Steroid-sensitive Nephrotic Syndrome Research Articles

Case of steroid-sensitive nephrotic syndrome in a child with orphan disease – leucinosis.

BACKGROUND. The article presents the case of a clinical and laboratory complex of a recurrent hormone-sensitive variant of nephrotic syndrome in a patient with leucinosis (maple syrup disease). THE AIM: to study the clinical laboratory features of nephrotic syndrome in a child with orphan disease – leucinosis. A PATIENT. A 4-year-old child born in a consanguineous marriage, who had previously been diagnosed with a rare genetic disease leucinosis, was examined. The manifestation of leucinosis began from the 8th day of birth. Based on the results of a molecular genetic study the diagnosis was pinpointed as leucinosis with an autosomal recessive mode of inheritance, classic neonatal (maple syrup disease). At the age of 4 the child developed a clinical and laboratory complex of nephrotic syndrome. RESULTS. The onset of nephrotic syndrome was characterized by a hormone-sensitive course. After completion of the course of glucocorticosteroid therapy, there was a relapse because of acute respiratory infection which also turned out to be hormone-sensitive. Kidney function was not impaired. There were no crises of leucinosis due to nephrotic syndrome. CONCLUSION. Taking into account the development of nephrotic syndrome in a child with a genetically determined disease, a molecular genetic examination should be done to exclude the hereditary nature of the developed nephrotic syndrome. The examination is of great clinical importance for determining treatment tactics, cytostatic therapy, doing a kidney biopsy in order to determine the morphological form of glomerulonephritis, prognosis of progression to the end-stage renal failure.

Low-dose versus conventional-dose prednisolone for nephrotic syndrome relapses: a randomized controlled non-inferiority trial.

Reduction of steroid exposure in relapses of steroid-sensitive nephrotic syndrome (SSNS) is under-researched. In this randomized controlled non-inferiority trial, 1-12-year-old children with relapse of SSNS were randomized to receive prednisolone 1 mg/kg/day (low dose) or 2 mg/kg/day (standard dose) until disease remission or day 15, whichever was earlier. Therapy was switched to 2 mg/kg/day in children in low-dose group not in remission by day 15. Primary outcome was days to remission, and secondary outcome being pattern of subsequent relapse(s) over 1 year. Estimating time to remission of 8 ± 2.5 days with standard-dose therapy, non-inferiority margin of 2 days, 90% power, and α-0.05, 60 patients were randomized. Of the 60 children (30 in each group) enrolled, 4 (one in low-dose group) failed remission by day 15. Time to remission was comparable between low-dose and standard-dose groups [9.0 ± 2.2 vs. 8.6 ± 2.2 days; mean difference (95% CI) 0.4 (- 0.79 to 1.59) days; p = 0.49], thus establishing non-inferiority of low dose. Median time to subsequent relapse was 86 (IQR 74.8, 97.2) and 150 (IQR 59.0, 240.9) days, in low- versus standard-dose groups, respectively (log rank p = 0.39). In follow-up, proportion of children having relapses, frequency of relapses, proportion with frequent relapse/steroid dependent (FR/SD), and cumulative corticosteroid dose taken were comparable between groups. This study shows that time to achieve remission after treatment of a relapse with low-dose prednisolone is non-inferior to that after treatment with conventional dose in children with SSNS. The proportion of children achieving remission, further course, and pattern of relapses was comparable between both groups.

POS-448 CORTICOSTEROID SPARING AGENTS IN FREQUENT RELAPSING AND STEROID DEPENDENT NEPHROTIC SYNDROME IN CHILDREN: A SINGLE CENTER RETROSPECTIVE STUDY

