A case report on primary collapsing glomerulopathy in a Filipino post-partum female and an updated review of literature

@#Collapsing Glomerulopathy (CG) is a rare entity presenting as nephrotic syndrome and rapidly progressive renal deterioration. It has been first identified among African-American patients and subsequently dubbed HIV-associated nephropathy after a number of patients with HIV were found to have CG. It has re-emerged recently among patients with COVID-19. To our knowledge, this is the first case of primary collapsing glomerulopathy in the country to be published. The case is a 36-year-old Filipino female admitted due to bipedal edema which started 2 weeks post-partum. She has no comorbidities and social history was negative for illicit drug use. Initial work up showed hypoalbuminemia and diffuse hepatic disease on ultrasound. She was referred to a gastroenterologist where albumin infusion and paracentesis was done but with no improvement. She developed anasarca and was admitted. Paracentesis obtained minimal ascitic fluid. Serum ascites albumin gradient was low and baseline laboratories showed high creatinine, hypoalbuminemia, and albuminuria. 24-hour urine protein was 11 grams, ANA and anti-DsDNA were negative and c3 and c4 levels were normal. Hepatitis profile was negative for infection. Abdominal CT scan revealed multiple hypoenhancing lesions. Tumor markers CA-125, CA 19-9 and CA 15-3 were high. Breast ultrasound showed simple breast cyst. Gynecology consult was called where pap smear was negative for atypical cells. Surgery service recommended monitoring for the pancreatic and breast lesions. Kidney biopsy was delayed due to new onset bacterial pneumonia. COVID-19 RT-PCR test was negative. Patient was discharged improved with no edema. On follow up, the kidney biopsy result came out to be collapsing glomerulopathy. HIV test was then done and was negative. Bipedal edema and albuminuria recurred. She was started on tacrolimus. She has been on regular follow up and currently has no edema, no proteinuria and normal creatinine level. This is an interesting case as the primary glomerular disease has been masked by the earlier laboratory findings which led us to think of liver disease then a paraneoplastic nephrotic syndrome. Ultimately, the renal biopsy revealed the diagnosis. This serves as an index case for primary collapsing glomerulopathy in a Filipino patient on remission after being treated with tacrolimus.

Minimal change disease associated with SARS-CoV-2 (COVID-19) infection among adult Filipinos: A report of two cases and review of related literature

@#A 40-year-old Filipino female with a history of right total mastectomy for a low-grade phyllodes tumor was admitted due to stillbirth. Her laboratory results revealed an incidental finding of a positive COVID-19 RT-PCR swab, serum creatinine 1.04 mg/dL, urine RBC 1/HPF, and a 24-hour urine protein of 9.22 grams with hypoalbuminemia and dyslipidemia. Serologic workup was noted to be negative. A kidney biopsy was performed which demonstrated unremarkable light microscopy (LM) and immunofluorescence (IF) with widespread podocyte-foot process effacement, consistent with minimal change disease. She was started on prednisone (1 mg/kg/day) and achieved complete remission after six weeks. A 61-year-old Filipino male with a history of Type 2 Diabetes Mellitus, Hypertension, Dyslipidemia, and mild COVID-19 infection four months prior, now presented with diarrhea. On admission, his COVID-19 RT-PCR swab revealed a reinfection. Workup demonstrated a serum creatinine 3.39 mg/dL, urine RBC 2/HPF, and urine ACR 2.6 g/g. Serologic tests were negative. He was diagnosed with Nephrotic Syndrome and underwent kidney biopsy. Findings showed an unremarkable LM and IF with widespread podocyte-foot process effacement, consistent with minimal change disease. He was started on prednisone (1 mg/kg/day) and achieved complete remission after eight weeks. SARS-CoV-2 (COVID-19) may present with a variety of kidney involvement which includes glomerulopathies such as MCD. An accurate diagnosis using the patient’s clinical presentation, renal histopathology, and adjunct laboratory examinations, is essential to direct effective management and good outcomes.

