Primary Nephrotic Syndrome Research Articles

Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome

Objective: To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers. Methods: The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types. Results: There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-old with the onset age of 4.5 (3.2, 6.8) years. The proportion of SRNS was significantly higher in patients >10-year-old than those ≤10-year-old (24.6% (29/118) vs. 15.9% (65/408), χ2=4.66, P=0.031). There was no statistical difference in the pathological types between >10-year-old and ≤10-year-old (P>0.05), with minimal change disease the most common type (56.0% (14/25) vs. 60.5% (26/43)). The percentage of cases with renal tubulointerstitial lesions was significantly higher in children >10-year-old compared to those ≤10-year-old (60.0% (15/25) vs. 23.3% (10/43), χ2=9.18, P=0.002). There were 29 cases presented with SRNS in PNS over 10-year-old, including 19 initial non-responders and 10 late non-responders. Analyzed by Kaplan-Meier curve, it was shown that the percentage of persistent proteinuria after 6 months of immunosuppressive treatments was significantly higher in initial non-responders than those of the late non-responders ((22±10)% vs. 0, χ2=14.68, P<0.001); the percentage of minimal change disease was significantly higher in patients of late non-responders than those of the initial non-responders (5/6 vs. 3/13, P=0.041). Of the 63 >10-year-old with steroid-sensitive nephrotic syndrome followed up more than one year, 38 cases (60.3%) had relapse, and 14 cases (22.2%) were frequent relapse nephrotic syndrome and steroid dependent nephrotic syndrome. Among the 45 patients followed up over 18-year-old, 22 cases (48.9%) had recurrent proteinuria continued to adulthood, 3 cases of SRNS progressed to kidney insufficiency, and one of them developed into end stage kidney disease and was administrated with hemodialysis. Conclusions: Cases over 10-year-old with PNS tend to present with SRNS and renal tubulointerstitial lesions. They have a favorable prognosis, but are liable to relapse in adulthood.

Epigenetic markers of podocyte repair in children with primary nephrotic syndrome

In terms of a glomerular injury research model, idiopathic nephrotic syndrome is the most prominent example. Worldwide, nephrotic syndrome is a socially significant disease and is considered one of the most common glomerulopathies in childhood, leading to the development of chronic kidney disease, and in the case of progression of the disease, to the formation of terminal chronic renal failure. This article presents data from our own study and discusses epigenetic markers of podocyte repair in children with primary nephrotic syndrome. We noted that in patients with steroid-sensitive variants of nephrotic syndrome, the expression of the WT1 (podocyte transcription factor) and NPHS1 (the gene encoding nephrin — a transmembrane protein that is a structural component of the slit diaphragm of the podocyte) genes is significantly higher than in the control group and in children with steroid resistant nephrotic syndrome. The data obtained open up prospects for the development of a personalized approach to the management of children with primary nephrotic syndrome by determining the markers of the staging and/or severity of the pathological process occurring in the glomeruli. Currently, genomic and post-genomic technologies are increasingly being used in clinical practice, which will eventually lead to the development of personalized diagnostic panels based on innovative technologies.

Significance of changes in FGF23 levels in childhood primary nephrotic syndrome and children who progress to end‑stage renal disease.

Fibroblast growth factor 23 (FGF23) is an important phosphaturic hormone, yet few studies have focused on FGF23 in children with primary nephrotic syndrome (PNS) and children who progressed to end-stage renal disease (ESRD). This cross-sectional study investigated the significance of changes in FGF23 levels in childhood PNS and children who progressed to ESRD. Of the 41 children included in the study, 17 had PNS with proteinuria and normal renal function (PNS group), 4 had ESRD (ESRD group), and 20 were healthy (control group). Following corticosteroid treatment, patients with PNS and proteinuria entered the remission phase. Serum levels of FGF23, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), and calcium were measured. It was found that FGF23 levels in the PNS and ESRD groups were higher than those in the control group, while serum 25-OH-D levels were lower. Serum PTH levels increased significantly in the ESRD group. In the control group, FGF23 levels were negatively correlated with serum PTH and positively correlated with serum 25-OH-D. FGF23 levels were positively correlated with serum calcium and corrected calcium levels in children with PNS during the remission phase. Increased FGF23 levels in children with PNS, particularly in children who progressed to ESRD. It was also confirmed that serum FGF23 levels begin to rise in children with PNS prior to Stage 1 chronic kidney disease. These findings indicated that increased FGF23 levels may be associated with the progression and severity of nephrosis in children, and that serum FGF23 levels were useful for early detection of abnormal mineral metabolism in children with PNS.

