Clinicopathological features and outcome of secondary steroid resistant nephrotic syndrome: A retrospective analysis.

Objective: To determine the clinico-pathological features and long-term outcome of secondary steroid-resistant nephrotic syndrome treated with steroids and calcineurin inhibitors. METHODS: The retrospective cohort study was conducted at the Sindh Institute of Urology and Transplant, Karachi, in June and July 2023, and comprised data from January 1, 2008, to December 31, 2020, of children aged 1-18 years who developed steroid resistance after initial sensitivity to steroids with at least 1-year of follow-up. Demographics as well as time taken to secondary steroid response were documented. Renal biopsy of all patients with secondary steroid resistance had been performed. Eventual outcomes after treatment with calcineurin inhibitors based on the degree of proteinuria and serum albumin levels were used to categorise complete remission, partial remission and no response. Kidney function, as determined by estimated glomerular filtration rate, was recorded. Data was analysed using SPSS 22. RESULTS: Of the 1,000 patients who underwent renal biopsy for steroid resistance, 48(4.8%) had idiopathic steroid-resistant nephrotic syndrome; 32(66.7%) males, 16(33.3%) females and median age of 5 years (interquartile range: 4-7.3 years). Median age at diagnosis of nephrotic syndrome was 5 years (interquartile range: 3.6-7.3 years). The median time from nephrotic syndrome to secondary steroid-resistant nephrotic syndrome was 23 months (interquartile range: 8.75-44.5 months). Biopsy results at diagnosis showed that 27(56.3%) had minimal change disease. The mean follow-up time was 6.1±3.2 years. Of the 43(89.5%) patients who received cyclosporin for 1 year, 29(67%) obtained complete remission, 5(12%) attained partial remission and no response was seen in 9(21%) patients. Conclusion: Majority of the children had minimal change disease at the time of diagnosis of secondary steroid-resistant nephrotic syndrome. The long-term response with calcineurin inhibitors was favourable at 1 year.

A Study of Dyslipidemia and Its Clinical Implications in Childhood Nephrotic Syndrome.

BACKGROUND: Nephrotic syndrome in children is characterized by dyslipidemia, which is an indirect risk factor for cardiovascular diseases, progressive glomerulosclerosis, and related complications. The objective is to determine the range of lipid profile abnormalities in relation to onset, relapse, and remission, as well as to determine if there is any relationship between dyslipidemia and the frequency of relapses. METHODS: One hundred and two diagnosed cases of nephrotic syndrome in the age group of less than 12 years were included, out of which 64 patients belonged to the first episode of nephrotic syndrome and 38 patients were relapse cases. Steroid-resistant nephrotic syndrome cases or patients with a history of diabetes mellitus, hypothyroidism, familial hypercholesterolemia, children with chronic kidney disease, and edema due to other causes were excluded from the study. RESULTS: There was a statistically significant increase in lipid parameters except for high-density lipoprotein (HDL) cholesterol at the disease onset when compared to remission in cases of the first episode as well as relapse cases of nephrotic syndrome. There was a positive correlation between relapse frequency and dyslipidemia. Dyslipidaemia was also associated with low serum albumin, with a p-value <0.001, which is statistically significant. CONCLUSION: Dyslipidemia is significantly higher in relapse cases of nephrotic syndrome and remains higher even during remission. Dyslipidemia is a directly associated risk factor for atherosclerosis and coronary heart disease (CAD), along with progressive glomerulosclerosis. Early identification and treatment of hyperlipidemia is therefore justified so that along with longevity, we can also improve the quality of life of children suffering from nephrotic syndrome.

The pattern of steroid sensitivity and steroid resistance in childhood idiopathic nephrotic syndrome: A 5-year retrospective observational descriptive study in a South-East Nigerian tertiary hospital.