Children with frequently relapsing nephrotic syndrome (FRNS) or Steroid-dependent nephrotic syndrome (SDNS) may be prescribed non-corticosteroid immunosuppressive agents whenever there is a failure to maintain remission with low-dose alternate-day prednisone and/or significant adverse effects of prednisone develop. A wide variety of immunosuppressive agents have been used in these patients to reduce the number of relapses and maintain remission. A retrospective study was conducted on all steroid-sensitive nephrotic syndrome (SSNS) children (1-11 years) who received any type of second line agents (e.g. CNI, MMF, cyclophosphamide, and Rituximab) over a period of 9 years from January 2010 to January 2019 in pediatric nephrology unit in Prince Sultan Military Medical City, Riyadh. The study included 24 patients. Their age at diagnosis ranged between 1 and 11 years with a mean of 3.8 years and standard deviation of (±) 2.6 years. During the first year of steroid therapy, relapse occurred among 87% of patients; of them, the number of relapses being 4 or more in 21.7%. Regarding indication for the second line of treatment, SDNS was the most frequent reported (60.9%), followed by FRNS (30.4%). Concerning agents used in the second line, MMF ranked first (58.4%), followed by Cyclophosphamide (33.3%). Number of relapses after starting steroid sparing agent was more than once among 41.7% of patients. Duration of remission after starting steroid sparing agent ranged between 2 and 72 months (14±14.1). Overall response to the second line of treatment was observed among majority of patients (91.7%). Renal biopsy was performed in 45.8% of patients. Concerning side effects of steroid sparing agents, electrolytes disturbances and hypertension were reported by two (8.3%) and one (4.2%) patients respectively. Duration of remission was significantly longer among patients treated with cyclosporine (48±33.9 months) compared to other lines of treatment, p<0.001. On the other hand, hypertension was only reported among patients treated with cyclosporine, p=0.003. The overall response of children with SDNS and FRNS to the second line agents was significant, with favorable longer remission free period with Cyclosporine use with no major side effects. Our results affected by the retrospective design of the study, as well as the small sample size. Therefore larger scale study with prospective design is highly encouraged.

POS-130 EXPERIENCE WITH LEVAMISOLE IN CHILDREN WITH FREQUENTLY RELAPSING AND STEROID DEPENDENT NEPHROTIC SYNDROME HAVING FOLLOW UP AT TIKUR ANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHIOPIA

Nephrotic syndrome is characterized by nephrotic range proteinuria, and hypoalbuminemia,most commonly associated with hyperlipidemia and edema. Without treatment,nephrotic syndrome in children is associated with high risk of death,most commonly from infections. Corticosteroids are the treatment of choice for idiopathic nephrotic syndrome (INS). Although about 80-90% of children with INS respond to corticosteroids, 20-30% become steroid dependent. Chronic corticosteroid therapy in patients with steroid dependent or frequently relapsing NS (FRNS or SDNS) is associated with numerous side effects. Levamisole is an anti helminthic agent with immunomodulatory effect. Levamisole has been considered the least toxic and least expensive steroid sparing drug for preventing relapses of steroid sensitive idiopathic nephrotic syndrome (SSINS). Though FDA doesn’t approve it for this purpose many researches done so far have shown that Levamisole is effective in treatment of children with FR/SDNS. We are using Levamisole in our Hospital but we have no data supporting or negating the use of levamisole as a good choice for treatment of children with SDNS/ FRNS to date. To determine the outcome of pediatric FR/SDNS treated with levamisole among children who had follow up at TASH pedaitric renal clinic. Methods: Retrospective cohort study on clinical records of patients with FR/SDNS having follow up at Tikur Anbessa Specialized Hospital from January 2016 to January 2019 . Charts of 80 patients reviewed and using exclusion criteria 33 patients were excluded from the study. Patient charts were retrieved using patients MRN and type of their disease from registration book at pediatrics renal clinic having follow up at our Hospital during the study period .The collected data was cleaned, Coded and analyzed using SPSS Version 25. Inclusion and Exclusion Criteria: Inclusion criteria: All patients who had FR/SD idiopathic nephrotic syndrome age between 1yr and 18 years attending follow up at TASH pediatric renal clinic. Exclusion criteria: All patients with steroid resistant nephrotic syndrome. All patients of Congenital or Infantile nephrotic syndrome. All patients with CKD. Nephrotic syndrome secondary to systemic illness Among 47 patients with FR/SDNS 32 were males and 15 were females, 21 (44.5%) were FRNS and 26 (55.5%) were SDNS. The duration of Nephrotic Syndrome was 8.75 3.7 yrs, the number of relapses before Levamisole treatment was 3, relapse after Levamisole was 0.7. The duration of Levamisole treatment was 19.9 during levamisole treatment. Levamisole is associated with significant reduction in relapses of FRNS/SDNS.It also significantly reduces adverse effects associated with corticosteroid treatment. The medication is not available in hospital pharmacies and treating those patients who have indications is difficult and the drug should be available at Hospital pharmacies.