Value of ultrasound imaging-omics features in the diagnosis of primary nephrotic syndrome

BackgroundPrimary nephrotic syndrome (PNS) is a common autoimmune systemic suppressive disease that, if left untreated, can develop into end-stage renal disease in severe cases, seriously threatening the health of patients. This disease is gradually attracting attention, and ultrasound imaging histology is being tried for PNS as a noninvasive examination method; however, ultrasound imaging histology has not yet seen clinical application in the diagnosis of PNS; therefore, this study investigates the value of ultrasound imaging histological features in the diagnosis of PNS. MethodsA total of 126 PNS patients hospitalized in the Nephrology Department of Hangzhou First People's Hospital from January 2016 to November 2020 were collected in the PNS group, and 11 7 volunteers from the physical examination center were in the normal control group (NC group). The 7:3 stratified sampling was divided into training set (171 cases) and validation set (72 cases), 396 imaging omics parameters of the right kidney ultrasound image were extracted, statistical different parameters were selected after dimension reduction, the prediction model was constructed by Logistics regression, and the ROC curve was drawn to evaluate the efficacy of PNS. Results 19 imaging omics parameters were obtained in Least Absolute Shrinkage and Selection Operator (Least Absolute Shrinkage and Selection Operator, LASSO) after dimension reduction, and the constructed model had good efficacy for predicting PNS. The area under the curve of training set was 0.82, the accuracy, specificity, sensitivity, positive predictive value and negative predictive value were 0.75,0.77,0.78 and 0.73; the validation set was 0.84, accuracy, specificity, sensitivity, positive, and ne gative predictive values were 0.76,0.80,0.72,0.79 and 0.74, respectively. ConclusionThe imaging omics parameters of the right kidney have the potential as non-invasive biological markers for PNS diagnosis, and can provide more accurate imaging basis for the diagnosis and treatment of PNS patients.PNS has a rapid onset and severe symptoms, especially the prevalence and incidence of PNS in children (Alfakeekh et al., 2019; Nephrology Group Pediatric Branch of Chinese Medical Association, 2017). Because the kidneys of PNS patients have no specific signs during routine imaging examination, puncture examination is mostly used clinically to determine the pathological type, but puncture is a traumatic examination and a secondary injury to the kidney, so seeking the noninvasive biological markers of PNS is the focus of current research. Imaging omics is a rapidly developing discipline in recent years. The imaging omics studies on kidney at home and abroad mainly include benign and malignant classification of kidney space, pathological classification of clear cell carcinoma, kidney stone research and so on (Farber et al., 2015; Homayounieh et al., 2021; Ursprung et al., 2020a, 2020b), However, imaging studies based on the kidney itself of nephrotic syndrome are still blank. In this study, the author conducted a retrospective study on the imaging omics analysis of the right kidney of PNS patients, and constructed a predictive model, aiming to provide a new method for the accurate diagnosis of PNS.

Inadequate treatment in a patient with minimal change disease (MCD) nephrotic syndrome: a case report

Introduction: Minimal change disease (MCD) is the cause of primary nephrotic syndrome in about 90% of children but is rare in adults and only found in about 10% to 15% of adults. Adequate steroid therapy can lead to complete remission in more than 80% of adults with MCD nephrotic syndrome. This study aimed to report a case of an adult patient with nephrotic syndrome with renal biopsy results of MCD and her clinical improvement after adequate therapy with glucocorticoids. Case Presentation: We report a case of a female patient, 35 years old, who complained of swelling all over the body 3 months before admission. Previously, the patient was diagnosed with nephrotic syndrome on December 2020 and received oral steroid therapy that had been tapered down early, which caused the clinical symptoms to recur. The patient underwent a kidney biopsy, and MCD was found on histopathological examination. The patient received supportive therapy and resumed steroid therapy with adequate dosage. On the six-month follow-up, the patient was in complete remission. Conclusion: MCD is a nephrotic syndrome with a good prognosis, and 80% of patients will respond to adequate therapy. Our patient's previous medical history was re-evaluated, and concluded that the previous patient had received inadequate therapy. The patient has now reached a state of complete remission. This case highlighted the importance of adequate therapy in managing nephrotic syndrome.