Background/Aim: Nephrotic syndrome is the most common glomerular disease of childhood. Majority of the idiopathic cases frequently respond to steroid therapy and are regarded as steroid-sensitive nephrotic syndrome. Several studies have reported a change in this usual pattern to steroid-resistant nephrotic syndrome in Nigerian children. This study aimed to determine the pattern of steroid sensitivity and steroid resistance in childhood idiopathic nephrotic syndrome seen at a tertiary hospital in Enugu, south-east Nigeria. Materials and Methods: A retrospective study conducted in children with idiopathic nephrotic syndrome seen at the University of Nigeria Teaching Hospital, Ituku-Ozalla Enugu, over 5 years (from 2016 to 2020). The demographic variables, clinical data, and histopathological pattern were documented. Renal biopsies were studied by light microscope only. Results: Of a total of 150 patients, 105 (70%) were males, while 45 (30%) were females. Ninety six (64%) were aged 1-10 years. Fifty four (36%) were aged 11-18 years. Forty eight (32%) were aged 1-5 years. Mean age was 8.67 ± 4.69 years. One hundred and six (71%) initially had steroid-sensitive nephrotic syndrome; 12 (11.3%) and seven (6.6%) later became frequent-relapsers and steroid-dependent, respectively. Forty four (29.3%) had steroid-resistant nephrotic syndrome. Sixty eight had renal biopsy; the most common indication being steroid-resistance. The most common histological pattern was focal segmental glomerulosclerosis seen in 63.2% of these patients. Only four (9%) had renal transplant. Conclusion: Although the prevalence of steroid-sensitive nephrotic syndrome is higher in this clime, there is a rising incidence of steroid-resistant pattern attributed to incident cases of focal segmental glomerulosclerosis.

Long-Term Efficacy and Safety of Rituximab Versus Tacrolimus in Children With Steroid Dependent Nephrotic Syndrome.

Introduction: In the Rituximab for Relapse Prevention in Nephrotic Syndrome (RITURNS) trial, we demonstrated superior efficacy of single-course rituximab over maintenance tacrolimus in preventing relapses in children with steroid dependent nephrotic syndrome (SDNS) during a 1-year observation. Here we present the long-term outcomes of all 117 trial completers, who were followed up for another 2 years. Methods: Relapsing patients in the rituximab arm received a second course of rituximab, either with (n = 44) or without mycophenolate mofetil (MMF) cotreatment (n = 15). In the tacrolimus arm, second line rituximab monotherapy was initiated after relapses (n = 32) or electively (n = 24). Results: All 12-month relapse-free patients in the rituximab arm relapsed in the second postexposure year, resulting in similar median relapse-free survival times in the 2 trial arms (62 vs. 59 weeks). Second line rituximab in the tacrolimus arm was less effective than first-line therapy in patients switched to rituximab following a relapse (relapse-free survival 55 vs. 63 weeks, P < 0.01). B-cell counts 6 months post-rituximab predicted relapse risk both for first and second line therapy. MMF cotreatment yielded much improved 2-year relapse-free survival as compared to rituximab monotherapy (67% vs. 9%, P < 0.0001). Higher grade 2 adverse event rates were observed post-rituximab versus on tacrolimus (0.87 vs. 0.53 per year). Conclusion: The superior therapeutic effect of rituximab in SDNS vanishes during the second year post-exposure. Rituximab appears to yield longer remission when applied as first line as compared to second line therapy. Maintenance MMF following rituximab induces long-term disease remission.

Incidence and risk factors of acute kidney injury among childhood nephrotic syndrome: a prospective cohort study.

Acute kidney injury (AKI) is a known independent risk factor for morbidity/mortality but there is scarcity of robust data on it among childhood nephrotic syndrome (NS). We assessed the incidence of AKI among hospitalized children with NS as well as looked for any significant risk factors. Prospective observational study conducted across two tertiary pediatric hospitals in Eastern India from September 2020 to August 2021. Children aged 1-18 years admitted with NS and without any nephritic features or pre-existing chronic kidney disease (CKD) were included. In 200 admissions (n = 176; 63% female, median age 4 years [IQR: 3-7]), AKI occurred in 36 (18%; 95% CI 13 to 36%). Two children required kidney replacement therapy and one death was recorded. In 27/36 (75%), AKI resolved within 48 h, 4 had persistent AKI, 3 acute kidney disease, and two progressed to CKD. On multivariate regression analysis: fractional excretion of sodium ≤ 0.2% (OR 12.77; 95% CI 3.5-46.4), male gender (OR 6.38; 95% CI 2.76-14.74), underlying infection (OR 5.44; 95% CI 2.4-11.86), nephrotoxic drugs (OR 4.83; 95% CI 2.21-10.54), and albumin ≤ 1.4 g/dl (OR 4.35; 95% CI 1.55-12.8) were associated with AKI. A predictive equation using these five variables on admission had high AUC (0.86) in correctly identifying 17 children who subsequently developed AKI.   Conclusion: In a low resource setting, AKI is common among hospitalized children with NS. Larger multi-center prospective studies are needed to refine prediction equations and test its utility in preventing AKI development. What is Known: • Acute Kidney Injury is a known independent risk factor for increased morbidity and mortality. • There are few studies to assess the incidence of Acute kidney injury in hospitalised cases of childhood nephrotic syndrome.. What is New: • This is the largest prospective cohort of children suffering from nephrotic syndrome, in India, proposing a novel algorithm for predicting the risk of AKI among hospitalised cases of childhood nephrotic syndrome.