Oral cyclophosphamide therapy in 100 children with steroid-sensitive nephrotic syndrome: experience from a developing country.

Oral cyclophosphamide (CYP) is an important therapeutic agent in treatment of steroid-sensitive nephrotic syndrome having a steroid-dependent (SD) or frequent relapsing (FR) course. This retrospective observational study aimed to determine response to oral CYP and factors associated with positive response in these patients. We studied 100 children (male; 75) with FR (19%) and SD (81%) NS treated with CYP in the Pediatric Nephrology clinic. Responders were defined as children in whom steroids were stopped for at least 6 months following CYP and factors affecting response were analysed. Relapse-free survival was estimated by Kaplan-Meier method. Median age at onset of NS was 3 years (IQR 2-5.2). Median age at CYP was 5.7 years (IQR 3.7-7.9). Fifty percent of patients were in the responder group at 6 months of CYP. Relapse-free survival post CYP therapy was 31% at 1 year, 11% at 2 years. Factors predicting good response were age at onset of NS > 3 years with 61.2% response at 6 months (p = 0.028) and older age at CYP initiation (> 5 years) with 61% response (p = 0.008). Multivariate regression analysis showed age at start of CYP > 5 years was an independent factor for good response (p = 0.044, OR = 2.903, CI -1.03 to 8.18). Judicious selection of patients, especially with age of onset of NS more than 3 years and initiation of CYP after age of 5 years, can predict better response in this group of patents.

Steroid treatment for the first episode of childhood nephrotic syndrome: comparison of the 8 and 12 weeks regimen using an individual patient data meta-analysis

Steroids are the cornerstone of the treatment of childhood nephrotic syndrome. The optimal duration for the first episode remains a matter of debate. The aim of this study is to determine whether the 8 weeks International Study of Kidney Disease in Children (ISKDC) regimen is equally effective as the 12 weeks steroid regimen from the German society of pediatric nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie [APN]). An individual patient data (IPD) meta-analysis of randomized controlled trials reporting on prednisolone treatment for a first episode of childhood nephrotic syndrome was conducted. European trials aimed at investigating the ISKDC and/or APN steroid regimen were selected. The lead investigators of the selected trials were requested to provide the IPD of the specific treatment groups. Four trials included European cohorts using dosing schedules according to the regimens studied. IPD of two trials were available. A significant difference was found in time to first relapse after cessation of steroid treatment between the 8 and 12 weeks treatment group with a median time to relapse of 29 and 63 days, respectively. Moreover, relapse rate ratios during total follow-up were 51% higher for the 8 weeks regimen. Finally, younger children have a significantly lower time to first relapse and frequently relapsing nephrotic syndrome.Conclusions: The results of this IPD meta-analysis suggest that the 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen. Moreover, this study highlights the importance of using uniform definitions to enable accurate comparison and interpretation of trial results.Trial registration: Registration number: CRD42020199244, date of registration 16-08-2020What is Known:• Steroids are the cornerstone of the treatment of childhood nephrotic syndrome, however the optimal duration for the first episode remains a matter of debate.• Currently, the 8 weeks ISKDC protocol and 12 weeks APN protocol are among the most frequently used protocols in Europe.What is New:• The 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen for the treatment of a first episode of nephrotic syndrome.• Younger children have a significantly shorter time to first relapse and time to frequent relapsing nephrotic syndrome.

Comparison the Serum Level of Paraoxonase Activity in Frequent Relapse and Infrequent Relapse Patients with Nephrotic Syndrome

Nephrotic syndrome (NS) is distinguished by heavy proteinuria (urine protein:creatinine ratio ?2000 mg/gor ?300 mg/dL, or 3+ protein on urine dipstick), hypoalbuminemia (?2.5 g/dL), and edema. Leakage ofmassive amounts of serum proteins into the urine leads to a hypercoagulable state, a higher rate of infectiousdisease, and the dysregulation of fluid balance. Idiopathic nephrotic syndrome (INS)is one of the most common renal problems in children encountered in day-to-day nephrology practices.The present study was aimed to evaluate the oxidant/ antioxidant status by measuring paraoxonase (PON)activities as well as total antioxidant capacity in steroid sensitive nephrotic syndrome (frequent and infrequentrelapse) and compares it with healthy control children . Paraoxonase activity by spectrophotometer in threegroups consisted of age and sex matched (30) patients with Frequent relapse nephrotic syndrome FRNS ,(30) patients with infrequent relapse nephrotic syndrome (IFRNS) and (30) healthy control children. Theserum level of paraoxonase activity in infrequent relapse group was 101.61±43.0 IU which far less thanfrequent relapse group (160.44±44.22 IU) or controls (228.35±32.35 IU) with highly significant differences.Of note, the difference between control group and frequent relapse group was highly significant.

