scholarly journals Predictive value of platelet indices in children with idiopathic nephrotic syndrome

2019 ◽  
Vol 6 (1) ◽  
pp. e04-e04
Author(s):  
Azar Nickavar ◽  
Sahar Sadr Moharerpour ◽  
Ehsan Abiry
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Platelet Volume ◽  
Distribution Width ◽  
Steroid Resistant ◽  
Qualitative And Quantitative ◽  
Platelet Counts ◽  
Steroid Sensitive ◽  
Quantitative Changes

Introduction: Different biomarkers have been investigated for prognosis of patients with nephrotic syndrome. Qualitative and quantitative changes have been reported in platelets in these patients. Objectives: The aim of this study was to identify platelet abnormalities and their prognostic value of steroid response in children with idiopathic nephrotic syndrome. Patients and Methods: Platelet counts and indices (mean platelet volume [MPV], platelet distribution width [PDW] and platelet larger cell ratio [PLCR]) were evaluated and compared in 122 children with active nephrotic syndrome (64%; steroid resistant and 36%; steroid sensitive). Results: Mean age at diagnosis was 55 months (6 to169 months), and males outnumbered females (1.7/1). Steroid resistant patients had significantly higher platelet counts and lower PLCR, compared to steroid sensitive group. Regarding area under the ROC curve, low MPV, high PDW and low PLCR showed relatively acceptable correlation with steroid resistance. Conclusion: Increased platelet counts in addition to low PLCR are the suggestive indicators of steroid resistance in children with idiopathic nephrotic syndrome.

Urinary Proteome of Steroid-Sensitive and Steroid-Resistant Idiopathic Nephrotic Syndrome of Childhood

2006 ◽  
Vol 26 (3) ◽  
pp. 258-267 ◽  
Author(s):  
Robert P. Woroniecki ◽  
Tatyana N. Orlova ◽  
Natasha Mendelev ◽  
Ibrahim F. Shatat ◽  
Susan M. Hailpern ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Urinary Proteome ◽  
Steroid Sensitive

scholarly journals SOCS3 is epigenetically up-regulated in steroid resistant nephrotic children.

2016 ◽  
Vol 63 (1) ◽  
Author(s):  
Katarzyna Zaorska ◽  
Piotr Zawierucha ◽  
Danuta Ostalska-Nowicka ◽  
Michał Nowicki
Keyword(s):  
Nephrotic Syndrome ◽  
Methylation Status ◽  
Study Groups ◽  
Epigenetic Mechanism ◽  
Steroid Resistance ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Steroid Resistant ◽  
Steroid Sensitive ◽  
Nephrotic Children

The mechanism of steroid resistance in children with the nephrotic syndrome is yet unknown. About 20% of patients demonstrate steroid unresponsiveness and progress to end stage renal disease. Aberrant SOCS3 and SOCS5 expression in steroid resistant and sensitive patients has previously been demonstrated. Here, we investigate genetic and epigenetic mechanisms of regulation of SOCS3 and SOCS5 transcription in nephrotic children. 76 patients with the nephrotic syndrome (40 steroid resistant and 36 steroid sensitive) and 33 matched controls were included in this study. We performed genotyping of a total of 34 single nucleotide polymorphisms for SOCS3 and SOCS5 promoters and evaluated their methylation status using MS-PCR and QMSP methods. Steroid resistant patients had a significantly lower methylation of one region of SOCS3 promoter in comparison with steroid sensitive patients and controls (p < 0.0001). However, the relative methylation level in the steroid sensitive patients and controls differed significantly even before the first steroid dose (p = 0.001758). Other SOCS3 and SOCS5 promoter regions displayed no differences in methylation or were fully methylated/unmethylated in all study groups, showing site-specific methylation. The allele and genotype distribution for SOCS3 and SOCS5 markers did not differ statistically between the groups. We demonstrate an epigenetic mechanism of SOCS3 up-regulation in steroid resistant children with the nephrotic syndrome. The assessment of methylation/unmethylation of SOCS3 promoter might be an early marker for steroid responsiveness in NS patients.

