Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model / Efeito do octreotide no estresse oxidativo em eritrócitos e no tecido renal no modelo de síndrome nefrótica experimental induzida por adriamicina

Abstract Introduction: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. Methods: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. Results: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. Conclusions: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

Resumo Introdução: Síndrome nefrótica (SN) é uma das causas de doença renal em estágio terminal. É importante elucidar a patogênese e oferecer novas opções de tratamento. Estresse oxidativo pode desencadear a patogênese sistemicamente ou isoladamente nos rins. O octreotide (OCT) tem efeitos antioxidantes benéficos. Nosso objetivo foi investigar a fonte de estresse oxidativo e efeito do OCT no modelo experimental de SN. Métodos: Dividimos 24 ratos albinos Wistar não urêmicos em 3 grupos. Grupo controle, 2 mL de solução salina intramuscular (im); grupo SN, adriamicina 5 mg/kg intravenosa (iv); grupo tratamento SN, adriamicina 5 mg/kg (iv) e OCT 200 mcg/kg (im) foram administrados no início do estudo (Dia 0). Aos 21 dias, mediram-se os níveis de creatinina e proteína em amostras de urina de 24 horas. Mediu-se a catalase (CAT) eritrocitária e renal e a substância reativa ao ácido tiobarbitúrico (TBARS). Avaliou-se também histologia renal. Resultados: Não houve diferença significativa entre os três grupos em termos de CAT e TBARS em eritrócitos. O nível de CAT renal foi menor no grupo SN e significativamente menor que no grupo controle. No grupo tratamento, o nível de CAT aumentou significativamente em comparação com o grupo SN. Quanto à histologia renal, as avaliações tubular e intersticial foram semelhantes em todos os grupos. O escore glomerular foi significativamente maior no grupo SN em comparação com o grupo controle e diminuiu significativamente no grupo de tratamento em comparação com o grupo SN. Conclusões: Estresse oxidativo na SN pode ser devido à diminuição do mecanismo de proteção antioxidante nos rins. O octreotide melhora níveis de antioxidantes e histologia do tecido renal e pode ser uma opção de tratamento.

Catéter peritoneal tunelizado para el manejo de ascitis refractaria en paciente con síndrome nefrótico

Introducción: la ascitis refractaria puede ser una complicación frecuente en el síndrome nefrótico (SN), existen casos reportados del uso de un catéter tunelizado de diálisis peritoneal en pacientes con cirrosis o neoplasias abdominales. Se presenta el caso de un paciente con SN en quién se utilizó un catéter para diálisis peritoneal (DP) para manejo de la ascitis refractaria. Objetivo: mostrar que el catéter peritoneal puede ser considerado como una alternativa para el manejo de la ascitis refractaria en pacientes con síndrome nefrótico. Presentación del caso: paciente varón de 19 años, sin antecedentes patológicos, cursó con edema progresivo y alteración de la función renal. Se evidenció síndrome nefrótico con anasarca y evolucionó con empeoramiento de la función renal ingresando a hemodiálisis de soporte. Se realizó biopsia renal: podocitopatía, glomerulopatía colapsante. Se inició tratamiento con corticoterapia, mejorando la función renal hasta suspender la hemodiálisis, pero presentó ascitis refractaria al tratamiento médico, por lo que se realizó paracentesis evacuatoria en reiteradas ocasiones. Se decidió colocación de catéter peritoneal tunelizado para el manejo de la ascitis refractaria. La ascitis fue disminuyendo progresivamente hasta el retiro del catéter peritoneal. Discusión y conclusión: el uso de catéter tunelizado de diálisis peritoneal es una opción de manejo efectiva en casos de síndrome nefrótico con ascitis refractaria.

Introduction: Refractory ascites can be a frequent complication in nephrotic syndrome (NS), there are reported cases of the use of a tunneled peritoneal dialysis catheter in patients with cirrhosis or abdominal neoplasms. The case of a patient with NS is presented in whom used a peritoneal dialysis (PD) catheter to manage refractory ascites. Purpose: To show that the peritoneal catheter can be considered as an alternative for the management of refractory ascites in patients with nephrotic syndrome. Presentation of the case: A 19-year-old male patient, with no pathological history, presented progressive edema and impaired renal function. Nephrotic syndrome with anasarca was evidenced, and it evolved with worsening renal function, entering supportive hemodialysis. Renal biopsy was performed: podocytopathy, collapsing glomerulopathy. Corticosteroid treatment was started, improving renal function until hemodialysis was discontinued, but he presented ascites refractory to medical treatment, for which evacuatory paracentesis was performed repeatedly. It was decided to place a tunneled peritoneal catheter for the management of refractory ascites. Ascites gradually decreased until the peritoneal catheter was removed. Discussion and conclusion: The use of a tunneled peritoneal dialysis catheter is an effective management option in cases of nephrotic syndrome with refractory ascites.

