Mast cells in the kidney biopsies of pediatric patients with lupus nephritis / Mastócitos em biópsias renais de pacientes pediátricos com nefrite lúpica

ABSTRACT Introduction: Mast cells may be involved in inflammation and contribute to the onset of fibrosis in lupus nephritis (LN). Objective: This study aimed to correlate the presence of mast cells in kidney biopsy specimens of pediatric patients with LN with activity (AI) and chronicity (CI) indices and assess how effectively mast cells may be used as a prognostic factor. Method: The study included 40 patients aged 6-18 years diagnosed with LN at the Renal Disease Service of the Federal University of Triângulo Mineiro between 1996 and 2015. Workup and epidemiological data were evaluated vis-à-vis AI, CI, and mast cell counts (MCC). Results: Significant positive correlations were found between mast cell counts (MCC) and AI (p = 0.003; r: 0.66) and MCC and CI (p = 0.048; r: 0.48). The ROC curve showed that mast cells were highly sensitive and specific in the differentiation of patients with an AI > 12 from individuals with an AI ≤ 12. Serum creatinine levels were higher in individuals with class IV LN than in patients with class V disease [1.50 (0.40-20.90) vs. 0.70 (0.62-0.90), p = 0.04]. Blood urea nitrogen had a positive significant correlation with MCC (p = 0.002; r: 0.75). A trend toward a negative correlation was observed between MCC and serum albumin (p = 0.06; r: -0.5459). Kidney biopsies of patients with nephrotic syndrome had higher MCC [2.12 (0.41-5.140) vs. 0.53 (0.0-3.94), p = 0.07]. Conclusion: Inflammatory cell infiltration and morphological differences between cell types in the inflammatory infiltrate are relevant factors in the assessment of the LN. Mast cell analysis and AI/CI assessment may be relevant prognostic indicators for pediatric patients with LN.

RESUMO Introdução: Mastócitos podem participar da inflamação e contribuir para fibrose na nefrite lúpica (NL). Objetivo: Correlacionar mastócitos em biópsias renais (BR) de pacientes pediátricos com NL com índices de atividade (IA) e cronicidade (IC), avaliando sua efetividade como fator prognóstico. Metodologia: Foram estudados 40 pacientes, entre 6 e 18 anos, diagnosticados com NL pelo Serviço de Nefropatologia da UFTM entre 1996 e 2015. Dados laboratoriais e epidemiológicos foram correlacionados com IA, IC e contagem de mastócitos (CM). Resultados: Encontramos correlação positiva e significativa entre contagem de mastócitos (CM) e IA (p = 0,003; r: 0,66) e entre CM e IC (p = 0,048; r: 0,48). Conforme a curva Roc, os mastócitos têm alta sensibilidade e especificidade na diferenciação de pacientes com IA menor ou maior do que 12. A creatinina sérica foi mais elevada na classe IV em relação à classe V [1,50 (0,40 - 20,90) versus 0,70 (0,62 - 0,90), p = 0,04]. Ureia sérica apresentou correlação positiva e significativa com CM (p = 0,002; r: 0,75). Observou-se tendência à correlação negativa entre CM e albumina sérica (p = 0,06; r: -0,5459). BR de pacientes com síndrome nefrótica apresentaram maior CM [2,12 (0,41 - 5,140) versus 0,53 (0,0 - 3,94), p = 0,07]. Conclusão: Não apenas o infiltrado inflamatório como também a diferenciação morfológica dos tipos celulares que o constituem são importantes para a avaliação da NL. Isso indica que a análise dos mastócitos, juntamente com a dos IA e IC, pode ajudar os nefrologistas a definirem o prognóstico de pacientes pediátricos.

Low triiodothyronine syndrome is associated with platelet function in patients with nephrotic syndrome

SUMMARY OBJECTIVE The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.

