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Abstract Background Fibronectin glomerulopathy (FNG) is a rare autosomal dominant glomerulopathy that can lead to nephrotic syndrome. Here we report the case of an elderly patient diagnosed with FNG, exhibiting nephrotic-range proteinuria, with a 2-year follow-up. Case presentation A 75-year-old Korean female visited the nephrology clinic after experiencing generalized edema for 2 months. Her serum creatinine was 1.36 mg/dL, and urine protein-to-creatinine ratio was 3.99 g/g. Kidney biopsy revealed mesangial and subendothelial dense deposits, and immunohistochemistry for fibronectin showed strong positivity in the glomerulus. The patient’s family history included non-specific renal disease in her mother and two siblings. Genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. She received conservative treatment, including angiotensin II receptor blockers (ARB). Two years after biopsy, the patient has preserved renal function and reduced proteinuria. Conclusion We report the case of a 75-year-old patient with nephrotic-range proteinuria, who was diagnosed with FNG, and found to harbor a FN1 gene mutation. In this case, conservative treatment including ARB yielded reduction of proteinuria and preservation of renal function.

Abstract Introduction Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. Case presentation A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. Conclusion The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates.

Heavy-chain deposition disease (HCDD) is a rare disorder characterized by the deposition of monoclonal immunoglobulin. Due to the disease's rarity and diagnostic challenges, its prognosis is generally poor. Herein, we report a case of successful treatment of HCDD coexisting with multiple myeloma. A 56-year-old man presented at an outpatient clinic with complaints of whole-body pain, edema, and dyspnea that had persisted for 2 weeks. Diagnostic tests confirmed nephrotic syndrome, hematuria, and progressive renal failure. Serum immunofixation electrophoresis identified the presence of IgG kappa paraprotein. A diagnosis of multiple myeloma was established following a bone marrow biopsy. A renal biopsy revealed antibodies specific to the heavy chains of IgG on immunofluorescence, and electron microscopy showed diffuse electron-dense "powdery" densities in the glomerular basement membrane. Based on these findings, the patient was diagnosed with both HCDD and multiple myeloma. Following the diagnosis, the patient immediately began anti-plasma cell therapy using bortezomib, lenalidomide, and dexamethasone. Intermittent hemodialysis was initiated due to persistent azotemia during the diagnostic process; however, renal function improved significantly after only 1 month of therapy, allowing the discontinuation of dialysis. Early intervention with anti-plasma cell therapy, such as bortezomib, is known to improve prognosis in the early stages of the disease. This case report is presented to enhance understanding of HCDD and underscore the importance of prompt diagnosis and treatment in managing this rare condition.

Abstract Background AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) was effective in suppressing inflammation, normalizing serum amyloid A protein levels, and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits. Case presentation A 61-year-old woman was referred to our hospital in 2011 due to oligoarthritis of both knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed for the possibility of polymyalgia rheumatica, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating, and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate, and nephrotic-range proteinuria were found. Autoantibodies and complements levels were normal. No signs of acute infections or cardiovascular disease were evidenced and amyloidosis was suspected. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both. Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition. Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria, and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits and the right knee MRI was normal, without evidence of amyloid synovitis. In 2017, isotopic synoviorthesis of both knees was performed due to repeated episodes of arthritis. Eight years after the start of Tocilizumab, the patient continues treatment and remains clinically stable, with no evidence of recurrence. Conclusions Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. According to the latest evidence, long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure for this disease. To our knowledge, this is the first case of regression of amyloid deposits both in biopsy and magnetic resonance after treatment with tocilizumab.

Abstract Background Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5’phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects. Results Overall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes. Conclusion Our results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.

Background The gut microbiota has a potential role in the development of nephrotic syndrome. Fecal short-chain fatty acid (SCFA) levels are representative of gut microbiota activity. Objective To assess for potential associations of fecal short-chain fatty acid levels in pediatric relapsing nephrotic syndrome. Methods This cross-sectional study was done on patients at the Pediatric Nephrology Subdivision of Prof. Dr. R.D. Kandou General Hospital, a referral hospital in Manado, Indonesia. Subjects were 25 patients aged less than 18 years with nephrotic syndrome (NS). We compared the levels of fecal acetic acid, propionic acid, butyric acid percentage, absolute butyric acid, and total short-chain fatty acid between children with relapsing and non-relapsing NS. A receiver operating characteristic (ROC) curve analysis was conducted to determine the significant SCFA cut-off level to diagnose NS. Results Comparison of fecal SCFAs between relapsing and non-relapsing NS groups showed significantly lower butyric acid percentages, absolute butyric acid level, and total SCFAs levels in the relapsing NS group, but not in acetic acid or propionic acid levels. Further multivariate analysis did not show a significant difference in total SCFA levels between relapsing and non-relapsing NS. Absolute butyric acid level had the strongest association with relapsing NS, with the highest predictive score. The absolute butyric acid cut-off value of 0.85 mg/mL had a high sensitivity (90%) and high specificity (93.3%) for predicting relapsing nephrotic syndrome. Conclusion Fecal acetic acid, propionic acid, and total short-chain fatty acid in stool are not associated with relapsing NS in children. However, fecal butyric acid measurements are inversely associated with relapsing NS.

Abstract Background Low albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients. Methods This study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software. Results There were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P

Abstract Background Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections. Case presentation We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic Coxiella burnetii-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely. Conclusions Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient.