Glomerular parietal epithelial expression of CD44 in minimal change nephrotic syndrome and primary focal segmental glomerulosclerosis: A clinico-pathological study

Introduction: Minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) are the two common causes of nephrotic syndrome (NS) in both children and adults with overlapping clinical features, but with distinct prognostic and therapeutic implications. The distinction between these relies entirely on histopathology, which can sometimes be difficult. CD44 is expressed by activated parietal epithelial cells, plays a role in matrix deposition and thus in the pathogenesis of FSGS. Aims: To assess the expression of CD44 in MCNS and FSGS and to evaluate its association with the known clinical and histopathological prognostic factors. Materials and Methods: Thirty cases each of MCNS and FSGS were studied. The clinical, laboratory, histopathological, and CD 44 immunohistochemical data were recorded. The findings were analyzed and correlated. A P value of < 0.05 was considered statistically significant. Results: Statistical association was noted between CD44 positivity and serum creatinine (p = 0.031), estimated glomerular filtration rate (p = 0.040), segmental sclerosis (p < 0.001), tubular atrophy (p = 0.027), interstitial fibrosis (p = 0.027), and histological diagnosis (p < 0.001). The sensitivity, specificity, positive predictive, and negative predictive values were 90%, 76.67%, 79.41% and 88.46%, respectively. Conclusions: CD44 immunostain can effectively distinguish MCNS from FSGS. The congruent results of CD44 positivity with known prognostic factors support the possibility of using the CD44 marker as a predictive tool in selecting high-risk patients and offering appropriate therapeutic measures.

Rituximab therapy for childhood onset idiopathic nephrotic syndrome: experience of a Portuguese tertiary center / Terapia com Rituximabe para síndrome nefrótica idiopática de início na infância: experiência de um centro terciário português

ABSTRACT Introduction: Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. Method: A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. Results: Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. Conclusion: Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.

Resumo Introdução: Rituximabe (RTX) é uma opção terapêutica na síndrome nefrótica (SN) idiopática pediátrica de difícil tratamento. Visamos avaliar eficácia e segurança do uso de RTX nestes pacientes. Método: Realizou-se estudo retrospectivo de todos os pacientes com SN idiopática tratados com RTX, em uma unidade de nefrologia pediátrica de um hospital terciário. Dados demográficos, antropométricos, clínicos e analíticos foram coletados antes do tratamento e aos 6, 12 e 24 meses. Resultados: Incluímos 16 pacientes (11 do sexo masculino), com idade mediana (percentil 25-75, P25-P75) de 2 (2,0-2,8) anos ao diagnóstico. Quinze eram sensíveis a esteroides, e 1 resistente a esteroides e sensível à ciclosporina.A idade mediana na administração do RTX foi 10 (6,3-14,0) anos. Durante um tempo mediano de acompanhamento de 2,5(1,0-3,0) anos, 6 (37,5%) pacientes alcançaram remissão parcial e 7 (43,8%) não tiveram recidivas e não estavam tomando imunossupressor no acompanhamento aos 24 meses. Quanto às complicações,1 paciente apresentou hipogamaglobulinemia persistente. Comparado ao período de12 meses anterior ao RTX, houve diminuição no número mediano de recidivas em 6 e 12 meses [3 (3,0-4,0) vs 0 (0-0,8) e 0,50 (0-1,0), respectivamente; p = 0,001] e na dose diária de esteroides (mg/kg/dia) aos 6, 12 e 24 meses [0,29 (0,15-0,67) >vs [0,10 (0,07-0,13); p = 0,001], [0,12 (0,05-0,22); p = 0,005] e [0,07 (0,04-0,18); p = 0,021], respectivamente. Houve também redução na mediana do escore z do IMC aos 24 meses [2,11 (0,45-3,70) vs 2,93 (2,01-3,98);p = 0,049]. Conclusões: Nossos resultados confirmam a eficácia e segurança do uso de RTX em SN idiopática pediátrica, destacando seus potenciais benefícios cardiometabólicos.