RESUMO OBJETIVO O objetivo deste estudo foi investigar os efeitos da síndrome do baixo triiodotironina (LT3S) na função plaquetária e nos fatores de coagulação em pacientes com síndrome nefrótica (SN). MÉTODOS Pacientes com síndrome nefrótica primária foram divididos em dois grupos, função tireoidiana normal (grupo A) e LT3S (grupo B), com base na presença ou não de LT3S. Indivíduos saudáveis foram selecionados como grupo de controle (grupo C). A função de coagulação do sangue foi analisada em cada grupo. A função de ativação plaquetária (CD62P, CD63) foi determinada por citometria de fluxo. A taxa de agregação plaquetária foi detectada por um método óptico usando adenosina difosfato e ácido araquidônico como indutores. RESULTADOS A proporção de síndrome nefrótica primária com LT3S foi de 23,2% (69/298). Em comparação com o grupo C, o grupo A apresentou níveis mais altos de CD62P e PAgTADP, e o grupo B apresentou maiores CD62P, CD63, PAgTAA e PAgTADP; a diferença teve significância estatística (P < 0,05). Não houve diferença significativa na patologia renal entre o grupo A e o grupo B (X2 = 4,957, P = 0,421). Em comparação com o grupo A, a proteína em urina de 24 horas, CD63, PAgTAA e PAgTADP foram maiores no grupo B, já APTT e Alb foram mais baixos. A diferença apresentou significância estatística (P < 0,05). A análise de regressão logística mostrou uma associação entre LT3S e CD36 (OR: 3,516; 95% IC: 1,742~8,186; P = 0,004) e PAgTAA (OR: 0,442; 95% IC: 1,001~1,251; P = 0,037). CONCLUSÃO Pacientes com síndrome nefrótica estão propensos à síndrome do baixo triiodotironina (LT3S). Pacientes com LT3S podem ter ativação plaquetária anormal e aumento da agregação plaquetária.

Trastornos glomerulares en la práctica médica / Glomerulopathies in the medical practice

RESUMEN Las glomerulopatías agrupan varias nefropatías con lesiones fundamentalmente del corpúsculo renal y que se expresan principalmente por proteinuria, hematuria, edemas e hipertensión arterial. La presentación clínica varía en dependencia del tipo de enfermedad de que se trate. Constituye la causa más frecuente de enfermedad renal crónica en adultos jóvenes, por lo que su estudio resulta imprescindible sobre todo para el nivel primario de salud. El propósito fue actualizar consideraciones pertinentes sobre la conducta diagnóstica y terapéutica integral ante una glomerulopatía y valorar emisión de recomendaciones al respecto. Se realizó una búsqueda, análisis y síntesis de información a través de Bases de datos ScieLO Cuba, ScieLO regional, Pubmed, Cumed, Clinical Key en el período 2012-2017 con las palabras clave: síndrome nefrótico, glomerulonefritis, diagnóstico, terapéutica, atención integral. El abordaje en las glomerulopatías es integral, multidisciplinario e individualizado. En Cuba constituyen la cuarta causa de enfermedad renal crónica y predomina el síndrome nefrítico agudo postinfeccioso. El método clínico juega en ello un papel trascendental a la hora de reconocer y registrar sus aspectos clínicos, su etiología, su fisiopatología, y los exámenes complementarios que confirman su presencia o sus complicaciones, así como un tratamiento oportuno que garanticen el perfeccionamiento asistencial. El arma más poderosa ante el reto de los trastornos glomerulares es la visión integradora y con enfoque individual y social protagonizado por el médico ante este grupo de nefropatías en adultos.

ABSTRACT Glomerulopathies encompass a group of several renal disorders with lesions, mainly in the renal corpuscle, expressed in proteinuria, hematuria, edemas and arterial hypertension. Their clinical manifestations change in dependence of the kind of disease. They are the most frequent cause of chronic renal disease in young adults; therefore their study is very important above all in the health care primary level. The aim was updating pertinent considerations on the diagnostic behavior and comprehensive therapy in the case of glomerulopathy, and evaluating the emission of recommendations regarding to them. A search, analysis and synthesis of information was carried out in the databases ScieLO Cuba, ScieLO regional, Pubmed, Cumed, and Clinical Key in the period 2012-2017, using the key words nephrotic syndrome, glomerulonephritis, diagnosis, therapeutics, comprehensive care. The approach to glomerulopathies is comprehensive, multidisciplinary and individualized. They are the fourth cause of chronic renal disease; the acute post-infectious nephritic syndrome predominates. The clinical method plays a transcendental role at the moment of recognizing and registering their clinical characteristics, etiology and physiopathology, while complementary tests confirm their presence or complications, and therefore an opportune treatment guarantying the healthcare improvement. The most powerful weapon against the challenge of the glomerular disorders is the integrated vision with an individual and social approach led by the physician in the case of these nephropathies in adults.

