Long-term outcomes of childhood steroid-sensitive nephrotic syndrome / 中华儿科杂志

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ2 or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ2=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ2=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.

Clinical assessment of moderate-dose glucocorticoid in the treatment of recurrence of primary nephrotic syndrome in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS).@*METHODS@#A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions.@*RESULTS@#There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018).@*CONCLUSIONS@#For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.

Efficacy of adrenocorticotropic hormone in children with frequently relapsing or steroid-dependent nephrotic syndrome / 中华儿科杂志

Objective: To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in children with frequently relapsing or steroid-dependent nephrotic syndrome. Methods: The clinical data of 38 children with frequently relapsing or steroid-dependent nephrotic syndrome who were admitted to the Department of Nephrology, the Children Hospital, Zhejiang University School of Medicine from January 2015 to December 2020 were retrospectively analyzed. The general information, clinical manifestations, laboratory data of the children and follow-up (till 12 months after treatment) were collected. The patients were divided into ACTH group and Glucocorticoid (GC) group according to treatment plan. Cumulative remission, average recurrence rate, GC dosage, height and weight change and peripheral blood CD19+B lymphocyte count were compared between the two groups to evaluate the efficacy and adverse reactions of ACTH. Fisher's exact test, t test or rank sum test was used for comparison between groups. Results: Among the 38 patients, 28 were male and 10 were female, aged 84 (24, 180) months; 19 were in ACTH group and 19 were in GC group. The cumulative remission rate of 12 months in ACTH group was higher than that in GC group (9/19 vs. 2/19,χ²=6.81,P=0.009), the average recurrence rate was lower than that in GC group ((0.7±0.8) vs. (1.7±1.1) times, t=-3.27, P=0.011), and the average dosage of GC was lower than that in GC group ((0.27±0.16) vs. (0.51±0.27) mg/(kg·d), t=-3.21, P=0.014). The increase in height was higher than that in the GC group (4 (3,5) vs. 3 (2, 3) cm/year, Z=2.58, P=0.010), and the peripheral blood CD19+B lymphocyte count was lower than that in the GC group ((223±149)×106 vs. (410±213)×106/L,t=-3.35, P=0.009). In safety, 19 cases had transient decreased urine volume, 7 cases had hyperglycemia, and 3 cases had hypertension during the infusion of ACTH, which could be relieved after drug withdrawal. Conclusion: ACTH has a better effect on children with frequently relapsing or steroid-dependent nephrotic syndrome, which can improve cumulative sustained remission rate, lower relapses rate and decrease the dosage of GC, with good safety.

Sinkihwan-gamibang ameliorates puromycin aminonucleoside-induced nephrotic syndrome / 中国天然药物

Nephrotic syndrome (NS) is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang (SKHGMB) was recorded in a traditional Chinese medical book named "Bangyakhappyeon ()" and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside (PAN). The experimental NS model was induced in male Sprague Dawley (SD) rats through injection of PAN (50 mg·kg-1)via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.

Expression of adipokines in children with primary nephrotic syndrome and its association with hyperlipidemia / 中国当代儿科杂志

OBJECTIVES@#To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia.@*METHODS@#A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels.@*RESULTS@#Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage (@*CONCLUSIONS@#Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.

Retos terapéuticos en el síndrome nefrótico idiopático / Therapeutic challenges in the idiopathic nephrotic syndrome

El diagnóstico, evaluación y tratamiento del síndrome nefrótico en el niño data de los tiempos de Hipócrates. Sin embargo, en la actualidad algunos pacientes con la enfermedad siguen siendo un reto terapéutico para el médico. Nos proponemos examinar en la literatura reciente, distintas propuestas o protocolos de tratamiento y las nuevas drogas que pueden utilizarse en la atención al paciente con esta enfermedad. Los protocolos de tratamiento varían con relativa frecuencia y las drogas, tanto en los síndromes nefróticos recaedores frecuentes, corticodependientes o corticorresistentes, no garantizan en muchas ocasiones la curación del paciente. Cuando fracasan los esteroides se pueden utilizar agentes alquilantes, inhibidores de la calcineurina, antiproliferativos, anticuerpos monoclonales y otros fármacos, pero existen pacientes que no tienen remisión de la proteinuria con ninguno de estos tratamientos. Por sus características evolutivas, algunos pacientes con síndrome nefrótico idiopático siguen siendo un reto para el médico que trata de evitar su evolución hacia la pérdida de la función renal. A pesar de todos los avances en la atención del niño con síndrome nefrótico, desde el descubrimiento de los esteroides, antibióticos, diuréticos e inmunosupresores, en la actualidad no sabemos exactamente cuál es el mejor tratamiento en las formas resistentes del síndrome nefrótico idiopático en niños(AU)

