Search

Astragali Radix (AR) is one of the monarch drugs of Fangji Huangqi decoction and has the effects of inducing diuresis to alleviate edema, tonifying and strengthening the body. However, there is a paucity of research regarding the effective fraction and the underlying metabolic mechanism of AR on nephrotic syndrome (NS). This work aims to elucidate the potential mechanisms of AR treating NS, as well as to identify effective part and components. Firstly, body weight, kidney index, 24‐h urea protein, and biochemical parameters were used to confirm the kidney injury. The most effective part of AR was determined based on the indicators above. Then, 1H NMR, UHPLC‐QTOF/MS, and GC‐MS‐based metabolomic approaches were used to investigate differential metabolites closely associated with the effective part against NS. A "C‐T‐P‐D" network (a network diagram of "TCM prescription–herbs–components–targets–metabolites–pathways–disease") was constructed by intersecting the targets of differential metabolites with those of AR treating NS. The efficacy indicators determined the n‐butanol part of AR as the best effective part. Multiplatform metabolomics and network pharmacology study indicated that the potential mechanism for treating NS may be related to targets (MIF, SRC, and GBA) and metabolic pathways (citrate cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, and glycolysis/gluconeogenesis). [ABSTRACT FROM AUTHOR]

Corticosteroid‐induced psychosis is rare and less reported in children compared to adults. However, psychosis is considered a severe adverse effect of corticosteroids in pediatric nephrotic syndrome. Steroid‐induced psychosis is dose‐dependent and should be treated by tapering the dose of steroids and usually initiating an atypical antipsychotic. A 13‐year‐old male child presented to the pediatrics outpatient department with complaints of anxiety, fearfulness, and seeing images of an old man crawling into his room and threatening to strangle him with a red rope, which led to decreased sleep. He was initiated on oral prednisolone 3 weeks ago after being diagnosed with nephrotic syndrome. A diagnosis of steroid‐induced psychosis was made, and he was tapered on steroids over 6 weeks. He was then initiated on tacrolimus, quetiapine, and lorazepam and was discharged after a week. At follow‐up in 4 weeks, his psychosis had resolved, and nephrotic syndrome was found to improve. Children on steroids should be closely monitored for psychotic symptoms over a prolonged duration. Although tapering the dose of steroids is the gold standard treatment of steroid‐induced psychosis, cases like nephrotic syndrome demand the continuous use of an immunosuppressant. In such cases, tacrolimus has been found to be an effective alternative, although continuous monitoring for nephrotoxicity is necessary. Similarly, atypical antipsychotics (like quetiapine) are preferred for psychosis because of their lesser risk for extrapyramidal side effects compared to typicals. Parental counseling and informed consent are utmost for children on steroids or tacrolimus. [ABSTRACT FROM AUTHOR]

Mercury contained in beauty‐enhancing cosmetics can cause chronic poisoning and membranous nephropathy (MN). We report two cases of nephrotic syndrome caused by MN with evidence of mercury poisoning due to the application of fairness cream in a short duration of a few months. The individuals were positive for neural epidermal growth factor‐like 1 [NELL‐1]. Discontinuation of the use of cosmetic products and modified Ponticelli regimen improved the nephrotic state in these individuals. We suggest that mercury poisoning should be considered in NELL‐1‐positive individuals with a history of application of beauty products. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that caused by NF1 mutations. NF1 gene encodes neurofibromin (a GTPase‐activating protein) and plays a regulatory role in many signalling pathway such as the Ras/MAPK pathway, which is important for regulating cell growth, proliferation and neural development. Therefore, NF1 gene mutations causes the excessive activation of signalling pathways and uncontrolled cell growth. NF1 exhibits complete genetic penetrance and clinical heterogeneity. Glomerular disease has rarely been reported in patients with NF1, especially in children. Currently, the relationship between NF1 and nephrotic syndrome is unclear. Here, we present a case of NF1 with nephrotic syndrome and further explore the association between NF1 and glomerular diseases. It also reminds clinicians that NF1 has complex and highly variable clinical manifestations and that a comprehensive workup is essential for patients. [ABSTRACT FROM AUTHOR]

Hyperosmolar hyperglycemic syndrome (HHS) is a common complication of diabetes mellitus. The episodes of HHS have been reported in patients with no prior history of diabetes. However, these incidents have rarely been reported in the literature. The present study reports the case of hyperosmolar hyperglycemic syndrome in a patient without diabetes history after being prescribed high‐dose steroid therapy. This case highlights the importance of regularly monitoring blood glucose levels in patients prescribed supraphysiological doses of steroids. The present study presents a 29‐year‐old male patient with no previous history of diabetes who presented with HHS, manifested by a decreased level of consciousness, lethargy, and history of polyuria. Laboratory work revealed significantly high serum glucose and high serum osmolality, with no ketones. Two weeks prior to the presentation, the patient was started on 1 mg/kg of oral prednisolone for his new diagnosis of minimal change disease with a nephrotic syndrome picture. The management of HHS included aggressive fluid intake and insulin therapy, and the steroid was tapered quickly. Hyperglycemia resolved completely with normalization of his HbA1c after the complete stoppage of steroids and he did not require to continue lifelong insulin. The present study highlights the importance of assessing the risk of hyperglycemia, screening, and regular glucose monitoring in patients prescribed supraphysiological doses of steroids, even if no prior history of diabetes has been recorded.. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To determine the duration of relapsing childhood idiopathic nephrotic syndrome (INS).In this population‐based study, we retrospectively analysed the computerised database of Israel's largest health maintenance organisation. Children (age 2–10 years) with a new INS diagnosis and a corticosteroid (CS) prescription between 2000 and 2010 were included. NS category was determined, according to CS and/or steroid‐sparing agents (SSA) purchases.Out of 1 669 977 eligible children, 608 fulfilled inclusion criteria. Patients in the fourth quartile of purchases (n = 132) had an older age at last relapse (17.9 ± 6.3 vs. 11.3 ± 5.9 years, p < 0.001) and more SSA use (78.8% vs. 20%, p < 0.001) compared to the remaining three quartiles. A single episode occurred in 84 patients. Of the remaining 524 patients (males 66%, diagnosis age: 4.8 ± 2.2 years, SSA prescribed: 35%) who were followed for 15.5 ± 5.1 years, 113 (21.6%) had a continuing disease at an age of 19.3 ± 6.3 years. The leftover 411 entered long‐lasting treatment‐free remission at age 11.2 ± 5.7 years.In this multicentre study, we identified INS disease course by medication delivery. NS long‐standing remission occurs at age 11.2 ± 5.7 years in most cases. However, the disease continues into adulthood in a fifth of the relapsing patients, implicating the need for proper transition to adult care. [ABSTRACT FROM AUTHOR]

