On- vs. Off-Pump CABG in Heart Failure Patients with Reduced Ejection Fraction (HFrEF): A Multicenter Analysis.

OBJECTIVE: This study aimed to compare postoperative outcomes and 30-day mortality in patients with reduced ejection fraction (<40%) who underwent isolated coronary artery bypass grafting (CABG) with (ONCAB) and without (OPCAB) the use of cardiopulmonary bypass. METHODS: data from four university hospitals in Germany, spanning from January 2017 to December 2021, were retrospectively analyzed. A total of 551 patients were included in the study, and various demographic, intraoperative, and postoperative data were compared. RESULTS: demographic parameters did not exhibit any differences. However, the OPCAB group displayed notably higher rates of preoperative renal insufficiency, urgent surgeries, and elevated EuroScore II and STS score. During surgery, the ONCAB group showed a significantly higher rate of complete revascularization, whereas the OPCAB group required fewer intraoperative transfusions. No disparities were observed in 30-day/in-hospital mortality for the entire cohort and the matched population between the two groups. Subsequent to surgery, the OPCAB group demonstrated significantly shorter mechanical ventilation times, reduced stays in the intensive care unit, and lower occurrences of ECLS therapy, acute kidney injury, delirium, and sepsis. CONCLUSIONS: the study's findings indicate that OPCAB surgery presents a safe and viable alternative, yielding improved postoperative outcomes in this specific patient population compared to ONCAB surgery. Despite comparable 30-day/in-hospital mortality rates, OPCAB patients enjoyed advantages such as decreased mechanical ventilation durations, shorter ICU stays, and reduced incidences of ECLS therapy, acute kidney injury, delirium, and sepsis. These results underscore the potential benefits of employing OPCAB as a treatment approach for patients with coronary heart disease and reduced ejection fraction.

Acylated- and unacylated ghrelin during an oral glucose tolerance test in humans at risk for type 2 diabetes mellitus.

BACKGROUND/OBJECTIVES: The orexigenic peptide hormone ghrelin has been implicated in the pathophysiology of obesity and type 2 diabetes mellitus through its effects on nutrient homeostasis. Ghrelin is subject to a unique post-translational acyl modification regulating its biochemical activity. SUBJECTS/METHODS: In this study we aimed to investigate the relation of acylated (AcG) as well as unacylated ghrelin (UnG) with body weight and insulin resistance in the fasting (n = 545) and post-oral glucose tolerance test (oGTT) state (n = 245) in a metabolically well characterized cohort covering a broad range of BMI (17.95 kg/m²-76.25 kg/m²). RESULTS: Fasting AcG (median 94.2 pg/ml) and UnG (median 175.3 pg/ml) were negatively and the AcG/UnG ratio was positively correlated with BMI (all p < 0.0001). Insulin sensitivity (ISI) correlated positively with AcG (p = 0.0014) and UnG (p = 0.0004) but not with the AcG/UnG ratio. In a multivariate analysis, including ISI and BMI, only BMI, but not ISI was independently associated with AcG and UnG concentrations. Significant changes of AcG and UnG concentrations were detectable after oGTT stimulation, with slight decreases after 30 min and increases after 90-120 min. Subject stratification into BMI-divergent groups revealed more pronounced AcG increases in the two groups with BMI < 40 kg/m². CONCLUSION: Our data demonstrate lower concentrations for both AcG and UnG with increasing BMI as well as an increased proportion of the biologically active, acylated form of ghrelin giving point to pharmacologic intervention in ghrelin acylation and/or increase in UnG for treatment of obesity despite decreased absolute AcG levels.

Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices.