Tacrolimus in the treatment of childhood nephrotic syndrome: Machine learning detects novel biomarkers and predicts efficacy.

STUDY OBJECTIVE: The pharmacokinetics and pharmacodynamics of tacrolimus (TAC) vary greatly among individuals, hindering its precise utilization. Moreover, effective models for the early prediction of TAC efficacy in patients with nephrotic syndrome (NS) are lacking. We aimed to identify key factors affecting TAC efficacy and develop efficacy prediction models for childhood NS using machine learning algorithms. DESIGN: This was an observational cohort study of patients with pediatric refractory NS. SETTING: Guangzhou Women and Children's Medical Center between June 2013 and December 2018. PATIENTS: 203 patients with pediatric refractory NS were used for model generation and 35 patients were used for model validation. INTERVENTION: All patients regularly received double immunosuppressive therapy comprising TAC and low-dose prednisone or methylprednisolone. In this observational cohort study of 203 pediatric patients with refractory NS, clinical and genetic variables, including single-nucleotide polymorphism (SNPs), were identified. TAC efficacy was evaluated 3 months after administration according to two different evaluation criteria: response or non-response (Group 1) and complete remission, partial remission, or non-remission (Group 2). MEASUREMENTS: Logistic regression, extremely random trees, gradient boosting decision trees, random forest, and extreme gradient boosting algorithms were used to develop and validate the models. Prediction models were validated among a cohort of 35 patients with NS. MAIN RESULTS: The random forest models performed best in both groups, and the area under the receiver operating characteristics curve of these two models was 80.7% (Group 1) and 80.3% (Group 2). These prediction models included urine erythrocyte count before administration, steroid types, and eight SNPs (ITGB4 rs2290460, TRPC6 rs3824934, CTGF rs9399005, IL13 rs20541, NFKBIA rs8904, NFKBIA rs8016947, MAP3K11 rs7946115, and SMARCAL1 rs11886806). CONCLUSIONS: Two pre-administration models with good predictive performance for TAC response of patients with NS were developed and validated using machine learning algorithms. These accurate models could assist clinicians in predicting TAC efficacy in pediatric patients with NS before utilization to avoid treatment failure or adverse effects.

The Diagnostic Journey of Childhood Idiopathic Nephrotic Syndrome: Perspectives of Children and Their Caregivers.

Background: Childhood nephrotic syndrome is a rare kidney disease characterized by sudden onset of edema, massive proteinuria, and hypoalbuminemia. Rare diseases can have a long and difficult trajectory to diagnosis. Objective: We aimed to explore the experiences of children with nephrotic syndrome and their caregivers in their search of a nephrotic syndrome diagnosis. Design: An exploratory, qualitative descriptive study design. Setting: The Alberta Children's Hospital outpatient nephrology program in Calgary, Alberta, Canada. Sample: Children aged 9 to 18 years with steroid-sensitive nephrotic syndrome and their caregivers. Methods: We undertook semi-structured interviews with children (alone or with a caregiver present) and their caregivers using a question guide suitable to their age and role. We used a thematic analysis approach to inductively code the data and characterize themes related to our research question. Results: Participants included 10 children aged 9 to 18 years (6 boys and 4 girls) and 18 caregivers (8 men and 10 women). We characterized 3 themes related to participants' experiences in search of a diagnosis of nephrotic syndrome: (1) unexpected and distressing symptom onset, (2) elusiveness of a diagnosis, and (3) encountering a diagnosis. Children with nephrotic syndrome and their caregivers described experiencing initial anxiety due to their unusual and unexpected symptom onset and lack of awareness about the disease. Perceived diagnostic delays and incorrect diagnosis early in the course of the disease contributed to multiple consultations with a variety of care providers. Overall, participants expressed a desire to move past their diagnosis, learn about nephrotic syndrome, and engage in their treatment plans. Limitations: The views expressed by participants may not reflect those of individuals from other settings. The time elapsed since participants' nephrotic syndrome diagnosis may have influenced their recall of events and reactions to this diagnosis. Conclusions: In characterizing the diagnostic experiences of children and their caregivers, our study provides insight into how patients with nephrotic syndrome and their caregivers can be supported by the healthcare team along this journey. Focused strategies to increase awareness and understanding of nephrotic syndrome among healthcare providers are needed to improve patients' and families' diagnostic experiences.