Variants in more than 60 different genes, most of which code for podocyte‐related proteins, have been found to be associated with monogenic forms of nephrotic syndrome (NS). Biallelic variants in DAAM2, a member of the formin family, were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid‐resistant nephrotic syndrome (SRNS). This case report represents only the fifth reported family of DAAM2‐associated NS and the first from India, with two sibs who presented with a complex phenotype characterized by steroid‐resistant nephrotic syndrome, short stature, dysmorphic facial features, deep‐set toenails, myopia, increased thickness of the calvarium of the skull, and sloping ribs. Both sibs were found to have a homozygous likely pathogenic nonsense variant c.196C>T (p.Arg66Ter; NM_001201427.2) in exon 3 of the DAAM2 gene through whole exome sequencing. The dysmorphic features could possibly be part of the DAAM2‐related phenotype which has hitherto not been reported or could represent a blended phenotype, with the extrarenal manifestations resulting from a yet to be identified coexisting genetic condition. [ABSTRACT FROM AUTHOR]

Background and purpose: Reports of patients who have autoimmune nodopathies concurrent with nephrotic syndrome are increasing. We investigated whether proteinuria could be a biomarker of autoimmune nodopathies. Methods: Qualitative urinalysis results were retrospectively obtained from 69 patients who were diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) at a hospital in Japan. Proteinuria was graded as mild to severe (i.e., mild, 30–99; moderate, 100–299; severe, 300 mg/dL or more) according to the results of the urine dipstick test. Autoantibodies against the paranodal proteins contactin 1 (CNTN1), neurofascin 155 (NF155), and contactin‐associated protein 1 (Caspr1) and the nodal protein neurofascin 186 (NF186) were measured, and the predominant IgG subclass was determined by enzyme‐linked immunosorbent assay in sera from the 69 patients. Results: Four patients (6%), five patients (7%), and one (1%) patient were positive for anti‐CNTN1, anti‐NF155, and anti‐Caspr1 IgG4 antibodies, respectively. No patients had IgG4 antibodies against NF186. Proteinuria of mild or greater levels was found in three patients with anti‐CNTN1 IgG4 and two patients with anti‐NF155 IgG4 antibodies. The autoantibody‐positive patients more frequently had proteinuria of mild or greater levels than the seronegative patients (p = 0.01). Conclusions: Proteinuria is a possible biomarker of autoimmune nodopathies associated with autoantibodies targeting CNTN1 or NF155. Urinalysis results should be carefully checked for quick differentiation of autoimmune nodopathies from CIDP. Patients who present with nephrotic syndrome should be tested for anti‐CNTN1 IgG4 antibodies, and patients who exhibit mild proteinuria should be tested for anti‐NF155 IgG4 antibodies. [ABSTRACT FROM AUTHOR]

Primary coenzyme Q10 deficiency‐1, caused by COQ2 disease‐causing variants, is an autosomal recessive disorder, and genetic testing is the gold standard for diagnosing this condition. A Chinese boy with steroid‐resistant nephrotic syndrome, focal segmental glomerulosclerosis, and progressive kidney insufficiency was included in the study. Electron microscopy revealed the glomerular basement membrane with irregular thickness and lamellation with diffuse effacement of foot processes in the podocytes, and swollen mitochondria with abnormal cristae in the podocytes. Coenzyme Q10 supplementation started about 3 weeks after the onset of mild kidney dysfunction did not improve the proband's kidney outcome. Proband‐only whole‐exome sequencing and Sanger sequencing revealed two heteroallelic COQ2 variants: a maternally inherited novel variant c.1013G > A[p.(Gly338Glu)] in exon 6 and a variant of unknown origin c.1159C > T[p.(Arg387*)] in exon 7. Subsequent long‐read sequencing demonstrated these two variants were located on different alleles. Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy. [ABSTRACT FROM AUTHOR]

Aim: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children. Methods: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D‐DIA proteomics were performed. Results: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis. Conclusion: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders". Summary at a glance: This study performed a comprehensive analysis of saliva from INS children and revealed that oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders". [ABSTRACT FROM AUTHOR]

There is evidence to suggest that M‐type phospholipase A2 (PLA2R) antibodies activate the mannose‐binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy‐confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow‐mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p <.01). MBL levels decreased significantly after immunosuppressive therapy (p =.04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p =.01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients. [ABSTRACT FROM AUTHOR]

The article presents a study on dental screening pathway developed for paediatric nephrology patients attending the Great North Children's Hospital in Newcastle upon Tyne, United Kingdom. Topics discussed include the aims of the study, the materials and methods used in the study, and the common renal diagnoses encountered.

Aim: Bilateral nephrectomy is commonly performed in patients with congenital nephrotic syndrome of the Finnish type. The optimal timing of nephrectomy is unclear. Methods: Growth, thromboembolic events, infections, transplant‐related complications and ability to eat were compared between infants with early (Group 1, n = 13) and late (Group 2, n = 10) nephrectomy. 'Early' was defined as nephrectomy at 7‐kg body weight followed by peritoneal dialysis and 'late' as nephrectomy at ≥10 kg followed by 3–4 weeks of haemodialysis and kidney transplantation. Patients were followed until the end of the first post‐transplant year. Results: Dialysis time was significantly longer in group 1 than in group 2. Late nephrectomy did not increase the risk for thromboembolic events or septicaemia but decreased tube feeding dependency (group 1 69% vs. group 2 20%, p = 0.019). Motor development at transplantation was considered normal in 80% of the infants with late nephrectomy compared to 31% in the early nephrectomy group (p = 0.019); however, the difference between the groups disappeared by the end of the follow‐up. Conclusion: Infants with late nephrectomy have comparative outcome but less feeding tube dependency and better motor development during the first post‐transplant months compared to infants with early nephrectomy. [ABSTRACT FROM AUTHOR]

