Steroid-sensitive Nephrotic Syndrome Research Articles

Patients with Steroid Sensitive Nephrotic Syndrome: A Case Series

Nephrotic syndrome (NS) is one of the most common kidney diseases found in childhood. The prevalence of nephrotic syndrome worldwide is approximately 16 cases per 100,000 children with an incidence of two to seven per 100,000 children. Nephrotic syndrome may affect adults and children of both genders and any race. Nephrotic syndrome in children can be classified into three groups; secondary, congenital, infantile, and idiopathic. In first case, a 3-year-old male patient was presented with complaints of fever, cough for 6 days and swelling all over the body, decreased urine output, oral intake for 2 days, edema of face, body and tiredness for 3 days. Laboratory investigations showed elevated ESR, ferritin and lipid profile. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis conveyed right basal pleural effusion. In second case, a 4-year-old male patient was presented with complaints of facial puffiness, fever, breathing difficulty, abdominal distension and pain but no edema. He had history of right inguinal hernia and atrial septal defect. Cholesterol level was found to be elevated. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis showed mild ascites and right pleural effusion. Presenting third case, a 12-year-old female patient was presented with complaints of edema and decreased urine output. Patient had history of recurrent episodes of edema and decreased urine output for 11 months. Laboratory investigations showed elevated total cholesterol, declined LFT test and RFT test was found to be normal. Urine routine examination showed elevated urine albumin levels (+++), pus cells, RBC, granular cast and bacteria present. USG abdomen and pelvis indicate acute glomerulo nephritis and acute to moderate ascites. Here case series with 3 cases showed the sequence of nephrotic syndrome which is treated with corticosteroid with its side effects and cumulative dose of steroid in children. Keywords: Nephrotic syndrome, Hypocholesteremia, Hypoproteinuria, Hyponatremia, pediatric

Saliva monitoring of prednisolone in children with first onset steroid-sensitive nephrotic syndrome: Is it possible?

Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). Children (age 2-16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8weeks (saliva and plasma) after first onset. A nonlinear mixed-effects model was used to estimate the PK parameters of unbound prednisolone and the saliva-to-plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring. From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h-1 70 kg-1 and 158 (7%) L 70 kg-1, respectively. Typical saliva-to-plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area-under-the-concentration-time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples. Saliva proved to be a reliable and patient-friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.

National Unified Renal Translational Research Enterprise: Idiopathic Nephrotic Syndrome (NURTuRE-INS) study

Abstract Background Idiopathic Nephrotic Syndrome (INS) is a heterogenous disease and current classification is based on observational responses to therapies or kidney histology. The National Unified Renal Translational Research Enterprise (NURTuRE)-INS cohort aims to facilitate novel ways of stratifying INS patients to improve disease understanding, therapeutics, and design of clinical trials. Methods NURTuRE-INS is a prospective cohort study of children and adults with INS with a linked biorepository. All recruits had at least one sampling visit collecting serum, plasma, urine and blood for RNA and DNA extraction, frozen within 2 hours of collection. Clinical histology slides and biopsy tissue blocks were also collected. Results In total, 739 participants were recruited from 23 centres to NURTuRE-INS, half of whom were diagnosed in childhood (n = 365, 49%). The majority were white (n = 525, 71%) and the median age at recruitment was 32 (interquartile range 12-54). Steroid-sensitive nephrotic syndrome (SSNS) was the most common clinical diagnosis (n = 518, 70%). Of patients diagnosed in childhood who underwent a kidney biopsy - for SSNS (n=103), 76 demonstrated minimal change disease (MCD); whereas for steroid-resistant nephrotic syndrome (n=80), 21 had MCD. Almost all patients diagnosed in adulthood had a kidney biopsy (n = 352, 94%); 187 MCD and 162 focal segmental glomerulosclerosis. Conclusions NURTuRE-INS is a prospective cohort study with high-quality biosamples and longitudinal data that will assist research into the mechanistic stratification of INS. Samples and data will be available through a Strategic Access and Oversight Committee.

Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome

The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P< 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

Low Birth Weight is Associated with More Severe Course of Steroid-Sensitive Nephrotic Syndrome in Children, Multicentric Study.