Proteinuria y síndrome nefrótico / Proteinuria and Nephrotic Syndrome

Introducción: El síndrome nefrótico es una patología que afecta el complejo glomerular del riñón, se caracteriza por una proteinuria mayor 3500 mg/d. De acuerdo a la respuesta de los esteroides se puede clasificar en síndrome nefrótico en esteroide resistente o esteroide sensible. Objetivo: Determinar la relación que existe entre la proteinuria y las variantes del síndrome nefrótico en adultos. Métodos: Se realizó un estudio descriptivo, retrospectivo, tipo serie de casos, con una población de 28 pacientes. Se recolectaron y se procesaron los datos a través del software Epi-Info 7,2TM; la frecuencia simple, la media estadística, prueba t de Student, y el coeficiente de correlación de Pearson. Resultados: En el análisis combinatorio de los fármacos adyuvantes para síndrome nefrótico, el grupo que utilizó antiproteinúricos pero no estatinas, demostró una diferencia estadísticamente significativa entre la proteinuria postratamiento media del grupo de síndrome nefrótico esteroideo resistente (6202 mg/d) vs síndrome nefrótico esteroideo sensible (65,9 mg/d) (valor de p 0,418). Existe una correlación negativa entre los niveles proteinuria postratamiento y el nivel de albúmina sérica postratamiento (r = - 0,7 valor de p < 0,00001). Conclusiones: Se demostró la ausencia de asociación entre la proteinuria inicial y las variantes de síndrome nefrótico esteroide sensible y esteroide resistente (valor de p = 0,8)(AU)

Introduction: Nephrotic syndrome is a pathology that affects the glomerular complex of the kidney, characterized by proteinuria greater than 3500 mg/d. According to the response to steroids, nephrotic syndrome can be classified as steroid-resistant or steroid-sensitive. Objective: To determine the relationship between proteinuria and the variants of the nephrotic syndrome in adults. Methods: A descriptive, retrospective, case series type study was carried out with a population of 28 patients. The data was collected and processed through Epi-Info 7.2TM software; simple frequency, statistical mean, student's t-test, and Pearson's correlation coefficient. Results: The statistically significant difference was obtained in the antiproteinuric and non-statin group, between the mean post-treatment proteinuria of the steroid resistant nephrotic syndrome group (6202 mg/d) in comparison to steroid sensitive nephrotic syndrome (65.9 mg/d) (p value 0.0418). There is negative correlation between post-treatment proteinuria levels and post-treatment serum albumin level (r= -0.7 p value <0.00001). Conclusions: The absence of association between initial proteinuria and steroid-sensitive and steroid-resistant variants of nephrotic syndrome was demonstrated (p value=0.8)(AU)

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.

Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Increased behavioural problems associated with corticosteroid use in children with nephrotic syndrome: a Southeast Asian perspective

INTRODUCTION@#The study was performed to determine the psychological problems in children with idiopathic nephrotic syndrome (INS) while they were on steroid therapy, as compared to healthy children.@*METHODS@#This prospective cohort study was conducted in a paediatric clinic of a tertiary hospital. Parents of the participants in the INS group and control group (comprising children without chronic illness) completed questionnaires using the Child Behavioural Checklist (CBCL). The CBCL measures a range of age-specific emotional and psychological problems, including internalising and externalising domains. Analyses of the CBCL scores between groups were done using Mann-Whitney U test.@*RESULTS@#A total of 140 children were recruited with an equal number in the INS and control groups. There was a significant difference in the mean total CBCL scores between the INS group and the control group, specifically in the withdrawal, somatic, anxious and aggressiveness subdomains. Similar findings were demonstrated in correlation between total psychological problems and corticosteroid dosage. In the INS group, steroid dose and cushingoid features were found to have a significant positive association with internalising psychological problems.@*CONCLUSION@#Children with INS on corticosteroid treatment showed an increase in internalising and externalising scores, as compared to healthy children.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome / 中华儿科杂志

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome / 中华儿科杂志

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.

Long-term outcomes of childhood steroid-sensitive nephrotic syndrome / 中华儿科杂志

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ2 or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ2=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ2=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.

