Pediatric Idiopathic Nephrotic Syndrome Research Articles

Immunogenicity, Immunological Memory and monitoring of disease activity following an anamnestic immunization with the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Children with Idiopathic Nephrotic Syndrome.

Anamnestic PCV13 immunization did not affect the relapse risk in pediatric Idiopathic Nephrotic Syndrome. PS-specific antibody titers increased significantly in all groups. Children receiving immunomodulatory treatments(IMTs) displayed significantly lower levels of PS-specific antibodies for 3/8 serotypes tested. PS-specific B-cell counts significantly increased only in healthy controls and patients receiving corticosteroids.

A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood.

The clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the first episode. In this monocentric prospective cohort study we set up a reproducible and standardized flow cytometry panel using two sample tubes (one for B-cell and one for T-cell subsets) to extensively characterized the lymphocyte repertoire of INS pediatric patients. A total of 44 children with INS at disease onset were enrolled, sampled before and 3 months after standard induction therapy with prednisone and followed for 12 months to correctly classify their disease based on relapses. Age-matched controls with non immune-mediated renal diseases or with urological disorders were also enrolled. Demographical, clinical, laboratory and immunosuppressive treatment data were registered. We found that children with INS at disease onset had significantly higher circulating levels of total CD19+ and specific B-cell subsets (transitional, mature-naïve, plasmablasts/plasmacells, CD19+CD27+, unswitched, switched and atypical memory B cells) and reduced circulating levels of Tregs, when compared to age-matched controls. Prednisone therapy restored most B- and T-cell alterations. When patients were subdivided based on disease relapse, relapsing patients had significantly more transitional, CD19+CD27+ memory and in particular unswitched memory B cells at disease onset, which were predictive of a higher risk of relapse in steroid-sensitive patients by logistic regression analysis, irrespective of age. In accordance, B-cell dysregulations resulted mainly associated with steroid-dependence when patients were stratified in different disease severity forms. Of note, Treg levels were reduced independently from the disease subgroup and were not completely normalized by prednisone treatment. We have set up a novel, reproducible, disease-specific flow cytometry panel that allows a comprehensive characterization of circulating lymphocytes. We found that, at disease onset, relapsing patients had significantly more transitional, CD19+CD27+ memory and unswitched memory B cells and those who are at higher risk of relapse had increased circulating levels of unswitched memory B cells, independently of age. This approach can allow prediction of clinical evolution, monitoring of immunosuppression and tailored treatment in different forms of INS.

Rituximab therapy for childhood onset idiopathic nephrotic syndrome: experience of a Portuguese tertiary center.

Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.

Urinary podocyte-derived large extracellular vesicles are increased in paediatric idiopathic nephrotic syndrome.

Journal Article Accepted manuscript Urinary podocyte-derived large extracellular vesicles are increased in pediatric idiopathic nephrotic syndrome Get access Robert L Myette, Robert L Myette Children's Hospital of Eastern Ontario, Division of Pediatric Nephrology, University of Ottawa, Ottawa, Ontario, CanadaKidney Research Center, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada https://orcid.org/0000-0002-6441-8612 Search for other works by this author on: Oxford Academic PubMed Google Scholar Fengxia Xiao, Fengxia Xiao Kidney Research Center, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Pavel Geier, Pavel Geier Children's Hospital of Eastern Ontario, Division of Pediatric Nephrology, University of Ottawa, Ottawa, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Janusz Feber, Janusz Feber Children's Hospital of Eastern Ontario, Division of Pediatric Nephrology, University of Ottawa, Ottawa, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Dylan Burger, Dylan Burger Kidney Research Center, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada Correspondence to: Dylan Burger; E-mail: dburger@uottawa.ca https://orcid.org/0000-0003-3951-2911 Search for other works by this author on: Oxford Academic PubMed Google Scholar Christopher R J Kennedy Christopher R J Kennedy Kidney Research Center, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada Correspondence to: Christopher R.J. Kennedy; E-mail: ckennedy@uottawa.ca Search for other works by this author on: Oxford Academic PubMed Google Scholar Nephrology Dialysis Transplantation, gfad086, https://doi.org/10.1093/ndt/gfad086 Published: 29 April 2023

IgM deposition is a risk factor for delayed remission and early relapse of the pediatric minimal change disease.