A genetic study of steroid-resistant nephrotic syndrome: relationship between polymorphism -173 G to C in the MIF gene and serum level MIF in children

2015 ◽  
Vol 7 (1) ◽  
pp. 102-107 ◽  
Author(s):  
O. R. Ramayani ◽  
N. Sekarwana ◽  
P. P. Trihono ◽  
A. H. Sadewa ◽  
A. Lelo
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Single Nucleotide ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Increased Risk ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 μg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme-linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance.

scholarly journals Sulfatase 2 Is Associated with Steroid Resistance in Childhood Nephrotic Syndrome

2021 ◽  
Vol 10 (3) ◽  
pp. 523
Author(s):  
Shipra Agrawal ◽  
Richard Ransom ◽  
Saras Saraswathi ◽  
Esperanza Garcia-Gonzalo ◽  
Amy Webb ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Experimental Studies ◽  
Protective Role ◽  
Binding Activity ◽  
Steroid Resistance ◽  
Blood Leukocytes ◽  
Steroid Resistant ◽  
Biologically Relevant ◽  
Steroid Sensitive ◽  
In Silico Algorithm

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.

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

2020 ◽  
Vol 7 (6) ◽  
pp. 1304
Author(s):  
Anitha Palaniyandi ◽  
Subramani Palaniyandi
Keyword(s):  
Nephrotic Syndrome ◽  
Age At Onset ◽  
Steroid Resistance ◽  
First Episode ◽  
Observation Study ◽  
Serum Triglycerides ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

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

scholarly journals Management of idiopathic nephrotic syndrome in childhood

2004 ◽  
Vol 132 (9-10) ◽  
pp. 352-359 ◽  
Author(s):  
Amira Peco-Antic
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Alkylating Agents ◽  
Oral Prednisone ◽  
Symptomatic Treatment ◽  
Dietary Regimen ◽  
Steroid Resistant ◽  
Steroid Dependent ◽  
Frequent Relapses ◽  
Steroid Sensitive

The management of idiopathic nephrotic syndrome (INS) in children includes immunosuppressive and symptomatic treatment. The response to corticosteroid therapy is the best prognostic marker of the disease. The majority of children with INS (about 85%) are steroid-sensitive as they normalize proteinuria within 4 weeks of daily, oral prednisone administration. The most of steroid-sensitive patients (94%) has minimal change of nephrotic syndrome, while the majority (80.5%-94.4%) of those who are steroid-resistant has focal segmental glomerulosderosis or mesangioproliferative glomerulonephritis. Initial therapy of INS consists of 60 mg/m2/day prednisone daily for 4 weeks followed by 40 mg/m2 on alternate days for 4 weeks, thereafter decreasing alternate day therapy every month by 25% over the next 4 months. Thus, the overall duration of the initial cortico-steroids course is 6 months that may be significantly protective against the future development of frequent relapses. Approximately 30% of patients experience only one attack and are cured after the first course of therapy; 10-20% have only 3 or 4 steroid-responsive episodes before permanent cure; the remaining 40-50% of patients are frequent relapsers, or steroid-dependent. Standard relapse therapy consists of 60 mg/m2/ day prednisone until urine is protein free for at least 3 days, followed by 40 mg/m2 on alternate days for 4 weeks. The treatment of frequent-relapses and steroid-dependent INS includes several different regimens: maintenance (6 months) alternate steroid therapy just above steroid threshold (0.1-0.5 mg/kg/ 48h), levamisole, alkylating agents (cyclophosphamide or chlorambucil) or cyclosporine. The worse prognosis is expected in steroid-resistant patients who are the most difficult to treat. Renal biopsy should be performed in them. At present, there is no consensus on therapeutic regimen for steroid-resistant patients. The following immunosuppressive drugs have been used with varying success: cyclosporine, intravenous methyl prednisone pulses alone or combined with or followed by alkylating agents, plasma-exchange, and angiotensin-converting enzyme (ACE) inhibitors. Symptomatic treatment includes: 1) dietary regimen with normal protein intake and salt restriction, 2) calcium and vitamin D are prescribed with steroids, 3) diuretics should be used in case of severe edema, 4) infusion of albumin in case of severe hypovolemia, 5) treatment of hypertension, 6) anticoagulant therapy, and 7) prophylactic antibiotics in high-risk patients.