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study / Desfechos de crianças com síndrome nefrótica idiopática córtico-resistente: um estudo observacional de centro único

ABSTRACT Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

RESUMO Introdução: A síndrome nefrótica idiopática córtico-resistente (SNICR) apresenta desfechos variáveis em crianças. O objetivo principal deste estudo foi avaliar a taxa de remissão cumulativa. Os objetivos secundários foram avaliar fatores que afetam status de remissão, sobrevida da função renal e efeitos adversos de medicamentos. Métodos: Foram incluídos 114 pacientes com SNCR. Utilizou-se protocolo de tratamento baseado em inibidores de calcineurina juntamente com prednisolona e inibidor da enzima conversora de angiotensina. Os pacientes foram acompanhados durante 5 anos. Resultados: A idade mediana foi 4,5 anos; 53,5% dos casos tinham entre 1 e 5 anos. 62 pacientes (54,4%) estavam em estágio inicial; 52 (45,6%) em estágio tardio da SNCR. A TFGecr mediana foi 83,5 mL/min/1,73 m2 na apresentação. Dos 110 pacientes, 63 (57,3%) alcançaram remissão [remissão completa 30 (27,3%), remissão parcial 33 (30%)], e 47 (42,7%) não apresentaram remissão. A sobrevida da função renal foi 87,3%; 14 casos (12,7%) progrediram para DRC (G3-8, G4-3, G5-1, G5D-2). A duração mediana do acompanhamento foi 36 meses (IIQ 24, 60). Idade no início, ciclosporina/tacrolimus, TFGecr e histopatologia (DLM/GESF) não afetaram a remissão. Igualmente, status de remissão, além da idade no início, protocolo de medicamentos e histopatologia não afetaram significativamente a função renal por 5 anos. Observou-se hipertensão, fácies cushingoide, baixa estatura, catarata e obesidade em 37,7; 29,8; 25,5; 17,5; e 0,7% dos casos, respectivamente. Conclusão: Aproximadamente metade dos casos alcançou remissão. Idade no início, uso de ciclosporina/tacrolimus e lesão histopatológica não afetaram o status de remissão nem a sobrevida da função renal a curto prazo na SNICR.

The challenges of the pandemic and the vaccination against covid-19 in pediatric patients with kidney disease / Os desafios da pandemia e a vacinação covid-19 na população pediátrica com doenças renais

ABSTRACT The covid-19 vaccine confers direct protection and reduces transmission rates of the virus and new variants. Vaccines from Pfizer/BioNTech and CoronaVac have been cleared for children in Brazil. They are safe, effective, and immunogenic. There are no known complications associated with the use of steroids or vaccines in pediatric patients with covid-19 and nephrotic syndrome. With or without immunosuppression, these patients are not at increased risk of severe covid-19, and steroids are safe for them. A milder form of covid-19 occurs in patients with chronic kidney disease without the need for hospitalization. The vaccine response may be reduced and/or the duration of antibodies after vaccination may be shorter than in the general population. However, considering risk of exposure, vaccination against covid-19 is recommended. It is believed that patients with hemolytic-uremic syndrome are at higher risk of severe covid-19. Vaccination is recommended, although specific data on the safety and efficacy of the covid-19 vaccine are limited. There is agreement that the benefits of induced immunity outweigh the risks of immunization. Vaccination against covid-19 is recommended for children and adolescents needing kidney transplantation or who have undergone transplantation. These patients present decreased immune response after vaccination, but immunization is recommended because the benefits outweigh the risks of vaccination. Current recommendations in Brazil stipulate the use of the messenger RNA vaccine. This paper aims to provide pediatric nephrologists with the latest knowledge about vaccination against covid-19 for children with kidney disease.