Aim: In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. However, apart from case reports, there is no evidence favoring ENaC blockade in patients with NS. Methods: The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amiloride (starting dose 5 mg/day, max. 15 mg/day) in comparison to standard therapy with the loop diuretic furosemide (40 mg/day, max. 120 mg/day) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (BCM, Fresenius). Depending on the OH response, diuretic dose was adjusted on days 2, 5, 8 and 12, and if necessary, hydrochlorothiazide (HCT) was added from d8 (12.5 mg/day, max. 25 mg/day). The primary endpoint was the decrease in OH on d8. The study was terminated prematurely due to insufficient recruitment and a low statistical power due to a low actual effect size. Results: Median baseline OH was +26.4 (interquartile range 15.5–35.1)% extracellular water (ECW) in the amiloride arm and + 27.9 (24.1–29.4)% ECW in the furosemide arm and decreased by 1.95 (0.80–6.40) and 5.15 (0.90–8.30)% ECW after 8 days, respectively, and by 10.10 (1.30–14.40) and 7.40 (2.80–10.10)% ECW after 16 days, respectively. OH decrease on d8 and d16 was not significantly different between both arms. Conclusion: The AMILOR study is the first randomized controlled pilot study suggesting a similar antiedematous effect as furosemide. Further studies are required to better define the role of amiloride in NS (EudraCT 2019‐002607‐18). [ABSTRACT FROM AUTHOR]

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. Methods: We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. Results: Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1–2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add‐on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. Conclusions: Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The commonest renal involvement after bee stings is acute kidney injury due to rhabdomyolysis. Nephrotic syndrome combined with AKI is unusual complication of Hymenoptera stings. We diagnosed a minimal change disease and six‐year follow up relapses. [ABSTRACT FROM AUTHOR]

Aims: Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side‐effects. Therapeutic drug monitoring using saliva would be a patient‐friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid‐sensitive nephrotic syndrome (SSNS). Methods: Children (age 2–16 years) with SSNS participating in a randomized, placebo‐controlled trial with levamisole were treated with an 18‐week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8 weeks (saliva and plasma) after first onset. A nonlinear mixed‐effects model was used to estimate the PK parameters of unbound prednisolone and the saliva‐to‐plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring. Results: From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h−1 70 kg−1 and 158 (7%) L 70 kg−1, respectively. Typical saliva‐to‐plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area‐under‐the‐concentration–time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples. Conclusion: Saliva proved to be a reliable and patient‐friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions. [ABSTRACT FROM AUTHOR]

The aim of this study is to report a case in which a patient with nephrotic syndrome underwent surgery to remove fibrous gum tissue (ulectomy). An 8‐year‐old patient, diagnosed with early onset nephrotic syndrome due to a mutation in the NUP107 gene, had received a kidney transplant and was therefore taking various medications, including immunosuppressants. On oral examination, the patient was found to have a fibrous gingiva that was preventing the eruption of the upper permanent central incisors. A ulectomy was performed and the gingival tissue was sent for histopathological analysis, which showed normal aspects. The upper right central incisor was seen in the oral cavity 15 days after surgery. A second procedure was carried out to facilitate the eruption of the upper left incisor, which was visualized in the oral cavity 30 days later. In addition, oral manifestations such as maxillary atresia, ogival palate and mouth breathing were observed. Therefore, the role of the dental surgeon in the lives of transplanted children is considered important, as they often take various medications that can affect their oral health. Thus, early diagnosis and effective treatment will be essential to prevent future malocclusions and thus improve the quality of life of these patients. [ABSTRACT FROM AUTHOR]

Background: The current study aims to explore the relationship between tumor necrosis factor‐α (TNF‐α) polymorphism and the risk of primary nephrotic syndrome (PNS). Methods: A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF‐α polymorphism were assessed using the polymerase chain reaction‐restriction fragment length polymorphism method. In addition, a meta‐analysis was conducted to analyze previously published literature on this topic. Results: No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta‐analysis results revealed a positive association between TNF‐α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p =.007), heterozygote comparison (p =.026), recessive genetic model (p =.011), and dominant genetic model (p =.000). Conclusions: TNF‐α rs1800629 polymorphism does not appear to confer any increased risk for PNS. [ABSTRACT FROM AUTHOR]

Membranous nephropathy is the most common cause of nephrotic syndrome (NS) in non‐diabetic adults; in 80% of patients it is idiopathic (PMN). PMN has an autoimmune pathogenesis, 70%‐85% of patients have increased titer of antibodies to the podocyte membrane antigen PLA2R. The etiological, prognostic and predictive role of the Ab anti‐PLA2R is demonstrated. Standard therapy consists in anti‐CD20 monoclonal antibody rituximab (RTX) combined with steroids or immunosuppressants according to the risk of progressive loss of kidney function. The immunosuppressive therapies are potentially associated to severe adverse events that lead to protocol suspension. Given their pivotal pathogenetic role, serum clearance of anti‐PLA2R with plasmapheresis could have a beneficial impact on NS, particularly in patients not requiring or tolerating standard therapies. In this series, we present three cases of PMN anti‐PLA2R related treated with a RTX plus plasmapheresis approach and demonstrate its overall effective role on anti‐PLA2R titer and clinical outcomes. [ABSTRACT FROM AUTHOR]

This article reports on a rare case of a patient with minimal change nephrotic syndrome, juvenile temporal arteritis (JTA), and eosinophilia. JTA is a rare disease characterized by localized vasculitis involving the temporal artery, and it is more commonly seen in younger male patients. Kimura's disease, another rare disease, often involves the internal organs, including the kidney, but the simultaneous development of JTA and nephrotic syndrome has not been reported before. The patient in this case study was a middle-aged woman, which is atypical for JTA. The authors suggest that further investigation is needed to determine if JTA is a manifestation of Kimura's disease. [Extracted from the article]