Contexte: Le syndrome néphrotique infantile est une néphropathie rare caractérisée par l'apparition soudaine d'un œdème, d'une importante protéinurie et d'une hypoalbuminémie. La trajectoire jusqu'au diagnostic d'une maladie rare peut être longue et difficile. Objectif: Nous voulions sonder l'expérience des enfants atteints du syndrome néphrotique et celles de leurs soignants pendant le processus d'un diagnostic de syndrome néphrotique. Conception: Étude descriptive exploratoire et qualitative. Cadre: Le program de néphrologie ambulatoire du Alberta Children's Hospital de Calgary (Alberta) au Canada. Participants: Des enfants (9 à 18 ans) atteints du syndrome néphrotique sensible aux stéroïdes, et leurs soignants. Méthodologie: Un questionnaire adapté selon l'âge et le rôle a servi de guide pour les entrevues semi-structurées menées avec les enfants (seuls ou en présence d'un soignant) et leurs soignants. Nous avons utilisé une approche d'analyze thématique pour coder les données de façon inductive et caractériser les thèmes liés à notre question de recherche. Résultats: L'étude a inclus 10 enfants âgés de 9 à 18 ans (6 garçons, 4 filles) et 18 soignants (8 hommes, 10 femmes). Trois thèmes liés à l'expérience des participants dans le processus de recherche d'un diagnostic de syndrome néphrotique ont été caractérisés: (a) l'apparition de symptômes inattendus et affligeants (b) le caractère insaisissable du diagnostic, et (c) l'annonce du diagnostic. Les patients et les soignants ont mentionné avoir d'abord ressenti de l'anxiété en raison de l'apparition soudaine de symptômes inhabituels et du manque de sensibilisation à la maladie. Des retards perçus dans le diagnostic et les erreurs de diagnostic dans les stades précoces ont entraîné de nombreuses consultations auprès de divers fournisseurs de soins. Dans l'ensemble, les participants ont exprimé leur désir de dépasser le diagnostic, d'en apprendre davantage sur le syndrome néphrotique et de s'engager dans le plan de traitement. Limites: Les avis exprimés par les participants pourraient ne pas refléter l'expérience d'autres individus dans d'autres contextes. Le temps écoulé depuis le diagnostic du syndrome néphrotique chez les participants peut avoir influencé leur rappel des événements et les réactions mentionnées face à ce diagnostic. Conclusion: En caractérisant les expériences de diagnostic des enfants et de leurs soignants, notre étude fournit un aperçu de la façon dont les patients atteints du syndrome néphrotique et leurs soignants pourraient être soutenus par l'équipe soignante tout au long de leur parcours. Des stratégies ciblées visant à accroître la sensibilisation au syndrome néphrotique et sa compréhension chez les prestataires de soins de santé sont nécessaires pour améliorer l'expérience des patients et des familles face au diagnostic.

Factors Predicting Short Term Outcome in Children With Idiopathic Nephrotic Syndrome: A Prospective Cohort Study.

Objective The objective of the article is to determine the risk factors associated with relapses in children with idiopathic nephrotic syndrome (INS). Material and methods Fifty-seven children with the first episode of INS were included and followed up prospectively for a minimum period of one year to identify the risk factors related to relapses. The study subjects were divided into early (less than eight days) and late (equal to or more than eight days) responder groups and were compared in terms of the number of days to achieve complete remission, time to first relapse, and the pattern of relapse at the last follow-up. Results Of the 57 children, 32 (56%) were male and 25 (44%) female. The mean age of the study cohort was 5.3 ± 3 years. Sixteen (55%) children with ages ranging from one to four years had a higher propensity to develop relapse, although the p-value (p=0.11) was not significant. Gender analysis did not reveal any significant correlation (p=0.32); however, a higher proportion of males (n=17; 63%) responded within eight days of starting steroids than female counterparts (n=10; 37%). Microscopic hematuria at the disease onset was seen in 12 (21%) children, and out of them, five (41.6%) remained in complete remission. The mean time to achieve complete remission was 8.1 ± 3.5 days, while the early responder group had delayed time to first relapse as compared to the late responders (3.1 ± 5.2 vs. 1.6± 3.8; p=0.21). Among all the study participants, a significant number of children (n=20; 51%) were in complete remission at their last follow-up visit. Baseline serum albumin, cholesterol, body mass index (BMI), and serum creatinine had no significant difference. Conclusion The delayed response to steroids and younger age at presentation can predict the time to first relapse and number of relapses in children with INS, respectively.