Background: Nephrotic syndrome is a special type of chronic kidney disease, the specific pathogenesis of which remains unclear. An increasing number of studies have suggested that B cells play an important role in the pathogenesis of nephrotic syndrome. Summary: Idiopathic nephrotic syndrome is a common kidney disease in children. While previously believed to be primarily caused by T-cell disorders, recent research has shifted its focus to B cells. Studies have shown that B cells play a significant role in the pathogenesis of NS, potentially even more so than T cells. This article provides a comprehensive review of the involvement of B cells in the development of idiopathic nephrotic syndrome. Key Messages: B cells are involved in the pathogenesis of nephrotic syndrome by producing autoantibodies and various cytokines.

Abstract Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts.

Abstract Introduction People with Tuberculosis (TB) infection may present with glomerulonephritis (GN). The range of presentations, renal pathologies, and clinical outcomes are uncertain. Whether clinical features that establish if GN etiology is medication or TB related, and possible benefits of immunosuppression remain uncertain. Methods A scoping review was completed, searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Conference Abstracts from Inception to December, 2023. The study population included patients with TB infection who developed GN and underwent renal biopsy. All data regarding presentation, patient characteristics, renal pathology, management of TB and GN, and outcomes were summarized. Results There were 62 studies identified, with 130 patients. These cases included a spectrum of presentations including acute kidney injury, nephrotic syndrome and hypertension, and a range of 10 different renal pathology diagnoses. Cases that included immunosuppression and outcomes ranged from complete remission to long-term dialysis dependence. The presence of granulomas (4/4, 100%), anti-glomerular basement membrane disease (3/3, 100%), amyloidosis (75/76, 98.7%), and focal segmental glomerulosclerosis (2/2, 100%) were specific for GN being TB-infection related. On the other hand, minimal change disease was specific for anti-TB therapy related (7/7, 100%). While patients with more aggressive forms of GN commonly were prescribed immunosuppression, this study was unable to confirm efficacy. Only rifampin or isoniazid were implicated in drug-associated GN. Discussion This study provides a clear rationale for renal biopsy in patients with TB and GN, and outlines predictors for the GN etiology. Thus, this study establishes key criteria to optimize diagnosis and management of patients with TB and GN.

Abstract Background Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50–60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults. Methods 130–150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant. Trial Registration TURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

Summary Background: Anaemia occurs in both acute glomerulonephritis (AGN) and nephrotic syndrome (NS). However, the influence of these two renal disorders on other haematologi cal profiles has not been widely and exhaustively studied in Nigerian children. Objectives: To determine and compare haematological changes that occur in the acute phases of AGN and NS. . Materials and Methods: The haematological profiles of all children admitted to the University of Ilorin Teaching Hospital with a diagnosis of AGN or NS between 1996 and 2004 were compiled. Those excluded from the study were children with NS who had a relapse or had commenced steroid or cytotoxic therapy before admission; others excluded were those with either disease, who had received blood transfusion during the three months immediately prior to the study. Results: Twenty nine and 28 children with AGN and NS respectively, met the study criteria. The mean packed cell volume (PCV) in children with AGN was 28+5 percent, while that among children with NS was 34+6 percent. Moderate anaemia occurred in 10 (34 percent). Children with AGN compared to three (11 percent) with NS. Neutrophilia was present in 45 percent and 54 percent respectively, of children with AGN and NS. Eosinophilia occurred in three (10.3 percent) children with AGN compared to three (10.7 percent) children with NS, and lymphocytosis was present in 11(37.9 percent) children with AGN compared to 12 (42.9 percent) children with NS. Conclusion: Severe anaemia was uncommon in the two groups, while children with AGN had lower mean PCV and were more prone to developing moderate anaemia compared to children with NS. Lymphocytosis, lymphopenia and neutrophilia occurred in some children with both conditions.

In this report, we described the case of a 14-year-old boy with steroid-sensitive nephrotic syndrome who developed hyperglycaemia and ultimately, diabetic ketoacidosis, following high-dose steroid therapy for a primary renal disease. The nephrotic syndrome was diagnosed based on generalized oedema, massive proteinuria, hypoalbuminaemia and hypercholesterolaemia. Serum creatinine and random blood glucose levels were normal and there was no glycosuria. He was commenced on high dose prednisolone 40 mg 12 hourly and by the 8th day on prednisolone, he achieved remission and was discharged. However, four weeks later, he developed features of diabetic ketoacidosis (DKA) which was confirmed by the resence of hyperglycaemia (random blood glucose19.4 mmol/L), acidosis (serum bicarbonate 10 mmol/L) and ketonuria (2+). The DKA was managed with intravenous fluid (0.9% sodium chloride), continuous insulin infusion and antibiotics. After resolution of the DKA, he was switched to subcutaneous soluble insulin and thereafter, premixed insulin twice daily with a reduction in the dose of prednisolone and was discharged home after 30 days on admission. Blood glucose level has remained within normal range one year after discontinuing insulin and he is still in remission with regard to the nephrotic syndrome at follow up. Conclusion: The risk of diabetic ketoacidosis should be considered in the course of steroid therapy for nephrotic syndrome. To avoid missing of cases of steroid-induced diabetes mellitus, and ultimately DKA, both fasting and postprandial blood glucose values should be monitored.