Minimal change disease (MCD) is the most common pathological subtype of pediatric idiopathic nephrotic syndrome (INS). It has been suggested that IgM deposition might predict kidney function deterioration in the course of MCD. However, the specific role of IgM deposition in the prognosis of MCD is still controversial. This study aims to investigate the clinical significance of IgM deposition on delayed remission and early relapse in a pediatric population. This study enrolled 283 children diagnosed with MCD by renal biopsy in a single center from 2010 to 2022. These cases were divided into two groups according to the histopathological deposition of IgM. Patients' demographics, clinical parameters, and follow-up data were collected and analyzed. The primary and secondary outcomes were defined as the time to the first remission and the first relapse. The IgM-positive group had a weaker response to steroids (steroid-sensitive: 23.5% vs. 40.8%; steroid-dependent: 74.0% vs. 51.0%; steroid-resistant: 18.4% vs. 8.2%, P = 0.001), and showed more recurrent cases (47.2% vs. 34.4%, P = 0.047) compared with the IgM-negative group. The Kaplan-Meier analysis showed that the IgM-positive group had a lower cumulative rate of the first remission (Log-rank, P < 0.001) and a higher rate of the first relapse (Log-rank, P = 0.034) than the IgM-negative group. Multivariate Cox analysis showed that IgM deposition was independently associated with the delayed first remission (hazard ratio [HR] = 0.604, 95% confidence interval [CI] = 0.465-0.785, P < 0.001) and the early first relapse (HR = 1.593, 95% CI = 1.033-2.456, P = 0.035). IgM deposition was associated with a weaker steroid response. MCD children with IgM deposition were prone to delayed first remission and early first relapse.

Changes in Patterns of Infection Associated with Pediatric Idiopathic Nephrotic Syndrome: A Single-Center Experience in Japan

We studied infection rates and risk factors for infection in current patients with idiopathic nephrotic syndrome (INS). This retrospective cohort study included the clinical data for children with diagnosed INS in our center between January 2010 and December 2020. The infection rates and risk factors were analyzed. We enrolled 187 patients, including 85 cases with steroid-dependent/frequently relapsing nephrotic syndrome and 45 with steroid-resistant nephrotic syndrome. Infection was observed a total of 84 times in 55 patients (95.5 per 1000 person-years). Pneumonia was the most common infection (21 cases, 23.9 per 1000 person-years), followed by febrile neutropenia (12 cases, 13.7 per 1000 person-years), whereas peritonitis and bacteremia were observed in only 3 and 2 cases, respectively. The multivariate analyses by logistic regression showed that rituximab treatment was significantly associated with infections in pediatric INS (P=.001). The infection rate during the B-cell-depleted state with immunosuppressants (318 per 1000 person-years) was greater than that with normal B-cell count with immunosuppressants (109 per 1000 person-years) or without immunosuppressants (76 per 1000 person-years). Common infections, such as peritonitis and bacteremia, decreased, whereas infections associated with medication (eg, rituximab) increased. The rate of infection increases during B-cell depletion after treatments with rituximab and other immunosuppressants.

A study to evaluate the pattern, causality, predictability, and severity of adverse drug reactions to corticosteroid therapy in pediatric idiopathic nephrotic syndrome at a tertiary care center

A study to evaluate the pattern, causality, predictability, and severity of adverse drug reactions to corticosteroid therapy in pediatric idiopathic nephrotic syndrome at a tertiary care center

Serum albumin level is associated with mycophenolic acid concentration in children with idiopathic nephrotic syndrome.