Several previous studies have reported a more severe course of nephrotic syndrome in children with low birth weight. Cohort of 223 children with idiopathic nephrotic syndrome. We aimed to investigate the association between course of nephrotic syndrome and low birth weight. Data from seven paediatric nephrology centres were used. Children with low birth weight had 3.84 times higher odds for a more severe course of steroid-sensitive nephrotic syndrome (95% CI 1.20-17.22, P=0.041), and those with low birth weight and remission after 7 days had much higher odds for a more severe course of disease (OR 8.7). Low birth weight children had a longer time to remission (median 12 vs. 10 days, P=0.03). They had a higher need for steroid-sparing agents (OR for the same sex=3.26 [95% CI 1.17-11.62, P=0.039]), and the odds were even higher in females with low birth weight (OR 6.81). There was no evidence of an association either between low birth weight and focal segmental glomerulosclerosis or between low birth weight and steroid-resistant nephrotic syndrome. We conducted the first multicentric study confirming the worse outcomes of children with NS and LBW and we found additional risk factors. Low birth weight is associated with a more severe course of steroid-sensitive nephrotic syndrome, while being female and achieving remission after 7 days are additional risk factors.

Lipidomic profiles in serum and urine in children with steroid sensitive nephrotic syndrome

BackgroundSteroid-sensitive nephrotic syndrome (SSNS) accounts for approximately 80% of cases of nephrotic syndrome. The involvement of aberrant lipid metabolism in early SSNS is poorly understood, warranting further investigation. This study aimed to explore alterations in lipid metabolism associated with SSNS pathogenesis. MethodsA screening cohort containing serum (50 SSNS, 37 controls) and urine samples (27 SSNS, 26 controls) was analyzed by untargeted lipidomic profiling using UHPLC-QTOF-MS. Then, a validation cohort (20 SSNS, 56 controls) underwent further analysis to check the potential clinical application by ROC curve analysis. ResultsLipidomic profiling of serum and urine samples revealed significant lipid alterations in SSNS patients, with the alterations in the serum samples being more significant. An elevated concentration of PE and PG and downregulated concentration of FA were observed in SSNS serum. A total of 38 dysregulated lipids and 5 lipid metabolic pathways were identified in the serum samples in SSNS patients. Validation in the second cohort confirmed differential regulation of nine kinds of lipids, including 5 up-regulated substances [SM d33:2 (m/z = 686.5361), SHexCer d34:1 (m/z = 779.521), PI 20:4_22:4 (m/z = 934.5558), Cer_NS d18:1_23:0 (m/z = 635.6216), and GM3 d36:1 (m/z = 1180.7431)], as well as 4 down-regulated substances: [CE 18:1 (m/z = 650.601), PE 38:6 (m/z = 763.5205), PC 17:0_20:4 (m/z = 795.5868) and EtherPC 16:2e_20:4 (m/z = 763.5498)]. ConclusionsUntargeted lipidomic analysis successfully identified specific lipid class changes in patients with SSNS, providing a deeper understanding of lipid alterations and underlying mechanisms associated with SSNS.

Nephrotic syndrome sera induce different transcriptomes in podocytes based on the steroid response.

As the molecular mechanism of nephrotic syndrome remains largely undiscovered, patients continue to be exposed to the pros and cons of uniform glucocorticoid treatment. We explored whether the exposure of invitro-cultivated podocytes to sera from children with steroid-sensitive or steroid-resistant nephrotic syndrome induces differences in gene expression profiles, which could help to elucidate the pathogenesis of the steroid response. Human immortalized podocytes were cultivated with patient sera for 3 days. After cell lysis, RNA extraction, 3'-mRNA libraries were prepared and sequenced. There were 34 significantly upregulated and 14 downregulated genes (fold difference <0.5 and >2.0, respectively, and false discovery rate-corrected p < 0.05) and 22 significantly upregulated and 6 downregulated pathways (false discovery rate-corrected p < 0.01) in the steroid-sensitive (n = 9) versus steroid-resistant group (n = 4). The observed pathways included upregulated redox reactions, DNA repair, mitosis, protein translation and downregulated cholesterol biosynthesis. Sera from children with nephrotic syndrome induce disease subtype-specific transcriptome changes in human podocytes invitro. However, further exploration of a larger cohort is needed to verify whether clinically distinct types of nephrotic syndrome or disease activity may be differentiated by specific transcriptomic profiles and whether this information may help to elucidate the pathogenesis of the steroid response.

