Research Progress of Monogenic Mutation in the Pathogenesis of Steroid-Resistant Nephrotic Syndrome / 罕见病研究

Steroid-resistant nephrotic syndrome (SRNS) is the second cause of chronic kidney disease in children. The SRNS has high risk of rapid progression to end-stage renal disease. With the advancement of high-throughput sequencing technology, more than 70 monogenic mutation having the Mendelian inheritance patterns are identified to be associated with SRNS. Most of these genes are involved in podocyte function. Accurate diagnosis of monogenic mutation in SRNS patients helps with guiding clinical treatment protocols and genetic counseling, avoiding the excessive use of steroids/immunosuppressive therapy, and opening up possibilities for targeted therapies in SRNS patients. In this article, our research team summarizes and generalizes the molecular mechanisms, genetic testing, and specific treatment for the major types of monogenic mutations associated with SRNS.

Research Progress of Monogenic Mutation in the Pathogenesis of Steroid-Resistant Nephrotic Syndrome / 罕见病研究

Steroid-resistant nephrotic syndrome (SRNS) is the second cause of chronic kidney disease in children. The SRNS has high risk of rapid progression to end-stage renal disease. With the advancement of high-throughput sequencing technology, more than 70 monogenic mutation having the Mendelian inheritance patterns are identified to be associated with SRNS. Most of these genes are involved in podocyte function. Accurate diagnosis of monogenic mutation in SRNS patients helps with guiding clinical treatment protocols and genetic counseling, avoiding the excessive use of steroids/immunosuppressive therapy, and opening up possibilities for targeted therapies in SRNS patients. In this article, our research team summarizes and generalizes the molecular mechanisms, genetic testing, and specific treatment for the major types of monogenic mutations associated with SRNS.

Frecuencia de mutaciones encontradas en niños con enfermedad renal crónica por síndrome nefrótico cortico-resistente / Frequency of mutations found in children with chronic kidney disease due to steroid-resistant nephrotic syndrome

RESUMEN La enfermedad renal crónica en niños puede tener como etiología un grupo cuya causa genética, incluye las anomalías congénitas del riñón y las vías urinarias y las nefropatías hereditarias. Objetivo: Describir la frecuencia de mutaciones en niños con síndrome nefrótico corticoresistente (SNRE). Material y métodos: Estudio multicéntrico, tipo serie de casos, realizado en niños con SNRE, mediante el resultado de secuenciamiento directo de los genes; NPHS1, NPHS2, NPHP1 y WT1. Resultados: Se enrolaron 33 pacientes pediátricos con enfermedad renal crónica, 45,5% mujeres, edad promedio 13±7 años, 78,8% de raza mestiza, 24,2% consanguíneos, 60,6% se encontraban en hemodiálisis, 72,7% presentaban síndrome nefrótico cortico resistente y de ellos 8/24 (33,3%) presentó al menos una mutación en los genes; WT1, NPHS1, NPHP1y NPHS2 siendo la frecuencia de estas mutaciones de 37,5% (3/8), 25% (2/8), 25% (2/8) y 12,5% (1/8), respectivamente. Conclusiones: El 33,3% de los pacientes pediátricos con enfermedad renal crónica con síndrome nefrótico corticoresistente (SNRE) presentaron mutaciones, la más frecuente fue en el gen WT1.

SUMMARY Chronic kidney disease in children may be caused by a group of genetic abnormalities of the kidney, urinary tract and hereditary nephropathies. Objective: To report the frequency of mutations in children with steroid-resistant nephrotic syndrome (SRNS). Methods: A multicentric case series among children with SRNS identified through direct sequencing of NPHS1, NPHS2, NPHP1 and WT1 genes. Results: 33 children were enrolled; 45.5% were females; mean age was 13±7 years; 78.8% were mestizo: 24.2% consanguineous; 60.6% were receiving dialysis: 72.7% had SRNS and 8/24 (33.3%) of them presented at least one mutation to WT1, NPHS1, NPHP1 and NPHS2 genes. Corresponding values for these mutations were 37.5% (3/8), 25% (2/8), 25% (2/8) and 12.5% (1/8), respectively. Conclusions: 33% of pediatric patients with SRNS presented gene mutations, the most frequent of these mutations was WT1.