Mycophenolate mofetil is effective for the treatment of pediatric idiopathic nephrotic syndrome (INS). The dosage of mycophenolate mofetil is adjusted according to the serum concentration of mycophenolic acid (MPA). Kidney function or cyclosporine (CsA) concentrations affect serum MPA levels. However, few studies have focused on the association between serum concentrations of MPA and albumin. This retrospective observational study aimed to evaluate the relationship between the serum concentrations of MPA and albumin in INS children. Subjects were children with INS who underwent the therapeutic drug monitoring of CsA and MPA. We obtained the serum albumin (sAlb) concentration, estimated glomerular filtration rate (eGFR), age, and MPA and CsA areas under concentration-time curves from 0 to 12h (AUC0-12). Multiple linear regression analysis and generalized estimating equations were performed to predict values for MPA AUC0-12. We obtained information for 51 INS children with 261 MPA AUC0-12 measurements. The standardized regression coefficients of sAlb, eGFR, CsA AUC0-12, and age were 0.54, - 0.21, - 0.07, and 0.04, respectively. Furthermore, MPA AUC0-12 levels positively correlated with sAlb concentrations (p < 0.001) and were inversely correlated with eGFR values (p = 0.005) but not with CsA AUC0-12 (p = 0.24) and age (p = 0.65).Conclusion: Serum albumin concentration was strongly associated with total MPA concentration compared with kidney function or CsA values. Although patients with INS may have a low serum concentration of total MPA in the presence of low sAlb concentration, close attention should be paid to the interpretation of the low MPA values. What is Known: • The dosage of mycophenolate mofetil is adjusted according to the serum concentration of total mycophenolic acid. • Kidney function, cyclosporin concentrations, or serum albumin concentrations influence serum mycophenolic acid levels. What is New: • Serum albumin concentration is more strongly associated with total mycophenolic acid concentration than kidney function or cyclosporin values. • In children with nephrotic syndrome, the total mycophenolic acid concentration may not increase in the presence of severe hypoalbuminemia.

Belimumab for the treatment of children with frequently relapsing nephrotic syndrome: the BELNEPH study.

Effectiveness of rituximab in pediatric idiopathic nephrotic syndrome suggests that B cells play a pathogenic role. We tested safety and efficacy of the B-cell-modulating agent belimumab in frequently relapsing nephrotic syndrome (FRNS). An open-label, prospective, single-arm pilot study (EUDRACT 2017-003839-11) was designed to treat 10 children with FRNS with i.v. belimumab for 12 months. Prednisone was tapered/stopped. Safety, number of relapses, cumulative prednisone dose and B-cell subset "levels" are referred to both B cell subset and immunoglobulin. Five patients were enrolled, and four reached the primary 6-month endpoint. Of these, two completed the 12-month endpoint. Three patients experienced ≥2 relapses while on belimumab, requiring additional immunosuppression. Compared to the 6 months before belimumab treatment, the mean number of relapses (1.4 vs. 2, p=0.21) and the mean cumulative prednisone dose (1.86 vs. 2.62 g/m2, p=0.17) were not significantly reduced during the 6 months on belimumab. This study was terminated by the steering committee after the interim evaluation because belimumab failed to show clear benefits to counterbalance the inconvenience of monthly i.v. infusion. During follow-up, total and mature-naïve B cells decreased, while no change in memory B-cells was observed. Serum immunoglobulins remained stable. No infusion reaction was observed. Short-term treatment with belimumab in pediatric FRNS was well tolerated. The number of patients was too small to draw conclusions on efficacy. Nonetheless, we did not observe clear improvements. The burden of monthly in-hospital i.v. infusions outweighed potential benefits. Persistence of circulating memory B cells supports their pathogenic role in the disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

Expressions of Toll like receptor-2, -4 , -6 in peripheral blood mononuclear cells and the association of serum IgG and IgM levels in children with idiopathic nephrotic syndrome

Objective To investigate expressions of Toll-like receptor(TLR)-2, TLR-4 and TLR-6 in peripheral blood mononuclear cells (PBMC) and serum immunoglobulin G (IgG) and IgM levels in pediatric idiopathic nephrotic syndrome (INS). The correlation between Toll-like receptors (TLR-2, TLR-4 and TLR-6) and serum immunoglobulin levels (IgG and IgM) will be proven in the pathogenesis of childhood INS in active stage (AS) and remission stage (RS). Methods Forty-two INS patients (experimental group, 32 boys, 10 girls) and 29 healthy individuals (healthy control group, 19 boys, 10 girls) were enrolled in the present study from June, 2017 to October, 2018 in the First Affiliated Hospital of Xinxiang Medical University. There were no significant differences in gender (χ2=0.966, P=0.326) and age (t=-0.139, P=0.89) between 2 groups.TLR-2 mRNA, TLR-4 mRNA and TLR-6 mRNA expressions of PBMC were evaluated by using real-time PCR in both INS children with AS and RS and healthy children.The blood samples were drawn to detect by way of immunoturbidimetry serum immunoglobulin (IgG and IgM) levels in both INS children with AS and healthy children.The correlation between Toll-like receptors (TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin (IgG, IgM) levels were analyzed by using spearman correlation analysis. Results The expression levels of TLR-2 mRNA in INS children with AS, RS and healthy children were 1.85±0.30, 1.00±0.23 and 0.85±0.12, respectively, and the expression levels of TLR-4 mRNA were 1.24±0.27, 0.80±0.23 and 0.68±0.09, respectively, while the expression levels of TLR-6 mRNA were 1.35±0.23, 0.92±0.19 and 0.79±0.15, respectively, so the differences were statistically significant(F=198.453, 67.013, 82.405, all P 0.05). Conclusions The results indicate that Toll-like receptors (TLR-2, TLR-4 and TLR-6) and immunoglobulin (IgG, IgM) might play a role in the pathogenesis of pediatric INS via distinct pathway. Key words: Idiopathic nephrotic syndrome; Child; Toll-like receptor; Peripheral blood mononuclear cell; Immunoglobulin