Key Clinical Message: Ankylosing spondylitis (AS) presents with renal failure and proteinuria in a minority of cases, usually due to secondary amyloidosis or IgA nephropathy. While focal segmental glomerulosclerosis (FSGS) is less common, it should still be in the differential regardless of the patient's clinical profile. [ABSTRACT FROM AUTHOR]

Aim: Rituximab (RTX) is a genetically engineered chimeric monoclonal antibody which binds directly to CD20 antigen and mediates inhibition of B cell development. Although RTX has been widely used in paediatric nephrology, there is no routine protocol for its use. In this study, paediatric nephrologists in Türkiye were asked to fill out a questionnaire to understand their practice in using RTX. This study aimed to determine common practices and clarify the uncertainties regarding the use of RTX in paediatric nephrology. Methods: This was a nationwide, multicenter, retrospective cohort study based on data evaluating the use of RTX in paediatric nephrology practice. An online questionnaire was sent to all paediatric nephrology centers in Türkiye. The questionnaire forms included information about how many patients in total applied RTX treatment, for which indications they use RTX, and whether they made any preparations before using RTX. Results: According to this survey on RTX use in Türkiye, paediatric nephrologists use it most commonly in SSNS and followed by SRNS, ABMR, SLE and AAV, respectively. Dosing was highly standard but there is significant heterogeneity in pre‐exposure tests and patient monitoring in the clinical practice of RTX. Also, the rate of encountering RTX‐related allergic and infectious side effects at least once during the professional experience of our physicians can be quite high. Conclusion: There is an increasing need for the preparation of a guideline on the indications for RTX use for each diagnosis, posology, and the practices to be performed before and after infusion. [ABSTRACT FROM AUTHOR]

Several theories have been proposed to explain the development of severe acute kidney injury (AKI) in patients with minimal change nephrotic syndrome (MCNS), but the exact mechanism remains unclear. We encountered an elderly patient with biopsy-proven MCNS who suffered from oliguric AKI, which required hemodialysis at the onset and during the first relapse of nephrotic syndrome. Throughout her relapse, we were able to monitor tubular injury markers, namely, urinary N-acetyl-β-D-glucosaminidase and urinary alpha-1-microglobulin levels. This patient had hypertension. 8.5 years after achieving complete remission, she experienced a relapse of nephrotic syndrome accompanied by AKI, necessitating hemodialysis. The hemodialysis was discontinued after 7 weeks of corticosteroid therapy and cyclosporin A treatment. During this relapse, we observed a correlation between the sudden increase in renal tubular injury markers and proteinuria levels and the progression of severe AKI. Conversely, a reduction in renal tubular injury markers and proteinuria was associated with the resolution of AKI. The abrupt elevation of both tubular injury markers and proteinuria levels suggests a possible breakdown in protein endocytosis in proximal tubular cells. Moreover, it is less likely that the acute reduction in intra-glomerular pressure is the primary cause of tubular injury, as it might result in a decrease in both glomerular filtration rate and proteinuria levels. It is conceivable that massive proteinuria, in conjunction with the patient's clinical characteristics, may contribute to tubular injury, ultimately leading to severe AKI in this patient. [ABSTRACT FROM AUTHOR]

Striae distensae is a common cutaneous phenomenon that begins as reddish linear atrophic plaques (striae rubra) that over time progress to silvery‐white coloration (stria alba). Striae distensae in rare occasions becomes edematous, ulcerative, emphysematous, or urticated. Bullous striae distensae is a sequela of conditions causing interstitial edema along with systemic glucocorticoids use. To our knowledge, only eight cases of bullous striae distensae have been reported in the literature. Herein, we report a 17‐year‐old female, known case of nephrotic syndrome, presented to our clinic with abdominal fluid‐fill cutaneous lesions only for 5 days. She had used systemic glucocorticoids for more than a decade before she was labeled as steroid resistant nephrotic syndrome. Cushingoid body habitus were observed during physical examination, in addition to translucent bullae overlying her previously known stretch marks. Punch biopsy of the lesions revealed dermal edema with thinned collagen bundles. Based on these clinicopathological findings, a diagnosis of bullous striae distensae was made. Awareness of this rare complication and unusual clinical presentation is fundamental to avoid unnecessary and excessive interventions whether investigatory or therapeutic in order to provide appropriate management of the underlying condition. [ABSTRACT FROM AUTHOR]

Congenital nephrotic syndrome is an autosomal recessive inherited disorder that manifests as steroid-resistant massive proteinuria in the first three months of life. Defects in the glomerular filtration mechanism are the primary etiology. We present a child who developed severe nephrotic syndrome at two weeks of age and eventually required a bilateral nephrectomy. Genetic testing revealed compound heterozygous variants in NPHS1 including a known pathogenic variant and a missense variant of uncertain significance. Light microscopy revealed crescent formation—an atypical finding in congenital nephrotic syndrome caused by nephrin variants—in addition to focal segmental and global glomerulosclerosis. Electron microscopy showed diffuse podocyte foot process effacement. Confocal and Airyscan immunofluorescence microcopy showed aggregation of nephrin in the podocyte cell body that is not a result of diffuse podocyte foot process effacement as seen in minimal change disease. These findings confirm the novel variant as pathogenic. [ABSTRACT FROM AUTHOR]

As the molecular mechanism of nephrotic syndrome remains largely undiscovered, patients continue to be exposed to the pros and cons of uniform glucocorticoid treatment. We explored whether the exposure of in vitro‐cultivated podocytes to sera from children with steroid‐sensitive or steroid‐resistant nephrotic syndrome induces differences in gene expression profiles, which could help to elucidate the pathogenesis of the steroid response. Human immortalized podocytes were cultivated with patient sera for 3 days. After cell lysis, RNA extraction, 3′‐mRNA libraries were prepared and sequenced. There were 34 significantly upregulated and 14 downregulated genes (fold difference <0.5 and >2.0, respectively, and false discovery rate‐corrected p < 0.05) and 22 significantly upregulated and 6 downregulated pathways (false discovery rate‐corrected p < 0.01) in the steroid‐sensitive (n = 9) versus steroid‐resistant group (n = 4). The observed pathways included upregulated redox reactions, DNA repair, mitosis, protein translation and downregulated cholesterol biosynthesis. Sera from children with nephrotic syndrome induce disease subtype‐specific transcriptome changes in human podocytes in vitro. However, further exploration of a larger cohort is needed to verify whether clinically distinct types of nephrotic syndrome or disease activity may be differentiated by specific transcriptomic profiles and whether this information may help to elucidate the pathogenesis of the steroid response. [ABSTRACT FROM AUTHOR]

