The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature

Kitsou, Konstantina; Askiti, Varvara; Mitsioni, Andromachi; Spoulou, Vana

doi:10.1007/s00431-021-04357-9

Cited by 11 publications

(4 citation statements)

References 81 publications

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“…When activated and phosphorylated, STAT6 regulates gene expression in different cells in the nucleus and mediates many pathological features of inflammatory responses in animal models [ 25 ]. Studies have shown that the significantly increased expression of STAT6mRNA may be connected with the early course of NS [ 26 ]. IL-13 promotes STAT6 phosphorylation and nuclear translocation, and may participate in inflammation and apoptosis in renal injury [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

Yao

Liu

et al. 2023

Pharmaceuticals

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The Stephania tetrandra–Astragalus membranaceus herbal pair (FH) is a classic herbal pair widely used in the treatment of nephrotic syndrome (NS). The effects of Stephania tetrandra (FJ) and Astragalus membranaceus (HQ) on NS have been reported, but the mechanism of their combination on the improvement of NS are still unclear. The NS model was established by injecting adriamycin into the tail vein. FH intervention reduced the levels of serum triglyceride, total cholesterol, interleukin-6 (IL-6), blood urea nitrogen (BUN), urinary protein, and the gene expression levels of aquaporin 2 (AQP2) and arginine vasopressin (AVP) in NS rats. In addition, FH improved kidney injury in NS rats by inhibiting the expression of interleukin 13 (IL-13), phospho-signal transducers, and activators of transcription 6 (p-STAT6), Bax, cleaved-caspase3, while promoting the expression of Bcl-2. By comprehensive comparison of multiple indexes, the effects of FH on lipid metabolism, glomerular filtration rate, and inflammation were superior to that of FJ and HQ. Metabonomic studies showed that, compared with FJ and HQ, FH intervention significantly regulated tricarboxylic acid (TCA) cycle, cysteine and methionine metabolism, and alanine, aspartic acid and glutamic acid metabolism. Pearson correlation analysis showed that succinic acid and L-aspartic acid were negatively correlated with urinary protein, cystatin C (Cys C) and BUN (p < 0.05). In summary, FH could reduce renal injury and improve NS through inhibiting the IL-13/STAT6 signal pathway, regulating endogenous metabolic pathways, such as TCA cycle, and inhibiting the expression of AQP2 and AVP genes. This study provides a comprehensive strategy to reveal the mechanism of FH on the treatment of NS, and also provides a reasonable way to clarify the compatibility of traditional Chinese medicine.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

Yao

Liu

et al. 2023

Pharmaceuticals

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“…Studies have shown that B cells participate in the immunological dysregulation of INS. 13 The reducing effects of RTX were delayed over time. B cells begin to recover 3-4 months after infusion, while memory B cells, particularly IgM memory B cells, remain low during the first year and then start to regenerate.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that B cells participate in the immunological dysregulation of INS 13. The reducing effects of RTX were delayed over time.…”

Section: Discussionmentioning

confidence: 99%

Protocol for an open-label, single-arm, multicentre clinical study to evaluate the efficacy and safety of rituximab in the first episode of paediatric idiopathic nephrotic syndrome

et al. 2022

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IntroductionRituximab (RTX) effectively prevents relapses in patients with complicated steroid-sensitive nephrotic syndrome (SSNS). The 1-year relapse-free survival rate is approximately 30% in children after the first episode of SSNS treated with standardised corticosteroids. Whether the benefits of RTX extend to the first relapse are unknown. The efficacy and safety of RTX in the first episode of paediatric idiopathic nephrotic syndrome (RTXFIRPedINS) trial (NCT04783675) will assess its effect on the risk of subsequent relapse.Methods and analysisRTXFIRPedINS is an open-label, single-arm, multicentre trial targeting patients aged 1–18 years with a first episode of SSNS. All patients will receive standardised corticosteroid treatment for 12 weeks. A sample size of 44 patients provides 80% power to detect a 20% increase in the 1-year relapse-free rate, assuming a dropout rate of 10%. After obtaining informed consent and screening, eligible patients will be treated with a single intravenous infusion of 375 mg/m2RTX within 1 week after achieving remission. Trimethoprim-sulfamethoxazole will be administered for 3 months after RTX administration to preventPneumocystis cariniiinfection. The follow-up period will be 1 year. The primary outcome is the 1-year relapse-free survival rate after RTX infusion. The secondary study outcomes are the number of days from the infusion of RTX to the occurrence of the first relapse, 6-month relapse-free survival rate, the B cell recovery time and treatment-related adverse events. Immunological factors will be studied as predictors of response.Ethics and disseminationThis trial was approved by the Ethics Committee of the Children’s Hospital of Fudan University and seven local ethics committees. We will publish our study results in peer-reviewed journals and present them at international scientific meetings.Trial registration numberNCT04783675

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“…It results from enhanced plasma protein permeability of the glomerular filtration membrane. Although most patients benefit from steroid treatment, 10%-20% of affected children have steroid-resistant nephrotic syndrome (SRNS) ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome

Elsehmawy,

Gouda,

Diab

et al. 2024

J Circ Biomark

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Background and aim: The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). Materials and methods: The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Results: Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. Conclusions: The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

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The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature

Cited by 11 publications

References 81 publications

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

Protocol for an open-label, single-arm, multicentre clinical study to evaluate the efficacy and safety of rituximab in the first episode of paediatric idiopathic nephrotic syndrome

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome

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