Factors Affecting the Statural Growth Retardation in Children using Steroids in Idiopathic Nephrotic Syndrome

Background and Aim: Idiopathic nephrotic syndrome or nephrosis causes massive protein leakage in the urine. Its treatment requires steroids (prednisone, methylprednisolone), often for a prolonged period, notably in case of steroid-dependence or steroid-resistance. In children, long-term use of steroids can lead to several side effects such as statural growth retardation/ stunting. This study evaluated the frequency of stunting in idiopathic nephrotic syndrome in children on steroids and identified the associated factors. Material and Methods: This was a retrospective, descriptive cohort study carried out in children aged 0 to 16 years treated at the paediatric nephrology unit of Aristide Le Dantec Hospital in Dakar, between 1 December 2017 and 31 May 2020. All records of nephrotic children treated in outpatient or inpatient setting were included. These children had to be on corticosteroid therapy for at least 30 months and have a height taken regularly during follow-up consultations. Results: Of 259 children followed for idiopathic nephrotic syndrome, 93 were included in the study. The median age was 96.5 months and the sex ratio was 1.9. The mean height of the children at the beginning of the follow-up was -0.26 DS, at the end it was -0.88 DS. At the beginning of the follow-up, 8 children had already stunting. At 12 months follow-up, 72 children (77.4%) had a decrease in z-score; and at 30 months, there were 7 more children (84.9%) who had a decrease in z-score. Methylprednisolone boluses were given to 17 children (18.3%). Calcium supplementation was done in 91 children (97.8%). Vitamin D supplementation was given to 91 children (97.8%). The mean number of relapses was 1.8. Factors associated with stunting were number of relapses ≤3 (p=0.03), duration of corticosteroid therapy >6 months (p<0.0001) and cumulative doses of prednisone >100 mg/kg (p=0.04). Conclusion: In prolonged nephrotic syndrome in children, corticosteroids can cause stunting.

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Clinical Features of Idiopathic Nephrotic Syndrome and Factors Associated with its Relapse in Children: A Population-Based Study

Journal of Comprehensive Pediatrics ◽

10.5812/compreped.108024 ◽

2020 ◽

Vol 11 (4) ◽

Author(s):

Abolhassan Seyezadeh ◽

Mohamad Reza Tohidi ◽

Somaye Sheikhi ◽

Mohammad Saleh Seyedzadeh ◽

Sara Hookari

Keyword(s):

Nephrotic Syndrome ◽

Recurrence Rate ◽

Clinical Features ◽

Idiopathic Nephrotic Syndrome ◽

Population Based ◽

Steroid Resistance ◽

Filtration Barrier ◽

The Mean ◽

First Recurrence

Background: Idiopathic Nephrotic Syndrome (INS), which is caused by a defect in the glomerular filtration barrier, is the most common chronic glomerular disease in children. Objectives: The present study aimed to assess the clinical features of INS and some recurrence-related factors in children. Methods: This population-based, cross-sectional study was conducted on 302 children with INS referring to the Pediatric Nephrology Clinic of Imam Reza Hospital of Kermanshah city, Iran, during 1998-2018. Results: The mean age (SD) at the time of diagnosis and the follow-up duration were 4.87 (2.89) years and 49.83 (37.52) months, respectively. The numbers of boys and girls were 185 (61.9%) and 114 (38.1%), respectively. The mean number (SD) of recurrences, annual recurrence rate during the follow-up, and the time to the first recurrence after responding to treatment were 1.71 (1.91), 0.48 (0.77), and 10.15 (10.63) months, respectively. The most common type of INS was steroid-dependent/frequent relapse, with a frequency of 151 (50.5%). Furthermore, 33 (11.0%) and 266 (89.0%) patients were resistant and respondent to treatment, respectively. There was a statistically significant relationship between age at the time of diagnosis and the type of INS (P = 0.007). Conclusions: This study revealed a statistically significant association between higher age and steroid resistance. However, in steroid responders, there was no relationship between gender, age at the time of diagnosis, and the time to the first recurrence, and the recurrence rate.