Adrenocortical suppression in children with nephrotic syndrome treated with corticosteroids.

Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. This cross-sectional study enrolled children (2-18years) both with steroid sensitive nephroticsyndrome (SSNS) (n = 27) and steroid resistant (SRNS) (n = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8weeks or having received > 2mg/kg/d for > 2weeks in the past 1year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1h. All patients with 1h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. Fifty-two (33 males) children were enrolled (mean age 9.4years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63-0.89), with sensitivity of 63.9% and specificity of 81.3%. A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression.

Steroid induced ocular complications in idiopathic nephrotic syndrome: a cross sectional single center study.

To screen children receiving steroids to identify ocular complications and their prevalence. The cross-sectional study was conducted at the Paediatric Nephrology and Ophthalmology departments of the Sindh Institute of Urology and Transplantation, Karachi, from May to October 2022, and comprised patients who received at least 1500mg cumulative steroid dose for a minimum of 3 months. They were screened for steroidsensitive or steroid-resistant nephrotic syndrome. Ocular examinations, including visual acuity, intraocular pressure, slit-lamp biomicroscopy, lens examination and fundus evaluation, were performed. Data was analysed using SPSS 22. Of the 124 subjects with mean age 8.15±2.03 years (range: 6-12 years), 64(51.6%) were boys. Steroidsensitive nephrotic syndrome was present in 97(78%) cases. The mean cumulative steroid dose was 3999.31±1564.22mg. Overall, 36(29%) children developed ocular complications. Blood pressure, number of relapses and the duration of treatment were significantly associated (p<0.05). Refractive errors were the most frequent side effects/complication seen among children with nephrotic syndrome who received prolonged corticosteroids.

Diversity of kidney care referral pathways in national child health systems of 48 European countries.

Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours. In 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology. The care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists. Gaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.

Factors associated with early relapses in children with steroid-sensitive nephrotic syndrome.

Objective: To determine different risk factors associated with relapse in children with steroid-sensitive nephrotic syndrome. Study Design: Cross-sectional study. Setting: Department of Pediatric Nephrology, The National Institute of Child Health, Karachi. Period: April 2021 to October 2022. Material &amp; Methods: With a sample size of 170 Children aged 1-12 years of either gender were included in the study by non-probability consecutive sampling. Patients who had congenital nephrotic syndrome previously received immunosuppressive treatment or had any other systemic disease leading to nephrotic syndrome were excluded from the study. Frequencies and percentages were calculated for the quantitative variables while chi-square test was applied for the qualitative variables-value of &lt;0.05 was considered significant. Results: The mean age of the patients was 4.87±2.54 years. The majority of the frequent relapsers (76) were male. The mean serum cholesterol of the patients was 318.71±61.61mg/dl. Of the total sample, 37 (21.76%) were infrequent relapsers and 133 (78.23 %) were frequent relapsers. A significant association was found between upper respiratory tract infection and frequent relapse with a p-value of 0.038. Conclusion: Our study showed a significant association between upper respiratory tract infection and relapse in children with steroid-sensitive nephrotic syndrome.

Shear wave elastography of kidneys in children: utility in distinguishing steroid-resistant and steroid-sensitive nephrotic syndrome.