Diagnosis, evaluation and treatment of nephrotic syndrome in children dates from Hypocrate times. However, nowadays some patients with this disease are still a therapeutic challenge for physicians. The aim of this work is to search in recent literature different proposals or treatment protocols, and new drugs that can be used in the care of patients with this disease. Treatment protocols vary with relative frequency and drugs, as well as in frequent relapsing nephrotic, corticodependent or corticoresistant syndromes, do not guarantee in many ocassions the cure of the patient. When steroids fail, alkylanting agents, calcineurin depressants, antispreading, monoclonal antibodies and other drugs can be ussed; but there are patients who do not have remission of proteinuria with any of these treatments. Due to their evolutive characteristics, some patients with idiopathic nephrotic syndrome are still a challenge for the physicians who try to avoid its evolution toward the loss of renal function. Although all the advances in the care of children with nephrotic syndrome due to the discover of steroids, antibiotics, diuretics and immunosupressive drugs, nowadays we do not exactly know which is the best treatment for the resistant types of idiopathic nephrotic syndrome in children(AU)

Inflammatory cytokines and lipid profile in children and adolescents with nephrotic syndrome receiving L. Plantarum: a randomized, controlled feasibility trial

SUMMARY This study aimed to evaluate the efficacy of the action of the Lactobacillus Plantarum probiotic as a immunomodulatory and hypolipidemic agent in dyslipidemic nephrotic children and adolescents. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial in pediatric, compensated or partially compensated nephrotic syndrome and dyslipidemic subjects undergoing regular outpatient follow-up. Serum lipid and TNF-α (proinflammatory) and IL-10 (anti-inflammatory) cytokine variations were evaluated. Cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the probiotic group there was a tendency to reduce TNF-α levels and increase IL-10 levels when compared to controls. Regarding the lipid profile, there was a decrease in serum triglyceride (6.0 mg / dL) and total cholesterol (41.5 mg / dL) levels in the probiotic group when compared to baseline levels, while in the control group there was an increase in serum triglyceride (49.5 mg / dL) and total cholesterol (8.0 mg / dL) levels, respectively. CONCLUSION: Preliminary results suggest that L. Plantarum showed an immunomodulatory and hypolipidemic effect in nephrotic and dyslipidemic pediatric subjects.

RESUMO: O objetivo deste estudo foi avaliar a eficácia da ação do probiótico Lactobacillus Plantarum como um agente imunomodulador e hipolipemiante em crianças e adolescentes dislipidêmicos com síndrome nefrótica. MÉTODOS: Este é um estudo randomizado, duplo-cego, controlado com placebo e realizado em pacientes pediátricos com síndrome nefrótica, compensados ou parcialmente compensados e dislipidêmicos passando por acompanhamento ambulatorial. Variações no lipídio sérico e nas citocinas TNF-α (pró-inflamatória) e IL-10 (anti-inflamatória) foram avaliadas. As citocinas foram analisadas por ensaio imunoenzimático (ELISA). RESULTADOS: No grupo probiótico, houve uma tendência de redução dos níveis de TNF-α e de aumento dos níveis de IL-10, quando comparado ao controle. Em relação ao perfil lipídico, houve uma diminuição nos níveis séricos de triglicérides (6,0 mg/dL) e colesterol total (41,5 mg/dL) no grupo probiótico em comparação aos níveis basais, enquanto no grupo de controle houve um aumento nos níveis séricos de triglicérides (49,5 mg/dL) e colesterol total (8,0 mg/dL). CONCLUSÃO: Os resultados preliminares sugerem que o L. Plantarum tem um efeito imunomodulador e hipolipemiante em pacientes pediátricos dislipidêmicos e com síndrome nefrótica.

Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report / Glomeruloesclerose Segmentar e Focal e Nefropatia Membranosa sobrepostas em paciente com Síndrome Nefrótica: relato de caso

Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.

Effect of prednisolone on linear growth in children with nephrotic syndrome / Efeito da prednisolona sobre o crescimento linear em crianças com síndromenefrótica

Abstract Objective This study aims at determining the relationship between prednisolone cumulative dose and linear growth in pre-pubertal children with idiopathic nephrotic syndrome. Method This cross-sectional study was conducted on all children with idiopathic nephrotic syndrome registered to the pediatric nephrology department at the main referral children's hospital in Southwestern Iran. Inclusion criteria included age (males <12 years; females <10 years), >6 months of use, and the minimum prednisolone cumulative dose of 152 mg/kg. The exclusion criteria were individuals who had entered puberty or had other diseases affecting linear growth. Based on the prednisolone cumulative dose of ≥550 mg/kg (four or more relapses), the children were divided into two groups. All data regarding age, height, and weight at disease onset and the last visit, bone age, and the parents' height were collected. Secondary variables including mid-parental target height and predicted adult height were also calculated. Height data were compared between the different rates of relapse. Results A total of 97 children (68% male) were enrolled. Their post-treatment mean height Z-score was less than that obtained before treatment (−0.584 vs. −0.158; p = 0.001). Subjects with higher prednisolone cumulative doses were found to have more reduction in height Z-score (p = 0.001). Post-treatment height prediction also showed less growth potential compared to pre-treatment target height (p = 0.006). Thirty-three children (34.4%) had four or more relapses, among whom more mean-height Z-score decreases were found compared to those with less-frequent relapses (−0.84 vs. −0.28; p = 0.04). Conclusion This study showed the negative effect of cumulative dosages of prednisolone on linear growth, which was greater in children with four or more relapses.

Resumo Objetivo Determinar a relação entre a dose cumulativa de prednisolona e o crescimento linear em crianças pré-púberes com síndrome nefrótica idiopática. Método Estudo transversal conduzido em todas as crianças com síndrome nefrótica idiopática registradas no departamento de nefrologia pediátrica no principal hospital infantil para encaminhamento no sudoeste do Irã. Os critérios de inclusão incluíram idade (meninos < 12 anos; meninas < 10 anos), > 6 meses e a dose cumulativa de prednisolona mínima de 152 mg/kg. Os critérios de exclusão foram indivíduos que entraram na puberdade ou tinham outras doenças que afetam o crescimento linear. Com base na dose cumulativa de prednisolona de ≥ 550 mg/kg (≥ 4 recidivas), as crianças foram divididas em dois grupos. Foram coletados todos os dados relacionados a idade, estatura e peso no início da doença e na última visita, idade óssea e estatura dos pais. Também foram calculadas as variáveis secundárias, inclusive estatura-alvo e estatura adulta prevista. Os dados de estatura foram comparados entre as diferentes taxas de recidivas. Resultados Foram inscritas 97 crianças (68% do sexo masculino). Seu escore z de estatura média pós-tratamento foi inferior ao obtido antes do tratamento (−0,584 em comparação com −0,158; p = 0,001). Os indivíduos com maiores doses cumulativas de prednisolona mostraram maior redução no escore z para estatura (p = 0,001). A estatura pós-tratamento também foi preditiva de menor potencial de crescimento em comparação com a estatura-alvo pré-tratamento (p = 0,006); 33 crianças (34,4%) apresentaram ≥ 4 recidivas, entre as quais foram encontradas mais reduções médias no escore z para estatura em comparação com as recidivas menos frequentes (−0,84 em comparação com −0,28; p = 0,04). Conclusão Este estudo mostrou o efeito negativo das doses cumulativas de prednisolona sobre o crescimento linear, que foi maior em crianças com ≥ 4 recidivas.