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MO291RITUXIMAB IS EFFECTIVE AND SAFE IN ADULTS WITH STEROID-DEPENDENT NEPHROTIC SYNDROME: A LONG-TERM, SINGLE-CENTER EXPERIENCE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0049 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Gemma Patella ◽

Alessandro Comi ◽

Giuseppe Coppolino ◽

Nicolino Comi ◽

Giorgio Fuiano ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Case Series ◽

Adult Patients ◽

Single Center ◽

Single Center Experience ◽

Steroid Dependent ◽

The Mean ◽

Steroid Dependent Nephrotic Syndrome

Abstract Background and Aims Steroid-dependent nephrotic syndrome (SDNS) may require a prolonged multi-drug therapy with risk of drug toxicity and renal failure. Rituximab (RTX) treatment has been found to be helpful in reducing the steroid dosage and the need for immunosuppressants (ISs), but little data are currently available regarding very long-term outcomes in adults. We herein describe a long-term, single-center experience of RTX use in a large series of adults with SDNS. Method We studied 23 adult patients with SDNS (mean age 54.2±17.1 y; 65% male; BMI 28.5±4.7), mostly consequent to membranous (47.8%) or focal glomerulonephritis (30.2 %) who were eligible to start a RTX regimen. Before entering the RTX protocol, proteinuria and eGFR were 7.06±3.87 g/24h and 65.9±28.2 ml/min/1.73 m2, respectively; albumin and CD19/CD20 ratio were 2.9±0.9 g/L and 0.99±0.01 respectively; the mean number of ISs was 2.39±0.89 and the mean annual rate of relapses was 2.2±0.9. Results Patients were followed over a mean follow-up of 64 months (range: 12-144). After RTX (mean dose: 1202.1±372.4 mg) the rate of relapses was virtually nullified (p<0.001). eGFR remained roughly stable (62.1±19.8 ml/min/1.73 m2, p=NS), while proteinuria, albumin, CD19/CD20 and BMI all significantly improved (p ranging from 0.01 to 0.001). The mean number of additional ISs was also reduced (0.44±0.12; p<0.001) and RTX enabled discontinuation of steroids in 13/23 (56.5%) patients. No major adverse events related to therapy were recorded. Conclusion Findings from this large case-series with a remarkable very long follow-up reinforce the role of RTX as an efficient and safe weapon to improve outcomes in adult patients suffering from SDNS.

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Prognosis and acute complications at the first onset of idiopathic nephrotic syndrome in children: a nationwide survey in Japan (JP-SHINE study)

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz185 ◽

2019 ◽

Cited By ~ 2

Author(s):

Mai Sato ◽

Kenji Ishikura ◽

Takashi Ando ◽

Kaori Kikunaga ◽

Chikako Terano ◽

...

Keyword(s):

Regression Analysis ◽

Nephrotic Syndrome ◽

Serum Albumin ◽

Ocular Hypertension ◽

Idiopathic Nephrotic Syndrome ◽

Cox Regression Analysis ◽

Management Of Complications ◽

First Onset ◽

Observation Period

Abstract Background Information on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce. Methods The Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients’ prognosis in this cohort. Results We obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8–9.4] and a median follow-up period of 4.1 years (IQR 2.5–5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin <1.0 g/dL) and severe bacterial infection were not independent factors, but female sex {hazard ratio [HR] 1.5 [95% confidence interval (CI) 1.1–1.7]} and hypertension [HR 4.0 (95% CI 2.6–6.0)] were significantly related to AKI. During the observation period, ocular hypertension requiring treatment occurred in 17.4% of patients, among which 0.4% received surgical treatment. Progression to frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome in 3 years was seen in 44.2% of the patients and was shown by the Cox regression analysis to be significantly related to younger age and days until remission at the first episode, but not to sex, hematuria, the minimum serum albumin level or AKI. Two patients died during the observation period. One patient showed progression to end-stage kidney disease. Conclusion Based on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory.