To assess the renal elasticity values using (SWE) and correlate the values with steroid sensitivity to distinguish between steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS) in children. In this IRB-approved cross-sectional study, 83 children (4-14years) diagnosed with nephrotic syndrome were included from July 2021 to December 2022. SWE measurements were done for each kidney's upper pole, interpolar region, and lower pole. Mean as well as median SWE were calculated. Correlation of the renal stiffness values was done with different laboratory findings (blood urea, serum creatinine, 24h urine protein, serum albumin, and serum cholesterol), the grayscale findings (cortical echogenicity, and corticomedullary differentiation), and the final diagnosis of SRNS and SSNS. The statistical tests were done at a significance level of α = 0.05. The median (IQR) overall SWE of kidneys was higher in SRNS group 12.64 (8.4-19.68) kPa than SSNS group 9.87 (8.20-12.56) kPa. The difference was significant (p = 0.004). At a cut-off of ≥ 10.694kPa (AUROC- 0.641), the overall SWE predicted SRNS group with a sensitivity of 70% and a specificity of 63%. A significant correlation (p < 0.05) was found between the SWE and 24-h urine protein, cortical echogenicity, and corticomedullary differentiation in SSNS, while only between SWE and corticomedullary differentiation in SRNS. The mean SWE was higher in children with SRNS. While SWE has potential to differentiate SSNS from SRNS, a different study design where SWE is performed at presentation is needed for confirmation.

Clinical Predictors of Steroid Resistance in Childhood Nephrotic Syndrome.

We aimed to evaluate the clinical parameters, histopathological findings of nephrotic syndrome (NS) patients, and independent factors predicting steroid resistance in a single tertiary center. One hundred and sixty-two children (57 girls and 105 boys) with NS who were followed between 1998 and 2018 were analyzed in this retrospective cohort. The median (interquartile range; range) age and follow-up time were 4.9 (5.7; 0.1-16.8) and 5.5 (5.4; 0.1-20.3) years. A total of 82.7% of the patients were steroid-sensitive nephrotic syndrome (SSNS) and 17.3% were steroid-resistant nephrotic syndrome (SRNS). The median age at first presentation was lower in the SSNS group (P = .002). The most common histopathological findings were focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Hypertension and macroscopic and microscopic hematuria were higher in the SRNS group (P < .001). The age and microscopic hematuria were independent risk factors for steroid resistance (P = .019 and P = .002, respectively). Complement 3 (C3) was evaluated in 148 patients and found low in 7 patients who were subsequently diagnosed as membranoproliferative glomerulonephritis. There is still no better clinical predictor for steroid response than late age of onset and microscopic hematuria. Hypertension may also give a hint for potential steroid resistance.

Tumor necrosis factor alpha gene polymorphism affects the pattern of idiopathic nephrotic syndrome in Kuwaiti Arab children.

TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases, but its association with idiopathic nephrotic syndrome (INS) is poorly understood. This study looked for an association of TNF-α gene polymorphisms with INS, as well as its effect on steroid responsiveness among Kuwaiti Arab children. Genotypes of the TNF-a gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism in 151 INS Kuwaiti Arab patients and 64 age and sex-matched controls. Clinical data of all subjects were reviewed. The heterozygous AG genotype was detected in 8.6% of INS patients compared 23.4% of the controls (p < 0.01). Comparing steroid responsiveness, AA genotype was significantly more common in steroid-sensitive nephrotic syndrome (SSNS) cases than steroid-resistant nephrotic syndrome (SRNS) patients (p = 0.001). However, AG genotype was significantly more common in SRNS patients compared to the SSNS cases (p = 0.001). No difference was found between these two subgroups in the GG genotype frequency. AG genotype of TNF-a gene polymorphisms may be considered a suitable marker for INS disease among Kuwaiti children. Both AA and AG genotypes may be useful in predicting steroid responsiveness among these cases of Arab ethnicity. The findings might open the era for the use of genetic markers in the early treatment of NS.

Retrospective Cross-Sectional Study Reviewing the Effectiveness of Mycophenolate Mofetil on Saudi Children With Nephrotic Syndrome.