Economic evaluation of human albumin use in patients with nephrotic syndrome in four Brazilian public hospitals: pharmacoeconomic study / Avaliação econômica do uso de albumina humana em pacientes com síndrome nefrótica em quatro hospitais públicos brasileiros: estudo de farmacoeconomia

ABSTRACT CONTEXT AND OBJECTIVE: In 2004, the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, ANVISA) published a resolution establishing guidelines for albumin use. Although the published data do not indicate any definitive conclusions about the benefits of albumin use in patients with nephrotic syndrome (NS), the guidelines recommend this procedure only in cases of edema that is refractory to use of diuretics. The aim here was to analyze albumin use among patients with nephrotic syndrome. DESIGN AND SETTING: Pharmacoeconomic study conducted in four large public referral hospitals for nephrology services in northeastern Brazil. METHOD: Cost-effectiveness and cost-utility economic evaluations were performed on a concurrent cohort of patients with nephrotic syndrome, who were divided into two groups according to compliance or noncompliance with the guidelines. Quality-of-life data were obtained from the SF36 and CHQ-PF50 questionnaires. RESULTS: This study enrolled 109 patients (60% adults and 56% women); 41.3% were using albumin in accordance with the guidelines. The weight, diuresis and fluid balance parameters were more cost-effective for patients who adhered to the guidelines. Regarding days of hospitalization avoided, the incremental ratio showed a daily cost of R$ 55.33, and guideline-compliant patients were hospitalized for five days or fewer. The quality of life improved by 8%, and savings of R$ 3,458.13/QALY (quality-adjusted life year) for the healthcare system were generated through guideline compliance. CONCLUSION: The economic analyses of this study demonstrated that there were greater cost benefits for patients whose treatment followed the guidelines.

RESUMO CONTEXTO E OBJETIVO: Em 2004, a Agência Nacional de Vigilância Sanitária (ANVISA) publicou uma resolução que estabelece diretrizes para o uso de albumina. Embora os dados publicados não indiquem conclusões definitivas sobre os benefícios do uso de albumina em pacientes com síndrome nefrótica (SN), a diretriz recomenda o procedimento apenas em casos de edema refratário ao uso de diuréticos. O objetivo aqui foi analisar o uso de albumina em pacientes com síndrome nefrótica. TIPO DE ESTUDO E LOCAL: Estudo farmacoeconômico realizado em quatro grandes hospitais públicos de referência em serviços de nefrologia no nordeste do Brasil. MÉTODO: Foram realizadas avaliações econômicas do tipo custo-efetividade e custo-utilidade em uma coorte concorrente de pacientes com síndrome nefrótica, divididos em dois grupos de acordo com o cumprimento ou descumprimento das diretrizes. Dados de qualidade de vida foram obtidos a partir dos questionários SF36 e CHQ-PF50. RESULTADOS: Este estudo incluiu 109 pacientes (60% adultos e 56% mulheres); 41,3% estavam usando albumina conforme as diretrizes. Os parâmetros de peso, diurese e balanço hídrico foram mais custo-efetivos para pacientes que aderiram às diretrizes. Quanto a dias de internação evitados, a razão incremental mostrou um custo diário de R$ 55,33, sendo que os pacientes que seguiram as diretrizes ficaram cinco dias a menos internados. A qualidade de vida melhorou 8%, gerando economia de R$ 3,458.13/QALY (quality-adjusted life year) para o sistema de saúde por meio do cumprimento das diretrizes. CONCLUSÃO: As análises econômicas deste estudo demonstraram maiores benefícios em termos de custo para os pacientes cujo tratamento seguiu as diretrizes.