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Bone mineral density and its influencing factors in children with idiopathic nephrotic syndrome: a prospective observational study

Tropical Doctor ◽

10.1177/0049475519868055 ◽

2019 ◽

Vol 49 (4) ◽

pp. 292-298

Author(s):

Indar K Sharawat ◽

Lesa Dawman ◽

Merabhai V Kumkhaniya ◽

Kusum Devpura ◽

Amarjeet Mehta

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Nephrotic Syndrome ◽

Bone Mineral ◽

Idiopathic Nephrotic Syndrome ◽

Serum Vitamin ◽

Z Score ◽

Mineral Density ◽

Serum Vitamin D ◽

Vitamin D Levels

Glucocorticoids are first-line therapy for children with idiopathic nephrotic syndrome (INS). These children are at risk of deranged bone metabolism and low bone mineral density (BMD). We studied 60 children with INS and divided them into two groups. Group 1 included 21 children (initial and infrequent relapsing) and group 2 included 39 children (frequent relapsing, steroid dependent and steroid resistant). Dual-energy X-ray absorptiometry of the lumbar spine was performed to assess BMD. Mean BMD Z-score was compared in both groups; this correlated significantly on univariate analysis with cumulative steroid dose, serum vitamin D levels and calcium supplementation. However, on multivariate analysis, serum vitamin D level was the only factor significantly predictive of low z-score.

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P1817DOES EPIGENETIC FACTORS LIKE HDAC2 PLAYS ROLE IN STEROID RESISTANCE VIA REGULATION OF P-GP AND MRP-1 IN CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1817 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

HARSHIT SINGH ◽

Narayan Prasad ◽

Vikas Agarwal ◽

Akhilesh Kumar Jaiswal

Keyword(s):

Nephrotic Syndrome ◽

Histone Acetylation ◽

Mrna Expression ◽

Idiopathic Nephrotic Syndrome ◽

Trichostatin A ◽

Fold Change ◽

Steroid Resistance ◽

Mrna Levels ◽

Inflammatory Genes ◽

Maximal Induction

Abstract Background and Aims The action of glucocorticoids is to switch off activated inflammatory genes. The activated glucocorticoid receptors (GR) interact with co-repressor molecules to impair NFκB-associated co-activator activity, reducing histone acetylation, chromatin remodelling. Reduction in histone acetylation occurs via recruitment of histone deacetylase (HDAC) 2 to the activated inflammatory gene complex by activated GR, resulting in efficacious suppression of activated inflammatory genes within the nucleus. To evaluate the effect HDAC 2 on P-gp and MRP-1 expression and function. Method Total of 78 subjects were considered in the study out of which 50 were steroid sensitive nephrotic syndrome (SSNS), and 28 were steroid resistant nephrotic syndrome (SRNS) patients. mRNA expression was analyzed on peripheral blood mononuclear cells (PBMCs) in SRNS patients (mean age 8.43±3.8 years), SSNS patients (mean age 7.54±3.5 years). PBMCs were treated with 1µM of Theophylline (HDAC2 stimulator) and 0.8µM of Trichostatin A (HDAC2 inhibitor) for a period of 48 hours. Quantitative PCR was performed using light cycler LC480 using SYBR green PCR technology with SYBR premix relative gene expression levels were calculated and normalized to the corresponding levels of the housekeeping gene (GAPDH). Results Expression of P-gp (4.79±0.970 v/s 2.13±0.72, p<0.0001) and MRP-1 (3.99 ±0.8 v/s 1.99 ±0.91, p<0.0001) on PBMCs was increased in SRNS as compared to that of SSNS. HDAC2 mRNA levels were significantly decreased in SRNS patients as compared to that of SSNS patients (2.97 ± 0.95 v/s 6.02 ± 1.13, p<0.0001). Theophylline(HDAC stimulator) for a period of 48 hours decreased mRNA levels of P-gp and MRP-1 in PBMCs of SRNS with maximal induction at 1µM (fold change 2.65 and 2.21, *p<0.0001) However HDAC2 mRNA expression increased significantly (fold change5.67, *p<0.0001). In SSNS patients P-gp and MRP-1 mRNA expression decreased at1µM (fold change 1.25, 1.24, *p<0.0001) while the mRNA expression was increased (fold change 6.93, *p<0.0001). TSA(HDAC inhibitor) for a period of 48 hours increased mRNA levels of P-gp and MRP-1 in PBMCs of SRNS with maximal induction at 0.8µM (fold change 7.51, 7.31, *p<0.0001) and significantly decreased the level of HDAC2 (fold change1.50, *p<0.0001) similarly in SSNS patients P-gp and MRP-1 mRNA expression increased at 0.8µM (fold change 3.49, 3.35, *p<0.0001) and HDAC2 decreased (fold change2.53, *p<0.0001) at 0.8µM. The functional activity of P-gp and MRP-1 was significantly higher in SRNS group as compared to SSNS group (p<0.001), whereas enzymatic activity of HDAC2 was increased in SSNS group as compared to SRNS group (p<0.001) Conclusion As we observed that HDAC2 regulates P-gp and MRP-1 efflux pumps, Inducer of HDAC2 may be a probable treatment stratergy for patients of Idiopathic Nephrotic Syndrome.