Background: The hallmark of Nephrotic syndrome is massive proteinuria, with associated enlarged kidneys. However the association between remission status and size of the kidneys in patients with nephrotic syndrome is not known. This study is aimed at determining the dimensions of the kidneys of children with nephrotic syndrome and to compare kidney dimensions in patients with nephrotic syndrome who were in remission compared with the dimensions in patients who were not in remission. Subjects and Methods: This is a case-control study, where fiftythree children with diagnosis of Nephrotic syndrome and fifty- seven age matched healthy controls were analysed. The kidneys of both cases and controls were scanned using the B- mode ultrasound and the kidneys Bipolar, anteroposterior and transverse dimensions and volume were determined. Results: The mean renal longitudinal, anteroposterior, transverse dimensions and volume were higher in cases compared to the controls, bilaterally (p

One of the urgent problems of medicine is to clarify the pathogenetic mechanisms of glomerulonephritis (GN) with refractory nephrotic syndrome (NS). In 30% of cases, refractory NS has a genetic nature. The role of human histocompatibility system (HLA) genes in the development of refractory NS has not been sufficiently studied. The purpose of this study was to study the association of two-locus haplotypes of HLA class II gene alleles with GN manifested by refractory NS. The typing of HLA class II genes in 136 patients with NS was performed by polymerase chain reaction (PCR), which included the identification of 13 alleles of the DRB1, 8 – DQA1, and 12 – DQB1 loci. The cohort of the examined patients was divided into two groups: a group of patients with refractory NS and a group of patients with rare relapses, with a lack of refractoriness to the therapy. Persons of Chuvash nationality were selected for the study. In the studied groups of patients, the values of the nonequilibrium coupling of alleles (D) were determined to identify characteristic two-locus haplotypes and their frequency according to the formulas of Piazza A. and coauthors. To assess the association of refractory NS with HLA haplotypes, relative risk values (RR) were calculated using the formula Woolf B. and Haldane J. The statistical significance of the association was assessed using the twosided Fisher exact method for four-field tables (PF). The highest value of RR was found in the haplotype HLA-DRB1*11(05)-DQA1*0301. Its value was 42.1 (PF = 0.005). Another statistically significant value was the RR value of the haplotype HLA-DRB1*15(02)-DQB1*0602-8, equal to 0.2 (PF = 0.004). As a result of the study, the haplotype DRB1*11(05)-DQA1*0301, associated with an increased risk of refractory NS, and the protective haplotype DRB1*15(02)-DQB1*0602-8, reducing the risk of refractory NS were found in the HLA genotype of individuals in the Chuvash population.

Abstract Background Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. Case presentation We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient’s extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient’s demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient’s diagnosis should be classified as a rare case of hemorrhagic varicella. Conclusion Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.

Abstract Background Infection is the most common complication of pediatric patients with nephrotic syndrome. The factors associated with infection in nephrotic syndrome are lacking. The objective of the study was to identify the prevalence and associated factors among children with nephrotic syndrome aged 2 to 18 years. Methods We conducted a hospital-based retrospective cross-sectional study. The data collector installed an Epi5 collector electronic data-collecting tool from Google Play. Then, we exported the data to Stata version 15.1 for analysis. The mean, standard deviation, frequency, and percentage were used for descriptive statistics. The logistic regression model was used to identify the factors associated with infection. Results In this study, the prevalence of infection among nephrotic syndrome children is 39.8% (95%CI: 30.7, 49.7). The types of infection identified were pneumonia, urinary tract infection, diarrheal disease, cutaneous fungal infection, intestinal parasitic infection, and sepsis. The presence of hematuria increased the odds of infection by 5-times. On the other hand, low level of serum albumin increased the odds of infection by 7%. Being a rural resident increased the odds of infection by 3.3-times as compared to urban. Conclusions Serum albumin level, presence of hematuria, and rural residence were significantly associated with infection. We recommended a longitudinal incidence study on large sample size at multicenter to strengthen this finding.

Abstract Background Nephrotic syndrome (NS) can occur as a paraneoplastic disorder in association with various types of carcinoma. However, paraneoplastic nephrotic syndrome (PNS) is often misdiagnosed as idiopathic nephrotic syndrome or as an adverse effect of oncology treatment, leading to delayed diagnosis and suboptimal treatment. The characteristics of NS associated with solid malignancies are not yet elucidated. We systematically summarized the clinical data for 128 cases of NS combined with solid malignancies with the aim of informing the clinical management of PNS. Methods We searched the PubMed database for articles published from the date of inception through to October 2023 using the following keywords: “cancer” or “malignant neoplasms” or “neoplasia” or “tumors” and “nephrotic syndrome”, “nephrotic” or “syndrome, nephrotic”. All data were extracted from case reports and case series, and the extraction included a method for identifying individual-level patient data. Results A literature search yielded 105 cases of PNS and 23 of NS induced by cancer therapy. The median age at diagnosis was 60 years, with a male to female ratio of 1.8:1. In patients with PNS, manifestations of NS occurred before, concomitantly with, or after diagnosis of the tumor (in 36%, 30%, and 34% of cases, respectively). Membranous nephropathy (49%) was the most prevalent renal pathology and found particularly in patients with lung, colorectal, or breast carcinoma. Regardless of whether treatment was for cancer alone or in combination with NS, the likelihood of remission was high. Conclusion The pathological type of NS may be associated with specific malignancies in patients with PNS. Prompt identification of PNS coupled with suitable therapeutic intervention has a significant impact on the outcome for patients.

Introduction: Anticoagulant use in specific clinical scenarios such as venous thromboembolic disease or atrial fibrillation is common, with clearly established management guidelines. However, there is currently no unified clinical guidance for managing thrombosis in unusual scenarios, presenting a significant therapeutic challenge. Objective: To review the indications for anticoagulation and their regimens in unusual clinical situations based on available evidence. Methods: A literature review was conducted from 1997 to 2022, using relevant MeSH terms for anticoagulation, oral anticoagulants, embolism, and thrombosis. Information was extracted and synthesized in a structured manner. Results: In nephrotic syndrome, warfarin is recommended, although alter-natives such as low molecular weight heparins, aspirin, or direct oral anti-coagulants exist. For intracavitary thrombus, warfarin is the drug of choice, with demonstrated equivalent efficacy to direct oral anticoagulants. For peripheral arterial disease, rivaroxaban at vascular protection dose + aspirin has shown benefit in major adverse cardiovascular outcomes depending on individual profile. Conclusions: Management of these scenarios requires proper clinical assessment and selection of the type of anticoagulant, ensuring maximum reduction of both thrombosis and bleeding risks.