T-lymphocyte-expressing inflammatory cytokines underlie persistence of proteinuria in children with idiopathic nephrotic syndrome / Os linfócitos T que expressam citocinas inflamatórias são subjacentes à persistência de proteinúria em crianças com síndrome nefrótica idiopática

Abstract Objective: There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. Methods: This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP ≥ 300 mg/24 h, n = 17) and low proteinuria or complete remission (LP < 300 mg/24 h, n = 27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. Results: The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Conclusion: Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.

Resumo Objetivo Há comprovação do importante papel das alterações no sistema imunológico no desencadeamento e manutenção da síndrome nefrótica idiopática (SNI). O objetivo deste estudo foi investigar a expressão das citocinas em populações de linfócitos de pacientes com SNI em comparação a indivíduos saudáveis e de acordo com a proteinúria. Métodos Este estudo transversal incluiu 44 pacientes com SNI e oito crianças saudáveis, pareados por idade e sexo (controles). Os pacientes foram subdivididos de acordo com a proteinúria: proteinúria persistente ou remissão parcial (PP ≥ 300 mg/24 h, n = 17) e proteinúria baixa ou remissão completa (PB < 300 mg/24 h, n = 27). A análise ex vivo de leucócitos no sangue periférico por citometria de fluxo foi feita utilizando marcadores de superfície para linfócitos T, TCD4, TCD8, células natural killer (NK), linfócitos NKT e B. As frequências das citocinas intracelulares foram analisadas nessas células. Resultados A frequência dos linfócitos B, células NK e células NKT foi menor em pacientes com SNI do que nos controles, ao passo que os pacientes com SNI apresentaram maior frequência de células CD4+fator de necrose tumoral (TNF)-α+ do que nos controles. Os linfócitos T citotóxicos que expressam interferon (IFN)-γ foram menores nos pacientes com SNI do que nos controles. Os pacientes com PP mostraram maiores frequências de linfócitos T CD4 que expressam IFN-γ e TNF-α que os controles. Os linfócitos CD8 que expressam TNF-α apresentaram aumento no grupo com PP, em comparação aos com PB e os controles, apesar de as células CD8+IFN-γ+ serem mais baixas nos pacientes com PB e nos controles. Conclusão Com relação ao nível de proteinúria, os pacientes com SNI apresentaram aumento na expressão de TNF-α nos linfócitos CD4 e expressão reduzida de IFN-γ nos linfócitos CD8. A persistência da proteinúria foi associada a maiores níveis de marcadores inflamatórios.

Bone mineral density in children with idiopathic nephrotic syndrome / Densidade mineral óssea em crianças com síndrome nefrótica idiopática

Abstract Objectives: To assess bone mineral density (BMD) in children with idiopathic nephrotic syndrome (NS) and normal glomerular filtration rate (GFR). Methods: Cross-sectional case-control study carried out on 50 children: 25 cases of NS (16 steroid-sensitive [SSNS] and nine steroid-resistant [SRNS] under follow up in the pediatric nephrology unit of Menoufia University Hospital, which is tertiary care center, were compared to 25 healthy controls with matched age and sex. All of the participants were subjected to complete history taking, thorough clinical examination, laboratory investigations (serum creatinine, blood urea nitrogen [BUN], phosphorus [P], total and ionized calcium [Ca], parathyroid hormone [PTH], and alkaline phosphatase [ALP]). Bone mineral density was measured at the lumbar spinal region (L2-L4) in patients group using dual-energy X-ray absorptiometry (DXA). Results: Total and ionized Ca were significantly lower while, serum P, ALP, and PTH were higher in SSNS and SRNS cases than the controls. Osteopenia was documented by DXA scan in 11 patients (44%) and osteoporosis in two patients (8%). Fracture risk was mild in six (24%), moderate in two (8%), and marked in three (12%) of patients. Conclusion: Bone mineralization was negatively affected by steroid treatment in children with NS.