MO248P-GLYCOPROTEIN EXPRESSING IL-17A+IFN-GAMA+ TH17/1 CELLS ARE REFRACTORY TO GLUCOCORTICOID IN NEPHROTIC SYNDROME*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Akhilesh Kumar Jaiswal ◽  
Narayan Prasad ◽  
Vikas Agarwal
Keyword(s):  
Nephrotic Syndrome ◽  
Th17 Cells ◽  
Steroid Resistance ◽  
Glycoprotein P ◽  
Steroid Resistant ◽  
P Glycoprotein ◽  
Cellular Source ◽  
Steroid Sensitive ◽  
Ifn Γ

Abstract Background and Aims Th17 cells are critical effectors mediating the autoimmunity in nephrotic syndrome (NS). Elevated IFN-γ has also been involved in NS; however, it remains unclear to what extent Th1 cells contribute to glucocorticoids resistance in NS. P-glycoprotein (P-gp) effluxes glucocorticoids outside the cells and selectively expressed differentially on T cell subtypes. In this study, we investigated the role of P-gp and cellular source of IFN-γ and assessed its contribution to glucocorticoids resistance in NS. Method We analyzed the frequency of pathogenic IL-17A+IFN-γ+ Th17/1 lymphocytes and P-gp expression on their surface by flow cytometry in SSNS (n = 32; mean age: 9.06 ± 5.84) and SRNS (n = 28; mean age: 11.29 ± 3.73) patients. We also included 15 age- and sex-matched healthy controls. All patients were of biopsy proven minimal change disease and all patients were treated with steroids. All patients were recruited as per the criteria of ISKDC. Results We found a significant IL-17A+IFN-γ+ Th17/1 population (P &lt; 0.001) in steroid resistant NS (SRNS) as compared to steroid sensitive NS (SSNS) patients. IL-12 and IL-23 are significantly higher in SRNS as compared to SSNS patients which are require for transition of pathogenic Th17 cells to IFN-γ producers. Of the IL-17A+IFN-γ+ Th17/1 population 95.8% cells were expressed P-gp on their surface in SRNS; however only 30.1% cells expressed P-gp in SSNS group (Figure 1). We also observed that P-gp expression correlate positively with IL-17A+IFN-γ+ Th17/1 population (r= 0.739, p&lt; 0.001) significantly. Conclusion The above findings clearly show that higher expression of P-gp on IL-17A+IFN-γ+ Th17/1 cells associated with steroid resistance in nephrotic syndrome through both IL-17A and IFN-γ.

scholarly journals Therapies for Glomerular Diseases in Children

2018 ◽  
Vol 54 (01) ◽  
pp. 043-053
Author(s):  
Arvind Bagga
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Steroid Resistance ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Dependence ◽  
Frequent Relapses ◽  
Steroid Sensitive

AbstractNephrotic syndrome is an important chronic disease of childhood, with a steroid sensitive course in most patients. Research on pathogenesis has emphasized the importance of T-lymphocyte dysregulation and vascular permeability factors that alter podocyte function and glomerular permselectivity. Mutations in genes that encode important podocyte proteins and therapeutic targets within podocytes have been identified. A hypothesis unifying available evidence on pathogenesis is yet to be proposed. An important proportion of patients have difficult disease course, characterized by frequent relapses, steroid dependence or steroid resistance, requiring therapy with alternative immunosuppressive agents. Clinical studies support the use of levamisole, cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNIs) and rituximab in patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult and patients failing to achieve remission show progressive renal damage. Prospective studies in patients with steroid sensitive and steroid resistant nephrotic syndrome are the basis of current guidelines while ongoing studies will help identify and formulate effective and safe therapies.

scholarly journals Molecular factors predicting steroid resistance in pediatric nephrotic syndrome

2021 ◽  
pp. 32-37
Author(s):  
Ie. A. Burlaka ◽  
I. V. Bagdasarova
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistance ◽  
Control Group ◽  
Activation Markers ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Cellular Hypoxia ◽  
Steroid Sensitive ◽  
Nephrotic Children

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. 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. 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. 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. Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children. 

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