Introduction: Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Methods: We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician’s discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results: Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1,000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months), 10 patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline (14 [100%] vs. 5 [35.7%]; 8/14 [57.1%] vs. 4/12 [33.3%]; 13/14 [92.9%] vs. 7/12 [58.3%]; 20 mg/day vs. 5.25 mg/day, respectively). Maintenance RTX therapy was used in 6 patients, with sustained complete remission. Infusion reactions were observed in 4 patients (one required treatment withdrawal). Conclusions: Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

Background: AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) was effective in suppressing inflammation, normalizing serum amyloid A protein levels, and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits. Case presentation: A 61-year-old woman was referred to our hospital in 2011 due to oligoarthritis of both knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed for the possibility of polymyalgia rheumatica, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating, and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate, and nephrotic-range proteinuria were found. Autoantibodies and complements levels were normal. No signs of acute infections or cardiovascular disease were evidenced and amyloidosis was suspected. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both. Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition. Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria, and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits and the right knee MRI was normal, without evidence of amyloid synovitis. In 2017, isotopic synoviorthesis of both knees was performed due to repeated episodes of arthritis. Eight years after the start of Tocilizumab, the patient continues treatment and remains clinically stable, with no evidence of recurrence. Conclusions: Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. According to the latest evidence, long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure for this disease. To our knowledge, this is the first case of regression of amyloid deposits both in biopsy and magnetic resonance after treatment with tocilizumab. [ABSTRACT FROM AUTHOR]

Background: In steroid-resistant nephrotic syndrome (SRNS), protracted proteinuria leads to the loss of thyroxine-binding proteins resulting in low thyroid hormones and in damage renal tubules and exhausts the thyroid reserve. This study aimed to assess thyroid function in those patients with SRNS and steroid-sensitive nephrotic syndrome (SSNS). A comparative cross-sectional study evaluated the thyroid status of 50 children with an equal age- and sex-matched SSNS, and controls were enrolled in this study. Demographic data, clinical examination, renal profile, and thyroid function tests were conducted for them. Results: Subclinical non-autoimmune hypothyroidism was significantly prevalent in 54% of SRNS patients and 12% of SSNS patients (p < 0.001). No cases of overt hypothyroidism were detected. Albumin and protein/creatinine ratio emerged as significant independent factors influencing subclinical hypothyroidism with odds ratio (OR) 0.624, 95% CI (0.425–0.916), and 1.315 OR (1.315) and 95% CI (1.035–1.672), respectively. Conclusion: Subclinical non-autoimmune hypothyroidism among patients with SRNS might occur, especially with protracted proteinuria necessitating regular screening of thyroid function in this cohort. [ABSTRACT FROM AUTHOR]

Background: Membranous glomerulonephritis, also known as membranous nephropathy (MN), is a common cause of nephrotic syndrome in adults. Despite extensive research on MN, bibliometric studies on the subject are scarce. Therefore, this study aimed to provide a visual analysis of global trends in membranous nephropathy research over the past 13 years. Methods: This study conducted a bibliometric and visual analysis of global trends in MN research from 2010 to 2023. Articles related to MN were retrieved from the Web of Science Core Collection (WoSCC) database. Tools such as CiteSpace and VOSviewer were utilized to analyze publications, countries, institutions, authors, publishing journals, co-cited references, and keywords to identify the current state and future trends in MN research. Results: The analysis encompassed 1,624 publications, showing an annual increase from 2010 to 2023. The People's Republic of China emerged as the most active country in this field, while France's Sorbonne Universite and Institut National de la Sante et de la Recherche Medicale (Inserm) led in publication volume among academic institutions. Debiec Hanna stood out as the most prolific author. BMC Nephrology had the highest number of publications, making it the most favored journal in the field. The article with the greatest co-citation intensity was "Primary Membranous Nephropathy," a review published in 2017. Conclusion: This study shows that there has been increasing interest in membranous nephropathy over the past 13 years. The most frequently encountered keywords were "membranous nephropathy" "nephrotic syndrome," and "glomerulonephritis." Analysis of emerging terms indicated that "a2 receptor antibody," "domain containing 7a," and "t cell" may remain prominent subjects of research in the forthcoming years. The findings highlight key research trends and areas of interest that can inform researchers, clinicians, and policymakers about the current state of MN research and help guide future research directions and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Fibronectin glomerulopathy (FNG) is a rare autosomal dominant glomerulopathy that can lead to nephrotic syndrome. Here we report the case of an elderly patient diagnosed with FNG, exhibiting nephrotic-range proteinuria, with a 2-year follow-up. Case presentation: A 75-year-old Korean female visited the nephrology clinic after experiencing generalized edema for 2 months. Her serum creatinine was 1.36 mg/dL, and urine protein-to-creatinine ratio was 3.99 g/g. Kidney biopsy revealed mesangial and subendothelial dense deposits, and immunohistochemistry for fibronectin showed strong positivity in the glomerulus. The patient's family history included non-specific renal disease in her mother and two siblings. Genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. She received conservative treatment, including angiotensin II receptor blockers (ARB). Two years after biopsy, the patient has preserved renal function and reduced proteinuria. Conclusion: We report the case of a 75-year-old patient with nephrotic-range proteinuria, who was diagnosed with FNG, and found to harbor a FN1 gene mutation. In this case, conservative treatment including ARB yielded reduction of proteinuria and preservation of renal function. [ABSTRACT FROM AUTHOR]

