Correlation between Toll-like Receptor Gene Polymorphisms and Idiopathic Nephrotic Syndrome in Chinese Children

Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.

Pediatric Nephrotic Syndrome in a Cameroonian Cohorte: The Beast to Slaughter

Background: Idiopathic nephrotic syndrome (INS) is a frequent pathology in children. There is little data on the future of NS in children in sub-Saharan Africa, particularly Cameroon. The aim of our study is to report the prognosis of children treated for nephrotic syndrome in the city of Yaoundé. Method: This was an analytical cross-sectional study with retrospective collection in 4 reference hospitals in the Cameroonian capital over a period of five years from January 1, 2018 to December 31, 2022. We included all medical records of patients treated for idiopathic INS. We excluded incomplete records and those with a history of chronic kidney disease. The sociodemographic, clinical, paraclinical, and therapeutic data, as well as the short-term evolution were collected in the files. Data was analysed using the software statistical package for social sciences version 25.0. Statistical significance was set at a p-value Results: A total of 131 children (58% boys) were included in our study over a period of 5 years. The median age was 8 [6 - 11] years. Median proteinuria was 5 g/24h [3 - 8.4], median serum protein was 39 [34 - 46] g/l and median estimated glomerular filtration rate was 130.36 [68 - 174.6] ml/min/1.73m2. During steroid therapy, 45.07% were in partial remission at 2 months, 16.9% were in complete remission at 4 and 6 months, and 37.25% had relapsed. Steroid sensitivity was reported in 28.17% of cases, steroid resistance in 64.78% of cases and steroid dependent in 7.04% of cases. The mortality rate was 12.97%. Survival time averaged 48.2 months, with an overall crude survival rate of 99.2% at 3 and 6 months and 98.4% at 1 year. Regarding renal survival, renal function was impaired in 8.33% of patients at 6 months and 9% at 12 months. Conclusion: Idiopathic nephrotic syndrome is a common disease in children. Its evolution depends on corticosteroid therapy. The long-term prognosis is dominated by the risk of progression to end-stage kidney disease or even death. Rigorous and affordable follow-up is essential to reduce the number of patients lost to follow-up and the occurrence of complications.

T-cell and B-cell repertoire diversity are selectively skewed in children with idiopathic nephrotic syndrome revealed by high-throughput sequencing

Background Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome(INS),but laboratory evidence is lacking.Therefore,this study explored T-cell receptor(TCR)and B-cell receptor(BCR)profiling in children with idiopathic nephrotic syndrome.Methods High-throughput sequencing technology was used to profile the TCR and BCR repertoires in children with INS.Peripheral blood was collected from ten INS patients,including five vinculin autoantibody-positive patients and five vin-culin autoantibody-negative patients,before and after treatment.TCR and BCR libraries were constructed by 5'-RACE and sequenced by a DNBSEQ-T7 sequencer,and sequence analyses were performed using ReSeqTools,FastP,MiXCR,and VDJtools.Results The TRA(T-cell receptorα),TRG(T-cell receptor y),and IGH(immunoglobulin heavy chain)repertoires of the INS group were occupied by highly abundant clonotypes,whereas small clonotypes occupied the healthy group,especially TRA.A significant increase in the Shannon-Weaver index was observed for the TRA and TRG repertoires after treatment in vinculin autoantibody-negative patients,but a significant increase in the IGH repertoire after treatment was observed in vinculin autoantibody-positive patients.The frequency of some V-J pairs was significantly enriched in steroid-sensitive nephrotic syndrome patients.The usage frequency of the V and J genes was skewed in patients,which seemed not related to immunosuppressive therapy.However,after effective treatment,dynamic changes in the size of the individual clonotype were observed.Conclusion T-cell and B-cell immunity contribute to the pathogenesis of different INSs.

Immunopathogenesis of idiopathic nephrotic syndrome in children:two sides of the coin

Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.

Serum erythropoietin and transferrin in children with idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome(INS)is char-acterized by marked urinary excretion of albumin and other intermediate-sized plasma proteins,such as trans-ferrin and vitamin D-binding protein.Some cases even develop anemia.The aim of this study was to investigate the changes in serum iron,transferrin,and erythropoietin,and the relationships between serum and urine transferrin and erythropoietin.Thirty-seven children with INS and 35 age-and sex-matched healthy children were investi-gated.The indexes related to iron metabolism,including serum iron,ferritin,transferrin,total iron-binding capa-city(TIBC),transferrin saturation,and hematological parameters[hemoglobin(Hb),mean corpuscular volume(MCV),mean corpuscular hemoglobin(MCH)],and urin-ary transferrin and erythropoietin were measured in 37 children with INS before treatment and at the remission stage.Thirty-five age-and sex-matched healthy children served as controls.Serum iron levels(18.8±3.8)mmol/L in INS patients before treatment were significantly lower than those of the healthy controls(22.2±3.8)mmol/L and those measured at the remission stage(21.0±3.5)mmol/L(all P<0.01).Serum transferrin levels in INS patients before therapy(1.9±0.3)g/L also decreased compared with the healthy controls(3.1±0.5)g/L and the measures at the remission stage(2.9±0.6)g/L(all P<0.01).In contrast,serum TIBC and transferrin saturation were sig-nificantly higher in INS patients before treatment than in the healthy controls[TIBC(56.4±9.2)mmol/L vs(50.7±6.8)mmol/L,P<0.01;transferrin saturation(55.7±9.2)%vs(46.4±8.2)%,P<0.01]and they were also higher than the measures at remission stage[(51.9±7.7)mmol/L and(47.4±13.3)mmol/L](all P<0.01).Serum transferrin was positively correlated with serum albumin(r= 50.609,P<0.01)and negatively correlated with urinary transferrin(r= 520.550,P<0.01)in INS patients before treatment.We conclude that serum iron,transferrin and erythropoietin levels are markedly decreased in INS patients,which may be partially related to the urinary loss of these indexes.