Childhood Nephrotic Syndrome in Africa: Epidemiology, Treatment Trends, and Outcomes.

Nephrotic syndrome is a common childhood glomerular disease that is associated with massive proteinuria and edema. Children with nephrotic syndrome are at risk of chronic kidney disease, disease-related complications, and treatment-related complications. Patients with frequently relapsing disease or steroid toxicity may require newer immunosuppressive medications. However, access to these medications is limited in many African countries owing to prohibitive cost, the need for frequent therapeutic drug monitoring, and a lack of appropriate facilities. This narrative review examines the epidemiology of childhood nephrotic syndrome in Africa, including trends in treatment and patient outcomes. In most of North Africa, as well as among White and Indian populations in South Africa, the epidemiology and treatment of childhood nephrotic syndrome closely resembles that of European and North American populations. Historically, secondary causes of nephrotic syndrome (eg, quartan malaria nephropathy and hepatitis B-associated nephropathy) were predominant among Blacks in Africa. Over time, the proportion of secondary cases has decreased, along with rates of steroid resistance. However, focal segmental glomerulosclerosis increasingly has been reported among patients with steroid resistance. There is a need for consensus guidelines for the management of childhood nephrotic syndrome in Africa. Furthermore, establishing an African nephrotic syndrome registry could facilitate monitoring of disease and treatment trends, and provide opportunities for advocacy and research to improve patient outcomes.

Dietary intakes of children with nephrotic syndrome.

BACKGROUND: Our multidisciplinary clinical pathway for treatment of childhood nephrotic syndrome (NS) was established with the goal of standardizing local clinical practice. This descriptive study aimed to assess nutrient intakes of children with newly diagnosed NS compared with nutrition goals defined by our pathway. METHODS: Our pathway includes evidence-based recommendations that target daily intakes during corticosteroid induction therapy: energy (Estimated Energy Requirements (EER) × Sedentary Physical Activity (PA)), sodium (1 mg/kcal), calcium (Dietary Reference Intake (DRI) + 500 mg elemental calcium), and vitamin D (DRI +800-1000 IU). After dietitian-led education at initial diagnosis, 3-day food records were completed at 4 weeks post-diagnosis. Daily nutrient intakes were compared to pathway targets and DRIs. RESULTS: Thirty-six children (median age 4.8 years, 44% female) with newly diagnosed NS submitted food records. Mean energy and sodium intakes were 103±22% and 99±53% of pathway targets, respectively. Fourteen (39%) children exceeded pathway sodium recommendations, with four (11%) exceeding them by greater than 50%. Seven (19%) children met DRI for calcium, while six (17 %) met pathway targets for calcium. No children met DRI for vitamin D from diet alone; and only one met the target with supplementation. CONCLUSIONS: This is the first study to describe dietary intakes of children with newly diagnosed NS. Our clinical pathway targets for energy and sodium were achievable; however, calcium and vitamin D intakes fell short of pathway guidelines and DRIs. Prescription of supplemental calcium and vitamin D may be needed to achieve target intakes of calcium and vitamin D.

Behavioral Problems, Quality of Life and Caregiver Burden in Children with Idiopathic Nephrotic Syndrome: Improving Outcomes by Pragmatic Interventions in a Resource-Poor Setting.

A cross-sectional questionnaire-based study was conducted on 38 children with idiopathic nephrotic syndrome. The prevalence and pattern of behavioral abnormalities was studied. Except in the conduct domain, the prevalence of behavioral problems was comparable with controls. Severe complications of disease and adverse drug effects were significantly associated with abnormal behavior. The Quality of life (QOL) of these children and their caregivers was assessed. It appeared to be unaffected by illness. Additional findings were high maternal literacy, no disruption of schooling, regular follow-up and good adherence to treatment. Behavioral problems in childhood nephrotic syndrome can be minimized by regular follow-up and supportive interventions to reduce caregiver burden. Such children and their caregivers can do well in terms of QOL, even in a resource-poor setting, with appropriate psycho-social support.