Background: Low albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients. Methods: This study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software. Results: There were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P < 0.01) and a higher rate of autoimmune disease (P = 0.03) than the low-albumin group. Membranous nephropathy (MN) was the most frequent pathological type of NS in patients with thromboembolic events, regardless of their albumin level. There were significantly fewer patients with anti-PLA2R (M-type phospholipase A2 receptor)-positive MN in the high-albumin group than in the low-albumin group (P < 0.01). Conclusions: Our study found that there was still a high risk for patients with NS and relatively high albumin levels to develop thromboembolic events. [ABSTRACT FROM AUTHOR]

Background: Recently, the C3-epimer of 25-hydroxyvitamin D [C3-epi-25(OH)D] has become a topic of interest among 25-hydroxyvitamin D [25(OH)D] metabolites. Although it can lead to an overestimation of vitamin D storage, its relationship with disease occurrence remains controversial, possibly related to the great extent of tracking of 25(OH)D by C3-epi-25(OH)D over time. This study aimed to investigate the differential performance of C3-epi-25(OH)D3 and its percentage [%C3-epi-25(OH)D3] with respect to 20 common paediatric diseases. Methods: This study involved 805 healthy children and adolescents and 2962 patients with common paediatric diseases. We investigated sex, age, and seasonal differences in C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels; their variations on 20 common paediatric diseases; and their degree of correlation with 25(OH)D3 levels and various diseases. Results: Among the healthy underage participants, C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 changed similarly, with no sex differences. Moreover, their levels were higher in the infant period than in the other periods (t = 5.329–5.833, t = 4.640–5.711, all Padj < 0.001), and in spring and summer than in autumn and winter (t = 3.495–6.061, t = 3.495–5.658, all Padj < 0.01). Under healthy and disease conditions, C3-epi-25(OH)D3 was positively correlated with 25(OH)D3 (ρ = 0.318 ~ 0.678, all P < 0.017), whereas %C3-epi-25(OH)D3 was not, except in patients with nephrotic syndrome (ρ=-0.393, P = 0.001). Before and after adjusting for 25(OH)D3, the relationship of C3-epi-25(OH)D3 with the diseases was notably different. However, it was almost consistent for %C3-epi-25(OH)D3. Our results indicated that %C3-epi-25(OH)D3 was associated with short stature, nephrotic syndrome, lymphocytic leukaemia, rickets, paediatric malnutrition, and hypovitaminosis D (OR = 0.80 ~ 1.21, all P < 0.05). Conclusions: The %C3-epi-25(OH)D3 can correct the properties of C3-epi-25(OH)D3 to better track 25(OH)D3 and may be more suitable for exploring its pathological relevance. Further detailed studies of each disease should be conducted. [ABSTRACT FROM AUTHOR]

Introduction: There is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders). Methods: This open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2–2.5 mg/kg once daily for a period of 8–12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800–1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria. Results: In the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25–11) compared to 7 months (IQR 3.5–12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468). Conclusions: The efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure. Registration of the study with Clinical Trials Registry of India: (http://ctri.nic.in;CTRI/2021/06/034421) (Dt: 28/06/2021). [ABSTRACT FROM AUTHOR]

Rituximab has been extensively used for managing B-cell lymphomas due to its anti-CD20 monoclonal antibody activity. Over the last decade, its application has been extended to manage frequent relapsing or steroid-dependent nephrotic syndrome. Its use has been comparatively safe, but few cases of adverse effects on the lung have been reported in the adult population. These lung injury presentations are rarely reported in a pediatric group with only four cases in the literature. Below is a rare case of rituximab-induced lung injury in a 9-year-old boy with frequent relapse of nephrotic syndrome, which developed after four days of rituximab infusion. Suspecting infection and sepsis, several antibiotics were started, but with no improvement in respiratory complaints, even antifungal and antituberculosis treatments were initiated. Finally, setting up a casual relation with the time of infusion to the development of complaints, association with rituximab was suspected. The patient responded to steroid therapy with complete resolution of respiratory complaints. To our knowledge, this is the first reported case of rituximab-induced cystic lesion in lungs from India. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze the medication characteristics and rules of traditional Chinese medicine patent compound in the treatment of nephrotic syndrome by using data mining technology, so as to provide reference for clinical treatment and new drug development. METHODS: Traditional Chinese medicine patent compound in the treatment of nephrotic syndrome in Announcement of Chinese Patent Publication of China National Intellectual Property Administration (http:/ / epub. cnipa. gov. cn) from Sept. 10th, 1985 to Nov. 1st, 2023 were retrieved. The drug frequency, theory of four natures, five flavors and meridian tropism, association rule analysis and systematic cluster analysis of traditional Chinese medicine patent compound that met the inclusion criteria were conducted by using the Ancient And Modern Medical Record Cloud Platform V2. 3. 7 and SPSS Statistics 26. 0 software. RESULTS: A total of 88 kinds of traditional Chinese medicine patent compound were enrolled, including 249 traditional Chinese medicines. In terms of drug frequency, in descending order, Hedysarum multijugum maxim, Atractylodes macrocephala koidz, Alisma orientale (Sam.) juz, Poria cocos (Schw.) wolf, and Rhizoma dioscoreae. In terms of four natures, five flavors and meridian tropism, the four natures were flat, the five flavors were sweet, and the meridian tropism was liver. In terms of association rules, the confidence levels from high to low were Atractylodes macrocephala koidz-Hedysarum multijugum maxim, Poria cocos (Schw.) Wolf-Hedysarum multijugum maxim, Alisma orientale (Sam.) juz-Hedysarum multijugum maxim. In terms of systematic clustering, the obtained drug combinations included Rehmanniae Radix Praeparata, Cornus Officinalis Sieb. Et Zucc, Rhizoma dioscoreae, Euryales semen, Leonuri herba, Imperatae rhizoma and Hedysarum multijugum maxim, Codonopsis Radix, and licorice. CONCLUSIONS: The treatment of nephrotic syndrome by traditional Chinese medicine patent compound focuses on spleen and kidney co-regulation, Qi, blood and water treatment, and takes strengthening the spleen and tonifying the kidney, inducing diuresis and eliminating dampness, activating blood circulation and removing blood stasis as the basic treatment, which can develop ideas and provide references for the clinical treatment of the disease and the research and development of new drugs. [ABSTRACT FROM AUTHOR]