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Association ofACEandMDR1Gene Polymorphisms with Steroid Resistance in Children with Idiopathic Nephrotic Syndrome

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2015.0077 ◽

2015 ◽

Vol 19 (8) ◽

pp. 454-456 ◽

Cited By ~ 4

Author(s):

Mohanapriya Chinambedu Dhandapani ◽

Vettriselvi Venkatesan ◽

Nammalwar Bollam Rengaswamy ◽

Kalpana Gowrishankar ◽

Prahlad Nageswaran ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Idiopathic Nephrotic Syndrome ◽

Steroid Resistance

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LONG-TERM FOLLOW-UP STUDY OF IDIOPATHIC NEPHROTIC SYNDROME (INS) IN CHILDHOOD

Pediatric Research ◽

10.1203/00006450-198008000-00167 ◽

1980 ◽

Vol 14 (8) ◽

pp. 1001-1001

Author(s):

S Fujisawa ◽

R Miyazaki ◽

K Okuhara ◽

F Suehiro ◽

Y Watanabe ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Idiopathic Nephrotic Syndrome ◽

Follow Up Study ◽

Long Term Follow Up

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Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

Immunopathologia Persa ◽

10.15171/ipp.2019.15 ◽

2019 ◽

Vol 5 (2) ◽

pp. e15-e15

Author(s):

Mohsen Akhavan Sepahi ◽

Najmeh Farahani ◽

Mohammad Reza Razavi ◽

Hossein Heydari ◽

Shahram Arsang-Jang

Keyword(s):

Clinical Trial ◽

Nephrotic Syndrome ◽

Intervention Group ◽

T Test ◽

Steroid Resistance ◽

Control Group ◽

Steroid Resistant ◽

Steroid Administration ◽

Frequent Relapses ◽

The Mean

Introduction: The most common complications of the nephrotic syndrome (NS) are the frequent relapses, steroid resistance, and long-term steroid administration. Objectives: This study aimed to compare the therapeutic effect of rituximab versus cyclophosphamide in the prevention of relapses and the complications of treatment in children with steroid-resistant NS. Patients and Methods: This clinical trial study was performed on 50 patients with resistant steroidal NS referred to Masoumeh hospital in Qom, Iran. Patients were randomly divided into the two groups including intervention (n=20) and control groups (n=30). In addition to the prednisolone, the intervention group received 375 mg/m2/weekly rituximab intravenously for 4 weeks. The control group received oral doses of cyclophosphamide 2 mg/kg/d for 3 months. During treatment, the frequency of relapses, the mean dose of steroid and the complications of treatment were compared with a paired t-test, independent t-test, and chi-square test. Results: A significant decrease in the mean dose of steroids and the mean number of relapses were seen in patients after administration of rituximab and cyclophosphamide (P<0.001). However, rituximab reduced the dose of steroid administration by 12.25 mg/d, while cyclophosphamide reduced only 2.83 mg/d (P<0.001). Rituximab reduced the relapse rate two times on average, while cyclophosphamide reduced only 0.5 times (P<0.001). The incidence of complications in the cyclophosphamide group was found to be more severe than the rituximab group. Conclusion: To compare rituximab versus cyclophosphamide regarding lower the frequency of recurrence after treatment, we found rituximab is a more suitable drug for the treatment of steroid-resistant NS than cyclophosphamide.

