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

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.

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Clinicopathological spectrum and treatment outcome of idiopathic steroid-resistant nephrotic syndrome in children at a tertiary care center

Medical Journal Armed Forces India ◽

10.1016/j.mjafi.2020.11.004 ◽

2020 ◽

Author(s):

A.W. Kashif ◽

Akhil Ranjan ◽

Suprita Kalra ◽

Datta Shravani Uttpal ◽

Ajay Malik

Keyword(s):

Nephrotic Syndrome ◽

Treatment Outcome ◽

Care Center ◽

Tertiary Care ◽

Tertiary Care Center ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome

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

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.06060519 ◽

2019 ◽

Vol 15 (1) ◽

pp. 89-100 ◽

Cited By ~ 15

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.

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

Pediatric Nephrology ◽

10.1007/s004670050487 ◽

1998 ◽

Vol 12 (6) ◽

pp. 459-462 ◽

Cited By ~ 22

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

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The role of cell signaling molecules in the pathogenesis of glomerulonephritis in children

The Moldovan Medical Journal ◽

10.52418/moldovan-med-j.64-2.21.07 ◽

2021 ◽

Vol 64 (2) ◽

pp. 37-41

Author(s):

Angela Ciuntu ◽

Keyword(s):

Nephrotic Syndrome ◽

Cell Signaling ◽

Clinical Manifestations ◽

Signaling Molecules ◽

Control Group ◽

Healthy Children ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Steroid Sensitive Nephrotic Syndrome ◽

Steroid Sensitive

Background: Cytokines are functional class of tiny proteins and glycoprotein and fundamentally they are monomers that function as soluble mediators in an autocrine or paracrine manner. Cytokines are produced by a number of cell types, predominantly leukocytes, and their targets implicate both immune and non-immune cells. Material and methods: This study was performed on 75 children with glomerulonephritis (GN), aged from 2 up to 17 years. There were 20 children with steroid-sensitive nephrotic syndrome (SSNS), 15 children with steroid-resistant nephrotic syndrome (SRNS), 20 children with chronic glomerulonephritis (CGN) nephrotic form and 20 children with CGN mixed form. This study was performed on patients experiencing disease relapse and clinical remission. The control group consisted of 20 healthy children. Results: The results of this study demonstrated increased levels of cell signaling molecules (IL-8, TNF-α, MCP-1, MIP-1α) in the urine during clinical manifestations, valuable result due to their major role in the immunopathogenic mechanism of proteinuria in nephrotic syndrome. Conclusions: Determination of urinary concentrations of cellular signaling molecules may be useful as a predictive non-invasive method for estimating disease activity, monitoring disease progression, differentiating steroid-sensitive nephrotic syndrome from steroid-resistant nephrotic syndrome, and assessing the effectiveness of treatment in children with different variants of GN

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Pattern of steroid-resistant nephrotic syndrome in children and the role of histopathology: A single-centre study

South African Journal of Child Health ◽

10.7196/sajch.607 ◽

2013 ◽

Vol 7 (4) ◽

pp. 153 ◽

Cited By ~ 1

Author(s):

Subal Kumar Pradhan ◽

Pawan Pradeep Mutalik ◽

Anil Kumar Mohanty

Keyword(s):

Nephrotic Syndrome ◽

Single Centre ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Centre Study ◽

Single Centre Study

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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

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007850 ◽

2015 ◽

Vol 7 (1) ◽

pp. 102-107 ◽

Cited By ~ 4

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.

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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

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20202138 ◽

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.

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Relative safety of steroid sparing agents in frequently relapsing, steroid dependent and steroid resistant nephrotic syndrome in pediatric patients

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20203172 ◽

2020 ◽

Vol 7 (8) ◽

pp. 1762

Author(s):

Sabnam Ara Begum ◽

Santanu Kumar Tripathi ◽

Mousumi Nandy ◽

Sanat Kumar Ghosh ◽

Shatavisa Mukherjee ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Adverse Events ◽

Tertiary Care ◽

Serious Adverse Events ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Steroid Dependent ◽

Relative Safety ◽

Tertiary Care Hospitals ◽

Steroid Sparing

Background: In patients with frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) and steroid resistant nephrotic syndrome (SRNS) steroids are either used for prolonged period of time or ineffective. To reduce the degree of steroid dependency and avoid steroid toxicity, several immunosuppressive steroid sparing agents (SPAs) have been proposed to treat these children. The present study tried to study the relative safety of most commonly steroid sparing agent in such children.Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.Results: A total 110 patients were screened, examined and enrolled. Levamisole, cyclophosphamide and MMF were commonly used SPAs. Of the two tertiary care hospitals, all the patients of FRNS and SDNS were started with levamisole and SRNS with cyclophosphamide in one set-up, while in the other hospital some SDNS patients were started with cyclophosphamide and SRNS with MMF but without clinically significant outcomes. In comparison with few minor adverse events in MMF group, some serious adverse events were documented in the both cyclophosphamide and levamisole groups.Conclusions: Levamisole being a very efficacious, safe and easily affordable drug, should be used as an initial first line SPA in treating FRNS and SDNS children. The side effect profiles of levamisole and MMF are much more patient friendly.

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.006 ◽

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 < 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< 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.

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