Daptomycin is a cyclic lipopeptide antibiotic with bactericidal effects against multidrug-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). For critically ill patients, especially in the presence of implants, daptomycin is an important therapeutic option. Left ventricle assist devices (LVADs) can be utilized for intensive care patients with end-stage heart failure as a bridge to transplant. We conducted a single-center prospective trial with critically ill adults with LVAD who received prophylactic anti-infective therapy with daptomycin. Our study aimed to evaluate the pharmacokinetics of daptomycin in the blood serum and wound fluids after LVAD implantation. Daptomycin concentration were assessed over three days using high-performance liquid chromatography (HPLC). We detected a high correlation between blood serum and wound fluid daptomycin concentration at 12 h (IC95%: 0.64 to 0.95; r = 0.86; p < 0.001) and 24 h (IC95%: -0.38 to 0.92; r = 0.76; p < 0.001) after antibiotic administration. Our pilot clinical study provides new insights into the pharmacokinetics of daptomycin from the blood into wound fluids of critically ill patients with LVADs.

Primary hiperoxaluria diagnosed after kidney transplantation: report of 2 cases and literature review / Hiperoxalúria primária diagnosticada após transplante renal: relato de dois casos e revisão da literatura

Abstract Primary hyperoxaluria (PH) is a very rare genetic disorder; it is characterized by total or partial deficiency of the enzymes related to the metabolism of glyoxylate, with an overproduction of calcium oxalate that is deposited in different organs, mainly the kidney, leading to recurrent lithiasis, nephrocalcinosis and end stage renal disease (ESRD). In patients with ESRD that receive kidney transplantation alone, the disease has a relapse of 100%, with graft loss in a high percentage of patients in the first 5 years of transplantation. Three molecular disorders have been described in PH: mutation of the gene alanin glioxalate aminotransferase (AGXT); glyoxalate reductase/hydroxy pyruvate reductase (GRHPR) and 4-OH-2-oxoglutarate aldolase (HOGA1). We present two cases of patients with a history of renal lithiasis who were diagnosed with primary hyperoxaluria in the post-transplant period, manifested by early graft failure, with evidence of calcium oxalate crystals in renal biopsy, hyperoxaluria, hyperoxalemia, and genetic test compatible; they were managed with proper diet, abundant oral liquids, pyridoxine, hydrochlorothiazide and potassium citrate; however, they had slow but progressive deterioration of their grafts function until they reached end-stage chronic renal disease.

Resumo A hiperoxalúria primária (HP) é um distúrbio genético muito raro, caracterizado por deficiência total ou parcial das enzimas relacionadas ao metabolismo do glioxilato, superprodução de oxalato de cálcio que se deposita em vários órgãos (principalmente os rins) resultando em litíase recorrente, nefrocalcinose e doença renal terminal (DRT). Nos pacientes com DRT que recebem transplante renal, a doença apresenta recidiva em 100% dos casos, com perda do enxerto nos primeiros cinco anos após o transplante num elevado percentual de pacientes. Três distúrbios moleculares foram descritos na HP: mutação dos genes da alanina-glioxilato aminotransferase (AGXT), glioxilato redutase/hidroxipiruvato redutase (GRHPR) e 4-OH-2-oxoglutarato aldolase (HOGA1). Apresentamos dois casos de pacientes com histórico de litíase renal diagnosticados com hiperoxalúria primária no período pós-transplante, manifestada na forma de perda precoce do enxerto com evidências de cristais de oxalato de cálcio na biópsia renal, hiperoxalúria, hiperoxalemia e testes genéticos compatíveis. Os pacientes foram tratados com abordagem nutricional, líquidos orais em abundância, piridoxina, hidroclorotiazida e citrato de potássio. Contudo, os pacientes apresentaram deterioração lenta e gradual da função do enxerto e evoluíram para doença renal terminal.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Primary hiperoxaluria diagnosed after kidney transplantation: report of 2 cases and literature review.