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.

Clinical features and pathological analysis of steroid resistant nephrotic syndrome in children in a single center / 中国综合临床

0bjective To analyze the clinical characteristics, pathological types, treatment and prognosis in children with steroid resistant nephrotic syndrome (SRNS) in Northwest China, in order to provide reference for the treatment of SRNS. Methods:The clinical data, renal pathological results, treatment plan and efficacy of 102 children diagnosed with SRNS in the Department of Nephrology, Xi'an Children's Hospital of Shaanxi Province from January 1st, 2018 to December thirty-first, 2020 were analyzed retrospectively. All children were divided into groups according to age, clinical classification, pathological type, treatment scheme and treatment outcome, and the risk factors affecting the prognosis of children with SRNS were discussed. The measurement datas conforming to normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Measurement datas that did not conform to normal distribution were represented by M ( Q1, Q3), and Kruskall-Wallis test was used for comparison between groups.Enumeration datas were compared by χ 2 test. Risk factors were analyzed by multiple factor Logistic regression analysis. Results:The median age of onset of 102 children with SRNS was 3.0 years. Focal segmental glomerulosclerosis (FSGS) accounted for 36.3% (37/102), minimal lesions accounted for 33.3% (34/102), and mesangial proliferative glomerulonephritis accounted for 23.5% (24/102). The prevalence rates of hypertension (35.1% (13/37)), 24-h urine protein quantification (130.5 (91.5, 159.6) mg/(kg·24 h) and renal insufficiency (21.6% (8/37)) in FSGS group were higher than those in non-FSGS group (13.8% (9/65), 65.8 (51.2,85.5) mg/(kg·24 h), 4.6% (3/65)). The differences between the two groups were statistically significant (statistical values were χ 2=6.32, Z=5.90, χ 2=7.09; P values were 0.012, <0.001, 0.008). Logistic multivariate regression analysis showed that the hypertension ( OR=4.055, 95% CI 1.178-3.962) and 24 hour urinary protein ( OR=1.036, 95% CI 1.020-1.053) were associated with the increased risk of FSGS ( P values were 0.026 and <0.001). ROC curve ananlysis showed that the optimal critical value of 24 hour urinary protein was 85.65 mg/(kg·24 h) in FSGS. After treatment, complete remission was 61.8%(63/102), partial remission was 14.7%(15/102), and no remission was 23.5%(24/102). By the end of follow-up the treatment effective rate in the small lesion group (94.1%(32/34)) was higher than that in the FSGS Group (51.3%(19/37)), and the difference between the two groups was statistically significant (χ 2=16.02, P<0.001). In the initial immunosuppressive treatment, the complete remission rate of hormone combined with calcineurin inhibitor group (77.1%(37/48)) was higher than that of hormone combined with cyclophosphamide Group (11.1%(3/27)). There was significant difference between the two groups ( Z=32.28, P<0.001). Conclusion:The most common pathological type in children with SRNS was FSGS, and the age of onset was generally small. The prognosis of patients with pathological type FSGS was the worst, and the prognosis of small lesions was better. Hypertension and 24-hour urinary protein quantification were the risk factors of FSGS. Calcineurin inhibitors were the first choice for the second-line immunosuppressants of SRNS in children.

Gene mutation and clinical analysis in children with steroid resistant nephrotic syndrome in a single center / 中国医师杂志