Resumo A vacina covid-19 confere proteção direta, reduz as taxas de transmissão do vírus e de novas variantes. No Brasil, estão liberadas para a população pediátrica as vacinas Pfizer/BioNTech e a CoronaVac, ambas seguras, eficazes e imunogênicas. Pacientes pediátricos com síndrome nefrótica e covid-19 têm curso clínico regular sem complicações relacionadas ao uso de esteroides ou vacinas. Esses pacientes, com ou sem imunossupressão, não apresentam maior risco de covid-19 grave e o tratamento com esteroides é seguro. Os pacientes com doença renal crônica têm covid-19 mais leve, sem necessidade de hospitalização. A resposta vacinal pode ser reduzida e/ou a duração dos anticorpos pós-vacinação pode ser menor do que na população geral. Entretanto, a vacina covid-19 está recomendada, considerando o risco de exposição. Acredita-se que pacientes com síndrome hemolítico-urêmica teriam maior risco de covid-19 grave. A vacina é recomendada, embora dados específicos sobre segurança e eficácia da vacina covid-19 sejam limitados. Há concordância que os benefícios da imunidade induzida superam quaisquer riscos da imunização. A vacina covid-19 é recomendada para crianças e adolescentes candidatos ao transplante renal ou já transplantados. Esses pacientes têm resposta imunológica reduzida após a vacina, entretanto ela é recomendada porque os benefícios superam qualquer risco dessa vacinação. A recomendação atual no Brasil é a vacina de tecnologia RNA mensageiro. O objetivo deste documento é levar aos nefrologistas pediátricos os conhecimentos mais recentes sobre a vacinação contra contra-19 em crianças com doenças renais.

AL Amyloidosis with Polycythemia, Leucocytosis and Thrombocytosis : A Case Report

A young lady presented to us with clinical and biochemical evidence of Nephrotic Syndrome. Her laboratory investigations also revealed Erythrocytosis, Leucocytosis and Thrombocytosis. A renal biopsy revealed a diagnosis of Amyloidosis which was further characterized as AL amyloidosis with further investigations (kappa chain monoclonal gammopathy). She was started with appropriate therapy and she showed significant decline in her monoclonal Proteins on follow up. Her Erythrocytosis, Leucocytosis and Thrombocytosis also normalized with the decline in the levels of monoclonal light chains. We postulate a link between the monoclonal protein associated growth factors and inflammatory markers which were responsible for this unique association between AL Amyloidosis and tri-lineage hematopoietic cell proliferation.

Proteinuria y síndrome nefrótico / Proteinuria and Nephrotic Syndrome

Introducción: El síndrome nefrótico es una patología que afecta el complejo glomerular del riñón, se caracteriza por una proteinuria mayor 3500 mg/d. De acuerdo a la respuesta de los esteroides se puede clasificar en síndrome nefrótico en esteroide resistente o esteroide sensible. Objetivo: Determinar la relación que existe entre la proteinuria y las variantes del síndrome nefrótico en adultos. Métodos: Se realizó un estudio descriptivo, retrospectivo, tipo serie de casos, con una población de 28 pacientes. Se recolectaron y se procesaron los datos a través del software Epi-Info 7,2TM; la frecuencia simple, la media estadística, prueba t de Student, y el coeficiente de correlación de Pearson. Resultados: En el análisis combinatorio de los fármacos adyuvantes para síndrome nefrótico, el grupo que utilizó antiproteinúricos pero no estatinas, demostró una diferencia estadísticamente significativa entre la proteinuria postratamiento media del grupo de síndrome nefrótico esteroideo resistente (6202 mg/d) vs síndrome nefrótico esteroideo sensible (65,9 mg/d) (valor de p 0,418). Existe una correlación negativa entre los niveles proteinuria postratamiento y el nivel de albúmina sérica postratamiento (r = - 0,7 valor de p < 0,00001). Conclusiones: Se demostró la ausencia de asociación entre la proteinuria inicial y las variantes de síndrome nefrótico esteroide sensible y esteroide resistente (valor de p = 0,8)(AU)

Introduction: Nephrotic syndrome is a pathology that affects the glomerular complex of the kidney, characterized by proteinuria greater than 3500 mg/d. According to the response to steroids, nephrotic syndrome can be classified as steroid-resistant or steroid-sensitive. Objective: To determine the relationship between proteinuria and the variants of the nephrotic syndrome in adults. Methods: A descriptive, retrospective, case series type study was carried out with a population of 28 patients. The data was collected and processed through Epi-Info 7.2TM software; simple frequency, statistical mean, student's t-test, and Pearson's correlation coefficient. Results: The statistically significant difference was obtained in the antiproteinuric and non-statin group, between the mean post-treatment proteinuria of the steroid resistant nephrotic syndrome group (6202 mg/d) in comparison to steroid sensitive nephrotic syndrome (65.9 mg/d) (p value 0.0418). There is negative correlation between post-treatment proteinuria levels and post-treatment serum albumin level (r= -0.7 p value <0.00001). Conclusions: The absence of association between initial proteinuria and steroid-sensitive and steroid-resistant variants of nephrotic syndrome was demonstrated (p value=0.8)(AU)