#5215 OFATUMUMAB AS A RESCUE THERAPY FOR PATIENTS WITH MEMBRANOUS NEPHROPATHY

Abstract Background and Aims Rituximab is the first-line treatment for patients with primary membranous nephropathy (MN) and nephrotic syndrome (NS) at high risk of progression to end-stage kidney disease. However, this drug is effective only in approximately two thirds of treated patients, and repeated rituximab infusions may be complicated by hypersensitivity reactions, which contraindicate retreatment. Ofatumumab, a fully human anti-CD20 antibody, could overcome these limitations. Method We retrospectively evaluated the response to a single 50–300 mg dose of intravenous ofatumumab in 17 MN patients referred to our institution who either experienced hypersensitivity reactions (rituximab-intolerant, n = 5) or failed to achieve NS remission after rituximab infusion (rituximab-resistant, n = 12). Results Over a median [IQR] follow-up of 5.0 [3.0-9.8] months, ten (58.8%) patients—five rituximab-resistant (41.7%) and all five rituximab-intolerant—achieved complete or partial NS remission, defined as proteinuria &amp;lt;0.3 g/day or proteinuria &amp;lt;3.5 g/day with ≥50% reduction from baseline, respectively. Ofatumumab infusion induced a progressive reduction in 24-hour urinary protein and IgG excretion, and a sharp increase in serum albumin and IgG levels. Peripheral B cells were depleted in all patients and started reconstituting by 3 months from baseline. Seven of the 12 subjects with PLA2R-related disease (i.e. with baseline anti-PLA2R antibody levels &amp;gt;2.7 RU/mL by ELISA) achieved antibody depletion during the follow-up (half of rituximab-resistant and all rituximab-intolerant). There were 14 non-serious infusion-related adverse events in nine patients, all of which completely resolved with temporary interruption of ofatumumab infusion. Conclusion Ofatumumab may be an effective and safe treatment option for all rituximab-intolerant and a substantial proportion of rituximab-resistant MN patients.

Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

Primary nephrotic syndrome in children in Cape Town, South Africa

Background. Histopathological patterns of childhood primary nephrotic syndrome (PNS) and clinical response to steroids have beenassociated with certain race groups in parts of South Africa. However, there are no recent studies of childhood PNS in Cape Town.Objectives. To describe the demographics, histological subtypes and steroid response of patients with PNS who underwent kidney biopsiesat Red Cross War Memorial Children’s Hospital (RCWMCH) over a 10-year period.Methods. Details of patients with PNS who underwent kidney biopsies in the Paediatric Nephrology Department at RCWMCH between2006 and 2015 were retrospectively recorded.Results. A total of 103 patients were included in the study. Most patients were either of mixed race (42%) or black (36%), with a mean age of6.8 years and a male-to-female ratio of 1.19:1. The most identified histopathological subtype was mesangioproliferative glomerulonephritis(MesPGN; 60% (n/N=62/103)). Of the patients with focal segmental glomerulosclerosis (FSGS), MesPGN and minimal change disease(MCD) 45% (n/N=43/95) were steroid-resistant, and 54% (n/N=51/95) were steroid-sensitive. There was no significant associationbetween any race group and steroid response. Patients with FSGS were more likely to be black, while MCD was more common in mixed-race patients (p=0.04). There was no difference in the likelihood of being mixed race or black between patients with FSGS and MesPGN(p=0.472).Conclusion. MesPGN was the most common histopathological subtype found in our study. There was no significant association betweenrace and steroid response. Patients with FSGS were more likely to be black than mixed race when compared with MCD patients. Race wasnot otherwise significantly associated with any histopathological subtype

Angiopoietin-like protein 3: a novel potential biomarker for nephrotic syndrome in children.