Background Nephrotic syndrome (NS) is characterized by urinary loss of proteins, including hormones and their carrier proteins, potentially resulting in endocrine disorders. This study aimed to assess thyroid dysfunction frequency and potential implications in NS. Methods In this case–control study, patients with severe NS (serum albumin ≤2.5 g/dl) and controls without proteinuria were evaluated for thyroid, haemostatic and nutritional parameters, including body composition. Results A total of 42 nephrotic and 40 non-proteinuric patients were enrolled. The NS group showed higher thyroid-stimulating hormone and lower free hormones, corresponding to a higher frequency of both euthyroid sick syndrome {ESS; 36% versus 5%; odds ratio [OR] 10.6 [95% confidence interval (CI) 2.2–50.0]} and hypothyroidism [31% versus 5%; OR 8.5 (95% CI 1.8–40.7)] compared with the control group. Levothyroxine supplementation was required for 11 NS patients (26% of the NS group). In addition, compared with control individuals, NS patients exhibited lower lean tissue mass and a trend towards hypercoagulability, which was evidenced by higher levels of most coagulation factors and fibrinolysis inhibitors, and reduced endogenous anticoagulants activities. Furthermore, NS patients with ESS presented with a 10.4 kg (95% CI −18.68 to −2.12) lower lean tissue mass. Those with hypothyroidism had significantly reduced activity of coagulation factor X [by −30% (95% CI −47 to −13)] and protein S [by −27% (95% CI −41 to −13)] compared with euthyroid NS individuals. Conclusions Thyroid dysfunction is common in severe NS, often necessitating levothyroxine supplementation, which supports routine thyroid workup. A potential link between thyroid, nutritional and coagulation disorders in NS requires further investigation. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) is an antibody-mediated autoimmune disease and the most common cause of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor 1 (PLA2R1) as the first target antigen in patients with MN 15 years ago has led to a paradigm shift in the pathobiological understanding of this disease. Autoantibodies against PLA2R1 as well as thrombospondin type-1 domain-containing 7A, the second identified antigen in adults, were shown to be disease-causing and act through local activation of the complement system, primarily via the classical and lectin pathways. These findings indicate that both plasma cells, the main source of antibodies and autoantibodies, as well as the complement system, the main pathogenic effector mechanism in MN, are rational and pathogenesis-based treatment targets in MN. This review summarizes pathomechanistic and clinical evidence for and against plasma cell– and complement-targeted treatments in MN. [ABSTRACT FROM AUTHOR]