Molecular factors predicting steroid resistance in pediatric nephrotic syndrome

Objectives: the objective of this paper was to study the levels of cellular hypoxia, apoptosis controlling factors in children with steroid-sensitive and steroid-resistant nephrotic syndrome.&#x0D; Background: patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. The search of the biochemical markers undergoing the steroid-resistance is under urgent need.&#x0D; Methods: an examination of kidney biopsies and blood of 56 patients (aged 10 to 15 years) with nephrotic syndrome was done. Conventional clinical investigations, immunohistochemistry, immunoblotting were used in this study.&#x0D; Results: patients with steroid-resistant nephrotic syndrome show an increased level of HIF-1 alfa (a marker of cellular hypoxia) as compared to the control group and children with steroid-sensitive nephrotic syndrome. Patients with steroid-resistant nephrotic syndrome show a down-regulation of anti-apoptotic marker BcL-xL as compared to the control group and children with steroid-sensitive nephrotic syndrome.&#x0D; Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children.

Steroid Sensitive Nephrotic Syndrome: Revised Guidelines

JustificationSteroid sensitive nephrotic syndrome (SSNS) is one of the most common chronic kidney diseases in children. These guidelines update the existing Indian Society of Pediatric Nephrology recommendations on its management.ObjectiveTo frame revised guidelines on diagnosis, evaluation, management and supportive care of patients with the illness.ProcessThe guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by review of literature and evaluation of evidence by experts in two face-to-face meetings.RecommendationsThe initial statements provide advice for evaluation at onset and follow up and indications for kidney biopsy. Subsequent statements provide recommendations for management of the first episode of illness and of disease relapses. Recommendations on the use of immunosuppressive strategies in patients with frequent relapses and steroid dependence are accompanied by suggestions for step-wise approach and plan of monitoring. Guidance is also provided regarding the management of common complications including edema, hypovolemia and serious infections. Advice on immunization and transition of care is given. The revised guideline is intended to improve the management and outcomes of patients with SSNS, and provide directions for future research.

Mycophenolate Mofetil Treatment in Childhood Steroid-sensitive Nephrotic Syndrome: Single Center Experience

Objective : We aimed to investigate the efficacy of mycophenolate mofetil (MMF) for maintaining remission and reduce the number of relapses in childhood steroid-sensitive nephrotic syndrome. The effects of MMF on growth and blood pressure parameters were also evaluated. Material and Methods: This retrospective, single-center observational study included patients with steroid-sensitive nephrotic syndrome who were treated using MMF between 2009 and 2019 in the Department of Pediatric Nephrology in our hospital. Results: Ten patients had steroid-dependent nephrotic syndrome; six patients frequently had relapsing nephrotic syndrome in this study. The mean duration of the disease was 93.3 ± 25.0 months and the mean duration of the MMF onset was 33.9 ± 16.7 months after diagnosis. Ten patients showed a 50% or greater reduction in the relapse rate and the prednisolone treatment was discontinued in eight patients for six months or more. Compared to the previous year, before the start of the MMF treatment, there was a 52.7% reduction in the relapse rate and a 36.6% reduction in the cumulative annual dose of steroid after 12 months of MMF treatment. The height z score and the median office systolic blood pressure standard deviation scores of the patients improved after MMF treatment (respectively p = 0.003, p = 0.01). Conclusion: The findings suggest that MMF may lead to decreased relapse rates and cumulative steroid dose, which has a positive effect on growth and blood pressure parameters in steroid-sensitive nephrotic syndrome.