Prolonged Impairment of Immunological Memory After Anti-CD20 Treatment in Pediatric Idiopathic Nephrotic Syndrome.

Anti-CD20 therapy is effective in idiopathic nephrotic syndrome (INS). However, transient or sustained hypogammaglobulinemia predisposing to an increased risk of infectious diseases can follow treatment in some patients. We analyzed the long-term effects of anti-CD20 therapy on immunological memory in 27 frequently-relapsing/steroid-dependent INS pediatric patients after more than 4 years from the first and at least 2 years from the last anti-CD20 infusion. Twenty-one INS children, never treated with anti-CD20 and under an intense oral immunosuppression with prednisone, mycophenolate mofetil, and calcineurin inhibitors were also included as control group. Levels of circulating B-cell subpopulations, total serum immunoglobulins and IgG and memory B cells directed against hepatitis B virus (HBV) and tetanus were determined and correlated with clinical characteristics. Nine patients never relapsed after more than 2 years from the last anti-CD20 administration (5 after the first, 3 after the second, and 1 after the fifth infusion). At last follow-up, most patients showed a complete recovery and normalization of total (27/27), transitional (27/27), and mature-naïve B cells (25/27). However, a sustained and significant reduction of total memory (20/27) and switched memory (21/27) B cells was found in most patients. 11/27 patients showed hypogammaglobulinemia at last follow-up and, among these, four presented with a severe hypogammaglobulinemia (IgG < 160 mg/dl). In contrast, no patient in the control group developed a severe hypogammaglobulinemia. Age at the time of first anti-CD20 administration was positively associated with IgG levels at last follow-up (p = 0.008); accordingly, younger patients had an increased risk of hypogammaglobulinemia (p = 0.006). Furthermore, severe hypogammaglobulinemia and delayed switched memory B-cell reconstitution were more frequent in non-relapsing patients. Reduced IgG levels against HBV and tetanus were observed at baseline and further declined at last follow-up. Antigen-specific memory B-cells were induced by re-immunization, but specific IgG titers remained low. In conclusion, anti-CD20 therapy can be disease-modifying in some INS patients. However, a prolonged impairment of immunological memory occurs frequently, independently from the number of anti-CD20 infusions, particularly in younger patients. Re-immunization may be necessary in these patients.

B cell phenotype in pediatric idiopathic nephrotic syndrome.

A pathogenic role of B cells in non-genetic nephrotic syndrome has been suggested by the efficacy of rituximab, a B cell depleting antibody, in maintaining a prolonged remission. However, little information is available on B cell homeostasis in nephrotic syndrome patients. We retrospectively analyzed by flow cytometry the distribution of different B cell subpopulations in 107 steroid-sensitive and in 6 genetic steroid-resistant nephrotic syndrome pediatric patients, compared with age- and sex-matched controls. Fifty-one steroid-sensitive patients at disease onset, before starting immunosuppression, presented significantly increased levels of total, transitional, memory, and switched memory B cells compared to controls. Oral immunosuppression strongly affected transitional and mature B cell levels in 27 patients in relapse and also in 29 patients in remission, whereas memory B cells were significantly higher compared to controls during relapse, despite the immunosuppressive treatment, and were normalized only in patients in remission. Children with genetic forms of steroid-resistant nephrotic syndrome presented no differences in B cell profile from controls. Our study indicates that memory B cells, more than other B cell subsets, are increased and appear to be pathogenically relevant in steroid-sensitive nephrotic syndrome pediatric patients.