Aim: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are podocytopathies characterized by damage to the glomerular filtration barrier, leading to proteinuria and nephrotic syndrome. The production of anti‐podocyte antibodies has been proposed as potential circulating factors contributing to the development of these conditions. The aim of the study is to evaluate the levels of anti‐nephrin antibodies in patients with podocytopathies and healthy subjects. Methods: In this study, a total of 77 patients with active glomerulopathy and 11 healthy subjects were included. Forty one patients were diagnosed with FSGS, 11 with MCD, and 25 with MN. To measure the levels of anti‐nephrin antibodies, enzyme‐linked immunosorbent assay was used. Results: The levels of antibodies to nephrin were significantly higher in patients with MCD 61.2 [28.9–66.3] ng/mL and FSGS 32.5 [17.2–58.4] ng/mL compared to MN 20.3 [14.4–38.4] and healthy individuals 15.3 [12–18.9] ng/mL, p <.05. In patients with primary FSGS, the levels of antibodies to nephrin were significantly higher 45.2 [20–64.3] ng/mL compared to patients with secondary FSGS 26.7 [11.2–44.1] ng/mL, p <.05. There were no significant differences in the remission rate between the anti‐nephrin antibodies positive and negative groups (log‐rank test: p =.158). Conclusion: The level of anti‐nephrin antibodies was found to be significantly higher in patients with MCD and pFSGS compared to those with sFSGS, MN, and healthy subjects. Anti‐nephrin antibodies in MCD and primary FSGS may be associated with the severity of podocytopathies, however they did not have an impact on the response to therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Nephrotic syndrome (NS) is associated with an increased incidence of venous thromboembolism (VTE), approximately 10%. We performed a systematic review to evaluate the efficacy and safety of prophylactic anticoagulation in patients with NS. Methods: Studies evaluating prophylactic anticoagulation in NS were identified by an electronic search of MEDLINE and EMBASE databases until December 2021. Weighted mean proportion and 95% confidence intervals (CIs) of thromboembolic and haemorrhagic events were calculated using a fixed‐effects and a random‐effects model. The differences in the outcomes among groups were estimated as pooled odds ratio (OR) and corresponding 95% CI. Statistical heterogeneity was evaluated using the I2 statistic. Results: Five cohort studies, for a total of 414 adult patients, were included. Only two studies had a control group. The weighted mean incidence of pulmonary embolism (PE) and deep vein thrombosis in patients who received VTE prophylaxis was 1.8% (95% CI: 0.6–3.5%; I2: 4.4%) and 0.9% (95% CI: 0.2–2.2%; I2: 43.4%) respectively. The weighted mean incidence of major bleeding in patients who received VTE prophylaxis was 2.3% (95% CI: 1–4.2%; I2: 25.4%). Patients with NS that received VTE prophylaxis had a non‐significant reduced risk of PE (OR: 0.63 (95% CI: 0.03–14.8; I2: 64.4%)) and an increased risk of major bleeding (OR: 2.08 (95% CI: 0.41–10.45; I2: 0%)) compared to patients with NS that did not receive VTE prophylaxis. Conclusions: Our findings suggest that prophylactic anticoagulation in adult patients with primary NS may reduce the risk of VTE, even if it may be associated with a not negligible bleeding risk. [ABSTRACT FROM AUTHOR]

Objective: To describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation. Methods: Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry. Results: The skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra. Conclusion: This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra). [ABSTRACT FROM AUTHOR]

The clinical syndrome caused by cleavage‐resistant RIPK1 is known as CRIA (Cleavage‐resistant RIPK1‐induced autoinflammatory) syndrome. We present a family with three generations affected by CRIA syndrome. Our index patient (P1), a boy born of a non‐consanguineous marriage, developed recurrent episodes of fever after 5 months of age, with variable periodicity. His father (P2) and paternal grandmother also had periodic fever. At 23 months of age, P1 was diagnosed with renal biopsy‐proven steroid‐responsive nephrotic syndrome. His first visit to our center was at 2 years of age. At presentation, he had failure to thrive, microcytic hypochromic anemia, and elevated inflammatory markers and interleukin‐6 levels. Amyloid A protein was elevated, serum creatinine was normal, and proteinuria resolved after addition of steroids. Next‐generation sequencing showed heterozygous mutation (c.970G>A, p.Asp324His) in RIPK1. This mutation has been reported to cause CRIA syndrome. P2 and P1's asymptomatic younger brother had the same mutation. All the affected members showed variability with respect to frequency and duration of periodic fever as well as the age of onset. Both P1 and P2 had elevated amyloid A, with no evidence of renal dysfunction. P1 and P2 showed improvement in the intensity of fever spikes with colchicine treatment; however, both continue to have periodic fever. [ABSTRACT FROM AUTHOR]

Background: The urine protein to creatinine ratio (UPCR) correlates well with the 24‐h urine protein test (24‐h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24‐h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24‐h UPT corrected for body surface area (BSA) (24‐h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24‐h UPT/BSA and FETP and 24‐h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. Methods: Thirty‐six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24‐h UPT/BSA and FETP and 24‐h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. Results: The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24‐h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24‐h UPT/BSA than with UPCR (p = 0.01). Conclusions: The FETP correlated more strongly with 24‐h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels. [ABSTRACT FROM AUTHOR]