Background Idiopathic nephrotic syndrome (INS) is the most common form of nephrotic syndrome (NS) in children. It is often associated with minimal change disease (MCD). Corticosteroid therapy is the initial treatment, but many patients experience relapses, leading to steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). To avoid prolonged steroid use, mycophenolate mofetil (MMF) is used as an immunosuppressive alternative. MMF is safe and effective for treating SDNS and FR-SSNS in children, with studies showing reduced relapse rates. The current study aims to evaluate MMF's effectiveness and safety in Saudi children with NS and identify factors that affect its efficacy. Methods A retrospective cross-sectional study was conducted at King Abdullah Specialized Children's Hospital (KASCH) in Riyadh, Saudi Arabia. The study included children aged one to 14 years diagnosed with NS who received MMF therapy. Data were collected from medical records from 2000 to 2020. Ethical considerations were followed, and statistical analysis was performed using IBM SPSS Statistics for Windows, version 25 (released 2017; IBM Corp., Armonk, New York, United States). Baseline characteristics and responsiveness to MMF were examined. Results In our study, 45 participants (25 males, 20 females) with NS were treated with MMF. Most participants were steroid-dependent (84.44%) and had frequent relapses. MMF was effective in 84.4% of cases, with a significant reduction in relapse; the mean number of relapses decreased from 3.5 before MMF to 1.6 after MMF (p-value = 0.00002). Moreover, 40% of the participants were completely free of relapse after the introduction of MMF. The average duration of the MMF therapy was 45 months. Post-MMF side effects were rare but documented. Gastrointestinal symptoms were extremely rare. Elevated liver enzyme levels were reported in 8.88% (four cases) of the participants. Leukopenia, a more common adverse effect, was reported in 26.66% of cases during the MMF therapy. The average daily dose of steroid was reduced from 12.5 mg/day pre MMF to 2 mg/day post MMF with a p-value of 0.00229. Conclusion Our study evaluated the use of MMF in 45 participants with NS. We found that MMF was effective in 84.4% of cases, leading to a significant reduction in the number of relapses. Post-MMF side effects were relatively rare, except for leukopenia that was reported in 26.66%. In addition, the average rate of reduction of steroid exposure before and after MMF was significant. These findings suggest that MMF is a promising treatment option for children with NS and an alternative therapy to long-term steroid use, due to its safety and effectiveness, although close monitoring for potential side effects is essential.

Efficacy and Safety of Single-Dose Rituximab Biosimilar in the Initial Episode of Paediatric Steroid-Sensitive Nephrotic Syndrome

Efficacy and Safety of Single-Dose Rituximab Biosimilar in the Initial Episode of Paediatric Steroid-Sensitive Nephrotic Syndrome

Assessing the Accuracy of Diagnostic Tests to Quantify Proteinuria in Nephrotic Children: A Cross-Sectional Study

Objective: To assess the diagnostic accuracy of 24-hour proteinuria estimation and urine dipstick-taking spot urine protein creatinine ratio as the gold standard in children with steroid-sensitive nephrotic syndrome. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Paediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi Pakistan, from Oct 2020 to Mar 2021. Methodology: Proteinuric children were enrolled to quantify proteinuria by 24-hour urine protein estimation, spot urine protein creatinine ratio and urine dipstick. Sensitivity analysis was performed, and receiver operating curves were plotted to assess the diagnostic accuracies of 24-hour proteinuria and urine dipstick against spot urinary protein creatinine ratio. Scatter plots compared the correlation of serum albumin and cholesterol with 24-hour urine protein estimation and spot urine protein creatinine ratio. Results: Forty-two children with a median age of 8 years (IQR 6–10) were included. Nephrotic range proteinuria was detected in 39(93%) children with spot ratio, 16(38%) cases using 24-hour proteinuria estimation and 50% with a urine dipstick.Twenty-four-hour protein estimation showed a sensitivity of 63.4%, and urine dipstick had a sensitivity of 53.8% in detecting nephrotic range proteinuria compared to spot ratio with a negative predictive value of 6.3% and 14.3%, respectively.Hypoalbuminemia and cholesterol correlated better with spot ratio than 24-hour proteinuria with r- values 0.0143 and 0.0713, respectively. Conclusion: Twenty-four-hour urine protein estimation and dipstick correlate with spot urine protein creatinine ratio in detecting nephrotic proteinuria with no statistical difference in diagnostic accuracy.

Genetic risk variants for childhood nephrotic syndrome and corticosteroid response.