Angiopoietin-like 3 (ANGPTL3) is a secretory glycoprotein. It has been demonstrated that ANGPTL3 level was upregulated in minimal change nephrotic syndrome (MCNS) kidney tissues. Subsequently, our group found that ANGPTL3 level was closely correlated with nephropathy in vivo and in vitro. Hence, whether ANGPTL3 level could be correlated with the proteinuria level, and assessment of disease severity of nephrotic syndrome (NS) remained to be investigated. This study aimed to analyzed the correlation between the levels of ANGPTL3 in serum and urine of patients with nephrotic syndrome and proteinuria, and assessed the severity of the patients' disease. In future clinical translation, the level of ANGPTL3 in serum, urine will be used as a biomarker to better predict the development of nephrotic syndrome. A total of 200 NS patients and 80 healthy controls (age, 1-18 years) were admitted to our institution between 2021 and 2022. The etiology of NS included primary nephrotic syndrome (PNS, n = 144) and NS with other causes (n = 56). A total of 280 serum samples and 244 urinary samples were collected to determine ANGPTL3 level using enzyme-linked immunosorbent assay (ELISA). Serum ANGPTL3 and urinary ANGPTL3/Cre were remarkably elevated in NS patients compared with those in healthy controls. Furthermore, serum ANGPTL3 and urinary ANGPTL3/Cre were significantly correlated with proteinuria level. Additionally, multivariate linear regression analysis demonstrated that serum ALB was independently correlated with serum ANGPTL3 and PRO/CR was independently correlated with urinary ANGPTL3/Cre in NS patients. Serum ANGPTL3 and urinary ANGPTL3/Cre showed a promising performance in the diagnosis of NS, and served as novel potential noninvasive biomarkers to assess disease severity of NS. Further exploration of the role of ANGPTL3 level may shed a new light on the treatment of NS.

Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome

Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in <I>FKBP5</I> and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of <I>FKBP5,</I> in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between <I>FKBP5</I> polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of <I>FKBP5</I> in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of <I>FKBP5</I> may be correlated with plasma lipid levels (LDL) in PNS patients.

Incidence of thromboembolism in children with primary nephrotic syndrome: a systematic review and metaanalysis

ObjectiveTo estimate the incidence of thromboembolism in children with primary nephrotic syndrome with Meta-analysis.MethodsRelevant studies published from January 1, 1980 to December 31, 2021 were retrieved from Pubmed, Web of science, Cochrane library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database(VIP) and Wangfang Database. Quality evaluation of the literatures included was conducted according to Agency for Healthcare Research and Quality(AHRQ) assessment tool, followed by data extraction and Meta-analysis with software RevMan 5.3.ResultsA total of seven studies involving 3675 subjects were included. The overall prevalence was 4.9% with 95% CI of 2.83 to 7.05.However, a significant heterogeneity (P < 0.001) was observed with I2 = 89%. The prevalence of venous thromboembolism was 3.3% with 95% CI of 1.7 to 4.9. The prevalence of arterial thromboembolism was 0.5% with 95% CI of 0.2 to 1.4.ConclusionChildren with nephrotic syndrome are prone to thromboembolism, and it may lead to disability or death, therefore prevention measures is critical to decreasing the prevalence of thromboembolism.

Mycophenolate mofetil in therapy of primary nephrotic syndrome in children

Idiopathic nephrotic syndrome is the most common glomerular disease in children, with a prevalence of 1.15–16.9 cases per 100,000 children per year worldwide. In some cases, nephrotic syndrome has a frequently relapsing course or dependence on steroid therapy is formed, which leads to the appointment of immunosuppressive therapy. So far, in clinical practice, there is no unambiguous approach among physicians to the management of patients with nephrotic syndrome, especially when it comes to the further choice of immunosuppressive therapy. Because of the serious side effects of long-term corticosteroid use, doctors prescribe steroid adjuvants to maintain remission and limit the cumulative effect of glucocorticosteroids. Among adjuvants, mycophenolate mofetil, with mycophenolic acid as the active ingredient, is believed to be the most preferred option due to fewer adverse events, acceptable tolerability and, at the same time, high efficacy. This article describes the advantages and features of the use of mycophenolic acid in clinical practice, provides data on pharmacodynamics and drug monitoring, and discusses issues of personalized medicine.