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Association Between Macrophage Migration Inhibitory Factor -173 G>C Gene Polymorphism and Childhood Idiopathic Nephrotic Syndrome: A Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2021.724258 ◽

2021 ◽

Vol 9 ◽

Author(s):

Daojing Ying ◽

Mengjie Jiang ◽

Liping Rong ◽

Hongjie Zhuang ◽

Lizhi Chen ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Gene Polymorphism ◽

Sequential Analysis ◽

Idiopathic Nephrotic Syndrome ◽

Meta Analysis ◽

False Negative ◽

Genetic Models ◽

Steroid Resistance ◽

Trial Sequential Analysis ◽

Type I

Background: Studies have identified that MIF -173 G>C gene polymorphism is associated with idiopathic nephrotic syndrome (INS) susceptibility and steroid resistance, but the results remain inconclusive.Methods: We searched PubMed, Embase, and Web of Science for relevant studies published before 31 March 2021. Pooled data were reported as odds ratio (OR) with 95% confidence interval (CI). Noteworthiness of significant OR was estimated by the false positive report probability (FPRP) test. Trial sequential analysis (TSA) was used to control type I and type II errors.Results: We selected seven case-control studies that included 1,026 INS children (362 were steroid-resistant NS and 564 were steroid-sensitive NS) and 870 controls. The results showed that MIF -173 G>C polymorphism was significantly associated with INS susceptibility in allelic, heterozygous and dominant genetic models (C vs. G: OR = 1.325, 95% CI: 1.011-1.738; GC vs. GG: OR = 1.540, 95% CI: 1.249-1.899; CC + GC vs. GG: OR = 1.507, 95% CI: 1.231-1.845), and FPRP test and TSA indicated that the associations were true in heterozygous and dominant models. The pooled results also revealed that MIF -173 G>C polymorphism was significantly associated with steroid resistance in allelic, homozygous and recessive models (C vs. G: OR = 1.707, 95% CI: 1.013-2.876; CC vs. GG: OR = 4.789, 95% CI: 2.109-10.877; CC vs. GC + GG: OR = 4.188, 95% CI: 1.831-9.578), but FPRP test indicated that all these associations were not noteworthy. Furthermore, TSA revealed that the non-significant associations between MIF -173 G>C polymorphism and steroid resistance in heterozygous and dominant models were potential false negative.Conclusions: This meta-analysis could draw a firm conclusion that MIF -173 G>C polymorphism was significantly associated with increased INS risk in heterozygous and dominant genetic models. MIF -173 G>C polymorphism was not likely to affect steroid responsiveness, but more studies were needed to confirm.

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The impact of a gluten-free diet on the growth pattern of Saudi children with celiac disease

Journal of the Pakistan Medical Association ◽

10.47391/jpma.1308 ◽

2021 ◽

pp. 1-17

Author(s):

Omar Ibrahim Saadah

Keyword(s):

Celiac Disease ◽

Growth Pattern ◽

Laboratory Data ◽

Gluten Free Diet ◽

Gluten Free ◽

Z Score ◽

The Mean ◽

The Impact ◽

Igfbp 3

Objective: To describe the growth pattern of children with celiac disease (CD) after introduction of a gluten-free diet (GFD). Methods: In this retrospective, children 2–16 years old with biopsy-proven CD in 2015–2018 were included in the study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Serial measurements of height-for-age z-score (HAZ) and weight-for-age z-score (WAZ), were recorded at 0, 4, 8, 12, and 16 months. Data on insulin-like growth hormone-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) obtained at diagnosis and during follow-up were retrieved. Clinical, demographic, and laboratory data were extracted from patients' medical files. Results: The median age for the patients was 8.9 years (range, 2.4–16 years). Males constituted 53.2%. The mean WAZ at diagnosis was -2.8±1.9 and the mean HAZ was -3±0.99. Trend analysis indicated a significant time effect for WAZ (p<0.001) and for HAZ (p<0.001). The mean IGF-1 was 133.4±96.8 ng/ml and the mean IGFBP-3 was 3174±1081 ng/ml. There was significant increase in the secretion of IGF-1 (p=0.01) and IGFBP-3 (p=0.004) during the first 8 months of a GFD. Conclusion: The administration of a GFD for Saudi children with CD normalizes their growth parameters within 16 months of follow-up and improves the endogenous secretion of growth factors. Keywords: Celiac disease, growth, child, Continuous...

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