Introduction: Monoclonal immunoglobulin deposition diseases (MIDDs) are a group of systemic diseases, characterized by deposition of monoclonal immunoglobulin predominantly in the kidney. In the absence of overt hematologic disease, MIDDs are classified as a part of monoclonal gammopathy of renal significance. Patients with MIDD may present with a nephrotic syndrome and kidney function impairment. Treatment usually includes anti-plasma cell therapy. Case Presentation: We report a case of a 54-year-old female who presented with nephrotic syndrome related to light chain deposition disease of lambda type. Due to a complicated clinical course (including cardiac injury and thromboembolic stroke), plasma cell-targeted therapy was stopped. A few months later, the patient presented with severe acute kidney injury. Kidney biopsy revealed crescentic glomerulonephritis, and immunofluorescence staining was positive for lambda chain. Treatment with daratumumab was initiated resulting in stabilization of kidney function and partial nephrotic syndrome remission. Conclusion: This case highlights an uncommon histologic manifestation in a patient diagnosed with light chain deposition disease. Furthermore, it underscores the significance of plasma cell-targeted therapy and the favorable clinical and hematological response observed with daratumumab. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influences of Neferine (Nef) on inflammatory injury in nephrotic syndrome (NS) rats by regulating the MAPK/NF-κB pathway. Methods: SD rats were separated into control check group (CK group), Model group, low-dose Nef group (Nef-L group, 2.5 mg/kg), high-dose Nef group (Nef-H group, 5 mg/kg), prednisone acetate group (PA group, 6.3 mg/kg), Anisomycin (MAPK agonist) group (5 μmol/L), Nef-H+Anisomycin group (5 mg/kg+5 μmol/L), with 12 rats in each group. Except for the CK group, all other groups were injected with doxorubicin through the tail vein to induce the NS rat model. Rats in CK group were injected with an equal volume of normal saline through the tail vein at the same time. After successful modeling, dosing treatment was performed once a day for 4 weeks. Detected 24-hour urine protein content, serum creatinine (Scr), albumin (ALB), urea nitro‑ gen (BUN) levels, renal tissue pathology, and levels of TNF-α, IL-6, and IL-1β in renal tissue; TUNEL staining was performed to detect cell apoptosis in rat kidney tissue; Western blot was performed to detect the expression of p-p38, p-JNK, p-ERK1/2 and p-NF-κB p65 proteins in rat kidney tissue. Results: Compared with CK group, Model group had severe renal tissue pathological damage, the 24 h urinary protein, Scr, BUN, TNF-α, IL-6, IL-1β, apoptosis rate, p-p38, p-JNK, p-ERK1/2, p-NF-κB p65 protein expressions were increased, while ALB level was decreased (P<0.05) ; compared with Model group, the renal tissue pathological damage of rats in Nef-L group, Nef-H group and PA group were severe, the 24 h urinary protein, Scr, BUN, TNF-α, IL-6, IL-1β, apoptosis rate, p-p38, p- JNK, p-ERK1/2, p-NF- κB P65 protein expressions were decreased, while ALB level was increased, the renal tissue pathological damage in the Anisomycin group was aggravated, the 24 h urinary protein, Scr, BUN, TNF-α, IL-6, IL-1β, apoptosis rate, p-p38, p-JNK, p-ERK1/2, p-NF-κB p65 protein expressions were increased, while ALB level was decreased (P<0.05) ; Anisomycin attenuated the effects of high doses of Nef on NS rats. Conclusion: Nef may alleviate the inflammatory injury in NS rats by inhibiting MAPK/ NF-κB signaling pathway [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is the most common malignancy in men. Secondary nephrotic syndrome, a feature of paraneoplastic syndrome, occurs in 11% of cases and is mainly caused by membranous glomerulopathy. The association between minimal change disease and prostate cancer is rare. Only one cause has been described in the available literature. Case presentation: We present the case of a 77-year-old patient who was admitted to our department with stage 3 acute kidney injury and with nephrotic syndrome with anasarca (creatinine: 168 µmol/L, eGFR: 33 mL/min/1.73 m2, albumin: 18.5 g/L, total cholesterol: 6.86 mmol/L, urine albumin creatinine ratio: 812.7 mg/mmol). In the differential diagnosis of nephrotic syndrome, looking for a secondary cause is essential, so the parainfectious causes of nephrotic syndrome were excluded. An elevated prostate-specific antigen (10.69 ng/L) was found when screening for oncological causes, and prostate adenocarcinoma was identified on biopsy. A renal biopsy was then performed with a finding of minimal change disease. Despite the generally accepted guidelines of prostate carcinoma in that stage and age of the patient being watchful waiting, antiandrogen therapy was started with the cooperation of a urologist. There was a significant improvement in renal parameters in the patient (creatinine: 87 µmol/L, eGFR: 73 mL/min/1.73 m2, albumin: 33.4 g/L, urine albumin creatinine ratio: 27.6 mg/mmol). Conclusion: This case shows the importance of multidisciplinary cooperation in the treatment of secondary causes of nephrotic syndrome. In the case of proven paraneoplastic syndrome, it is necessary to start treating the malignancy; however, in general, a conservative approach without treatment is recommended. [ABSTRACT FROM AUTHOR]

Objective: Acute post-streptococcal glomerulonephritis (APSGN) is a common cause of acute glomerulonephritis in children. The condition may present as acute nephritic and/or nephrotic syndrome and rarely as rapidly progressive glomerulonephritis. ChatGPT (OpenAI, San Francisco, California, United States of America) has been developed as a chat robot supported by artificial intelligence (AI). In this study, we evaluated whether AI can be used in the follow-up of patients with APSGN. Methods: The clinical characteristics of patients with APSGN were noted from patient records. Twelve questions about APSGN were directed to ChatGPT 3.5. The accuracy of the answers was evaluated by the researchers. Then, the clinical features of the patients were transferred to ChatGPT 3.5 and the follow-up management of the patients was examined. Results: The study included 11 patients with an average age of 9.08±3.96 years. Eight (72.7%) patients had elevated creatinine and 10 (90.9%) had hematuria and/or proteinuria. Anti-streptolysin O was high in all patients (955±353 IU/mL) and C3 was low in 9 (81.8%) patients (0.56±0.34 g/L). Hypertensive encephalopathy, nephrotic syndrome, and rapidly progressive glomerulonephritis were observed in three patients. Normal creatinine levels were achieved in all patients. Questions assessing the definition, epidemiologic characteristics, pathophysiologic mechanisms, diagnosis, and treatment of APSGN were answered correctly by ChatGPT 3.5. All patients were diagnosed with APSGN, and the treatment steps applied by clinicians were similarly recommended by ChatGPT 3.5. Conclusions: The insights and recommendations offered by ChatGPT for patients with APSGN can be an asset in the care and management of patients. With AI applications, clinicians can review treatment decisions and create more effective treatment plans. [ABSTRACT FROM AUTHOR]