Establishment and validation of clinical prediction model for steroid-resistant nephrotic syndrome in children / 中华儿科杂志

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ2=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ2=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway / 中国天然药物

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Enfermedad de cambios mínimos cortico-resistente e hipotiroidismo. Reporte de caso / Steroid-resistant minimal change disease and hypothyroidism: Case report

Introducción: La enfermedad de cambios mínimos es una causa rara de síndrome nefrótico en el adulto, y su relación con el hipotiroidismo es más rara aún. Se considera que esta patología renal responde favorablemente al manejo con glucocorticoides y tiene una baja frecuencia de resistencia. Su abordaje hoy en día es objeto de investigación. Objetivo: Describir una rara etiología de síndrome nefrótico en el adulto con presentación, tratamiento y desenlace infrecuentes. Presentación del caso: Paciente femenino de 53 años quien inicia con síndrome nefrótico por enfermedad de cambios mínimos cortico-resistente y su asociación con un hipotiroidismo descontrolado, quien requiere manejo con rituximab y control de la enfermedad endocrinológica asociada, como enfermedad de base. Conclusiones: En este caso clínico se muestra como las enfermedades citadas pueden coexistir y el tratamiento en conjunto es necesario. El establecimiento de nuevas terapias en la población adulta como el rituximab podría mostrar beneficio, como en este caso. Sin embargo, aún existe la necesidad de estudios de mayor evidencia que validen firmemente la efectividad de los diferentes tratamientos en este tipo de pacientes.

Introduction: Minimal change disease is a rare cause of nephrotic syndrome in adults, and its association with hypothyroidism is even more exceptional. This renal pathology is considered to respond favorably to glucocorticoid management and has a low resistance frequency. How to approach this disease is currently under investigation. Objective: To describe a rare etiology of adult nephrotic syndrome with unusual presentation, treatment, and outcome. Case presentation: A 53 years-old female patient who initially experienced nephrotic syndrome due to steroid-resistant minimal change disease, which was also associated with uncontrolled hypothyroidism. She required management with rituximab and control of the associated endocrinological disease, which was considered as the underlying disease. Conclusions: This clinical case shows (i) how the two aforementioned diseases can coexist and (ii) that a joint treatment is necessary. Establishing new therapies may be beneficial for adult populations, such as the benefits seen in this case with the use of rituximab. However, further studies are needed to strongly validate the effectiveness of the different treatments for these types of patients.

Efficacy of adrenocorticotropic hormone in children with frequently relapsing or steroid-dependent nephrotic syndrome / 中华儿科杂志

Objective: To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in children with frequently relapsing or steroid-dependent nephrotic syndrome. Methods: The clinical data of 38 children with frequently relapsing or steroid-dependent nephrotic syndrome who were admitted to the Department of Nephrology, the Children Hospital, Zhejiang University School of Medicine from January 2015 to December 2020 were retrospectively analyzed. The general information, clinical manifestations, laboratory data of the children and follow-up (till 12 months after treatment) were collected. The patients were divided into ACTH group and Glucocorticoid (GC) group according to treatment plan. Cumulative remission, average recurrence rate, GC dosage, height and weight change and peripheral blood CD19+B lymphocyte count were compared between the two groups to evaluate the efficacy and adverse reactions of ACTH. Fisher's exact test, t test or rank sum test was used for comparison between groups. Results: Among the 38 patients, 28 were male and 10 were female, aged 84 (24, 180) months; 19 were in ACTH group and 19 were in GC group. The cumulative remission rate of 12 months in ACTH group was higher than that in GC group (9/19 vs. 2/19,χ²=6.81,P=0.009), the average recurrence rate was lower than that in GC group ((0.7±0.8) vs. (1.7±1.1) times, t=-3.27, P=0.011), and the average dosage of GC was lower than that in GC group ((0.27±0.16) vs. (0.51±0.27) mg/(kg·d), t=-3.21, P=0.014). The increase in height was higher than that in the GC group (4 (3,5) vs. 3 (2, 3) cm/year, Z=2.58, P=0.010), and the peripheral blood CD19+B lymphocyte count was lower than that in the GC group ((223±149)×106 vs. (410±213)×106/L,t=-3.35, P=0.009). In safety, 19 cases had transient decreased urine volume, 7 cases had hyperglycemia, and 3 cases had hypertension during the infusion of ACTH, which could be relieved after drug withdrawal. Conclusion: ACTH has a better effect on children with frequently relapsing or steroid-dependent nephrotic syndrome, which can improve cumulative sustained remission rate, lower relapses rate and decrease the dosage of GC, with good safety.