Objective:To analyze the gene mutation, clinical manifestations and prognosis of children with steroid resistant nephrotic syndrome (SRNS), and to provide reference for the treatment of hereditary SRNS in children.Methods:The clinical data of 29 patients with SRNS and whole exon sequencing (WES) diagnosed in Xi′an Children′s Hospital from January 1, 2018 to December 31, 2020 were retrospectively analyzed.Results:In 29 cases of SRNS with genetic testing, 10 cases (34.5%) were gene mutations, including 2 cases of congenital nephrotic syndrome. The onset age of the patients with gene mutation ranged from 0.1 to 10.7(4.06±3.73)years, and the median age of onset was 3.3 years. The clinical type was mainly nephritis (8/10), and the pathological type was mainly focal segmental glomerulosclerosis (FSGS) (5/7). The main mutant genes were NPHS1 (2 cases), NPHS2 (2 cases), WT1 (2 cases), SMARCAL1 (1 case), COQ8B (1 case), TRPC6 (1 case) and COL4A3 gene (1 case). The main types of genetic variation were missense mutations, and 6 (60%) cases were new mutations that had never been reported in the database containing human pathogenic mutations before. Compared with the non-gene mutation group, 24 hour urinary protein was higher [(177.92±164.59)mg/(kg·24 h) vs (84.99±40.79)mg/(kg·24 h)] in gene mutation group, with statistically significant difference ( P<0.05). In the gene mutation group, there were 2 cases of complete remission, including 1 case of complete remission treated with coenzyme Q10, 1 case of partial remission, and 8 cases of immunosuppression treatment, with an effective rate of 2/8, while in the non-gene mutation group, the effective rate of immunosuppression treatment was 17/19, with statistically significant difference in prognosis between the two groups ( P<0.05). Conclusions:The pathological type of children with hereditary SRNS is mainly FSGS, which are often ineffective to immunosuppressive therapy, poor prognosis and easy to progress to end-stage renal disease. Gene detection is of great significance for etiological diagnosis, treatment and prognosis evaluation in children with SRNS.

Case report of sphingosine phosphate lyase insufficiency syndrome / 中华实用儿科临床杂志

The data of a child with sphingosine phosphate lyase insufficiency syndrome (SPLIS) admitted to Children′s Hospital of Hebei Province on February 4, 2020 were retrospectively analyzed.The child had edema, complicated with ichthyosis, adrenal calcification, and hearing loss from the early infancy.Laboratory examination results suggested a low albumin level, hypercholesterolemia, a high proteinuria level, abnormal liver and renal functions, and hyponatremia.The child gave up treatment and died at home.Whole Exome Sequencing (WES) results showed two hete-rozygous mutations of SGPL1 gene (chr10: 72604336, c.134G>A, p.W45X; chr10: 72629563, c.719G>T, p.S240I). SPLIS is inherited in an autosomal recessive manner.It starts in infancy, and affects the kidney, skin, endocrine, nervous and immune systems.It is suggested that SPLIS patients should take genetic examination.Early diagnosis, appropriate intervention, and vitamin B 6 treatment may relieve some symptoms of SPLIS patients.Adeno-associated virus mediated SGPL1 gene replacement therapy can be a novel cure of SPLIS and is worthy of investigation.

Treatment progress of pediatric steroid-resistant nephrotic syndrome / 中华实用儿科临床杂志

Primary nephrotic syndrome (PNS) is one of the most common glomerular diseases in children.Steroid-resistant nephrotic syndrome (SRNS) is defined as no remission of nephrotic syndrome after daily Prednisone treatment at an adequate oral dose for 4 weeks, which is classified as idiopathic SRNS and inherited SRNS according to the presence or absence of monogenic disorder.At present, steroid combined with calcineurin inhibitor (CNI) is preferred to idiopathic SRNS, and 50%-70% of children can achieve complete or partial remission.A small proportion of children with idiopathic SRNS and the majority of inherited SRNS may be resistant to different immunosuppressive agents with two different mechanisms, including CNI.They, unfortunately, gradually progress to end-stage renal disease within 5-10 years.In this paper, the therapeutic advances and future prospects in pediatric SRNS are reviewed.

Schimke immune osseous dysplasia: a rare case report

Schimke immune-osseous dysplasia (SIOD) is primarily characterized by the combination of spondyloepiphyseal dysplasia (SED), unique clinical phenotype, immune complex nephropathy (focal segmental glomerulosclerosis) and progressive immune defects with T-cell immunodeficiency. SIOD is caused by mutations in SMARCAL1 gene. Here we report a case of a 6-year-old girl who presented to us with disproportionate short stature, short neck kyphoscoliosis, hyper pigmented macules and severe herpes zoster. On further evaluation, she had evidence of T cell deficiency and nephrotic range of proteinuria. Renal histopathology documented focal segmental glomerular sclerosis. Genetic analysis confirmed homozygous missense mutation of SMARCAL gene on exon 8 variant c1358G>c. On extensive literature survey, this is noted to be the first case of SIOD reported from India. These children need close surveillance to watch for infections and progressive renal failure and require special care during administration of certain drugs and live vaccines.