Primary hyperoxaluria (PH) is a very rare genetic disorder; it is characterized by total or partial deficiency of the enzymes related to the metabolism of glyoxylate, with an overproduction of calcium oxalate that is deposited in different organs, mainly the kidney, leading to recurrent lithiasis, nephrocalcinosis and end stage renal disease (ESRD). In patients with ESRD that receive kidney transplantation alone, the disease has a relapse of 100%, with graft loss in a high percentage of patients in the first 5 years of transplantation. Three molecular disorders have been described in PH: mutation of the gene alanin glioxalate aminotransferase (AGXT); glyoxalate reductase/hydroxy pyruvate reductase (GRHPR) and 4-OH-2-oxoglutarate aldolase (HOGA1). We present two cases of patients with a history of renal lithiasis who were diagnosed with primary hyperoxaluria in the post-transplant period, manifested by early graft failure, with evidence of calcium oxalate crystals in renal biopsy, hyperoxaluria, hyperoxalemia, and genetic test compatible; they were managed with proper diet, abundant oral liquids, pyridoxine, hydrochlorothiazide and potassium citrate; however, they had slow but progressive deterioration of their grafts function until they reached end-stage chronic renal disease.

Hemolytic uremic syndrome due to gemcitabine in a young woman with cholangiocarcinoma. / Síndrome hemolítico-urêmica causada por gencitabina em uma paciente jovem com colangiocarcinoma.

Gemcitabine is a medication used to treat various types of malignant neoplasms. Its association with hemolytic uremic syndrome (HUS) has been described in few cases, although these cases have resulted in mortality rates of at least 50%. We report on the case of a 25-year-old patient with cholangiocarcinoma in remission who developed microangiopathic hemolytic anemia with acute anuric renal failure after receiving 5 cycles of gemcitabine chemotherapy; this condition was consistent with HUS caused by the side effects of this drug. The administration of gemcitabine was stopped, and hemodialysis, blood transfusions, plasma exchanges, steroids, doxycycline, and rituximab were used to treat the patient. A favorable outcome was achieved; in particular, hemolysis was controlled, and renal function was completely recovered.

Síndrome hemolítico-urêmica causada por gencitabina em uma paciente jovem com colangiocarcinoma / Hemolytic uremic syndrome due to gemcitabine in a young woman with cholangiocarcinoma

Resumo A gencitabina é um fármaco utilizado no tratamento de vários tipos de neoplasias malignas. Há poucas descrições de associação entre a droga e a síndrome hemolítico-urêmica (SHU), apesar de os pacientes em questão terem ido a óbito em pelo menos 50% dos casos. O presente artigo relata o caso de uma paciente com 25 anos de idade em remissão diagnosticada com colangiocarcinoma que apresentou anemia hemolítica microangiopática acompanhada de insuficiência renal aguda anúrica após cinco ciclos de quimioterapia com gencitabina; as manifestações eram condizentes com SHU causada pelos efeitos colaterais do medicamento. A administração de gencitabina foi interrompida, e a paciente foi tratada com hemodiálise, transfusões de sangue, trocas de plasma, corticosteroides, doxiciclina e rituximabe. Foi atingido um desfecho favorável; mais especificamente, a hemólise foi controlada e a função renal foi plenamente restabelecida.

Abstract Gemcitabine is a medication used to treat various types of malignant neoplasms. Its association with hemolytic uremic syndrome (HUS) has been described in few cases, although these cases have resulted in mortality rates of at least 50%. We report on the case of a 25-year-old patient with cholangiocarcinoma in remission who developed microangiopathic hemolytic anemia with acute anuric renal failure after receiving 5 cycles of gemcitabine chemotherapy; this condition was consistent with HUS caused by the side effects of this drug. The administration of gemcitabine was stopped, and hemodialysis, blood transfusions, plasma exchanges, steroids, doxycycline, and rituximab were used to treat the patient. A favorable outcome was achieved; in particular, hemolysis was controlled, and renal function was completely recovered.

Tuberculosis in renal transplant patients: the experience of a single center in Medellín-Colombia, 2005-2013.

INTRODUCTION: Tuberculosis is a common opportunistic infection in renal transplant patients. OBJECTIVE: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. METHODS: Retrospective and descriptive study. RESULTS: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. CONCLUSION: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant.

Tuberculosis in renal transplant patients: The experience of a single center in Medellín-Colombia, 2005-2013 / Tuberculose em pacientes transplantados renais: experiência de um único centro em Medellín-Colômbia, 2005-2013

Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .

Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .

Prevention of contrast induced nephropathy with sodium bicarbonate (the PROMEC study).

INTRODUCTION: Contrast-induced nephropathy is a common complication of radiographic procedures. Different measures have been used to avoid this damage, but the evidence is controversial. New investigations are required to clarify it. We investigated the efficacy and safety of sodium bicarbonate solution compared with sodium chloride solution to prevent contrast induced nephropathy in patients with or at risk of renal dysfunction. METHODS: A prospective, single-center, randomized clinical trial conducted from May 1, 2007 to February 8, 2008. Inpatients in a tertiary center, scheduled to undergo a procedure with the nonionic radiographic contrast agent iohexol. There were 220 patients with serum creatinine levels of at least 1.2 mg/dL (106.1 µmol/L) and/or type 2 diabetics, who were randomized to receive an infusion of sodium chloride (n = 113) or sodium bicarbonate (n = 107) before and after contrast dye administration. The intervention were "A" group received 1 ml/kg/hour of normal saline solution, starting 12 hours before and continuing 12 hours after iohexol contrast. "B" group received 3 ml/kg of sodium bicarbonate solution (150 mEq/L) one hour prior to procedure and then drip rate was decreased to 1 ml/kg/hour until 6 hours post procedure. Our main outcome measure was change in serum creatinine. RESULTS: The mean creatinine value after the procedure was 1.26 mg/dL in the saline group and 1.22 mg/dL in the bicarbonate group (mean difference: 0.036; CI 95%: -0.16 to 0.23, p = 0.865). The diagnosis of contrast-induced nephropathy, defined by increase in serum creatinine on 25% or more within 2 days after administration of radiographic contrast, was done in twelve patients (12%) in the bicarbonate group and eighth patients (7.1%) in the saline group (RR: 1.68, CI 95%: 0.72 to 3.94). CONCLUSION: Our investigation showed that there were no differences between normal saline solution (extended infusion) vs. bicarbonate solution for nephroprotection.

Prevention of contrast induced nephropathy with sodium bicarbonate (the PROMEC study) / Prevenção de nefropatia por contraste com bicarbonato de sódio (o estudo PROMEC)

Introduction: Contrast-induced nephropathy is a common complication of radiographic procedures. Different measures have been used to avoid this damage, but the evidence is controversial. New investigations are required to clarify it. We investigated the efficacy and safety of sodium bicarbonate solution compared with sodium chloride solution to prevent contrast induced nephropathy in patients with or at risk of renal dysfunction. Methods: A prospective, single-center, randomized clinical trial conducted from May 1, 2007 to February 8, 2008. Inpatients in a tertiary center, scheduled to undergo a procedure with the nonionic radiographic contrast agent iohexol. There were 220 patients with serum creatinine levels of at least 1.2 mg/dL (106.1 µmol/L) and/or type 2 diabetics, who were randomized to receive an infusion of sodium chloride (n = 113) or sodium bicarbonate (n = 107) before and after contrast dye administration. The intervention were "A" group received 1 ml/kg/hour of normal saline solution, starting 12 hours before and continuing 12 hours after iohexol contrast. "B" group received 3 ml/kg of sodium bicarbonate solution (150 mEq/L) one hour prior to procedure and then drip rate was decreased to 1 ml/kg/hour until 6 hours post procedure. Our main outcome measure was change in serum creatinine. Results: The mean creatinine value after the procedure was 1.26 mg/dL in the saline group and 1.22 mg/dL in the bicarbonate group (mean difference: 0.036; CI 95%: -0.16 to 0.23, p = 0.865). The diagnosis of contrast-induced nephropathy, defined by increase in serum creatinine on 25% or more within 2 days after administration of radiographic contrast, was done in twelve patients (12%) in the bicarbonate group and eighth patients (7.1%) in the saline group (RR: 1.68, CI 95%: 0.72 to 3.94). Conclusion: Our investigation showed that there were no differences between normal saline solution (extended infusion) vs. bicarbonate solution ...