Doença de lesões mínimas e glomeruloesclerose segmentar e focal em adultos: resposta a corticoide e risco de insuficiência renal / Minimal change disease and focal segmental glomerulosclerosis in adults: response to steroids and risk of renal failure

Resumo Introdução: O perfil clínico de pacientes brasileiros adultos com síndrome nefrótica por doença de lesões mínimas (LM) e glomeruloesclerose segmentar e focal (GESF) é pouco conhecido. Objetivo: Avaliamos as características clínico-laboratoriais e resposta a tratamento em pacientes adultos com síndrome nefrótica e diagnósticos histológicos de LM ou GESF. Métodos: Fez-se a análise retrospectiva de 50 pacientes adultos com LM e 120 com GESF. Todos os pacientes foram inicialmente tratados com corticosteroide. Os desfechos do estudo foram: resposta a corticosteroide, prevalência de remissão total, progressão para doença renal crônica estágio 5 (DRC5) e necessidade de terapia de substituição renal por DRC5. Resultados: Níveis iniciais de creatinina sérica foram 24% mais elevados entre pacientes com GESF (p = 0,02) e os de proteinúria foram 36% mais altos em LM (p < 0,001). Pacientes com LM foram córtico-sensíveis em 80% dos casos, com remissão total em 74%, e os pacientes com GESF em 58% (p = 0,01), com remissão total em 30% (p = 0,002). A prevalência de insuficiência renal aguda em pacientes com GESF foi de 39% (vs. 12%, p = 0,013) e DRC5 de 10% (vs. 0%, p < 0,001). Remissão completa ou parcial com o uso de corticosteroide reduziu em 83% o risco de DRC5 (p < 0,001) e remissão total associou-se a redução no risco de DRC5 de 89% (p < 0,001). Conclusão: A resposta positiva à corticoterapia foi o fator mais importante relacionado à preservação da função renal ao longo de mais de uma década de seguimento, e GESF relacionou-se a menor índice de resposta a corticosteroide.

Abstract Introduction: There is scarce data on the clinical profile of adult Brazilian patients with nephrotic syndrome caused by minimal change disease (MCD) and focal segmental glomerulosclerosis. Objective: We evaluated the clinical characteristics and response to treatment in adult patients with nephrotic syndrome having a histological diagnosis of MCD or FSGS. Methods: This is a retrospective analysis of 50 patients with MCD and 120 with FSGS. All patients were initially treated with steroids. The study outcomes were: steroid responsiveness, prevalence of total remission, progression to chronic renal failure and need of renal replacement therapy due to end-stage renal disease (ESRD). Results: Initial serum creatinine level was 24% higher among patients with FSGS (p = 0.02), and proteinuria levels were 36% higher in MCD (p < 0.001). Patients with MCD were sensitive to steroid therapy in 80% of the cases, with total remission in 74%, while patients with FSGS were sensitive in 58% (p = 0.01), with total remission in 30% (p = 0.002). Patients with FSGS had an acute renal failure prevalence of 39% (vs. 12%, p = 0.013) and ESRD of 10% (vs. 0%, p < 0.001). Steroid responsiveness reduced in 83% the risk of ESRD (p < 0.001), while total remission was associated to a reduction in risk of 89% (p < 0.001). Conclusion: A positive response to steroid therapy was the most important factor related with preservation of renal function and FSGS was related with less steroid responsiveness.

Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease / Síndrome nefrótica idiopática córtico-resistente na criança: evolução e fatores de risco para falência renal crônica

INTRODUTION: Steroid resistant idiopathic nephrotic syndrome (SRINS) in children is one of the leading causes of progression to chronic kidney disease stage V (CKD V)/end stage renal disease (ESRD). OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy of immunosuppressive drugs (IS) and to identify risk factors for progression to ESRD in this population. METHODS: Clinical and biochemical variables at presentation, early or late steroid resistance, histological pattern and response to cyclosporine A (CsA) and cyclophosfamide (CP) were reviewed in 136 children with SRINS. The analyzed outcome was the progression to ESRD. Univariate as well as multivariate Cox-regression analysis were performed. RESULTS: Median age at onset was 5.54 years (0.67-17.22) and median follow up time was 6.1 years (0.25-30.83). Early steroid-resistance was observed in 114 patients and late resistance in 22. Resistance to CP and CsA was 62.9% and 35% respectively. At last follow-up 57 patients reached ESRD. The renal survival rate was 71.5%, 58.4%, 55.3%, 35.6% and 28.5% at 5, 10, 15, 20 and 25 years respectively. Univariate analysis demonstrated that older age at onset, early steroid-resistance, hematuria, hypertension, focal segmental glomerulosclerosis (FSGS), and resistance to IS were risk factors for ESRD. The Cox proportional-hazards regression identified CsAresistance and FSGS as the only predictors for ESRD. CONCLUSION: Our findings showed that CsA-resistance and FSGS were risk factors for ESRD.

