scholarly journals Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

2021 ◽  
Vol 25 (2) ◽  
pp. 92-111
Author(s):  
Jiwon M. Lee ◽  
Yo Han Ahn ◽  
Seon Hee Lim ◽  
Hee Gyung Kang
Keyword(s):  
Nephrotic Syndrome ◽  
Pediatric Patients ◽  
Serum Markers ◽  
Urine Specimen ◽  
Vitamin D Binding Protein ◽  
Steroid Resistant ◽  
Number Of Patients ◽  
Steroid Sensitive ◽  
Cellular Phenotypes ◽  
Steroid Responsiveness

Purpose: Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness.Methods: We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency.Results: A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required.Conclusions: The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

scholarly journals Pediatric Patients With Steroid-Sensitive Nephrotic Syndrome Have Higher Expression of T Regulatory Lymphocytes in Comparison to Steroid-Resistant Disease

2019 ◽  
Vol 7 ◽  
Author(s):  
Fabio Tadeu Lourenço Guimarães ◽  
Rodrigo Novaes Ferreira ◽  
Gustavo Eustáquio Alvim Brito-Melo ◽  
Etel Rocha-Vieira ◽  
Wagner de Fátima Pereira ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Pediatric Patients ◽  
Steroid Resistant ◽  
Resistant Disease ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive ◽  
Regulatory Lymphocytes

scholarly journals Role of urinary nitrites in predicting steroid responsiveness of nephrotic syndrome: a study conducted in tertiary care center

2020 ◽  
Vol 7 (4) ◽  
pp. 918
Author(s):  
Yerroju Kodandapani ◽  
Ajay Mohan Varahala ◽  
Rajesh Kumar Songa
Keyword(s):  
Nephrotic Syndrome ◽  
Care Center ◽  
Tertiary Care ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Selective Permeability ◽  
Chronic Disorder ◽  
Steroid Sensitive ◽  
Steroid Responsiveness

Background: Nephrotic Syndrome (NS) is a common chronic disorder, characterized by alterations of selective permeability at the glomerular capillary wall, resulting in its inability to restrict the urinary loss of protein. Urinary nitrite excretion serves as a useful investigation in differentiating between steroid responsive and steroid resistant nephrotic syndrome. The aim of the study was to assess the relation between urinary nitrite levels and steroid responsiveness in nephrotic syndrome in children.Methods: 76 children were enrolled in the study suffering with nephrotic syndrome of which 58 children were Steroid Sensitive (SSNS) and 18 were Steroid Resistant (SRNS). 25 children were enrolled as controls. The urinary nitrites were estimated in these subjects and the results were analyzed.Results: All the control subjects were tested negative for urinary nitrites. After achieving remission with steroids, out of 58 SSNS subjects’ 27 subjects tested positive for urinary nitrites, remaining 31 tested negatives for the same. Of the 18 SRNS subjects 1 subject tested positive for urinary nitrites remaining 17 subjects were tested negative for the same.Conclusions: The findings of present study suggest that urinary nitrite excretion is increased in patients with steroid responsive nephrotic syndrome. The urinary nitrite estimation has low NPV and high PPV in predicting steroid responsiveness.

scholarly journals Limited Role of Antithrombin Deficiency in Hypercoagulopathy Associated with Nephrotic Syndrome

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 294-294
Author(s):  
Eman Abdelghani ◽  
Amanda P. Waller ◽  
Katelyn J Wolfgang ◽  
Bryce A. Kerlin
Keyword(s):  
Nephrotic Syndrome ◽  
Disease Severity ◽  
Thrombin Generation ◽  
Molecular Mechanisms ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Plasma Albumin ◽  
Steroid Resistant ◽  
Steroid Sensitive ◽  
At Deficiency

Abstract Background: Nephrotic syndrome (NS) is associated with an acquired hypercoagulopathy that drives venous thromboembolic comorbidities. The molecular mechanisms underlying NS-associated hypercoagulopathy are incompletely understood, however previous studies proposed marked urinary loss of antithrombin (AT) as a primary etiology. We have previously demonstrated, in rodent NS models, that there is no correlation between AT antigen and thrombin generation, which we have previously used to characterize the hypercoagulopathy. The objective of this study is to examine the association between AT antigen, AT activity, and hypercoagulopathy along with NS disease severity markers (proteinuria and plasma albumin) in 2 cohorts that include both pediatric and adult NS patients. Methods: Plasma samples were obtained from both cohorts as follows: (1) Samples were obtained on presentation from 147 adult and pediatric patients participating in the NEPTUNE prospective observational cohort study (2) Samples were obtained on presentation and after 7 weeks of glucocorticoid therapy (GC) in steroid sensitive and steroid resistant pediatric patients participating in the PNRC study. AT antigen and activity assays were performed using ELISA and chromogenic assays, respectively. Thrombin generation assay, plasma albumin, and urine protein-to-creatinine ratio were determined as previously described. Results: There was no significant relationship between AT antigen or AT activity and thrombin generation parameters. AT antigen and activity also did not correlate with NS severity markers (plasma albumin and proteinuria) in the NEPTUNE cohort (Figure1). In PNRC pediatric cohort, no significant correlation was found between AT antigen and thrombin generation or other disease severity markers. However, AT activity was significantly associated with both plasma albumin and endogenous thrombin potential at presentation (Figure 2) and at follow-up. Interestingly, GC therapy significantly improved AT activity in steroid-sensitive but not steroid-resistant NS patients (Figure 3). A comprehensive literature review and meta-analysis was also performed which revealed that clinically significant AT deficiency (<0.7 IU/mL) is uncommon in both pediatric and adult NS patients. Conclusion: AT antigen does not correlate with thrombin generation-defined hypercoagulopathy in adult or pediatric NS patients. AT activity does correlate with hypercoagulopathy in pediatric NS patients and improves significantly with successful remission inducing therapy. These data suggest that pediatric NS patients may have a qualitative, but not quantitative, AT deficiency that is responsive to therapy. The mechanism underlying this qualitative deficiency should be characterized in future studies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Distribution of serum adiponectin isoforms in pediatric patients with steroid-sensitive nephrotic syndrome