Relative safety of steroid sparing agents in frequently relapsing, steroid dependent and steroid resistant nephrotic syndrome in pediatric patients

Background: In patients with frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) and steroid resistant nephrotic syndrome (SRNS) steroids are either used for prolonged period of time or ineffective. To reduce the degree of steroid dependency and avoid steroid toxicity, several immunosuppressive steroid sparing agents (SPAs) have been proposed to treat these children. The present study tried to study the relative safety of most commonly steroid sparing agent in such children.Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.Results: A total 110 patients were screened, examined and enrolled. Levamisole, cyclophosphamide and MMF were commonly used SPAs. Of the two tertiary care hospitals, all the patients of FRNS and SDNS were started with levamisole and SRNS with cyclophosphamide in one set-up, while in the other hospital some SDNS patients were started with cyclophosphamide and SRNS with MMF but without clinically significant outcomes. In comparison with few minor adverse events in MMF group, some serious adverse events were documented in the both cyclophosphamide and levamisole groups.Conclusions: Levamisole being a very efficacious, safe and easily affordable drug, should be used as an initial first line SPA in treating FRNS and SDNS children. The side effect profiles of levamisole and MMF are much more patient friendly.

Comparison of clinical and lab profile between steroid sensitive and steroid resistant nephrotic syndrome at onset of disease and evaluating predictors for developing steroid resistance in nephrotic syndrome

Background: Nephrotic syndrome is a notable chronic disease in children. The objective of this study was to compare the clinical and lab profile between steroid sensitive nephrotic syndrome and steroid resistant nephrotic syndrome at the onset of disease. Certain parameters were tested if they could be significate predictors of developing steroid resistance at the onset of first episode of nephrotic syndrome.Methods: Retrospective observation study done children 1-12 years diagnosed with nephrotic syndrome in Sri Ramachandra Medical College and Hospital, Department of Paediatrics, Chennai. Sample size 150. Period of study Jan 2013- Dec 2015. Variables considered were age at onset, sex, parental consanguinity with essential lab parameters done at the onset of nephrotic syndrome proteinuria, pyuria, microscopic hematuria, urine protein creatinine ratio, serum creatinine, serum triglycerides and serum albumin. Children less than 1 year of age, cases with secondary causes of nephrotic syndrome and steroid dependant nephrotic syndrome, children with incomplete records were not included in this study. 150 cases who fulfilled the study criteria were included in this study.Results: 75 cases of steroid sensitive nephrotic syndrome (SSNS) were compared with an equal number of steroid resistant nephrotic syndrome (SRNS). 85 children had onset of disease before 3 years of age and majority had 3+ proteinuria and males predominated in both the groups. The overall consanguinity rates were higher among SRNS group. Triglyceride level >300 mg/dl predominated in SRNS group along with a higher severity of hypoalbuminemia when compared to SSNS group. None of the parameters tested were significant predictors of developing SRNS subsequently.Conclusions: Comparing steroid sensitive with steroid resistance nephrotic syndrome, no lab parameter could identify the risk of a child developing steroid resistance subsequently. This could be a field of interest in future studies that could predict the development of steroid resistance at the onset of first episode of nephrotic syndrome itself.

Application of rituximab in children with primary nephrotic syndrome / 医学研究生学报

Childhood primary nephrotic syndrome (PNS) is a challenging and persistent renal disorder. Corticosteroids is the first-line drug for the treatment of PNS. To reduce the side effects caused by the accumulation of corticosteroids dose and to maintain the remission state of the disease, immunosuppressants are applied to the treatment of PNS. However, many children with PNS still cannot get remission. Rituximab (RTX) is a novel immunosuppressive agent. In recent years, many studies have reported the treatment of PNS in children with RTX. This review analyzes the mechanism, course of treatment, dose, efficacy, and safety of RTX in the treatment of children with PNS.