Néphrologie pédiatrique : que doit savoir un néphrologue d’adulte sur ces pathologies ?

In nephrology, some diseases begin specifically during childhood; however, they must be known by adult nephrologists so that to ensure continuity and homogeneity for their management. The aim of this review is therefore to propose a brief overview of the main pediatric diseases, for which a specific knowledge is warranted, and notably pediatric idiopathic nephrotic syndrome, cystinosis, primary hyperoxaluria and hereditaries tubulopathies.

Combined supplementation with α-tocopherol and vitamin C improves the blood pressure of pediatric idiopathic nephrotic syndrome patients

Summary The purpose of the present study was to investigate the effects of combined supplementation with α-tocopherol and vitamin C on blood pressures and levels of ox-LDL and NOx in with pediatric idiopathic nephrotic syndrome patients. A total of thirty-six pediatric idiopathic nephrotic syndrome patients was involved in the study, which was assigned randomly into two groups, the control group of pediatric idiopathic nephrotic syndrome patients who received a standard therapy and placebo and the group of pediatric idiopathic nephrotic syndrome patients who received a standard therapy plus α-tocopherol and vitamin C. α-tocopherol and vitamin C were administered at a dose of 10–15 mg/kg/day for 12 weeks. An analysis of lipid profile and NOx was performed by means of a spectrophotometer. An analysis of ox-LDL was performed by using the enzyme-linked immunosorbent assay technique. There was a significant decrease in the number of prehypertensive and hypertensive patients in the supplementation group relative to the control group (p 0.50). In conclusion, the combined supplementation with α-tocopherol and vitamin C may improve blood pressure in pediatric idiopathic nephrotic syndrome patients. Thus, combination of α-tocopherol and vitamin C can be used in the clinical management of pediatric idiopathic nephrotic syndrome.

MDR-1 and CYP3A5 Polymorphisms in Pediatric Idiopathic Nephrotic Syndrome: Impact on Susceptibility and Response to Steroids (Preliminary Results).

Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). However, resistance to this treatment has been observed in some patients. Here, we investigated the association of two steroid metabolism-related genes with susceptibility to childhood NS and the steroid response. We genotyped the single nucleotide polymorphisms (SNP) of MDR-1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and the CYP3A5 gene (A6986G) in 63 NS patients and 110 age and gender matched controls by PCR-RFLP. Based on multivariate logistic regression analysis carrying the G2677A A allele seemed to multiply both the risk of NS and the risk of developing glucocorticoid (GC) resistance by three-fold (OR = 3.50, [1.37 - 7.06] , p < 0.001, OR = 3.07, [1.06 - 26.10], p = 0.048, respectively). When combined into haplotype, the TAT (1236_T, 2677_A, and 3435_T) haplotype conferred a two-fold NS risk (OR = 2.26, [1.11 - 4.58], p = 0.023) and almost three-fold risk to develop resistance to GC (OR = 2.69, [1.12 - 8.79], p = 0.044). However, TAT carriers seemed to have less risk to develop NS at late age (OR = 0.34, [0.12 - 0.92], p = 0.037). The C1236T (MDR-1) and the A6986G (CYP3A5) polymorphisms showed a trend of association to GC resistance but these associations did not reach the statistical significance (OR = 2.83, [0.54 - 14.67], p = 0.294), (OR = 2.11, [0.53 - 8.38], p = 0.28), respectively. Here we report that only the G2677A polymorphism was associated to NS susceptibility and steroid resistance. The TAT haplotype was associated with NS susceptibility especially at an early age and with steroid resistance.

Apolipoprotein C-I Levels Are Associated with the Urinary Protein/Urinary Creatinine Ratio in Pediatric Idiopathic Steroid-Sensitive Nephrotic Syndrome: A Case Control Study.