Application and effect of self-management ability-oriented focus solution model in children with nephrotic syndrome / 中国实用护理杂志

Objective:To explore the application effect of self-management ability-oriented focus solution model in children with nephrotic syndrome, and to observe the optimal value of self-management and coping style for children with nephrotic syndrome.Methods:This was a class trial study. A total of 96 children with nephrotic syndrome in Children′s Hospital of Nanjing Medical Universityfrom March 2018 to April 2020 were selected as the research object by convenient sampling method, 48 cases of children from March 2018 to February 2019 for the control group, using conventional psychological counseling, 48 cases of children from March 2019 to April 2020 for the observation group, with self management ability oriented focus solution mode. The self-management and response changes after 2 months of intervention were compared between the two groups.Results:The scores of treatment management, psychological management, diet management and social activity inself-management behavior after intervention were (32.79 ± 2.94), (19.43 ± 1.76), (22.34 ± 1.64), (39.79 ± 2.97) points in the observation group, and (27.42 ± 3.25), (16.79 ± 1.52), (18.46 ± 1.58), (35.28 ± 2.64) points in the control group, the differences were statistically significant ( t values were 7.86-11.80, all P<0.05). The scores of escape, acceptance, negative emotional response, and total score after intervention were (12.41 ± 2.15), (20.41 ± 1.85), (25.89 ± 1.68), (99.37 ± 8.94) points in the observation group, and (11.22 ± 3.04), (19.30 ± 2.09), (24.80 ± 2.10), (95.12 ± 9.02) points in the control group, the differences were statistically significant ( t values were 2.21-2.81, all P<0.05). Conclusions:The self-management-oriented focus solution model for children with nephrotic syndrome can promote the improvement of self-management behavior, and promote the improvement of coping methods in terms of avoidance, acceptance and negative emotional response, which has reference and complementary value for the care of children with nephrotic syndrome.

Advances in kidney transplantation for children with hereditary nephrotic syndrome / 中华实用儿科临床杂志

Hereditary nephrotic syndrome (NS) has a high risk of progression to end-stage renal disease.Renal transplantation is the optimal renal replacement therapy.The specificity of hereditary NS in the field of kidney transplantation has not been systematically illustrated yet.Due to the large amount of hormone uses before operation, the difference of immunosuppressive therapy in patients with hereditary NS should be well concerned, including the selection of immune induction and maintenance regimens.Relatives of patients with hereditary NS should undergo genetic testing before living donor transplantation, and donors are qualified only after a thorough risk assessment and informed consent.Post-transplant recurrence of hereditary NS is rare, with an acceptable response to plasma exchange.This review aims to describe the characteristics of hereditary NS in children in the field of kidney transplantation, thus providing guidance for kidney transplantation for hereditary NS.

Significance of PLCE1 gene polymorphism detection in children with primary nephrotic syndrome in Guangxi Zhuang Autonomous Region / 中华实用儿科临床杂志

Objective:To investigate the correlation between the single nucleotide polymorphism (SNP) of the PLCE1 gene and children with primary nephrotic syndrome (PNS) in Guangxi Zhuang Autonomous Region. Methods:This study was a retrospective study, a case-control study was used to select 155 cases of PNS in Guangxi Zhuang children attending the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2017 to January 2021 (PNS group), and 100 healthy Guangxi Zhuang children who were physically examined during the same period (healthy control group). Genotyping of PLCE1 SNP rs3765524, and rs2274223 were performed using the second-generation gene sequencing technology, and their correlation with the development of PNS was analyzed. Logistic regression analysis was used for correlation analysis, and Chi- square test or Fisher′ s exact probability method was used for comparison between groups. Results:(1)Compared with the healthy control group, PLCE1 rs3765524 was correlated with the risk of PNS in children of PNS group, and the TT genotype may reduce the risk of PNS in the co-dominant model ( OR=0.435, 95% CI: 0.238-0.794, P=0.007). There were no significant differences in the genotype of PLCE1 rs2274223 and the frequency of allele distribution between PNS group and healthy control group (all P>0.05). (2) A strong linkage disequilibrium existed at PLCE1 SNP rs3765524 and rs2274223.(3) There were no significant differences in the frequency of the distribution of haplotypes AC, AT and GT between PNS group and healthy control group (all P>0.05). Conclusions:PLCE1 SNP rs3765524 is correlated with the risk of PNS in children in Guangxi Zhuang Autonomous Region, and the TT genotype may be a protective factor for PNS in children in Guangxi Zhuang Autonomous Region.