A child with diffuse mesangial sclerosis caused by a missense mutation of TRPC6 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis.@*METHODS@#Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family.@*RESULTS@#A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic.@*CONCLUSION@#The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.

Sinkihwan-gamibang ameliorates puromycin aminonucleoside-induced nephrotic syndrome / 中国天然药物

Nephrotic syndrome (NS) is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang (SKHGMB) was recorded in a traditional Chinese medical book named "Bangyakhappyeon ()" and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside (PAN). The experimental NS model was induced in male Sprague Dawley (SD) rats through injection of PAN (50 mg·kg-1)via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.

Clinical assessment of moderate-dose glucocorticoid in the treatment of recurrence of primary nephrotic syndrome in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS).@*METHODS@#A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions.@*RESULTS@#There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018).@*CONCLUSIONS@#For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.

Tratamiento con tocilizumab en amiloidosis AA: informe de casos y revisión de la literatura / Tocilizumab treatment in aa amyloidosis: case report and literature review

Introducción: la amiloidosis AA puede ser una complicación de ciertos trastornos inflamatorios crónicos, aunque entre el 21% y 50% puede ser idiopática. No existe un tratamiento específico. El tocilizumab, dirigido contra el receptor de IL-6 y orientado a disminuir la producción de SAA, podría ser eficaz. Métodos: en este estudio informamos datos de 6 pacientes con amiloidosis AA tratados con tocilizumab monoterapia subcutáneo en el período 2011-2018. Los criterios de valoración principales fueron la mejora clínica y bioquímica de los órganos afectados y los parámetros bioquímicos marcadores de inflamación. Resultados: el riñón estaba afectado en todos los pacientes, manifestándose con caída del filtrado glomerular y síndrome nefrótico. La hemorragia digestiva se presentó en un paciente y otro tenía afectación pulmonar en la biopsia. Luego del posterior al tratamiento, todos mejoraron el hematocrito, la albúmina sérica y el índice de masa corporal. El SAA disminuyó en 5 pacientes. Un paciente mejoró su función renal, mientras 4 se mantuvieron estables. Tres pacientes disminuyeron los valores de proteinuria. Conclusión: el tratamiento con tocilizumab podría ser eficaz en el tratamiento de los pacientes con amiloidosis AA. (AU)

Introduction: AA amyloidosis can be a complication of certain chronic inflammatory disorders, although between 21% and 50% can be idiopathic. There is no specific treatment. Tocilizumab, directed against the IL-6 receptor and aimed at decreasing SAA production, could be effective. Methods: in this study, we report data from 6 patients with AA amyloidosis treated with subcutaneous tocilizumab monotherapy between the period 2011-2018. The main endpoints were the clinical and biochemical improvement of the affected organs and the biochemical parameters markers of inflammation. Results: the kidney was affected in all patients, manifesting with a fall in glomerular filtration rate and nephrotic syndrome. Gastrointestinal bleeding occurred in one patient and another had lung involvement on biopsy. After treatment, all improved hematocrit, serum albumin, and body mass index. SAA decreased in 5 patients. One patient improved his kidney function, while 4 remained stable. Three patients decreased proteinuria values. Conclusion: treatment with tocilizumab could be effective in the treatment of patients with AA amyloidosis. (AU)

Nephrotic syndrome associated with primary atypical hemolytic uremic syndrome / Síndrome nefrótica associada à síndrome hemolítico-urêmica atípica primária

Abstract Primary atypical hemolytic-uremic syndrome is a rare disease characterized by non-immune microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction; it is related to alterations in the regulation of the alternative pathway of complement due to genetic mutations. The association with nephrotic syndrome is unusual. We present here a pediatric patient diagnosed with primary atypical hemolytic-uremic syndrome associated with nephrotic syndrome who responded to eculizumab treatment.

Resumo A síndrome hemolítico-urêmica atípica primária é uma doença rara, caracterizada por anemia hemolítica microangiopática não-imune, trombocitopenia e disfunção renal; está relacionado a alterações na regulação da via alternativa do complemento devido a mutações genéticas. A associação com a síndrome nefrótica é incomum. Apresentamos aqui um paciente pediátrico com diagnóstico de síndrome hemolítico-urêmica atípica primária associada à síndrome nefrótica que respondeu ao tratamento com eculizumab.