Salivary cytokines in children with nephrotic syndrome versus healthy children: a comparative study

Pollák, Dávid; Borovitz, Yael; Levy, Dana Rubi; Klein, Yehuda; Bernfeld, Nathalie; Davidovits, Miriam; Davidovich, Esti

doi:10.21203/rs.3.rs-19893/v1

Cited by 2 publications

(4 citation statements)

References 20 publications

(25 reference statements)

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“… 28 A few other reports have identified cytokines in plasma, urine, and saliva as markers of persistence of proteinuria or SRNS in childhood NS. 13 A Brazilian study compared peripheral blood leukocytes and their intracellular cytokines in post-therapy samples from 44 pediatric patients, classified as having persistent proteinuria (partial remission) versus low proteinuria (complete remission). These investigators identified higher levels of inflammatory markers with persistent proteinuria.…”

Section: Discussionmentioning

confidence: 99%

“…To try to better identify those patients highly unlikely to respond to GC, and thus avoid its unnecessary toxicity, a few studies have tried to identify urinary, plasma, and salivary biomarkers for SRNS in children using cytokine profiling and omics approaches such as proteomics, metabolomics, and transcriptomics. 8 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 As a result, recently T lymphocytes expressing inflammatory cytokines and macrophage migration inhibitory factor in plasma, and MCP-1 in urine have been implicated in persistent proteinuria and SRNS in childhood NS. 8 , 19 , 20 However, despite these efforts, we still lack understanding of the molecular mechanisms regulating GC resistance in NS, and there remain no plasma or urine biomarkers that have been validated to reliably predict GC resistance in NS prior to initiation of GC therapy.…”

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confidence: 99%

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Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome

Agrawal

Brier

Kerlin

et al. 2021

Kidney International Reports

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Introduction Glucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although ∼10% to 20% of children develop steroid-resistant NS (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at initial disease presentation. We hypothesized that a plasma cytokine panel could predict SRNS at disease presentation, and identify potential pathways regulating SRNS pathogenesis. Methods Paired plasma samples were collected from 26 children with steroid-sensitive NS (SSNS) and 14 with SRNS at NS presentation and after ∼7 weeks of GC therapy, when SSNS versus SRNS was clinically determined. Plasma cytokine profiling was performed with a panel of 27 cytokines. Results We identified 13 cytokines significantly different in Pretreatment SSNS versus SRNS samples. Statistical modeling identified a cytokine panel (interleukin [IL]-7, IL-9, monocyte chemoattractant protein–1 [MCP-1]) able to discriminate between SSNS and SRNS at disease presentation (receiver operating characteristic [ROC] value = 0.846; sensitivity = 0.643; specificity = 0.846). Furthermore, GC treatment resulted in significant decreases in plasma interferon-γ (IFN-γ), tumor necrosis factor–α (TNF-α), IL-7, IL-13, and IL-5 in both SSNS and SRNS patients. Conclusions These studies suggest that initial GC treatment of NS reduces the plasma cytokines secreted by both CD4 + T H 1 cells and T H 2 cells, as well as CD8 + T cells. Importantly, a panel of 3 cytokines (IL-7, IL-9, and MCP-1) was able to predict SRNS prior to GC treatment at disease presentation. Although these findings will benefit from validation in a larger cohort, the ability to identify SRNS at disease presentation could greatly benefit patients by enabling both avoidance of unnecessary GC-induced toxicity and earlier transition to more effective alternative treatments.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome

Agrawal

Brier

Kerlin

et al. 2021

Kidney International Reports

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“…iNS is characterized by complex abnormalities in blood tests and treatment by steroids, immunosuppressants or cytostatics, and dietary regimens, which may be reflected in the saliva composition. Unfortunately, we could not compare our results with those of others because data in the literature are scarce and concern the excretion of endogenous proteins (albumin, transferrin, IgG1, and IgG4) [ 24 ], salivary cortisol concentration [ 25 ] and salivary cytokines [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, undisturbed salivary gland activity could be suggested. Polak et al [ 26 ] found a lower total protein concentration in the saliva of children with steroid-sensitive nephrotic syndrome than in the control group.…”

Section: Discussionmentioning

confidence: 99%

Selected salivary parameters in children with idiopathic nephrotic syndrome: a preliminary study

et al. 2021

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Background Disturbances in the levels of serum constituents occurring in chronic renal diseases can be reflected in the saliva composition. The aim of this study was to assess some selected salivary components in children suffering from idiopathic steroid-sensitive nephrotic syndrome (iNS). Methods A case–control study was performed on iNS and healthy participants. In unstimulated mixed saliva, pH, buffer capacity, total protein, α-amylase, peroxidase, calcium, magnesium, inorganic phosphate, fluoride, urea, uric acid and salivary flow rate were measured. Oral condition was assessed using dmft, DMFT, API and GI indices, usage of fluoride specimens and frequency of tooth brushing. Statistical analysis was performed by Shapiro–Wilk, Brown-Forsythe, Student’s t, ANOVA, Tukey’s and Pearson’s chi-square tests, Pearson’s and Spearman’s correlations, logistic regression and receiver operating characteristic (ROC) curve analysis. Results The study involved 94 participants of both genders aged 4–17 (47 cases in relapse or remission phase of iNS and 47 controls) who were treated in the clinic of pediatric nephrology or outpatient dental clinic. Neither group differed in the number of caries-affected primary and permanent teeth, gingival condition or use of fluoride specimens. The iNS group presented lower levels of magnesium (0.41 ± 0.34 vs. 0.60 ± 0.38 mg/dL, P < 0.05) and fluoride (0.15 ± 0.10 vs. 0.21 ± 0.10 ppm, P < 0.01) and higher contents of urea (35.19 ± 15.55 vs. 25.21 ± 10.78 mg/dL, P < 0.01) and uric acid (2.90 ± 1.23 vs. 2.34 ± 1.04 mg/dL, P < 0.05) than the controls. In the iNS participants with relapse, a higher peroxidase activity and lower magnesium content than in the remission phase were found. ROC analysis showed a weak discriminatory power of these salivary constituents for the differentiation of participants with and without disease (accuracy from 66.0 to 67.0%, area under the ROC curve (AUC) from 0.638 to 0.682) and the relapse and remission phases (accuracy 70.2% and 68.1% and AUC 0.717 and 0.675, respectively). Conclusions Levels of urea, uric acid, magnesium and fluoride in saliva can be associated with the course of iNS. Salivary levels of peroxidase and magnesium can be related to the phase of the disease. However, the measurements of these parameters cannot be useful as a noninvasive tool in diagnosing iNS and the phase of the disease.

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Salivary cytokines in children with nephrotic syndrome versus healthy children: a comparative study

Cited by 2 publications

References 20 publications

Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome

Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome

Selected salivary parameters in children with idiopathic nephrotic syndrome: a preliminary study

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