Progress on the mechanism of rituximab in the treatment of primary nephrotic syndrome / 国际儿科学杂志

In recent years, rituximab(RTX) has been increasingly used in the treatment of refractory primary nephrotic syndrome in children, and has achieved positive effects.Experimental evidence suggests that RTX may exert its therapeutic effects by directly acting on B cells and T cells, interfering with the interaction between B cells and T cells, and directly protecting podocytes.However, the number of studies on the mechanism of RTX in the treatment of nephrotic syndrome is limited and there is no definitive evidence, so there is no consensus in the academic community.This article summarizes experimental research results and reasonable speculations put forward by many scholars in recent years, and summarizes the significance of the research on the mechanism of RTX and the existing research gaps in this field, in order to provide theoretical guidance for the clinical application of RTX.

Therapeutic Effect of Canagliflozin on Nephrotic Syndrome and Its Ultrasonic Evaluation / 中山大学学报(医学科学版)

ObjectiveTo investigate the therapeutic effect of antidiabetic drug canagliflozin （CGLZ） on adriamycin-induced nephrotic syndrome （NS） in rats， and the evaluation of contrast-enhanced ultrasound （CEUS） combined with color Doppler flow imaging （CDFI） during the treatment. MethodsA total of 56 male SD rats were randomly divided into normal group （NG）， model group （MG）， prednisone （PAT） group （PG）， low-dose single CGLZ group （LSCG）， high-dose single CGLZ group （HSCG）， low-dose CGLZ + PAT group （LUCG） and high-dose CGLZ + PAT group （HUCG）， with 8 rats in each group. The NS model in rats was induced by injecting adriamycin twice into the tail vein， and then the NS rats were treated by intragastric administration daily for 6 weeks with reference of PAT. Twenty-four hour urine total protein （24 h-UTP） was assessed one day before the start of oral administration and at the end of 2， 4 and 6 weeks after oral administration， respectively. CDFI and CEUS were performed on the right renal artery at the end of 6 weeks after oral administration， and the blood of abdominal aorta was taken for serological test the next day. ResultsCompared with those detection index of NG rats， the 24-hour UTP of MG rats increased （P＜0.01）， the serum ALB decreased and TG， TC， LDL increased （P＜0.01）， and CDFI shows that RRCT was thinner （P＜0.01） and the renal artery blood flow indicators RA-PI， RA-RI， RA-S/D all increased （P＜0.05）， and CEUS image shows that the TIC curve parameters TTP， AT， AUC all increased and DPI decrease in MG rats （P＜0.01）. After drug treatment， compared with those detection index of MG rats， 24 h-UTP decrease in LSCG after 2 weeks （P＜0.01）， and decrease significantly in all drug groups after 6 weeks （P＜0.01）； the serological test results show that the serum ALB in all CGLZ groups increased （P＜0.05）， TG decrease in LSCG （P＜0.01）， TC and LDL also decrease in LUCG after 6 weeks （P＜0.05）； CDFI shows that the RRCT thinning degree in all CGLZ is reduced （P＜0.01）， and the RA-PI in LSCG， RA-RI in PG， and RA-S/D in PG， LSCG， HSCG and LUCG rats all decreased （P＜0.05）； CEUS shows that the TTP， AT and AUC of renal TIC curve in drug treatment groups all decreased （P＜0.01）， and the DPI in PG， HSCG， LUCG and HUCG rats increased （P＜0.01）. ConclusionsCGLZ has the effect of treating NS， and the small dose is the best. CEUS combined with CDFI can be used to evaluate the renal morphology and hemodynamic changes of NS model rats before and after drug treatment， which is helpful to guide clinical application.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway / 中国天然药物

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

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.

Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Effect of intravenous albumin in patients with liver cirrhosis and nephrotic syndrome / 西安交通大学学报(医学版)

【Objective】 To investigate the outcomes of intravenous injection of human albumin (HA) in patients with both liver cirrhosis and nephrotic syndrome. 【Methods】 We retrospectively studied 101 liver cirrhosis patients with ascites and nephrotic syndrome treated in our hospital from January 2018 to November 2021. All the patients received oral diuretic and intravenous albumin therapy. Their baseline characteristics were collected and the changes in serum albumin and creatinine levels before and after treatment were evaluated. The patients with elevated albumin levels after treatment greater than the median value (1.8 g/L) were defined as response group. The rest of the patients were classified as the non-response group. And Logistic regression analysis was used to evaluate the relevant influencing factors for treatment response. 【Results】 All the patients’ symptoms of abdominal distension related to moderate to great ascites were clinically lessened at the end of treatment, and no case of acute kidney injury occurred during the treatment. Of them, 32 patients had repeated hospitalizations within six months after discharge. The serum albumin level was significantly increased after treatment [(26.5±5.9) g/L vs. (29.9±4.9) g/L, P<0.001] and there was no significant difference in serum creatinine before and after treatment [(111.9±118.4)μmol/L vs. (108.5±87.9)μmol/L, P=0.816]. Fifty-three patients were defined as treatment response group. The differences in characteristics including age, sex, etiology of cirrhosis, and proteinuria were not statistically significant. However, the serum creatinine level was significantly lower in the response group than in the non-response group [(84.1±51.2)μmol/L vs. (142.7±158.4)μmol/L, P=0.017\]. A similar trend of difference was observed with respect to urea nitrogen level \[(8.7±5.1)mmol/L vs. (11.8±9.1)mmol/L, P=0.039\]. Multivariate analyses demonstrated that the serum creatinine level was a risk factor for non-response to treatment (hazard ratio=1.025, 95% CI: 1.010-1.049, P=0.037). In addition, the correlation analysis showed that the baseline albumin levels were negatively correlated with hospital stay time (r=-0.340, P=0.001), daily HA usage (r=-0.546, P<0.001), and baseline proteinuria levels (r=-0.654, P<0.001), respectively. 【Conclusion】 Intravenous injection of HA in cirrhotic patients with nephrotic syndrome was safe and effective for the treatment of ascites. Kidney function affects serum albumin levels and response to treatment.

Long-term outcomes and influencing factors of idiopathic nephrotic syndrome in children / 中华肾脏病杂志

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.

Influencing factors of early non-remission of proteinuria in patients with idiopathic membranous nephropathy / 中华肾脏病杂志

Objective:To investigate the influencing factors of non-remission of proteinuria in patients with nephrotic syndrome (NS) and idiopathic membranous nephropathy (IMN).Methods:The study was a retrospective observational study. The clinical data of patients with NS who were diagnosed as IMN by renal biopsy and serum albumin recovered normal after six months of treatment were collected from Beijing Anzhen Hospital, Capital Medical University from June 1, 2010 to January 31, 2022. Patients were divided into proteinuria remission group and non-proteinuria remission group according to whether urinary protein < 3.5 g/24 h and decreased 50% from the onset. The differences of clinical and pathological characteristics between the two groups at baseline were compared. The logistic regression model was used to analyze the influencing factors of non-remission of proteinuria.Results:Ninety-five NS patients with renal pathology of IMN were included in this study, with age of 57(43, 65) years old and 50 males (52.6%). There were 75 patients in the proteinuria remission group and 20 patients in the non-proteinuria remission group. Compared with the proteinuria remission group, the non-proteinuria remission group had higher baseline body mass index [(26.83±4.03) kg/m 2vs. (24.68±3.97) m 2, t=-2.149, P=0.034] and proportion of overweight (85.0% vs. 58.7%, χ2=4.765, P=0.029), and larger waist circumference [88.5(85.3, 101.5) cm vs. 87.0(77.5, 92.0) cm, Z=2.362, P=0.018]. Renal pathological results showed that the proportions of diabetes nephropathy (10.0% vs. 0, P=0.043) and glomerular hypertrophy (45.0% vs. 20.0%, χ2=5.227, P=0.022) were higher, and the average diameter of hypertrophic glomeruli was longer [(197.96±6.37) μm vs. (193.51±8.50) μm, t=2.029, P=0.041] in the proteinuria remission group than those in the non-proteinuria remission group. Multivariate logistic regression analysis results showed that waist circumference was an independent influencing factor of non-proteinuria remission in patients with IMN under waist circumference > 90 cm in men and >85 cm in women ( OR=1.083, 95% CI 1.005-1.168, P=0.037). Conclusion:Abdominal obesity is an independent risk factor of non-remission of proteinuria in NS patients with IMN after early treatment.