Aim: To investigate the need, in the Northern European setting, to perform kidney biopsy in children with steroid‐sensitive nephrotic syndrome. Methods: In this retrospective study 124 individuals aged 1–18 years with idiopathic nephrotic syndrome, followed in the paediatric hospitals in southern Sweden from 1999 to 2018, were included. Results: There was a median follow‐up time of 6.5 (0.2–16.8) years. The majority (92%) of children were steroid‐sensitive and of them, 60.5% were frequently relapsing or steroid‐dependent. Microscopic haematuria was found at onset in 81.1% and hypertension in 8.7%. At least one kidney biopsy was performed in 93 (75%). The most common indication was a steroid‐dependent or relapsing course (58.4%). One of 79 steroid‐sensitive children had another histological diagnosis than minimal change nephropathy 1.3%, 95% confidence interval (0.002, 0.068). Bleeding occurred after eight biopsies (6.6%). Twenty individuals (30.7%) were transferred to adult units, 18 still on immunosuppression. Conclusion: We have in our cohort of unselected children with idiopathic nephrotic syndrome confirmed that a kidney biopsy rarely gives important medical information in steroid‐sensitive children without any other complicating factor and that the liberal policy of kidney biopsy in the Nordic countries safely can be changed. [ABSTRACT FROM AUTHOR]

Low‐density lipoprotein apheresis (LDL‐A) therapy has shown reasonable efficacy in treating nephrotic syndrome (NS) refractory to initial drug therapy and has been covered by National Health Insurance for the indication of drug‐resistant focal segmental glomerulosclerosis (FSGS) since 1992 in Japan and has contributed to liberating substantial number of patients of this disease from entering into end‐stage renal disease by easier practical application in actual clinical settings. Subsequently, various beneficial evidence of this treatment has accumulated on those other than FSGS, however, due to the limitation of covered disease insurance only for FSGS, patients with diseases other than FSGS are unlikely to benefit from this treatment in practice. This review summarizes the therapeutic evidence of the beneficial effect of LDL‐A accumulated to date and the mechanisms of action analyzed from multifaceted perspectives. examines the applicability of expanding insurance coverage for diseases other than FSGS. [ABSTRACT FROM AUTHOR]

This article discusses two cases of children with atopic dermatitis (AD) and idiopathic nephrotic syndrome (INS) who were treated with dupilumab. Both patients had previously been treated with cyclosporin for their kidney disease but had no improvement in their skin disease. After starting dupilumab, both patients experienced significant improvement in their AD symptoms. The authors suggest that dupilumab may be an effective and safe treatment option for AD patients with concomitant INS, but further studies are needed to confirm its efficacy and safety in this population. [Extracted from the article]

Background: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates. Case Presentation: A 14‐year‐old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow‐up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis. Conclusion: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway. [ABSTRACT FROM AUTHOR]

14‐3‐3 proteins are a ubiquitously expressed family of adaptor proteins. Despite exhibiting high sequence homology, several 14‐3‐3 isoforms have isoform‐specific binding partners and roles. We reported that 14‐3‐3β interacts with FKBP12 and synaptopodin to maintain the structure of actin fibers in podocytes. However, the precise localization and differential role of 14‐3‐3 isoforms in kidneys are unclear. Herein, we showed that 14‐3‐3β in glomeruli was restricted in podocytes, and 14‐3‐3σ in glomeruli was expressed in podocytes and mesangial cells. Although 14‐3‐3β was dominantly co‐localized with FKBP12 in the foot processes, a part of 14‐3‐3β was co‐localized with Par3 at the slit diaphragm. 14‐3‐3β interacted with Par3, and FKBP12 bound to 14‐3‐3β competitively with Par3. Deletion of 14‐3‐3β enhanced the interaction of Par3 with Par6 in podocytes. Gene silencing for 14‐3‐3β altered the structure of actin fibers and process formation. 14‐3‐3β and synaptopodin expression was decreased in podocyte injury models. In contrast, 14‐3‐3σ in podocytes was expressed in the primary processes. 14‐3‐3σ interacted with vimentin but not with the actin‐associated proteins FKBP12 and synaptopodin. Gene silencing for 14‐3‐3σ altered the structure of vimentin fibers and process formation. 14‐3‐3σ and vimentin expression was increased in the early phase of podocyte injury models but was decreased in the late stage. Together, the localization of 14‐3‐3β at actin cytoskeleton plays a role in maintaining the foot processes and the Par complex in podocytes. In contrast, 14‐3‐3σ at vimentin cytoskeleton is essential for maintaining primary processes. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is one of the most common kidney disorders seen by pediatric nephrologists and is defined by the presence of heavy proteinuria (>3.5 g/24 h), hypoalbuminemia (<3.5 g/dL), edema, and hyperlipidemia. Most children with NS are steroid‐responsive and have a good prognosis following treatment with prednisolone. However, 10%–20% of them have steroid‐resistant nephrotic syndrome (SRNS) and fail to respond to treatment. A significant proportion of these children progress to kidney failure. Methods: This retrospective study aimed to determine the underlying genetic causes of SRNS among Omani children below 13 years old, over a 15‐year period and included 77 children from 50 different families. We used targeted Sanger sequencing combined with next‐generation sequencing approaches to perform molecular diagnostics. Results: We found a high rate of underlying genetic causes of SRNS in 61 (79.2%) children with pathogenic variants in the associated genes. Most of these genetically solved SRNS patients were born to consanguineous parents and variants were in the homozygous state. Pathogenic variants in NPHS2 were the most common cause of SRNS in our study seen in 37 (48.05%) cases. Pathogenic variants in NPHS1 were also seen in 16 cases, especially in infants with congenital nephrotic syndrome (CNS). Other genetic causes identified included pathogenic variants in LAMB2, PLCE1, MYO1E, and NUP93. Conclusion: NPHS2 and NPHS1 genetic variants were the most common inherited causes of SRNS in Omani children. However, patients with variants in several other SRNS causative genes were also identified. We recommend screening for all genes responsible for SRNS in all children who present with this phenotype, which will assist in clinical management decisions and genetic counseling for the affected families. [ABSTRACT FROM AUTHOR]

A 29-year-old, otherwise healthy Indian male, presented to us with a 2-year history of repeated episodes of painful erythematous nodules associated with high-grade fever. Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug-resistance testing in leprosy?. [Extracted from the article]