A study to assess the prevalence of hypertension in children with nephrotic syndrome

Background: Hypertension is been one of the most common co morbidity of this disease. It was mostly attributed to sodium retention, which is a major clinical feature of nephrotic syndrome. These mechanisms likely have a role in the development of hypertension in nephrotic syndrome, where hypertension may be difficult to control, and provide new therapeutic options for the management of blood pressure in the setting of nephrotic syndrome. Objective of study the prevalence of hypertension in children with NS and also the number of antihypertensive required to control it.Method: A Retrospective study of the hospital records of 100 children diagnosed with nephrotic syndrome admitted to Pediatric and Nephrology Ward at YMCH was accessed.Results: In our study 35 (35%) of them were Infrequent relapse nephrotic syndrome (IFNS) and 35(35%) were' Frequent relapse nephrotic syndrome (FRNS) ,while 30 cases (30%) were First episode nephrotic syndrome (FENS). 65 cases were steroid sensitive, while 28 and 7 of them were steroid dependent and resistant respectively. Of the 100 study population 54 of them had hypertension while 46 of them did not develop it .Of the 54 hypertensive nephrotic syndrome children, 15 of them (28.%) required three anti hypertensives to control the pressure, while 19 (35%) and 20 (37%) required single and dual anti hypertensives respectively.Conclusion: Prevalence of hypertension is increasing among the children with nephrotic syndrome. Its more prevalent among the male then female FRNS, SRNS and SDNS are more prone to develop hypertension and also they needed two or more antihypertensives to control the hypertension, whereas hypertension in SSNS could be managed with single drug.

Clinical application of Tacrolimus to infant steroid-resistant nephrotic syndrome / 中华实用儿科临床杂志

Objective To analyze the peculiarity of infants steroid-resistant nephrotic syndrome (SRNS) and to assess the efficacy,side-effect and relapse of various of Tacrolimus prescribed in infants SRNS.Methods A total of 76 case of infant SRNS from August 2012 to August 2015 in Guangzhou Weman and Children's Medical Center grouped into oral Tacrolimus (TAC group),Methyprenisolone pulse therapy (MP group) and Methyprenisolong combined Cyclophosphamide(CTX) pulse therapy(MP + CTX group),were observed for 1 year,and the urine protein excretion,renal function (CCr),blood glucose (B G),urine retinal-binding-protein (URBP),lymphocyte count etc.were recorded and the situation of infection and relapse regularly were monitored regularly.The data were retrospectively analyzed by the statistical method.Results All SRNS children underwent kidney biopsy,and 36 cases of minimal change disease,32 cases of mesangial proliferative glomerulonephritis and 8 cases of focal segmental glome-rulosclerosis were contained in the patients.The pathological constituent ratios were not obviously different among these 3 groups.By 6-month follow-up,the complete remission ratio of TAC group was 63.64％,the total remission ratio was 95.45％,which were remarkably higher than those of MP group (26.09％,60.87％) and MP + CTX group (41.94％,74.19％);the urine protein excretion of TAC group [(7.8 ± 8.6) mg/(kg · d)] was distinctly lower than that of pretreatment and lower than that of MP group [(144.2 ± 118.3) mg/(kg · d)],and lower than that of MP + CTX group [(91.3 ± 87.4) mg/(kg · d)],and the difference was significant (F =22.69,P ＜ 0.05).The remission time of TAC group was about 2 months,that of other two groups was about 3 months.By 1-year follow-up,the lymphocyte counts including total T-cell (CD3 +),the helper T-cell (CD4 +) and the inhibited T-cell (CD8 +) of TAC group decreased obviously(all P ＜ 0.01),which were extremely lower than those of the M P group and MP + CTX group,and there were significant differences (all P ＜ 0.05).By 1-year follow-up,the person-time of infection existed superior to the other 2 groups,TAC group was compared with MP plus group,the rank sum was 348.5 (U =-3.69,P ＜ 0.01);compared with MP + CTX plus group,the rank sum was 369.5 (U =-4.18,P ＜ 0.01).During the observation the URBP of TAC group was distinctly higher than that of the MP group and the MP + CTX group [(13.77 ± 19.19) mg/L vs.(2.50 ± 1.77) mg/L,(2.06 ±3.63) mg/L],and the differences were significant(t =3.16,2.99,all P ＜0.05);the TAC group with BG and CCr maintained stably.Conclusions Tacrolimus shows its own advantages of more reliable effect and less side-effect in the infants with SRNS over MP therapy and MP combined CTX therapy,but it could not lessen the recurrence of the disease,and its long-term prognosis is still not very clear.