2021 ◽  
Author(s):  
Tetsuro Tamai ◽  
Kaori Kamijo ◽  
Yoshifusa Abe ◽  
Satoshi Hibino ◽  
Shunsuke Sakurai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Nephrotic Syndrome ◽  
Pediatric Patients ◽  
Serum Adiponectin ◽  
Total Serum ◽  
Control Subjects ◽  
Remission Period ◽  
Total Adiponectin ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Abstract Background Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. Methods We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. Results The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 μg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. Conclusions In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.

scholarly journals Possible mechanisms of LDL apheresis for pediatric patients with steroid resistant and refractory nephrotic syndrome

2010 ◽  
Vol 23 (2) ◽  
pp. 154-159
Author(s):  
Hiroaki Ueda ◽  
Yuko Akioka ◽  
Masakazu Miyamura ◽  
Kiyonobu Ishizuka ◽  
Mamiko Suehiro ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Pediatric Patients ◽  
Ldl Apheresis ◽  
Steroid Resistant ◽  
Refractory Nephrotic Syndrome

scholarly journals Reverse Phenotyping after Whole-Exome Sequencing in Steroid-Resistant Nephrotic Syndrome

2019 ◽  
Vol 15 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Samuela Landini ◽  
Benedetta Mazzinghi ◽  
Francesca Becherucci ◽  
Marco Allinovi ◽  
Aldesia Provenzano ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Signs ◽  
Long Term Outcome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Steroid Sensitive

Background and objectivesNephrotic syndrome is a typical presentation of genetic podocytopathies but occasionally other genetic nephropathies can present as clinically indistinguishable phenocopies. We hypothesized that extended genetic testing followed by reverse phenotyping would increase the diagnostic rate for these patients.Design, setting, participants, & measurementsAll patients diagnosed with nephrotic syndrome and referred to our center between 2000 and 2018 were assessed in this retrospective study. When indicated, whole-exome sequencing and in silico filtering of 298 genes related to CKD were combined with subsequent reverse phenotyping in patients and families. Pathogenic variants were defined according to current guidelines of the American College of Medical Genetics.ResultsA total of 111 patients (64 steroid-resistant and 47 steroid-sensitive) were included in the study. Not a single pathogenic variant was detected in the steroid-sensitive group. Overall, 30% (19 out of 64) of steroid-resistant patients had pathogenic variants in podocytopathy genes, whereas a substantial number of variants were identified in other genes, not commonly associated with isolated nephrotic syndrome. Reverse phenotyping, on the basis of a personalized diagnostic workflow, permitted to identify previously unrecognized clinical signs of an unexpected underlying genetic nephropathy in a further 28% (18 out of 64) of patients. These patients showed similar multidrug resistance, but different long-term outcome, when compared with genetic podocytopathies.ConclusionsReverse phenotyping increased the diagnostic accuracy in patients referred with the diagnosis of steroid-resistant nephrotic syndrome.

Association of DQB1*0302 Alloantigens in Japanese Pediatric Patients with Steroid-Sensitive Nephrotic Syndrome

Nephron ◽  
1995 ◽  
Vol 70 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Kasumi Kuramitsu Abe ◽  
Isao Michinaga ◽  
Toshiki Hiratsuka ◽  
Satoru Ogahara ◽  
Setsuya Naito ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Pediatric Patients ◽  
Steroid Sensitive Nephrotic Syndrome ◽  
Steroid Sensitive

Levamisole treatment in steroid-sensitive and steroid-resistant nephrotic syndrome

1998 ◽  
Vol 12 (6) ◽  
pp. 459-462 ◽  
Author(s):  
K. Tenbrock ◽  
J. Müller-Berghaus ◽  
A. Fuchshuber ◽  
D. Michalk ◽  
U. Querfeld
Keyword(s):  
Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Steroid Sensitive

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.

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