Resumo Objetivos: Avaliar a densidade mineral óssea (DMO) em crianças com síndrome nefrótica idiopática (SNI) e com taxa de filtração glomerular (TFG) normal. Métodos: O estudo transversal de caso-controle foi feito com 50 crianças: 25 casos de SNI [16 sensíveis a esteroides (SNSE) e nove resistentes a esteroides (SNRE) com acompanhamento na unidade de nefrologia pediátrica do hospital da Menoufia University, centro de cuidados terciário] foram comparados com 25 controles saudáveis do grupo de controle com idade e sexo equivalentes. Todos os participantes foram submetidos a anamnese completa, exame clínico completo, exames laboratoriais [creatinina sérica, nitrogênio ureico no sangue (BUN), fósforo (P), cálcio (Ca) total e ionizado, paratormônio (PTH) e fosfatase alcalina (ALP)]. A densidade mineral óssea foi mensurada na região da coluna lombar (L2-L4) no grupo de pacientes com a absorciometria por raios X de dupla energia (DXA). Resultados: Os níveis de cálcio total e ionizado eram significativamente menores, ao passo que o fósforo sérico, a FA e o PTH eram maiores em casos de SNSE e SNRE do que nos controles. A osteopenia foi documentada pelo exame DXA em 11 pacientes (44%) e a osteoporose em dois (8%). O risco de fratura era leve em seis (24%), moderado em dois (8%) e acentuado em três (12%). Conclusão: A mineralização dos ossos foi afetada negativamente pelo tratamento com esteroides em crianças com SNI.

Maduración ósea y estado nutricional antropométrico en niños, niñas y adolescentes con síndrome nefrótico / Bone maturation and anthropometric nutritional status in children and adolescents with nephrotic syndrome

Los glucocorticoides, comúnmente utilizados en el tratamiento del síndrome nefrótico, pudieran interferir en elcrecimiento y desarrollo del niño. La maduración ósea (MO) por el método Tanner- Whitehouse II (TW I2) constituye un indicador para evaluar el desarrollo somático. Analizar el comportamiento de la MO con relación al estado nutricional antropométrico y a las características clínico – patológicas en niños, niñas y adolescentes con Síndrome Nefrótico. Estudio transversal, exploratorio, descriptivo y correlacional. Se evaluaron 28 pacientes (11 niñas, 17 varones) entre 2 y 16 años con síndrome nefrótico, que acudieronentre agosto y octubre de 2008 a la consulta de nefrología del Hospital Pediátrico Dr. Elías Toro, cuyos padres autorizaron las medicionesde peso y talla y la realización de una radiografía de mano y muñeca izquierdas para edad ósea TW2. Se utilizaron la prueba de ANOVAsimple, t de Student y coeficiente de correlación de Pearson, con nivel de significación estadística de p <0,05. Predominó el género masculino(60,7%). Dos pacientes tuvieron un índice de masa corporal en exceso y ninguno con déficit. Predominó la edadósea normal (85,7%), adelantada en tres niños (10,7%) y retardada en uno. Se observó una relación inversa entre el número de recaídas y el porcentaje de maduración ósea alcanzada en los pacientes masculinos con corticoresistencia (p < 0,05). Este estudio reveló diferencias en el comportamiento de la maduración ósea, según el género y la condición de corticoresistencia

Glucocorticoids, commonly used in the treatment of nephrotic syndrome could interfere in children’s growth and development. Skeletal maturity determined by Tanner-Whitehouse II method (TW2) constitutes an indicator of bone maturation. To analyze the behavior of bone age (BA) related to anthropometric nutritional status and to clinical and pathological characteristics of children and adolescents with nephrotic syndrome. This is a cross-sectional, exploratory, descriptive andcorrelational study. Twenty eight patients (11 girls, 17 boys) diagnosed with nephrotic syndrome that attended the nephrology outpatient clinic of the Pediatric Hospital Dr. Elías Toro, from August to October 2008. Weight and height were measured using international techniques, and a left hand and wrist X-ray was evaluated by the TW2-method. ANOVA, t-Student test and Pearson correlation coefficient were calculated with a significance level of p< 0.05. Results: boys predominated (60.7%). Body mass index was abovenormal in 2 patients and normal in the rest. BA was normal in 24 children (85.7%), advanced in three (10.7%) and delayed in one. An inverse relationship was found between the number of relapses and the percentage of maturity reached in steroid resistant male patients (p < 0.05). This study shows a probable difference in the behavior of BA, according to gender steroid resistance

Proteomic profiling of nephrotic syndrome in serum using magnetic bead based sample fractionation & MALDI-TOF MS.