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome.

BACKGROUND: Approximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant. METHODS: This is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed. DISCUSSION: The study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols. TRIAL REGISTRATION: This trial was prospectively registered to the Clinicaltrial.gov ( NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/ ) and Clinical Trials Registry of India ( CTRI/2019/04/018517 dated 09/04/2019).

Rhabdomyosarcoma in a child with nephrotic syndrome treated with cyclosporine: a case report with literature review.

BACKGROUND: In patients with frequently relapsing nephrotic syndrome, immunosuppressive therapy such as cyclosporine are often required to maintain remission. Cyclosporine has been noted to have tumorgenesis effects. In this case report, we present a child with relapsing nephrotic syndrom developed a rhabdomyosarcoma on her tongue after adout 4 years of continual immunosuppressive therapy. CASE PRESENTATION: A 2-year-old female child had nephrotic syndrome (urine protein-creatinine ratio 749.1 mg/mg; blood urea nitrogen 11 mg/dL; serum creatinine 0.3 mg/dL; and serum albumin 1.8 g/dL.) Proteinuria resolved on treatment with daily prednisolone for 4 weeks at the dose of 45 mg (2.5 mg/kg/day) but recurred with taper from 25 mg/day to 10 mg/day. At least five more episodes of relapse occurred within about a 3-year period. After the third relapse, she was treated with prednisolone and cyclosporine (at initial dose of 50 mg/day [1.7 mg/kg/day]) for immunosuppression. About 4 years after the diagnosis of nephrotic syndrome had been made, an embryonal rhabdomyosarcoma developed on her tongue. The cancer was treated with TPOG-RMS-LR protocol, with vincristine, actinomycin, and cyclophosphamide. Magnetic resonance imaging scan, performed about 3 years after the start of TPOG-RMS-LR therapy, revealed complete remission of the cancer. CONCLUSIONS: Although treatment with cyclosporine cannot be conclusively implicated as the cause the rhabdomyosarcoma in this patient, the association should prompt consideration of its use in the treatment of frequently relapsing nephrotic syndrome in children.

The long-term outcome of childhood nephrotic syndrome in Germany: a cross-sectional study.

BACKGROUND: Long-term outcomes of children with nephrotic syndrome have not been well described in the literature. METHODS: Cross-sectional study data analysis of n = 43 patients with steroid-sensitive (SSNS) and n = 7 patients with steroid-resistant (SRNS) nephrotic syndrome were retrospectively collected; patients were clinically examined at a follow-up visit (FUV), on average 30 years after onset, there was the longest follow-up period to date. RESULTS: The mean age at FUV was 33.6 years (14.4-50.8 years, n = 41). The mean age of patients with SSNS at onset was 4.7 years (median 3.8 years (1.2-14.5 years), the mean number of relapses was 5.8 (0 to 29 relapses). Seven patients (16.3%) had no relapses. Eleven patients were "frequent relapsers" (25.6%) and four patients still had relapses beyond the age of 18 years. Except of cataracts and arterial hypertension, there were no negative long-term outcomes and only one patient was using immunosuppressant therapy at FUV. 55% of patients suffered from allergies and 47.5% had hypercholesterolemia. Two patients suffered a heart attack in adulthood. A younger age at onset (< 4 years) was a risk factor for frequent relapses. An early relapse (within 6 months after onset) was a risk factor and a low birth weight was not a significant risk factor for a complicated NS course. The mean age of patients with SRNS at onset was 4.6 ± 4.4 years and 27.5 ± 9.9 years at FUV. Three patients received kidney transplantations. CONCLUSIONS: The positive long-term prognosis of SSNS can reduce the concern of parents about the probability of the child developing a chronic renal disease during the clinical course after onset.

Immunosuppressive burden and risk factors of infection in primary childhood nephrotic syndrome.