Update on the treatment of steroid-sensitive nephrotic syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) is a rare condition that develops primarily in preadolescent children after the age of 1 year. Since the 1950s, oral corticosteroids have been the mainstay of treatment of all children presenting with nephrotic syndrome, with most patients responding within 4 weeks to an oral course of prednisone (PDN). However, corticosteroids have important side effects and 60-80 % of patients relapse, developing frequently relapsing or steroid-dependent forms. For these reasons, many patients require second-line steroid-sparing immunosuppressive medications that have considerably improved relapse-free survival, while avoiding many PDN-related toxicities. Since most patients will eventually heal from their disease with a normal kidney function, the morbidity of SSNS is primarily related to side effects of drugs that are used to maintain prolonged remission. Therefore, treatment is essentially based on balancing the use of different drugs to achieve permanent remission with the lowest cumulative number of side effects. Treatment choice is based on the severity of SSNS, on patient age, and on drug tolerability. This review provides an update of currently available therapeutic strategies for SSNS.

Seroprotection for Diphtheria, Pertussis, Tetanus and Measles in Children With Nephrotic Syndrome

To determine seroprotective titres for diphtheria, pertussis, tetanus and measles in children with nephrotic syndrome who had received essential immunization. Children (2-18 years) with steroid sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome (SRNS) who were in disease remission and had received essential childhood immunization were included. Anti-diphtheria, anti-pertussis, anti-tetanus and anti-measles antibody titres were measured. Seventy-six (40 with SSNS; 36 with SRNS) children with mean (SD) age 7.54 (3.96) years were enrolled. The time elapsed since last vaccination was >5 years in 68.4% patients. The seroprotection rates for diphtheria, tetanus, pertussis, and measles were 86.8%, 93.4%, 31.6% and 77.6% respectively; lower in SRNS subjects compared to SSNS. Robust seroprotection titers (1.0 IU/mL) for diphtheria were seen in 23.8% SSNS and 17.9% SRNS; P=0.04, and for tetanus in 69.3% SSNS and 43.8% of SRNS subjects; P=0.03, respectively. Children with nephrotic syndrome especially those with SRNS have lower seroprotective titers for diphtheria, tetanus, pertussis and measles, necessitating a booster dose of DPT/DT/Td and MR/MMR.

STUDY ON THE ROLE OF VENTILATION-PERFUSION SCAN IN DETECTION OF SILENT PULMONARY EMBOLISM IN NEPHROTIC SYNDROME CHILDREN

INTRODUCTION: Clinically silent pulmonary thromboembolism is commoner than symptomatic one in children with nephrotic syndrome. The present study was done to look for the occurrence of asymptomatic pulmonary thromboembolism in children with nephrotic syndrome using V IQ scan, which is noninvasive, cost effective. MATERIALS AND METHODS: This prospective study conducted at a tertiary care centre over a period of one year on one hundred children with nephrotic syndrome between the ages of 5 and 15 years with a median age of 8 years attending the Pediatric Nephrology Clinic were taken up for the study. Patients showing defect in Tc99m-MAA perfusion scintigraphy underwent ventilation scan within 24-48 hours. Scan ndings were interpreted by two nuclear medicine physicians independently who were unaware of illness of the patients. The results were interpreted according to Modied Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria. The overall incidence of abnormal V/Q RESULTS: scan in our study was 14%. Individually the incidence was 13.9% in group I, 22.22% in group II and 3.6% in group III, which indicates that patients with steroid resistant and steroid sensitive nephrotic syndrome in relapse were prone to develop thromboembolic complications more than those who were in remission. Combined scintigraphic evidence of pulmonary thromboembolism was 18.05% in Groups I and II compared to 3.6% in controls (Group III). Patients with abnormal ventilation-perfusion scan showed s CONCLUSION: ignicantly larger (p&lt;0.05) duration of illness (mean 69.7±55.3 months) and signicantly greater degree (p&lt;0.001) of proteinuria as compared to patients with normal ventilation-perfusion scan who had mean duration of illness of 45.5±38.0 months.

Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome.

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

Sulfatase 2 Is Associated with Steroid Resistance in Childhood Nephrotic Syndrome.