Introdução: A nefropatia induzida por contraste é uma complicação comum de procedimentos radiográficos. Medidas diferentes têm sido utilizadas para evitar estes problemas, mas a evidência é controversa. Novos estudos são necessários para esclarecer isso. Investigamos tanto a eficácia quanto a segurança de uma solução de bicarbonato de sódio em comparação com a solução de cloreto de sódio para evitar nefropatia por contraste em pacientes com ou em risco de desenvolver disfunção renal. Métodos: Estudo prospectivo, randomizado clínico, conduzido em um único centro, entre 01 de maio de 2007 e 8 de fevereiro de 2008. Os pacientes internados em um centro terciário, agendados para passar por um procedimento radiográfico com uso de contraste não iônico., Havia 220 pacientes com níveis de creatinina sérica de pelo menos 1,2 mg/dL (106,1 mmol/L) e/ou diabéticos do tipo 2, que foram escolhidos aleatoriamente para receber uma infusão de cloreto de sódio (n = 113) ou bicarbonato de sódio (n = 107) antes e após a administração do meio de contraste. A intervenção foi: grupo "A" recebeu 1 ml/kg/hora de solução salina normal, começando 12 horas antes e continuando por 12 horas após o uso do contraste iohexol. Os pacientes do grupo "B" receberam 3 ml/kg de uma solução de bicarbonato de sódio (150 mEq/L), 1 hora antes do procedimento e, em seguida, o gotejamento foi reduzido a 1 ml/kg/hora por até 6 horas após o procedimento. Nosso principal indicador de desfecho foi a alteração na creatinina sérica. Resultados: O valor médio da creatinina após o procedimento foi de 1,26 mg/dL no grupo que recebeu a solução salina e 1,22 mg/dL no grupo do bicarbonato (diferença média: ...

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience.

INTRODUCTION: [corrected] Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience / Tratamento com imunossupressores em crianças com síndrome nefrótica resistente a corticosteróide: experiência de um único centro

INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

INTRODUÇÃO: A síndrome nefrótica é uma das mais frequentes doenças glomerulares em crianças e o tratamento com corticosteróides ainda é o tratamento de escolha. Apesar disso, 10 a 15% dos pacientes são resistentes a corticosteróides, e o melhor tratamento para tais casos ainda não foi definido. O ácido micofenólico (AM) é um dos tratamentos usados em tais situações. OBJETIVO: Descrever o comportamento clínico de crianças diagnosticadas com síndrome nefrótica resistente a corticosteróide (SNRC) e avaliar a resposta terapêutica ao AM. MÉTODOS: Esse foi um estudo retrospectivo e descritivo. RESULTADOS: 26 registros de pacientes com SNRC; 70% homens e 30% mulheres. Todos os pacientes foram submetidos a biópsias renais, o que mostrou predominância de glomeruloesclerose segmentar focal (GESF). Os medicamentos imunossupressores utilizados foram: Mofetil Micofenolato (MMF) 100%; Ciclosporina 69,2%; Ciclosfosfamida 23,1%; e Rituximabe 23%. Um mês após início do tratamento com MMF, 61,5% tiveram remissão. A mediana das recidivas por ano para os pacientes foi de 3 (p25: 2,75 - p75: 4). Essa mediana se tornou 1 (p25: 1 - p75: 3,25) após o uso da medicação (p = 0,08). Além disso, antes do início do tratamento com MMF, a mediana da dose de corticosteróide foi de 1 (p25: 0.5 - p75: 1.62) mg/k/ dia. Após a utilização do MMF, essa mediana se tornou 0,07 (p25: 0 - p75: 0,55) mg/k/dia (p < 0,001), em 8 pacientes a prednisolona foi interrompida. CONCLUSÃO: em nossa casuística, o tratamento com MMF mostrou resultados positivos, tais como a redução na frequência de recidivas, menos proteinúria, e redução da dose de corticosteróide administrada sem deterioração nas taxas de filtração glomerular. Entretanto, mais estudos são necessários para se avaliar a eficácia, segurança e otimização da dosagem.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.