Background & objectives: At present, the diagnosis of nephrotic syndrome (NS) requires a renal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate serum petidome in NS patients. Methods: The fasting blood samples from 49 patients diagnosed with NS by renal biopsy, including 17 mesangial proliferative glomerulonephritis (MsPGN), 12 minimal change nephrotic syndrome (MCNS), 10 focal segmental glomerulosclerosis (FSGS) and 10 membranous nephropathy (MN), were collected and screened to describe their variability of the serum peptidome. The results in NS group were compared with those in 10 control healthy individuals. Specimens were purified with magnetic beads-based weak cation exchange chromatography and analyzed in a MALDI-TOF MS. Results: The results showed 43, 61, 45 and 19 differential peptide peaks in MsPGN, MCNS, MN and FSGS groups, respectively. A Genetic Algorithm was used to set up the classification models. Cross validation of healthy controls from MsPGN, MCNS, MN and FSGS was 96.18, 100, 98.53 and 94.12 per cent, respectively. The recognition capabilities were 100 per cent. Interpretation & conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may give an early idea of the pathology of nephrotic syndrome.

The Clinical Characteristics of Steroid Responsive Nephrotic Syndrome of Children according to the Serum Immunoglobulin E Levels and Cytokines

PURPOSE: The nephrotic syndrome (NS) is characterized by the favorable response to glucocorticoid therapy and the development of NS may be associated with dysfunctional immune systems. In order to investigate the serum immunoglobulin E (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid responsive NS patients and 5 healthy controls were enrolled in this study. MATERIALS AND METHODS: All patients were divided into two groups according to the initial serum IgE levels, such as normal and high IgE group, and their clinical characteristics were evaluated. In addition, serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-beta were compared and correlated with serum albumin, proteinuria by means of disease severity, and cytokines. RESULTS: In the high IgE group, the higher comorbidity of allergic diseases and relapsing rate, the longer duration of steroid therapy before initial remission, and the higher serum IL-4 and IL-5 levels were found. In all patients, initially higher serum levels of IL-4 and IL-5 declined to normal levels after steroid therapy, whereas the serum IL-10 levels showed no significant difference between nephrotic phase (heavy proteinuria) and remission phase (no proteinuria) of NS. The serum TGF-beta levels of the nephrotic phase were significantly lower than those of remission phase or control group, and returned to normal control levels after steroid therapy. CONCLUSION: This study indicates that initial IgE level is associated with steroid responsiveness and disease severity, and cytokine activities may also be related to the pathogenesis of pediatric steroid responsive NS.

Increased glycated hemoglobin level in non-diabetic nephrotic children is associated with oxidative stress.

Glycation and lipid peroxidation are spontaneous reactions believed to contribute to the pathogenesis of nephrotic syndrome. Possible interrelations of glycated hemoglobin with reduced glutathione and malondialdehyde were evaluated in nephrotic syndrome patients. Eighteen nephrotic syndrome patients and 15 healthy controls were enrolled for this study. Glycated hemoglobin, reduced glutathione, malondialdehyde and fasting glucose were analyzed for their correlation in both the groups. In nephrotic syndrome patients, while glycated hemoglobin and malondialdehyde levels were found to be significantly increased, glutathione levels decreased significantly when compared with controls. Glycated hemoglobin was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. Erythrocytes depleted of glutathione, by pre-treatment with 1-chloro-2, 4-dinitrobenezene, were found to have higher glycated hemoglobin levels when compared with erythrocytes incubated with glucose alone. These data suggest that glycated hemoglobin levels are closely associated with malondialdehyde and glutathione in nephrotic syndrome patients.

The Clinical Significance of Serum and Urinary Neopterin Levels in Several Renal Diseases

Neopterin is a pyrazino-pyrimidine compound, and is known to be a marker associated with cell-mediated immunity in various diseases. We hypothesized that the levels of serum and urine neopterin would be elevated in renal disease, and would correlate with certain clinical parameters. We evaluated serum and urinary neopterin levels in patients with several renal diseases, including nephrotic syndrome (NS, n=19), chronic renal failure (CRF, n=8), end stage renal disease (ESRD, n=64) and controls (n=22). Serum neopterin was elevated in patients with CRF and ESRD, as compared to controls. Urinary neopterin levels were also found to be elevated in patients with CRF and ESRD, as compared to controls. Serum neopterin levels showed significant positive correlation with age, serum BUN and creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, serum albumin and total iron binding capacity. Urine neopterin levels exhibited positive correlation with age and serum creatinine levels, and inverse correlation with WBC, hemoglobin, hematocrit, BUN and serum albumin. In conclusion, increased serum and urinary neopterin levels were found in some patients with renal disease and were correlated with certain clinical parameters.