Differential diagnosis of secondary hypertension based on deep learning

Secondary hypertension is associated with higher risks of target organ damage and cardiovascular and cerebrovascular disease events. Early aetiology identification can eliminate aetiologies and control blood pressure. However, inexperienced doctors often fail to diagnose secondary hypertension, and comprehensively screening for all causes of high blood pressure increases health care costs. To date, deep learning has rarely been involved in the differential diagnosis of secondary hypertension. Relevant machine learning methods cannot combine textual information such as chief complaints with numerical information such as the laboratory examination results in electronic health records (EHRs), and the use of all features increases health care costs. To reduce redundant examinations and accurately identify secondary hypertension, we propose a two-stage framework that follows clinical procedures. The framework carries out an initial diagnosis process in the first stage, on which basis patients are recommended for disease-related examinations, followed by differential diagnoses of different diseases based on the different characteristics observed in the second stage. We convert the numerical examination results into descriptive sentences, thus blending textual and numerical characteristics. Medical guidelines are introduced through label embedding and attention mechanisms to obtain interactive features. Our model was trained and evaluated using a cross-sectional dataset containing 11,961 patients with hypertension from January 2013 to December 2019. The F1 scores of our model were 0.912, 0.921, 0.869 and 0.894 for primary aldosteronism, thyroid disease, nephritis and nephrotic syndrome and chronic kidney disease, respectively, which are four kinds of secondary hypertension with high incidence rates. The experimental results show that our model can powerfully use the textual and numerical data contained in EHRs to provide effective decision support for the differential diagnosis of secondary hypertension.

Systematic Evaluation and Reevaluation of Oral Chinese Herbal Decoction in the Treatment of Primary Nephrotic Syndrome

Systematic Evaluation and Reevaluation of Oral Chinese Herbal Decoction in the Treatment of Primary Nephrotic Syndrome

Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis.

Therapeutic options with immunosuppressive agents for glomerular diseases have widened with refinements to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines from 2012 to 2021. However, international guidelines do not necessarily match the reality in each country. Expensive therapies such as rituximab and calcineurin inhibitors are sometimes inaccessible to patients with refractory nephrotic syndrome due to cost or regulations. Under the Japanese medical insurance system, rituximab is accessible but still limited to steroid-dependent patients who developed idiopathic nephrotic syndrome in childhood. Based on international KDIGO guidelines and other national guidelines, possible applications of immunosuppressive agents for nephrotic syndrome are comprehensively examined in this review. While rituximab has become the mainstay of immunosuppressive therapy for nephrotic syndrome, clinical trials have indicated that options such as cyclophosphamide, calcineurin inhibitors, and mycophenolate mofetil would be preferable. Given the rising number of patients with nephrotic syndrome worldwide, KDIGO guidelines mention the need for further consideration of cost-effectiveness. If the new option of rituximab is to be the first choice in combination with steroids for nephrotic syndrome, its cost-effectiveness should also be verified. Among the few studies examining the cost-effectiveness of treatments for nephrotic syndrome, administration of rituximab to young adults has been shown to be cost-beneficial, at least in Japan. However, further large-scale studies involving multiple facilities are needed to verify such findings. Network meta-analyses have concluded that the efficacy of rituximab remains controversial and confirmation through high-quality studies of large cohorts is needed. To this end, the mechanisms of action underlying immunosuppressive agents, both old and new, need to be understood and experience must be accumulated to evaluate possible effects and side effects.

WCN23-1097 Primary steroid resistant nephrotic syndrome as part of Schimke-immunoosseous dysplasia features in a girl: a case report

WCN23-1097 Primary steroid resistant nephrotic syndrome as part of Schimke-immunoosseous dysplasia features in a girl: a case report

Treatment with rituximab and hydroxychloroquine in a patient with membranous nephropathy and diabetic nephropathy: A case report

Abstract Nephrotic syndrome (NS), which includes primary and secondary types, is one of the causes of end-stage kidney disease. Common causes in adults include diabetic nephropathy (DN), membranous nephropathy (MN), and focal segmental glomerulosclerosis. About 30%–40% of diabetics can develop into DN. The incidence of primary nephrotic syndrome in diabetic patients was not significantly different from that in the general population. Herein we present a windfall from the treatment of rituximab combined with hydroxychloroquine in a patient with primary MN and DN. A 51-year-old Chinese man, diagnosed with type 2 diabetes mellitus (T2DM) 12 years ago, was admitted to the hospital due to edema of bilateral lower limbs and severe proteinuria. Serology showed the obvious elevation of the anti-phospholipase A2 receptor (anti-PLA2R) level and renal biopsy showed MN concomitant with DN. After low dosage of prednisone and standard dosage of rituximab, the patient’s proteinuria decreased; however, the effect was unsatisfactory and proteinuria was elevated again in 8 months. Thus, treatment with rituximab and hydroxychloroquine was initiated, which resulted in proteinuria diminishing significantly and albumin returning to normal level. Therefore, even complicated with DN, patients diagnosed with primary MN still have a promising remission after being treated with rituximab and hydroxychloroquine.