INTRODUÇÃO: A síndrome nefrótica idiopática córtico-resistente (SNICR) é uma das principais causas de falência renal crônica (FRC)/doença renal crônica estadio V (DRC V) em crianças. Objetivo: Avaliar a resposta aos imunossupressores e identificar fatores de risco para a FRC. MÉTODOS: Variáveis clínicas e bioquímicas na apresentação, resistência inicial ou tardia aos esteroides, lesão histológica e resposta à ciclosporina A (CsA) e à ciclofosfamida (CF) foram analisados retrospectivamente em 136 crianças com SNICR. O desfecho analisado foi a progressão para FRC e os métodos utilizados foram a análise univariada e a regressão multivariada de Cox. RESULTADOS: A idade mediana do início da doença foi de 5,54 anos (0,67-17,22) e o tempo mediano de seguimento foi de 6,1 anos (0,25-30,83). Resistência inicial aos esteroides ocorreu em 114 pacientes e tardia em 22. Resistência à CF e à CsA ocorreu em 62,9% e 35% dos pacientes, respectivamente. FRC ocorreu em 57 pacientes. A sobrevida renal foi de 71,5%, 58,4%, 55,3%, 35,6% e 28,5% aos 5, 10, 15, 20 e 25 anos, respectivamente. A análise univariada demonstrou que a idade maior ao início da doença, resistência inicial aos esteroides, hematúria, hipertensão, glomeruloesclerose segmentar e focal (GESF) e resistência aos imunossupressores foram fatores de risco para FRC. A regressão de Cox identificou a resistência à CsA e a GESF como os únicos fatores preditores para FRC. CONCLUSÃO: Nossos achados mostraram que a resistência à ciclosporina e a presença de GESF foram fatores de risco para a progressão para DRCV.

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.

Pharmacokinetics of cyclosporin: a microemulsion in children with idiopathic nephrotic syndrome

OBJECTIVE: We present a prospective study of a microemulsion of cyclosporin to treat idiopathic nephrotic syndrome in ten children with normal renal function who presented cyclosporin trough levels between 50 and 150 ng/ml and achieved complete remission with cyclosporin. To compare the pharmacokinetic parameters of cyclosporin in idiopathic nephrotic syndrome during remission and relapse of the nephrotic state. METHOD: The pharmacokinetic profile of cyclosporin was evaluated with the 12-hour area under the timeconcentration curve (auc0-12) using seven time-point samples. This procedure was performed on each patient during remission and relapse with the same cyclosporin dose in mg/kg/day. The 12-hour area under the timeconcentration curve was calculated using the trapezoidal rule. All of the pharmacokinetic parameters and the resumed 4-hour area under the time-concentration curve were correlated with the 12-hour area under the timeconcentration curve. ClinicalTrials.gov:NCT01616446. RESULTS: There were no significant differences in any parameters of the pharmacokinetic of cyclosporin during remission and relapse, even when the data were normalized by dose. The best correlation with the 12-hour area under the time-concentration curve was the 4-hour area under the time-concentration curve on remission and relapse of the disease, followed by the 2-hour level after cyclosporin (c2) dosing in both disease states. CONCLUSIONS: These data indicate that the same parameters used for cyclosporin therapeutic monitoring estimated during the nephrotic state can also be used during remission. Larger controlled studies are needed to confirm these findings.