Conformational Transitions and Glycation of Serum Albumin in Patients with Minimal-Change Glomerulopathy

BACKGROUND: There has been a lack of study on the structural changes of serum albumin in patients with minimal change disease (MCD). To determine whether glycation and/or conformational transitions of albumin are involved in the pathogenesis of albuminuria, nine patients with MCD were enrolled in a prospective follow-up study for comparison of these parameters in serum albumin during the remission and relapse of nephrotic syndrome. METHODS: Circular dichroism measurements were made with purified albumin. Ellipticities at each wavelength were transformed to mean residue ellipticity. Monosaccharide composition was analyzed by high-pH anion-exchange chromatography with pulsed amperometric detection. RESULTS: There was no difference in the proportions of alpha-helix, beta-conformation, and beta-turn of albumin between the sera of control patients and those with nephrotic syndrome. However, the proportion of the random configuration was slightly higher in the plasma albumin of patients in relapse than in those in remission. The proportion of the random configuration was lower in the albumin of the serum than in the urine of patients with nephrotic syndrome, but there was no difference in the proportions of alpha-helix, beta-conformation, and beta-turn of albumin between their plasma and urine. CONCLUSION: Our results suggest that conformational changes in albumin are involved in albuminuria in patients with MCD.

High dose methylprednisolone therapy in nephrotic syndrome.

This study was done to determine the efficacy of oral high dose methylprednisolone (HDMP) therapy in the treatment of childhood nephrotic syndrome (NS). Fifteen patients were enrolled in the study. Patients were arbitrarily divided into two groups. Group I received prednisolone (daily 60 mg/m2 for 4 weeks, 45, 30, 20, 10, 5 mg/m2 on alternate days for 4 weeks) and group II received HDMP (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days, 10 mg/kg/ for a week, before 9 am, orally). The patients were followed-up for a duration of 38.0 +/- 5.5 months (range 24-68 months) in group I and 42.1 +/- 5.5 months (range 16-72 months) in group II. No significant difference was obtained in the duration of remission between both groups (p > 0.05), while HDMP induced early remission than prednisolone (p < 0.05). The mean relapse rate was 0.8/year in group I and 0.8/year in group II (p > 0.05). Although, the number of the patients were limited in the study it can be recommended that patients with NS can be treated with oral HDMP therapy as an alternative to standard oral prednisolone therapy.

Hemostatic profile in nephrotic syndrome.

OBJECTIVE: To evaluate the coagulation profile and its relation to steroid therapy, and the frequency of thromboembolic complications and its correlation with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based. SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups, namely, fresh cases, steroid dependent, remission after therapy and steroid resistant. An equal number of age and sex matched children served as controls. In all the study and control subjects, detailed clinical examination, liver function tests, renal function tests and detailed coagulation profile were done. Evaluation of renal veins and inferior vena cava for the presence of thrombosis was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected in 57.5% and the degree of thrombocytosis was directly related to the amount of proteinuria. The mean prothrombin and thrombin times were within normal range in the study children. The activated partial thromboplastine time (APTT) was prolonged in six cases (15%) and three out of these six children had thromboembolic complications. Antithrombin-III level was significantly lower (p < 0.001) whereas protein C and S were significantly elevated (p < 0.001) as compared to controls. The levels became normal with remission of the disease. Steroid therapy significantly increased the levels of proteins C, protein S. AT-III and fibrinogen as compared to controls. Thromboembolic complications were seen in 3 cases (7.6%) and were associated with very low levels of AT-III and protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The importance of coagulation profile in nephrotic syndrome is highlighted and a high index of suspicion for thromboembolic complications is warranted in patients with thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low levels of AT-III, protein C and protein S.

Peripheral blood lymphocyte subsets in idiopathic nephrotic syndrome of childhood.