INTRODUCTION: Patients with primary childhood nephrotic syndrome (PCNS) develop alterations in their cellular and humoral immunity that predisposes them to the development of infection, and lead them to have frequent relapses. Also, infection could be significantly enhanced by immunosuppressive agents. This study aims to estimate the immunosuppressive burden, rate of infection and identify possible risk factors in PCNS requiring hospitalization. METHODOLOGY: A cross-sectional study of hospitalized children≤14years of age diagnosed with PCNS in King Abdul-Aziz Medical City, Riyadh from January 2003 to December 2013. RESULT: Out of 111 patients admitted with PCNS, 84 (76%) had both minor and major types of infection. Upper respiratory tract infection (URTI) was the most predominant type (n=44, 52%). Among the major types of infection, urinary tract infection (UTI) was the most common infection (n=21, 25%) followed by pneumonia (n=17, 20%) then cellulitis (n=6, 6%). Infection in children who received a higher annual cumulative dose of steroids (CDS) strikingly had a higher rate of infection in comparison to those who received lower CDS (p<0.01). Moreover, those who received primary and secondary immunosuppressant's had 100% infection rate. CONCLUSION: About half of infection encountered by PCNS patients were URTI followed by UTI and pneumonia. Higher annual CDS, combination of primary and secondary immunosuppressants were the highest independent risk factors for infection. Among the infection, URTI was considered as the predominant entity whereas among the major infection, UTI was predominant followed by pneumonia then cellulitis.

Childhood nephrotic syndrome at the University of Abuja Teaching Hospital, Abuja, Nigeria: a preliminary report supports high steroid responsiveness.

The response to steroid in childhood nephrotic syndrome (CNS) varies across geographical regions, depending on aetiology, genetics, and the underlying pathology. Recently, there is an increasing steroid responsiveness among Nigerian children with nephrotic syndrome (NS). This is the first report of CNS at the University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria, between 15th January 2016 and 30th June 2018. Prednisolone was administered to all the children with NS according to the regimen of the International Study of Kidney Disease in Children. There were 46 children aged 17 months to 18 years, including 37 males and 9 females. The peak age was 6-10 years with a mean age of 8.2 ± 4.4 years. Forty-one (89.1%) had idiopathic NS (INS). Secondary NS occurred in five (10.9%) children with hepatitis B infection, sickle cell anaemia, haemolytic-uraemic syndrome, and post-infectious glomerulonephritis (two cases). Plasmodium malariae was not seen. Overall, steroid-sensitive NS (SSNS) was seen in 34 (73.9%) and in 32 (78%) with INS. Five (16.7%) of the 30 with SSNS relapsed on follow-up. Twelve (26.1%) were resistant to steroid (steroid-resistant NS, SRNS). Renal biopsies in five SRNS revealed focal segmental glomerulosclerosis in three, minimal change lesion in one, and severe interstitial fibrosis/glomerulosclerosis in another one. Four (8.7%) children who had SRNS died. A child with SRNS is surviving on renal transplant from a living-unrelated donor. The study supports the notion that steroid responsiveness is increasing among ethnic black Nigerian children. Pre-treatment renal biopsy may be unwarranted.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS: ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

Tumor necrosis factor alpha gene polymorphisms and haplotypes in Egyptian children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) characterized by complex pathogenesis and clinical course with relapses; and needs novel breakthroughs for decades. Polymorphisms of cytokines genes including tumor necrosis factor alpha (TNF-α)may influence susceptibility to NS as well as different patients' steroid responses. In the current study, we demonstrated the potential roles of TNF-α promoter gene polymorphisms [-238, -308, -863] and haplotypes in susceptibility to childhood NS. Also, elucidating their possible influence on patients' steroid response and serum TNF-α level. METHODS: This case-control study included 150 children suffering from NS and 150 healthy children. Polymerase chain reaction- restriction-fragment length polymorphism (PCR-RFLP) was performed to evaluate different TNF-α gene polymorphism. TNF-α serum levels were assessed by ELISA. RESULTS: Serum TNF-α levels were significantly higher in NS patients than in controls and in steroid resistant NS (SRNS) than in steroid sensitive NS (SSNS) (P<0.001 for each). The risk of NS in patients carrying TNF-α-238GA genotype, and TNF-α-308GA or AA genotypes and allele A was significantly increased compared to healthy children. While no significant association was detected between TNF-α-863 and NS. The risk of resistance to steroid therapy was significantly high in NS carrying TNF-α-238GA genotype and A allele, TNF-α-308, AA genotypes and A allele, and TNF-α-863CA, AA genotypes and A allele. The TNF-α GCG (-308/-863/-238) haplotype has protective roles against NS and steroid resistance. However, the risk of NS was significantly high in TNF-α AAG and AAA haplotype's carriers compared to healthy children. Additionally the risk of steroid resistance was significantly high in TNF-α AAA haplotype's NS carrier (OR (95%CI): 2.2 (1.19-4.36), P=0.01). Moreover, we found significant higher serum TNF-α levels NS patients including SSNS and SRNS carrying mutant allele TNF-α-238GA genotype, -308GA and AA and -863CA and AA wild genotype's carriers than in those GG, GG and CC respectively. Interstingely, TNF-α levels were significantly higher in healthy children carrying TNF-α(-308/-863/-238) [AAG and AAA haplotypes], NS cases carrying [ACA, AAG, AAA haplotypes], and in SSNS carrying [ACA and AAA haplotypes] than in those carrying GCG, haplotype of wild alleles. CONCLUSION: This study reported, for the first time, that TNF-α promoter gene polymorphisms and/or haplotypes are risk factors of NS and resistance to steroid among Egyptian children.