Initiation of renin-angiotensin system inhibitors and first complete remission in patients with primary nephrotic syndrome: a nationwide cohort study.

Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. This cohort study included 84 adults (median age, 65years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR. Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced firstCR (incidence rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR] 2.27, 95% confidence interval [CI] 1.06-4.84), and lower (aIRR: 0.17, 95% CI 0.04-0.68) firstCR in patients with membranous nephropathy and other pathologies, respectively. RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy.

Left ventricular global longitudinal strain can detect subclinical left ventricular systolic dysfunction in adult patients with primary nephrotic syndrome.

It has been shown that there is an increased risk of cardiovascular events such as heart failure and death in nephrotic syndrome. Left ventricle global longitudinal strain (LVGLS) is a more sensitive measure of assessing myocardial dysfunction and is more reproducible than left ventricle ejection fraction (LVEF%). LVGLS can detectsubclinical deterioration in the left ventricle early. In this study, we aimed to investigate LVGLS in Primary Nephrotic Syndrome (PNS) patients with normal LVEF%. Patients with histopathologically confirmed PNS were evaluated for this prospective single-center study. Patients with similar age and gender characteristics without nephrotic syndrome were included as the control group. LVGLS measurements were performed by 2D speckle tracking echocardiography. A total of 171 patients, 57 with PNS and 114 in the control group, were included in the study. The mean age was 38±12 years in the study population, and 95(56%) of the patients were women. LVEF% was 60.2±4.2 in the PNS group and 61.1±3.2 in the control group, and there was no significant difference between the two groups (p=0.111). LVGLS was found to be significantly lower in the PNS group (-19.3±2.3% vs.-20.8±1.5 %, p<0.001). A significant relationship was observed between PNS and LVGLS in the multivariable linear regression analysis (β= 4.428, CI 95% =0.57?1.48, p<0.001). A significant relationship was observed between PNS and LVGLS, and LVGLS was found to be lower in PNS patients. In patients with PNS, subclinical left ventricular systolic dysfunction may be detected in the early period by measuring LVGLS.

Primary nephrotic syndrome relapse within 1year after glucocorticoid therapy in children is associated with gut microbiota composition at syndrome onset.

Children with primary nephrotic syndrome (PNS) who relapse after glucocorticoid therapy are shown to have a decreased total proportion of butyrate-producing bacteria in the gut at onset. Glucocorticoid treatment changes the gut microbiota composition. It is unclear whether gut microbiota at remission right after therapy and gut bacteria other than butyrate-producing bacteria are associated with PNS relapse. PNS relapse of paediatric patients within 1year after glucocorticoid therapy was recorded. The gut microbiota composition, profiled with 16S rRNA gene V3-V4 region sequencing, was compared between relapsing and non-relapsing PNS children at onset before glucocorticoid treatment (preT group) and in PNS children at remission right after treatment (postT group), respectively. The gut microbiota composition of postT children significantly differed from that of preT children by having lower levels of Bacteroides, Lachnoclostridium, Flavonifractor, Ruminococcaceae UBA1819, Oscillibacter, Hungatella and Coprobacillus and higher levels of Ruminococcaceae UCG-013 and Clostridium sensu stricto 1 group. In the preT group, compared with non-relapsing patients, relapsing patients showed decreased Blautia, Dialister and total proportion of butyrate-producing bacteria and increased Oscillibacter, Anaerotruncus and Ruminococcaceae UBA1819. However, relapsing and non-relapsing postT children showed no difference in gut microbiota composition. PNS relapse-associated gut microbiota dysbiosis at onset, which includes alterations of both butyrate-producing and non-butyrate-producing bacteria, disappeared right after glucocorticoid therapy. It is necessary to study the association of the longitudinal changes in the complete profiles of gut microbiota after glucocorticoid treatment with later PNS relapse.