESULTS: Pulmonary hypertension was verified 12 (36%) of the 33 patients with adenotonsillar hypertrophy. Adenoidectomy or adenotonsillectomy was associated to a significant 27% decrease in mean PAP (27 ± 2.8 to 20 ± 5.1 mmHg, p<0.001) and to a non significant 26% decrease in systolic PAP (35 ± 6.2 mmHg to 25 ± 0.5 mmHg, p=0.243). The PAP values in children with no pulmonary hypertension were not changed after the surgery. CONCLUSIONS: In children with pulmonary hypertension associated to adenotonsillar hypertrophy, the adenotonsillectomy decreased PAP to normal values in all patients.

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition.

OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50 ± 5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56 ms, medulla = 17.21 ± 1.47 ms and cortex = 10.30 ± 0.44 ms, medulla = 16.06 ± 1.74 ms, respectively; and left kidney, cortex= 11.79 ± 1.85 ms, medulla = 17.03 ± 0.88 ms and cortex = 10.89 ± 0.91 ms, medulla = 16.43 ± 1.49 ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition

OBJECTIVE: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. METHOD: R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50±5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. RESULTS: A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56ms, medulla = 17.21 ± 1.47ms and cortex = 10.30 ± 0.44ms, medulla = 16.06 ± 1.74ms, respectively; and left kidney, cortex= 11.79 ± 1.85ms, medulla = 17.03 ± 0.88ms and cortex = 10.89 ± 0.91ms, medulla = 16.43 ± 1.49ms, respectively. CONCLUSIONS: This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Fluid overload and changes in serum creatinine after cardiac surgery: predictors of mortality and longer intensive care stay. A prospective cohort study.

INTRODUCTION: Fluid overload is a clinical problem frequently related to cardiac and renal dysfunction. The aim of this study was to evaluate fluid overload and changes in serum creatinine as predictors of cardiovascular mortality and morbidity after cardiac surgery. METHODS: Patients submitted to heart surgery were prospectively enrolled in this study from September 2010 through August 2011. Clinical and laboratory data were collected from each patient at preoperative and trans-operative moments and fluid overload and creatinine levels were recorded daily after cardiac surgery during their ICU stay. Fluid overload was calculated according to the following formula: (Sum of daily fluid received (L)--total amount of fluid eliminated (L)/preoperative weight (kg) × 100). Preoperative demographic and risk indicators, intra-operative parameters and postoperative information were obtained from medical records. Patients were monitored from surgery until death or discharge from the ICU. We also evaluated the survival status at discharge from the ICU and the length of ICU stay (days) of each patient. RESULTS: A total of 502 patients were enrolled in this study. Both fluid overload and changes in serum creatinine correlated with mortality (odds ratio (OR) 1.59; confidence interval (CI): 95% 1.18 to 2.14, P = 0.002 and OR 2.91; CI: 95% 1.92 to 4.40, P <0.001, respectively). Fluid overload played a more important role in the length of intensive care stay than changes in serum creatinine. Fluid overload (%): b coefficient = 0.17; beta coefficient = 0.55, P <0.001); change in creatinine (mg/dL): b coefficient = 0.01; beta coefficient = 0.11, P = 0.003). CONCLUSIONS: Although both fluid overload and changes in serum creatinine are prognostic markers after cardiac surgery, it seems that progressive fluid overload may be an earlier and more sensitive marker of renal dysfunction affecting heart function and, as such, it would allow earlier intervention and more effective control in post cardiac surgery patients.

Analgesia pós-operatória em cirurgia torácica / Postoperative analgesia in thoracic surgery

Os autores visam descrever e comparar as principais técnicas de analgesia no pós-operatório de cirurgia torácica

Transporte de membrana celular / Transport of cell membranes

As células humanas säo circundadas por uma membrana externa. A funçäo celular é dependente da composiçäo e funçäo desta membrana plasmática, cuja anormalidades podem estae envolvidas em processos patológicos. Esta revisäo aborda aspectos da estrutura e funçäo de transporte através da membrana celular

Malária por falciparum na infância / Malaria by falciparum in childhood

A malária, doença extremamente prevalente em vários países em desenvolvimento, afeta milhöes de crianças em todo o mundo, sendo muitas vezes fatal. Nas áreas endêmicas, a doença apresenta-se tipicamente em crianças com menos de cinco anos, com anorexia, vômitos, febre, cefaléia, alteraçöes do nível de consciência e convulsöes. A severidade, em geral, dos quadros clínicos se deve à demora no diagnóstico e início do tratamento. Quinino é a droga de escolha em todo o mundo e o tratamento deve ser feito por via endovenosa. Entretanto, o uso desta droga näo tem sido extensamente estudado em crianças, e nestas, o tratamento ideal ainda näo é conhecido. A resistência à cloroquina já está amplamente difundida e portanto só deve ser usada se quinino näo for disponível. Nas áreas de alta resistência à cloroquina, suplementos com tetraciclina säo usados. A quimioprofilaxia para malária em crianças, nas zonas estáveis, é controversa, pelo medo de promover resistência à droga