Aim: This study aimed to investigate the incidence of relapse and FR/SDNS in Chinese children with SSNS and to develop clinical prediction models for relapse and FR/SDNS. Methods: This retrospective cohort study involved 339 newly onset SSNS patients between 2006 and 2016. The incidence of relapse and FR/SDNS were estimated using the Kaplan–Meier method. Prediction models were constructed based on Cox proportional‐hazards regression. Results: The median follow‐up time was 8.7 years. The cumulative incidence of relapse at 1‐, 2‐, and 5‐year was 51.0%, 62.5%, and 66.6%. The cumulative incidence of FR/SDNS at 1‐, 2‐, and 5‐year was 18.4%, 29.0%, and 32.9%. The final prediction model for first relapse included four variables (serum albumin, triglycerides, IgM, and time to first remission). The model's discriminative ability was low (Harrell's C index = 0.62). The final prediction model for FR/SDNS included four variables (serum albumin, lipoprotein(a), time to first remission, and time to first relapse). The discrimination and calibration of the prediction model for FR/SDNS were acceptable (Harrell's C index = 0.73, Brier score at 1‐ and 2‐year were 0.11 and 0.17). Conclusion: The first relapse and FR/SDNS mainly occurred in the first 2 years after initial SSNS onset. The prediction model for relapse developed using common clinical parameters performed poorly, while the prediction model for FR/SDNS might be useful. Summary at a Glance: The incidence of relapse in Chinese children with SSNS might not be as high as previously reported in cohort studies or randomized controlled trials of other countries. Besides, this study developed a valuable prediction model for FR/SDNS in SSNS children using common clinical and laboratory variables. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Most children with nephrotic syndrome heal without any sequelae. However, rare life‐threatening complications such as thromboembolism may occur in pediatric nephrotic syndrome and should be considered in those with a new‐onset neurologic deficit. The thromboembolism (TE) as a complication of nephrotic syndrome (NS) is rare and serious, and may involve renal, cerebral, pulmonary, or peripheral venous and/or arterial thrombosis. Here, we describe a 4.5‐year‐old male with a history of nephrotic syndrome, who developed hemorrhagic stroke in the territory of middle cerebral artery (MCA). [ABSTRACT FROM AUTHOR]

Background: Steroid‐resistant nephrotic syndrome recurrence post‐transplant unresponsive to immunoadsorption is a dilemma, and no reliable treatment strategy has been identified to induce remission so far. Case presentation: A 2‐year‐old girl presented first with idiopathic nephrotic syndrome. She did not reach remission after 30 days of oral steroids and remained resistant to steroid pulses, oral tacrolimus, IV cyclosporine, and to 30 sessions of plasma exchange. Bilateral nephrectomy was performed because of extrarenal complications. Two years later, she received an allograft from a deceased donor and idiopathic nephrotic syndrome relapsed immediately post‐transplantation. She did not reach remission after immunosuppressive therapy including tacrolimus, mycophenolate mofetil, methylprednisolone pulses, daily immunoadsorption, and B‐cell depletion. She received obinutuzumab 1 g/1.73 m2 injections weekly for 3 weeks and then daratumumab 1 g/1.73 m2 weekly for 4 weeks. One week after the last daratumumab infusion, urine protein/creatinine ratio began to decrease. Proteinuria was negative for the first time at Day 99. Immunoadsorption was stopped 147 days after, and she remained relapse‐free at last follow‐up (18 months post‐transplantation). The treatment was complicated by a pneumocystis jirovecii pneumonia with a favorable outcome and persistent hypogammaglobulinemia. Conclusion: A obinutuzumab and daratumumab combination seems to be a promising strategy in post‐transplantation SRNS recurrence without response to standard treatment options. [ABSTRACT FROM AUTHOR]

Key Clinical Message: There may be a connection between pemphigus vulgaris and nephrotic syndrome, as evidenced by the occurrence of focal segmental glomerulosclerosis in our pemphigus vulgaris patient and reviewing relevant literature. Therefore, if a patient with pemphigus vulgaris presents with bilateral lower extremity edema or proteinuria detected during urinalysis, it could indicate involvement of the kidneys. Pemphigus vulgaris is a type of autoimmune blistering disease characterized by the presence of IgG autoantibodies against desmogleins 3 and 1. It is important to evaluate potential autoimmune associations in patients with pemphigus vulgaris so that appropriate laboratory and physical examinations can be performed to monitor for any increased risk of other autoimmune disorders. This case report describes a 55‐year‐old woman who presented with oral and axillary erosions, which were diagnosed as pemphigus vulgaris based on skin histopathology and immunofluorescence. During follow‐up, the patient was found to have proteinuria, which led to referral to a nephrologist. The patient was diagnosed with nephrotic syndrome and minimal change disease after a biopsy. Despite treatment, the patient's proteinuria persisted and serum creatinine levels increased, leading to a second biopsy which confirmed the diagnosis of focal segmental glomerulosclerosis. This study reports on the first case of pemphigus vulgaris with focal segmental glomerulosclerosis and reviews the literature on the co‐occurrence of acquired immunobullous diseases and nephrotic syndrome of any kind. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome is common in children and adults worldwide, and steroid‐sensitive nephrotic syndrome (SSNS) accounts for 80%. Aberrant metabolism involvement in early SSNS is sparsely studied, and its pathogenesis remains unclear. Therefore, the goal of this study was to investigate the changes in initiated SSNS patients‐related metabolites through serum and urine metabolomics and discover the novel potential metabolites and metabolic pathways. Methods: Serum samples (27 SSNS and 56 controls) and urine samples (17 SSNS and 24 controls) were collected. Meanwhile, the non‐targeted analyses were performed by ultra‐high‐performance liquid chromatography‐quadrupole time of flight‐mass spectrometry (UHPLC‐QTOF‐MS) to determine the changes in SSNS. We applied the causal inference model, the DoWhy model, to assess the causal effects of several selected metabolites. An ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was used to validate hits (D‐mannitol, dulcitol, D‐sorbitol, XMP, NADPH, NAD, bilirubin, and α‐KG‐like) in 41 SSNS and 43 controls. In addition, the metabolic pathways were explored. Results: Compared to urine, the metabolism analysis of serum samples was more clearly discriminated at SSNS. 194 differential serum metabolites and five metabolic pathways were obtained in the SSNS group. Eight differential metabolites were identified by establishing the diagnostic model for SSNS, and four variables had a positive causal effect. After validation by targeted MS, except XMP, others have similar trends like the untargeted metabolic analysis. Conclusion: With untargeted metabolomics analysis and further targeted quantitative analysis, we found seven metabolites may be new biomarkers for risk prediction and early diagnosis for SSNS. [ABSTRACT FROM AUTHOR]