Effects of steroid treatment on bone mineral metabolism in children with Glucocorticoid-sensitive Nephrotic Syndrome / Efectos del tratamiento de esteroides sobre el metabolismo mineral del hueso en niños con Síndrome Nefrótico Sensible a los Glucocorticoides

Glucocorticoids have been used in nephrotic syndrome (NS) treatment for many years. In this study, we aimed to evaluate the effect of steroids on bone mineralization in children with glucocorticoid-sensitive nephrotic syndrome (GSNS). Twenty children who were first diagnosed as GSNS received glucocorticoid therapy for four months. Before treatment, at the 4th and 12th week of initial therapy, bone mineral density (BMD) and levels of the markers for bone turnover were evaluated. At the 4th and 12th week of treatment, mean serum calcium (Ca) and osteocalcin levels were found to be significantly lower than those at the beginning ofthe therapy. Mean serum total alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and urine calcium creatinine ratio (Ca/Cr), urinary deoxypyridinoline levels were significantly increased in comparison to the beginning of therapy. There was no significant relationship between serum levels of phosphate and parathyroid hormone (PTH) at the beginning of treatment and at the 4th and 12th week of treatment. Mean value of BMD was significantly lower at the 4th and 12th week of treatment than that at the beginning of the therapy. In conclusion, bone mineralization was negatively affected by steroid treatment in children with NS. These children should undergo regular BMD evaluation, and an appropriate therapeutic approach should be planned.

Por muchos años se han venido usando glucocorticoides en el tratamiento del síndrome nefrótico (SN). Este estudio se encamina a evaluar el efecto de los esteroides sobre la mineralización ósea en niños con síndrome nefrótico sensible a los glucocorticoides (SNSG). Veinte niños que fueron diagnosticados primeramente con SNSG, recibieron terapia con glucocorticoides durante cuatro meses. Antes del tratamiento, en las semanas 4 y 12 de la terapia inicial, se evaluaron la densidad mineral ósea (DMO) y los niveles de los marcadores del recambio óseo. En el tratamiento de las semanas 4 y 12, se halló que el calcio (Ca) sérico promedio y los niveles de osteocalcina eran significativamente más bajos que los existentes a comienzos de la terapia. Los niveles de fosfatasa alcalina sérica total promedio, fosfatasa alcalina (t-ALP), fosfatasa alcalina especifica ósea media (b-ALP), la relación calcio/creatinina en la orina (Ca/Cr), y los niveles de deoxipiridinolina urinaria, aumentaron significativamente en comparación con los existentes al comienzo de la terapia. No hubo relación significativa alguna entre los niveles séricos de fosfato y hormona paratiroidea (PTH) ni al principio del tratamiento ni en las semanas 4 y 12 de tratamiento. El valor promedio de la DMO fue significativamente más bajo en las semanas 4 y 12 de tratamiento que al principio de la terapia. En conclusión, la mineralización del hueso fue afectada negativamente por el tratamiento con esteroides en los niños con SN. Estos niños deben tener una evaluación regular de DMO, para lo cual es necesario planear un enfoque terapéutico apropiado.

Nephrotic syndrome associated with toxoplasmosis: report of seven cases / Síndrome nefrótica associada à toxoplasmose: relato de sete casos

The concomitance of nephrotic syndrome and acute infection by Toxoplasma gondii is a rare occurrence in humans. In this paper seven cases of children, ranging from 11 months to 7 year-old, with concomitant nephrotic syndrome and asymptomatic acute T. gondii infection are reported. In one of those patients only the administration of anti-Toxoplasma therapy was enough to control the clinical and laboratory manifestations of the disease. In the other patients it was necessary to introduce corticosteroids or other immunosuppressant drugs. Three patients had complete clinical and laboratory improvement and the remaining showed only a partial response.

Ocorrência concomitante de síndrome nefrótica e infecção aguda por Toxoplasma gondii em seres humanos é situação pouco frequente. No presente trabalho são relatados sete casos de crianças, com idade variável entre 11 meses e sete anos, que apresentavam síndrome nefrótica e infecção aguda por T. gondii assintomática. Em um dos pacientes o tratamento específico anti-Toxoplasma foi suficiente para controlar clínica e laboratorialmente as manifestações da doença. Nos demais foi preciso administrar corticosteróides ou outras drogas imunossupressoras. Após introdução desse esquema três pacientes apresentaram remissão completa dos sintomas; os demais apenas remissão parcial.