Glucocorticoid (GC) resistance complicates the treatment of ~10–20% of children with nephrotic syndrome (NS), yet the molecular basis for resistance remains unclear. We used RNAseq analysis and in silico algorithm-based approaches on peripheral blood leukocytes from 12 children both at initial NS presentation and after ~7 weeks of GC therapy to identify a 12-gene panel able to differentiate steroid resistant NS (SRNS) from steroid-sensitive NS (SSNS). Among this panel, subsequent validation and analyses of one biologically relevant candidate, sulfatase 2 (SULF2), in up to a total of 66 children, revealed that both SULF2 leukocyte expression and plasma arylsulfatase activity Post/Pre therapy ratios were greater in SSNS vs. SRNS. However, neither plasma SULF2 endosulfatase activity (measured by VEGF binding activity) nor plasma VEGF levels, distinguished SSNS from SRNS, despite VEGF’s reported role as a downstream mediator of SULF2’s effects in glomeruli. Experimental studies of NS-related injury in both rat glomeruli and cultured podocytes also revealed decreased SULF2 expression, which were partially reversible by GC treatment of podocytes. These findings together suggest that SULF2 levels and activity are associated with GC resistance in NS, and that SULF2 may play a protective role in NS via the modulation of downstream mediators distinct from VEGF.

Persistent Abnormalities of Fatty Acids Profile in Children With Idiopathic Nephrotic Syndrome in Stable Remission.

Steroid-sensitive nephrotic syndrome is an immunological disorder mediated by still poorly defined circulating factor(s) that target the podocyte and damage the filtration barrier. Fatty acids (FA) have several biological roles and, in particular, are strictly involved in cell to cell communication, inflammatory processes and regulation of lymphocyte pools. Studies of FAs during INS have been mainly focused on biochemical changes during the phase of proteinuria; while no information is available about FA profile in patients with idiopathic nephrotic syndrome (INS) on stable remission. Aim of this study is to assess differences in blood FA profile between pediatric patients with INS during the phase of stable remission. Blood fatty acid profile of 47 pediatric patients on stable remission and 47 matched healthy controls were evaluated with gas chromatography. Patients with INS on stable remission had significantly higher levels of PUFA and omega-6 than controls (40.17 vs. 37.91% and 36.95 vs. 34.79%), lower levels of SFA and MUFA. Considering the single fatty acids, levels of omega-6 18:2n6 linoleic acid and omega-6 20:4n6 arachidonic acid were significantly higher in patients with INS than in controls (23.01 vs. 21.55%, p-value 0.003 and 10.37 vs. 9.65%, p-value 0.01). Moreover, patients with INS showed lower levels of SFA 14:0 (0.74 vs. 0.92%) and 18:0 (10.74 vs. 11.74%) and MUFA 18:1n9 oleic acid (18.50 vs. 19.83%). To the best of our knowledge this is the first study assessing FAs profile in children with INS in stable remission. In a population of 47 patients, we were able to demonstrate a higher blood level of linoleic and arachidonic acid, and consequently of omega-6 and PUFA, compared to controls. Persistently higher than normal levels of either linoleic or arachidonic acid, could be viewed as candidate biomarker for a state of risk of relapse in children with idiopathic nephrotic syndrome.

Levamisole and ANCA positivity in childhood nephrotic syndrome

This study aimed to determine the prevalence of ANCA positivity in children managed with levamisole as a steroid-sparing agent for nephrotic syndrome (NS). Medical records of children with steroid-sensitive NS managed with levamisole therapy at Sydney Children’s Hospital between 1/1/2000 and 31/12/2018 were retrospectively reviewed. Main outcome measure was side effects of levamisole therapy including ANCA positivity. Seventy-one children, median age 3 years and 1 month (IQR 29–68 months) at first presentation, were subsequently managed with levamisole. 60.6% were male and 65% Caucasian. 47.9% had frequently relapsing (FR)NS and 52.1% steroid-dependent (SD)NS. Overall, there was a median reduction in relapses from 3 (IQR 1–5) to 0.4 relapses (IQR 0–1) per year after levamisole was commenced. Levamisole was successful in preventing relapse in 19 (29%) patients and was used for median 24 (22 to 25) months. Levamisole was discontinued due to relapse in 25 patients (38%) after median 12 (5–28) months. Side effects occurred in 28 patients (42.4%); the most common side effect was ANCA positivity in 12 patients. In eleven of these patients, levamisole was discontinued; in one patient, low-level titres were documented and spontaneously resolved without cessation of levamisole. Two patients developed ANCA-associated vasculitis. ANCA positivity is a common side effect of levamisole and was seen in 18.2% of our patients. Monitoring is required to determine side effects including ANCA positivity and treatment modified accordingly.