The etiology of most cases of nephrotic syndrome (NS) remains unknown, therefore patients are phenotypically categorized based on response to corticosteroid therapy as steroid sensitive NS (SSNS), or steroid resistant NS (SRNS). Genetic risk factors have been identified for SSNS from unbiased genome-wide association studies (GWAS), however it is unclear if these loci are disease risk loci in other forms of NS such as SRNS. Additionally, it remains unknown if these risk loci are associated with response to therapy. Thus, we investigated the association between SSNS risk loci and therapy response in a large, multi-race cohort of children along the entire spectrum of childhood-onset NS. We enrolled 1,000 patients with childhood-onset NS comprised of SSNS and SRNS. Genotyping was done using TaqMan and Direct Sanger Sequencing for 9 previously reported childhood SSNS risk loci. We compared the allele frequencies (AF) and variant burden between NS vs. controls and SRNS vs. SSNS. All 9 risk loci were associated with NS compared with healthy controls (p = 3.5 × 10-3-<2.2 × 10-16). Variant burden greater than 7 was associated with risk of SRNS (OR 7.4, 95% CI 4.6-12.0, p = 8.2 × 10-16). Our study showed that genetic risk loci for childhood SSNS are associated with pattern of therapy response, may help predict disease outcome, and set the stage for individualized treatment of NS.

The association between dental caries and steroid-sensitive nephrotic syndrome in children.

Pathogenesis and relapse of steroid-sensitive nephrotic syndrome (SSNS) are primarily associated with infection. Dental caries is the most common chronic progressive oral infection in children. However, clinical studies of SSNS combined with dental caries in children are rare. In our retrospective cohort study from January 2021 to June 2022, 145 children with SSNS were included in the baseline analysis and 105 in the follow-up analysis. The follow-up period was 1year. The primary study endpoints were the relapse-free period and frequently relapsing nephrotic syndrome (FRNS). Secondary endpoints included the number and triggers of relapses and concomitant medications. The median age was 5.5years, with a caries rate of 60.7%, themean DMFT/dmft was 3.86, and the caries filling rate was 1.6%. Except for the lower proportion of high household income and high parental education observed in the caries group, no statistical differences were found when comparing the other baseline data with the non-caries group. The caries group had a shorter relapse-free period and a lower 1-year cumulative relapse-free survival rate (HR = 1.90, 95% CI 1.17-3.09, P = 0.009). Univariate regression analysis showed caries associated with FRNS (OR = 2.714, 95% CI 1.021-7.219, P = 0.045), but the correlation no longer remained in the multivariate analysis. Additionally, seven cases of caries-derived pulpal periapical inflammation triggered SSNSrelapses. The caries group had more infection triggers and concomitant medication use. Dental caries and relapse of SSNS are potentially associated, but careful evaluation is needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

A Cross-Sectional Study of Urinary Neutrophil Gelatinase-Associated Lipocalin and its Association with Steroid Responsiveness in Iraqi Children with Idiopathic Nephrotic Syndrome

Background: Steroid-resistant nephrotic syndrome (SRNS)is associated with serious complications and financial burdens. Studies reported increased urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in children with idiopathic nephrotic syndrome (INS). Objectives: This study aimed to evaluate the uNGAL potential to distinguish SRNS from steroid-sensitive nephrotic syndrome (SSNS) in Iraqi children. Patients and Methods: Children with SRNS (n=31) and SSNS (n=32) were recruited from Babylon Hospital for Maternity and Pediatrics from March to June 2022. Patients' data included demographics, clinical characteristics, and urinary lab tests. The uNGAL concentrations were measured via a commercially available ELISA kit. Results: A significantly higher uNGAL median (p-value&lt;0.001) was noted in the SRNS group (median [IQR] = 131.512 [30.28] ng/mL) than in the SSNS group (88.45 [41.6] ng/mL). The correlation between uNGAL levels and estimated glomerular filtration rate (eGFR) was negative (Spearman's rho coefficient = − 0.599, p&lt;0.001). The discriminatory power ofuNGAL to discern SRNS from SSNS was significantly high (AUC=0.899, p&lt;0.0001) with a sensitivity of 87.1% and specificity of 87.5% at an optimal cut-off value of 111.091 ng/mL. Conclusion: uNGAL is associated with a reliable discriminatory strength to distinguish, noninvasively, children with SRNS from those with SSNS. Received: Jan. 2023 Accepted: Jul, 2023 Published: Oct.2023