Humoral factors may cause idiopathic steroid-sensitive nephrotic syndrome (ISSNS). In the present study, we analyzed serum proteins using mass spectrometry (MS) to identify proteins associated with the pathophysiology of pediatric ISSNS. We collected serial serum samples from 33 children during each ISSNS phase; Phase A1 is the acute phase prior to steroid treatment (STx), Phase A2 represents the remission period with STx, and Phase A3 represents the remission period after completion of STx. Children with normal urinalyses (Group B) and children with a nephrotic syndrome other than ISSNS (Group C) served as controls. No significant differences in urinary protein/urinary creatinine (UP/UCr) ratios were observed between the children with phase A1 ISSNS and Group C. We used surface-enhanced laser desorption/ionization time of flight MS for sample analysis. Four ion peaks with a mass-to-charge ratio (m/z) of 6,444, 6,626, 8,695, and 8,915 were significantly elevated during ISSNS Phase A1 compared to Phase A2, Phase A3, and Group C. The intensity of an m/z of 6,626 significantly correlated with the UP/UCr ratio and an m/z of 6,626 was identified as apolipoprotein C-I (Apo C-I). Apo C-I levels correlate with the UP/UCr ratio in pediatric ISSNS. Our findings provide new insights into the pathophysiology of ISSNS.

SXR rs3842689: a prognostic factor for steroid sensitivity or resistance in pediatric idiopathic nephrotic syndrome.

of the study was to analyse the impact of SXR rs3842689 polymorphism on the response to corticosteroids in pediatric idiopathic nephrotic syndrome. 66 children (56 steroid-sensitive, ten steroid-resistant) were studied for SXR gene polymorphism distribution. Steroid sensitive patients accounted for 96% of cases with In/In polymorphism, but only for 53% of cases with Del/Del polymorphism At odds ratio analysis, Del/Del represented a clear risk factor of steroid resistance (OR: 20.57; p = 0.009), while In/In was a favourable prognostic factor of steroid sensitivity. The analysis of SXR polymorphism is a promising tool to predict both the favourable response to corticosteroids and the risk of developing steroid resistance.

In vitro sensitivity to methyl-prednisolone is associated with clinical response in pediatric idiopathic nephrotic syndrome.

The aim of this study was to evaluate the in vitro steroid sensitivity as a predictor of clinical response to glucocorticoids in childhood idiopathic nephrotic syndrome (INS). Seventy-four patients (median age 4.33, interquartile range [IQR] 2.82-7.23; 63.5% male) were enrolled in a prospective multicenter study: in vitro steroid inhibition of patients' peripheral blood mononuclear cell proliferation was evaluated by [methyl-(3) H] thymidine incorporation assay at disease onset (T0) and after 4 weeks (T4) of treatment. Steroid dependence was associated with increased in vitro sensitivity at T4 assessed both as drug concentration inducing 50% of inhibition (IC50 ; odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.24-0.85; P = 0.0094) and maximum inhibition at the highest drug concentration (Imax ; OR = 1.13, 95% CI = 1.02-1.31; P = 0.017). IC50 > 4.4 nM and Imax < 92% at T4 were good predictors for optimal clinical response. These results suggest that this test may be useful for predicting the response to glucocorticoid therapy in pediatric INS.

Single Nucleotide Polymorphisms in Pediatric Idiopathic Nephrotic Syndrome.

Polymorphic variants in several molecules involved in the glomerular function and drug metabolism have been implicated in the pathophysiology of pediatric idiopathic nephrotic syndrome (INS), but the results remain inconsistent. We analyzed the association of eleven allelic variants in eight genes (angiopoietin-like 4 (ANGPTL4), glypican 5 (GPC5), interleukin-13 (IL-13), macrophage migration inhibitory factor (MIF), neural nitric oxide synthetase (nNOS), multidrug resistance-1 (MDR1), glucocorticoid-induced transcript-1 (GLCCI1), and nuclear receptor subfamily-3 (NR3C1)) in 100 INS patients followed up till adulthood. We genotyped variants using PCR and direct sequencing and evaluated estimated haplotypes of MDR1 variants. The analysis revealed few differences in SNP genotype frequencies between patients and controls, or in clinical parameters among the patients. Genotype distribution of MDR1 SNPs rs1236, rs2677, and rs3435 showed significant (p < 0.05) association with different medication regimes (glucocorticoids only versus glucocorticoids plus additional immunosuppressives). Some marginal association was detected between ANGPTL4, GPC5, GLCCI1, and NR3C1 variants and different medication regimes, number of relapses, and age of onset. Conclusion. While MDR1 variant genotype distribution associated with different medication regimes, the other analyzed gene variants showed only little or marginal clinical relevance in INS.

小児特発性ネフローゼ症候群の初発患者における入院期間短縮化の検討

小児特発性ネフローゼ症候群の初発患者における入院期間短縮化の検討