Efficacy of Tacrolimus in Treating Nephrotic Syndrome Children.

Nephrotic Syndrome (NS) is primarily a pediatric disorder, common in pre-schooler and school aged children. Immunosuppresive drugs like prednisolone, cyclophosphamide, cyclosporine A (CsA) has been the main treatment regimen in the management of Nephrotic syndrome. This has remain still the same therapy which is not satisfactory in the management of nephrotic syndrome children. The management of children with idiopathic Steroid-Resistant Nephrotic Syndrome (SRNS) and Steroid-Dependent Nephrotic Syndrome (SDNS) are difficult to treat but there is no consensus on the most appropriate treatment therapy. Pneumonia and urinary tract infection are also a challenge in the management of NS. The main goal of treatment is complete or partial remission of proteinuria, which is the most important marker of long term outcome. Calcineurin inhibitors (CNIs) are used to avoid steroid toxicity in children with NS. There are limited data on the relative efficacy and safety of calcineurin inhibitors and alkylating agents for NS in children. There are different immunosuppressant drugs but tacrolimus can be used in the treatment of childhood NS which is less expensive, have less cosmetic side effects and easy to administered. In this review we discuss the safety and efficacy of tacrolimus, a new drug which can be administered orally as a twice daily dose in the management of childhood NS. Some study suggests that application of tacrolimus can be a new turning point for the treatment of nephrotic syndrome.

Síndrome nefrótico idiopático: recomendaciones de la Rama de Nefrología de la Sociedad Chilena de Pediatría. Parte 2 / Idiopathic Nephrotic Syndrome: recommendations of the Nephrology Branch of the Chilean Society of Pediatrics. Part two

El síndrome nefrótico idiopático es la glomerulopatía más frecuente en la infancia, afecta a 1-3/100 mil niños menores de 16 años y se presenta con más frecuencia entre los 2 y 10 años. Su causa es desconocida, y la mayoría de las veces responde a corticoides, con buen pronóstico a largo plazo. El síndrome nefrótico corticorresistente representa un 10-20% de los síndromes nefróticos idiopáticos en pediatría. Tiene mal pronóstico, y su manejo constituye un desafío terapéutico significativo. La mitad de los pacientes evoluciona a insuficiencia renal crónica terminal en un plazo de 5 años, estando expuestos además a las complicaciones secundarias a un síndrome nefrótico persistente y a efectos adversos de la terapia inmunosupresora. El objetivo fundamental del tratamiento es conseguir una remisión completa, pero una remisión parcial se asocia a una mejor sobrevida renal que la falta de respuesta. Este documento surgió de un esfuerzo colaborativo de la Rama de Nefrología de la Sociedad Chilena de Pediatría con el objetivo de ayudar a los pediatras y nefrólogos infantiles en el tratamiento del síndrome nefrótico idiopático en pediatría. En esta segunda parte, se discute el manejo del síndrome nefrótico corticorresistente, así como de las terapias no específicas.

Idiopathic nephrotic syndrome is the most common glomerular disease in childhood, affecting 1 to 3 per 100,000 children under the age of 16. It most commonly occurs in ages between 2 and 10. Its cause is unknown, and its histology corresponds to minimal change disease in 90% of cases, or focal segmental glomerulosclerosis. Steroid-resistant nephrotic syndrome represents 10-20% of idiopathic nephrotic syndrome in pediatrics. It has a poor prognosis, and its management is a significant therapeutic challenge. Half of patients evolve to end-stage renal disease within 5 years, and are additionally exposed to complications secondary to persistent NS and to the adverse effects of immunosuppressive therapy. The primary goal of treatment is to achieve complete remission, but even a partial remission is associated with a better renal survival than the lack of response. This paper is the result of the collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with aims at helping pediatricians and pediatric nephrologists to treat pediatric idiopathic nephrotic syndrome. In this second part, handling of steroid-resistant nephrotic syndrome as well as nonspecific therapies are discussed.