Trends in the Epidemiology of Childhood Nephrotic Syndrome in Africa: A Systematic Review

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online and WHO Global Health Library for articles in English or French reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8,131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported in European populations. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding Statement: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program. Declaration of Interests: The authors have no competing interests or conflicts to declare.

Selected salivary parameters in children with idiopathic nephrotic syndrome: a preliminary study

BackgroundDisturbances in the levels of serum constituents occurring in chronic renal diseases can be reflected in the saliva composition. The aim of this study was to assess some selected salivary components in children suffering from idiopathic steroid-sensitive nephrotic syndrome (iNS).MethodsA case–control study was performed on iNS and healthy participants. In unstimulated mixed saliva, pH, buffer capacity, total protein, α-amylase, peroxidase, calcium, magnesium, inorganic phosphate, fluoride, urea, uric acid and salivary flow rate were measured. Oral condition was assessed using dmft, DMFT, API and GI indices, usage of fluoride specimens and frequency of tooth brushing. Statistical analysis was performed by Shapiro–Wilk, Brown-Forsythe, Student’s t, ANOVA, Tukey’s and Pearson’s chi-square tests, Pearson’s and Spearman’s correlations, logistic regression and receiver operating characteristic (ROC) curve analysis.ResultsThe study involved 94 participants of both genders aged 4–17 (47 cases in relapse or remission phase of iNS and 47 controls) who were treated in the clinic of pediatric nephrology or outpatient dental clinic. Neither group differed in the number of caries-affected primary and permanent teeth, gingival condition or use of fluoride specimens. The iNS group presented lower levels of magnesium (0.41 ± 0.34 vs. 0.60 ± 0.38 mg/dL, P < 0.05) and fluoride (0.15 ± 0.10 vs. 0.21 ± 0.10 ppm, P < 0.01) and higher contents of urea (35.19 ± 15.55 vs. 25.21 ± 10.78 mg/dL, P < 0.01) and uric acid (2.90 ± 1.23 vs. 2.34 ± 1.04 mg/dL, P < 0.05) than the controls. In the iNS participants with relapse, a higher peroxidase activity and lower magnesium content than in the remission phase were found. ROC analysis showed a weak discriminatory power of these salivary constituents for the differentiation of participants with and without disease (accuracy from 66.0 to 67.0%, area under the ROC curve (AUC) from 0.638 to 0.682) and the relapse and remission phases (accuracy 70.2% and 68.1% and AUC 0.717 and 0.675, respectively).ConclusionsLevels of urea, uric acid, magnesium and fluoride in saliva can be associated with the course of iNS. Salivary levels of peroxidase and magnesium can be related to the phase of the disease. However, the measurements of these parameters cannot be useful as a noninvasive tool in diagnosing iNS and the phase of the disease.

Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome

IntroductionGlucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although ∼10% to 20% of children develop steroid-resistant NS (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at initial disease presentation. We hypothesized that a plasma cytokine panel could predict SRNS at disease presentation, and identify potential pathways regulating SRNS pathogenesis.MethodsPaired plasma samples were collected from 26 children with steroid-sensitive NS (SSNS) and 14 with SRNS at NS presentation and after ∼7 weeks of GC therapy, when SSNS versus SRNS was clinically determined. Plasma cytokine profiling was performed with a panel of 27 cytokines.ResultsWe identified 13 cytokines significantly different in Pretreatment SSNS versus SRNS samples. Statistical modeling identified a cytokine panel (interleukin [IL]-7, IL-9, monocyte chemoattractant protein–1 [MCP-1]) able to discriminate between SSNS and SRNS at disease presentation (receiver operating characteristic [ROC] value = 0.846; sensitivity = 0.643; specificity = 0.846). Furthermore, GC treatment resulted in significant decreases in plasma interferon-γ (IFN-γ), tumor necrosis factor–α (TNF-α), IL-7, IL-13, and IL-5 in both SSNS and SRNS patients.ConclusionsThese studies suggest that initial GC treatment of NS reduces the plasma cytokines secreted by both CD4+ TH1 cells and TH2 cells, as well as CD8+ T cells. Importantly, a panel of 3 cytokines (IL-7, IL-9, and MCP-1) was able to predict SRNS prior to GC treatment at disease presentation. Although these findings will benefit from validation in a larger cohort, the ability to identify SRNS at disease presentation could greatly benefit patients by enabling both avoidance of unnecessary GC-induced toxicity and earlier transition to more effective alternative treatments.