Lymphocyte subsets in the peripheral blood were examined in 34 patients with nephrotic syndrome [27 with minimal change nephrotic syndrome (MCNS), 7 with significant lesions] and 10 normal children. The investigations were done at the onset of disease before administering corticosteroids (n = 34), during the subsequent remission (n = 27), and the first relapse (n = 12). The proportions of T cell subsets (CD3, CD4 and CD8) were determined by immuno-alkaline phosphatase staining; interleukin-2 receptor (IL-2 R) positive cells, natural killer (NK) cells and B cells were studied by indirect immunofluorescence. No significant differences were found in the proportion of CD3, CD4, CD8 and IL-2 R positive cells in patients with MCNS as compared to controls. An increased proportion of NK and B cells was not specific to MCNS and was detected even in those with significant renal lesions. Our findings suggest that T lymphocyte subsets in MCNS are similar to those in normal children.

Lipoprotein abnormalities in adult nephrotic syndrome.

The lipid and lipoprotein profiles including apolipoprotein A1 and B100 are measured in 50 idiopathic nephrotic patients (males 26, females 24) with mean age of 32 + 13.6 yrs, serum creatinine 1.32 +/- 0.43 mg/dl compared with 50 age matched normal controls. The renal histology consist of IgM nephropathy 70 per cent, membranous 12 per cent, and IgA 2 per cent. The serum cholesterol, triglycerides, LDL- cholesterol, VLDL-cholesterol, apolipoprotein B (521.6 +/- 201.6, 291.4 +/- 156.2, 438.8 +/- 207.4, 58.3 +/- 31.2, 265.1 +/- 119.8) are statistically significantly higher than controls (p < 0.001). The HDL-cholesterol (30.2 +/- 16.1) is also significantly lower than controls (p < 0.001) but apolipoprotein A is not different from normal subjects. The most common hyperlipoprotein type is type IIb (66%), less common are type IIa (22%), IV (6%) and III (4%) respectively. There is no correlation between serum lipids, lipoproteins and urinary protein, serum albumin, and histological diagnosis. The ratio of cholesterol: HDL, LDL: HDL and Apo A1: B are all significantly higher than normal control (p < 0.001) and correlate with urinary protein levels. This study shows that the nephrotic patients who have persistent heavy proteinuria have dyslipidemia which is highly atherogenic and probably increases the incidence of coronary heart disease.

Dietary cholesterol induced changes in lipid profile in patients with nephrotic syndrome and chronic renal failure.

Fifteen patients with nephrotic syndrome (9 aged below 30 years), 6 patients with chronic renal failure and 26 healthy males (14 below 30 years) were studied. After estimating the basal serum levels of total cholesterol (STC), triglycerides (STG), high density lipoprotein (HDL) and low density lipoprotein (LDL), the patients were given a high cholesterol and high fat breakfast (containing 32 g fat and 527 mg cholesterol) for 7 days. Lipoprotein levels were again estimated on days 8 and 16. In the basal state, all patients with nephrotic syndrome had markedly elevated levels of STC and LDL. In patients aged below 30 years, STG and VLDL levels were also elevated, while HDL levels were similar in both the groups in comparison to their respective age group controls. In patients with renal failure, basal levels of all lipoproteins were similar to levels in controls. After the high cholesterol fat diet, there was an insignificant rise in all lipoprotein values in patients with nephrotic syndrome and renal failure. However, HDL levels rose significantly in patients with nephrotic syndrome aged below 30 years. Patients with nephrotic syndrome and chronic renal failure can safely be given high cholesterol and high fat diet despite abnormalities in lipid lipoprotein metabolism.

Perfil lipídico en niños con nefrosis / Lipid profile in children with nephrosis

Se estudiaron los niveles séricos de lípidos en 25 niños con síndrome nefrótico idiopático de lesiones glomerulares mínimas. Todos los casos mostraron valores de colesterol total y triglicéridos por encima del 95 percentil para su edad y sexo (417 + - 119 mg/dL y 448 + - 313 mg/dL respectivamente). El 92%de los enfermos mostró lipoproteína de baja densidad (LBD) por encima del 95 percentil para su edad y sexo (307 + - 108 mg/dL), y un 72%exhibió lipoproteína de alta densidad (LAD) en el límite inferior normal por debajo del 5o. percentil para su edad y sexo (26.9 + -13.7mg/dL). una proporción importante de los enfermos mostró lipoproteína de muy baja densidad (LMBD) elevada (90.8 + -61.0 mg/dL). Se encontró una relación directamente proporcional entre el colesterol total y la LBD (r=0.854); sin embargo, no se observó la relación inversa entre el colesterol total y la LAD (r= 0.315), ni entre colesterol total y albúmina sérica (r= 0.248)