Steroid-resistant nephrotic syndrome accompanied with irreversible leukoencephalopathy：one case report / 临床儿科杂志

Objectives To analyze the diagnosis and management of steroid-resistant nephrotic syndrome (SRNS) accompanied with irreversible leukoencephalopathy in children. Methods The clinical, laboratory and imaging data were retrospectively analyzed in a SRNS child accompanied with irreversible leukoencephalopathy. A literature review was performed. Results After clinical diagnosis of SRNS, glucocorticoid, immunosuppressant, and hemodialysis were administrated for 10 months. During the course of treatment, the seizures, visual problems, and hypertension were repeatedly occured. The cranial MRI showed bilateral occipital parietal lobe hyperintensity and right frontotemporal lobe hyperintensity on T2-weighted imaging and bilateral occipital parietal lobe hypointensity on T2-Flair imaging, which indicated that encephalomalacia was accompanied with gliosis. Conclusions A variety of reasons may induce leukoencephalopathy in children. The accompanied irreversible leu-koencephalopathy should be strongly considered in management of SRNS.

Tratamiento del síndrome nefrótico idiopático en niños / Treatment of idiopathic nephrotic syndrome in children

La incidencia anual del síndrome nefrótico se ha estimado en 1-3 por cada 100,000 niños menores de 16 años de edad. En niños, la causa más común del síndrome nefrótico es el síndrome nefrótico idiopático (SNI), que se define por la presencia de proteinuria e hipoalbuminemia y es, por definición, una enfermedad primaria. En el estudio de la biopsia renal se pueden encontrar alteraciones histológicas renales no específicas que incluyen lesiones mínimas, glomeruloesclerosis segmentaria y focal y proliferación mesangial difusa. En todos los pacientes con SNI se indica el tratamiento con corticosteroides, ya que, habitualmente, no se requiere de una biopsia renal antes de iniciar el tratamiento. La mayoría de los pacientes (80-90%) responden a este tratamiento. Los niños con SNI que no presentan remisión completa con el tratamiento con corticosteroides generalmente presentan glomeruloesclerosis segmentaria y focal, y requieren tratamiento con inhibidores de calcineurina (ciclosporina o tacrolimus), mofetil micofenolato o rituximab, además del bloqueo del sistema renina-angiotensina. En este artículo se revisan las recomendaciones recientes aceptadas para el tratamiento de los niños con SNI.

The annual incidence of the nephrotic syndrome has been estimated to be 1-3 per 100,000 children < 16 year of age. In children, the most common cause of nephrotic syndrome is idiopathic nephrotic syndrome (INS). INS is defined by the presence of proteinuria and hypoalbuminemia and by definition is a primary disease. Renal biopsy study shows non-specific histological abnormalities of the kidney including minimal changes, focal and segmental glomerular sclerosis, and diffuse mesangial proliferation. Steroid therapy is applied in all cases of INS. Renal biopsy is usually not indicated before starting corticosteroid therapy. The majority of patients (80-90%) are steroid-responsive. Children with INS who do not achieve a complete remission with corticosteroid therapy commonly present focal and segmental glomerular sclerosis and require treatment with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil or rituximab, plus renin-angiotensin system blockade. In this article we review the recent accepted recommendations for the treatment of children with INS.

Latest update on diagnosis and treatment of steroid-resistant nephrotic syndrome in children / 临床儿科杂志

Steroid-restant nephrotic syndrome (SRNS) is often continuously relapsed, and even develops into end-stage renal di-sease. It has been a great difficulty in the treatment of nephritic syndrome in children. In recent years, many researchers of children SRNS on diagnosis, pathology, treatment have been carried on domestically and in abroad. This paper reviews the latest update on the di-agnosis and treatment of SRNS in children.

Steroid-resistant nephrotic syndrome and MYO1E mutation / 国际儿科学杂志

MYO1E gene is located on chromosome 15 and encodes myosin 1e,which acts as an actin-based molecular motor of cytoskeleton. Myosin 1e is critical to maintain the podocyte function and the conse-quent integrity of the glomerular filtration barrier. Mutations in MYO1E gene has been indentified to be the cause of childhood-onset,familial steroid-resistant focal segmental glomerulosclerosis. Surprisingly,three patients with MYO1E mutations had partial remission by cyclosporine therapy. Detection of the MYO1E gene in the patients suffering from steroid-resistant nephrotic syndrome will be beneficial to make therapeutic decisions and predict prognoses.