Setting New Directions for Research in Childhood Nephrotic Syndrome: Results From a National Workshop.

BACKGROUND: We report on the proceedings of a national workshop held in Canada with the aims to identify priorities for research in childhood nephrotic syndrome and to develop a national strategy to address these priorities. METHODS: A diverse group of participants attended the meeting, including patients, family members, researchers, and health care providers. We used small group discussions to explore priorities as perceived by patients and families and by health care providers and researchers. RESULTS: Research evaluating glucocorticoid minimization or glucocorticoid-sparing regimens was a consistent theme in the patient and family discussion group. Families also indicated the need for precise prognostic information at diagnosis, more information to help them choose the best available therapy, and more resources for disease management. Health care providers emphasized the importance of better disease characterization including genotyping and phenotyping patients, better understanding the pathogenesis, and the need of providing targeted therapy and precise prognostic information. CONCLUSIONS: These priorities will inform the development and future directions of the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project, a national research initiative to improve care and outcomes of patients with childhood onset nephrotic syndrome.

CONTEXTE: Nous rapportons les travaux d'un atelier national qui s'est tenu au Canada et qui avait pour objectif de définir les priorités dans la recherche sur le syndrome néphrotique de l'enfant et d'élaborer une stratégie nationale pour répondre à celles-ci. MÉTHODOLOGIE: Un groupe diversifié de participants a assisté à la réunion, notamment des patients, des membres de leurs familles, des chercheurs et des fournisseurs de soins de santé. Nous avons utilisé de petits groupes de discussion pour explorer les priorités telles que perçues par les patients et leurs familles, de même que par les fournisseurs de soins et les chercheurs. RÉSULTATS: La recherche évaluant la minimisation des glucocorticoïdes ou les traitements substituant les glucocorticoïdes a été un thème récurrent dans le groupe de discussion constitué des patients et de leurs familles. De plus, les familles ont souligné le besoin d'obtenir des informations précises sur le pronostic au moment du diagnostic. Ils ont notamment parlé d'obtenir plus d'informations pour aider à choisir le meilleur traitement disponible et davantage de ressources pour la gestion de la maladie. Les fournisseurs de soins de santé ont quant à eux insisté sur l'importance d'une meilleure caractérisation de la maladie, incluant le génotypage et le phénotypage des patients, une meilleure compréhension de la pathogenèse de la maladie et la nécessité de fournir des thérapies ciblées et des renseignements précis sur le pronostic. CONCLUSIONS: Ces priorités guideront le développement et les futures orientations du Canadian Childhood Nephrotic Syndrome project (CHILDNEPH), une initiative de recherche nationale visant à améliorer les soins et les résultats des patients atteints du syndrome néphrotique apparu durant l'enfance.

Glomerular Glucocorticoid Receptors Expression and Clinicopathological Types of Childhood Nephrotic Syndrome.

Glucocorticoids are primary therapy of idiopathic nephrotic syndrome (INS). However, not all children respond to steroid therapy. We assessed glomerular glucocorticoid receptor expression in fifty-one children with INS and its relation to response to steroid therapy and to histopathological type. Clinical, laboratory and glomerular expression of glucocorticoid receptors were compared between groups with different steroid response. Glomerular glucocorticoid expression was slightly higher in controls than in minimal change early responders, which in turn was significantly higher than in minimal change late responders. There was significantly lower glomerular glucocorticoid receptor expression in steroid-resistance compared to early responders, late responders and controls. Glomerular glucocorticoid expression was significantly higher in all minimal change disease (MCD) compared to focal segmental glomerulosclerosis. In INS, response to glucocorticoid is dependent on glomerular expression of receptors and peripheral expression. Evaluation of glomerular glucocorticoid receptor expression at time of diagnosis of NS can predict response to steroid therapy.