Clinical Observation of Senile Idiopathic Nephrotic Syndrome Treated with Integrated Traditional Chinese and Western Medicine

Objective: To observe the clinical effect of integrated traditional Chinese and western medicine (TCM-WM) in treating senile idiopathic nephrotic syndrome (SINS). Methods: Eighty-two patients of SINS were randomly divided into two groups. The 41 patients in the TCM-WM group were treated with prednisone, Cytoxan (CTX) and Chinese medicinal herbs according to Syndrome-type, and the 41 patients in the control group were treated with western medicine alone. The clinical remission rate and time, recurrence rate in patients as well as adverse reaction rate occurred were observed. Results: The complete remission rate and total effective rate of the TCM-WM group were 58.5% and 85.4%, which were significantly higher than those of the control group (39.0% and 63.4%, P<0.01). The adverse reaction rate in the TCM-WM group was 36.6%, which was significantly lower than that of the control group (80.5%, P<0.01). A follow-up of 35.1±9.7 months showed that there was no significant difference in the recurrence rate between the two groups (P>0.05), but the average remission period (30.6±3.8 months) of the TCM-WM group was significantly longer than that of the control group (12.7±3.7 months, P<0.01). Conclusion: TCM-WM treatment is obviously superior to that with western medicine alone in increasing clinical remission rate, relieving adverse reaction rate and extending remission period.

Histopathology Review of Idiopathic Steroid Resistant Nephrotic Syndrome and Outcome in Children in North-West of Iran

Introduction: There is currently little information in the literature on the spectrum of histopathologic patterns in children presenting with idiopathic steroid-resistant nephrotic syndrome (iSRNS) in Iran. We conducted to compare the histopathologic distribution of different subtypes’ glomerular morphologic patterns in iSRNS and the clinical and biochemical parameters at the time of diagnosis and outcome of patients after immunosuppressive therapy. Material and Methods: This cross sectional study was done in two hundred children, aged 1 - 15 years, who were diagnosed for iSRNS and no response to 4 weeks of standard prednisone therapy (60 mg/m2/day) referred to nephropathology Department of Emam Reza hospital between 2005 and 2013. Demographic, clinical, laboratory, and histopathological data were retrieved from files and original renal biopsy reports. We discussed histopathologic diagnosis and outcome of iSRNS after initial therapy in patients separately. This study investigated prognostic effects of histopathologic pattern on outcome of iSRNS. Results: The study included 200 children with iSRNS: 141 (70.5%) were males and 59 (29.5%) females, with male-to-female ratio of 2.4:1. The mean age was 7.23 ± 4.37 years (range: 1 - 15 years). Upon pathologic investigation of iSRNS cases, focal segmental glomerulosclerosis (NOS subtype) was the first, with a highest prevalence at a rate of 102/200 (51%) and MGN was the last, at a rate of 7/200 (3.5%). Children with iSRNS secondary to MCD are more likely to achieve remission and have better long term prognostic value (P 0.00). Focal segmental glomerulosclerosis (FSGS) (Tip and Collapse subtypes) is more likely to have worse outcome in response to immunosuppressive therapy (P 0.04). Conclusions: This study defines the true spectrum of clinicohistopathology patterns underlying iSRNS in children in Northwest of Iran. Also this study shows that the response to cyclosporine can be correlated with the underlying histopathology patterns which have been earned by adequate renal biopsy.

Idiopathic Adult Nephrotic Syndrome: A Clinicopathological Study and Response to Steroid in a Sub-Saharan African Country

Introduction: Idiopathic nephrotic syndrome represents 25% to 30% of glomerulonephritis in adults. These glomerulonephritides are responsible of about the half of chronic kidney failure examined as well in United States as in Europe or Africa. The aim of this study was to determine the anatomoclinic, therapeutic and progression patterns of idiopathic nephritic syndrome in Dakar. Patients and Methods: It is a retrospective ten-year study in the nephrology department of Aristide Le Dantec Hospital. Patients with idiopathic nephrotic syndrome were included. We analyzed anatomoclinic, therapeutic and progression data of idiopathic nephrotic syndrome. Results: On 202 patients with nephrotic syndrome, 156 (77%) were primitive. The mean age was 29.7 ± 12 years with a sex ratio of 2.4. Edema was found in 98 patients (62.8%) and hypertension in 63 patients (40%). The mean proteinuria was 6.8 ± 4.8 g/24h. Histologic lesions found at renal biopsy were focal segmental glomerulosclerosis in 71 patients (45.5%), minimal change disease in 68 patients (43.5%) and membranous nephropathy in 8 patients (5%). 134 patients (85.8%) received steroids alone, 12 patients (7.6%) received cyclophosphamide and 4 patients (2.5%) azathioprine in association with steroids. 44 patients (28.2%) reached remission. The factors of poor prognosis were: age, above 40 years, proteinuria above 10 g/24h, existence of renal failure at admission, absence of use of steroids therapy. Conclusion: This study shows that idiopathic nephrotic syndrome is frequent in our country with a prevalence of 77%. The most common lesion found at the renal biopsy is the focal segmental glomerulosclerosis. Remission is found only in 28% which is very low. 33% of patients progress towards chronic kidney disease due to the lack of early diagnosis and the use of traditional medicine.