Aim: The earlier the onset of proteinuria, the higher the incidence of genetic forms. Therefore, we aimed to analyse the spectrum of monogenic proteinuria in Egyptian children presenting at age <2 years. Methods: The results of 27‐gene panel or whole‐exome sequencing were correlated with phenotype and treatment outcomes in 54 patients from 45 families. Results: Disease‐causing variants were identified in 29/45 (64.4%) families. Mutations often occurred in three podocytopathy genes: NPHS1, NPHS2 and PLCE1 (19 families). Some showed extrarenal manifestations. Additionally, mutations were detected in 10 other genes, including novel variants of OSGEP, SGPL1 and SYNPO2. COL4A variants phenocopied isolated steroid‐resistant nephrotic syndrome (2/29 families, 6.9%). NPHS2 M1L was the single most common genetic finding beyond the age of 3 months (4/18 families, 22.2%). Biopsy results did not correlate with genotypes (n = 30). On renin–angiotensin–aldosterone system antagonists alone, partial and complete remission occurred in 3/24 (12.5%) patients with monogenic proteinuria each, whereas 6.3% (1/16) achieved complete remission on immunosuppression. Conclusion: Genotyping is mandatory to avoid biopsies and immunosuppression when proteinuria presents at age <2 years. Even with such a presentation, COL4A genes should be included. NPHS2 M1L was prevalent in Egyptian children (4 months–2 years) with proteinuria, demonstrating precision diagnostic utility. [ABSTRACT FROM AUTHOR]

In paediatric patients, there is no data on the recommended area under the concentration–time curve from 0 to 12 h (AUC0−12) for free mycophenolic acid (fMPA), which is the active form of the drug, responsible for the pharmacological effect. We decided to establish the limited sampling strategy (LSS) for fMPA for its use in MPA therapeutic monitoring in children with nephrotic syndrome treated with mycophenolate mofetil (MMF). This study included 23 children (aged 11 ± 4 years) from whom eight blood samples were collected within 12 h after MMF administration. The fMPA was determined using the high‐performance liquid chromatography with fluorescence detection method. LSSs were estimated with the use of R software and bootstrap procedure. The best model was chosen based on a number of profiles with AUC predicted within ± 20% of AUC0−12 (good guess), r2, mean prediction error (%MPE) of ±10% and mean absolute error (%MAE) of less than 25%. The fMPA AUC0−12 was 0.1669 ± 0.0697 μg h/mL and the free fraction was within 0.16%–0.81%. In total, there were 92 equations developed of which five fulfilled the acceptance criteria for %MPE, %MAE, good guess >80% and r2 > 0.900. These equations consisted of three time points: model 1 (C1, C2, C6), model 2 (C1, C3, C6), model 3 (C1, C4, C6), model 5 (C0, C1, C2), and model 6 (C1, C2, C9). Although blood sampling up to 9 h after MMF dosing is impractical, it is crucial to include C6 or C9 in LSS to assess fMPA AUCpred correctly. The most practical fMPA LSS, which fulfilled the acceptance criteria in the estimation group, was fMPA AUCpred = 0.040 + 2.220 × C0 + 1.130 × C1 + 1.742 × C2. Further studies should define the recommended fMPA AUC0−12 value in children with nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Syphilis is a known cause of membranous nephropathy. We describe a case of a patient presenting with nephrotic syndrome whose renal biopsy demonstrated a 'full house' immunohistochemical pattern with positive IgG, IgM, C1q, IgA, C3c, and C4d staining. He was treated with immunosuppressive agents for minimal change nephropathy and subsequently class V lupus nephritis, before syphilis infection was confirmed. Following treatment with a single dose of intramuscular benzathine penicillin there was complete and rapid resolution of nephrotic syndrome. With progressive rising incidence in the western world, syphilis is an important and under‐recognised differential diagnosis in cases of nephrotic syndrome. [ABSTRACT FROM AUTHOR]

The article focuses on the impact of the COVID-19 omicron variant on pediatric patients with idiopathic nephrotic syndrome (INS) in 2022. Topics include the incidence and severity of COVID-19 in these patients, the use of immunosuppressive treatments, and the recurrence rates of INS during the pandemic.

Ephedra herba is a conventional Chinese medicine to treat cold, fever, asthma, edema, and lung diseases in the clinic. At present, most pharmacokinetic studies focus on the pharmacokinetic process of alkaloids in normal animals. However, the non‐alkaloid components are also active. In addition, the pharmacokinetic studies under pathological state make more sense for clarifying the material basis of efficacy. In this study, a sensitive and rapid ultra‐high‐performance–tandem mass spectrometry method was developed and applied to determine nine bioactive components (ephedrine, pseudoephedrine, methylephedrine, (+)‐catechin, epicatechin, vitexin, vicenin‐2, cinnamic acid, and ferulic acid) in normal, common cold and nephrotic syndrome rats after the oral administration of Ephedra herba. Compared to the normal group, except for ferulic acid, the exposure levels of the other eight components were significantly increased and the plasma clearance clearly declined in common cold rats. Similarly, the exposure levels of seven components other than cinnamic acid and ferulic acid were also significantly augmented and the plasma clearance decreased significantly in nephrotic syndrome rats. In brief, the pathological conditions of the common cold and nephrotic syndrome could lead to alterations in the pharmacokinetics profiles of the nine components, which provide a reference for further exploration of the pharmacodynamics basis of Ephedra herba. [ABSTRACT FROM AUTHOR]

Kimura disease (KD) is a rare condition with a challenging diagnosis because it may be misdiagnosed and not differentiated from other disorders. We reported a 13‐year‐old patient who presented with growing neck masses and was hospitalized due to the nephrotic syndrome relapse but was eventually diagnosed with KD. [ABSTRACT FROM AUTHOR]