Background: Usingsteroids as a medical line of treatment for pediatric idiopathic nephrotic syndrome (INS) has a noxious aftereffect on the course of bone mineralization in the targeted children. Searching for new markers of bone mineralization seems to be an imperative issue. Sclerostin (Scl), a glycoprotein which is coded by the SOST gene, is noted as a pivotal controller of bone setup via its repressing outcome on Wnt signaling. The aim of this study was to assess the concentration of Scl level in children with INS and to correlate Scl level with other existing markers of bone metabolism. Method: A case control study achieved on 70 children including 35 patients with INS on corticosteroid therapy and 35apparently well age and sex alike children as a control group. Kidney function testing, bone markers, parathyroid hormone, and serum sclerostin, were assayed in both research groups. Results: There was a statistically significant difference in serum Scl level between the studied groups, being higher in the nephrotic children than the control group (mean ± SD: 10.07 ± 3.650 vs. 5.29 ± 1.92, respectively with p<0.001). Among factors significantly correlated with serum sclerostin, only serum calcium was significantly independently associated with it (unstandardized β=-1.356). There was a statistically significant relation between serum Scl, steroid response and disease activity (p value= 0.001, 0.001 respectively). Conclusion: The sclerostin serum level can serve as an indicator of bone mineralization in children with INS utilizing corticosteroids as a therapeutic agent. [ABSTRACT FROM AUTHOR]

Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. Results: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (− 0.13 ± 1.21 vs. − 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β − 7.5 × 10−6, CI − 1.2 × 10−5, − 3 × 10−6, p = 0.001) and incident cases of NS (vs. prevalent) (β − 1.1, CI − 2.22, − 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (β 0.16, CI 0.04, 0.29, p = 0.01) over time. Conclusion: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score. [ABSTRACT FROM AUTHOR]

Background: Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. Methods: We evaluated obesity and longitudinal growth among children (1–18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996–2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. Results: We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26–12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95–2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. Conclusions: Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature. [ABSTRACT FROM AUTHOR]

Nuclear factor kappa B (NF-κB) family plays a central role in the human immune system. Heterozygous variants in NFKB2 typically cause immunodeficiency with various degrees of central adrenal insufficiency, autoimmunity, and ectodermal dysplasia. No reported case has presented kidney failure as an initial symptom. Moreover, documentation of kidney involvement of this disease is limited. Case diagnosis: A 2-year-old female who presented with dyspnea and hypertensive emergency in the setting of new-onset nephrotic syndrome with acute-on chronic kidney injury with resultant chronic kidney disease (CKD) was found to have a novel heterozygous N-terminal variant in NFKB2 (c.880del: p. Tyr294Ilefs*4) with mild hypogammaglobulinemia, but no adrenal insufficiency or ectodermal dysplasia. She became dialysis-dependent during her initial hospitalization and developed CKD stage 5D, requiring continued peritoneal dialysis. She is currently awaiting kidney transplantation. Conclusions: Whether nephrotic syndrome or kidney injury or failure is the primary symptom of this variant or secondary to some event remains unknown. Further case accumulation is warranted. [ABSTRACT FROM AUTHOR]

Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype–phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations. [ABSTRACT FROM AUTHOR]

Primary glomerular diseases are rare entities. This has hampered efforts to better understand the underlying pathobiology and to develop novel safe and effective therapies. NEPTUNE is a rare disease network that is focused on patients of all ages with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. It is a longitudinal cohort study that collects detailed demographic, clinical, histopathologic, genomic, transcriptomic, and metabolomic data. The goal is to develop a molecular classification for these disorders that supersedes the traditional pathological features-based schema. Pediatric patients are important contributors to this ongoing project. In this review, we provide a snapshot of the children and adolescents enrolled in NEPTUNE and summarize some key observations that have been made based on the data accumulated during the study. In addition, we describe the development of NEPTUNE Match, a program that aims to leverage the multi-scalar information gathered for each individual patient to provide guidance about potential clinical trial participation based on the molecular characterization and non-invasive biomarker profile. This represents the first organized effort to apply principles of precision medicine to the treatment of patients with primary glomerular disease. NEPTUNE has proven to be an invaluable asset in the study of glomerular diseases in patients of all ages including children and adolescents. [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]

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]

Haematuria and proteinuria are common findings on urinalysis in childhood. They usually occur in either children with specific symptoms e.g. macroscopic haematuria or nephrotic syndrome, or in those who have non-specific symptoms (usually when looking to exclude urinary tract infection) and sometimes in asymptomatic children. The majority of children fall into the latter two groups, the finding is temporary and not associated with long term renal disease. If the finding is persistent or patients have specific clinical features then renal abnormalities are more frequent and appropriate investigation is required. This review provides a rationale for an approach that allows reassurance to be given to children and their families in whom the finding is transient and benign, whilst identifying those in whom renal abnormalities are present and treatment required. It describes algorithms for macroscopic haematuria (MaH), asymptomatic microscopic haematuria (MiH) and proteinuria. [ABSTRACT FROM AUTHOR]

Background: Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections. Case presentation: We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic Coxiella burnetii-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely. Conclusions: Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient. [ABSTRACT FROM AUTHOR]

Background: Chronic subdural hematoma (CSDH) is a common complication of neurosurgery. Craniocerebral trauma is the likely cause. There are no reports relating CSDH with nephrotic syndrome. Its pathogenesis is very rare, and there are no previous reports on treatments for this disease. We report a case of chronic subdural hematoma that may be caused by nephrotic syndrome and review the previous literature on this subject. Case summary: We report a rare case of chronic subdural hematoma that may be caused by nephrotic syndrome. After the patient was admitted to the hospital, relevant laboratory tests were conducted, and a large amount of protein was detected in the patient's urine, indicating hypoproteinaemia and hyperlipidemia. The patient was diagnosed with nephrotic syndrome. After the exclusion of related surgical contraindications, the patient underwent trepanation and drainage of the chronic subdural hematoma. Subsequent treatment with oral atorvastatin was provided after surgery. The patient was transferred to the nephrology department for further treatment of nephrotic syndrome if his neurological condition improved. No neurological sequelae were detected at the follow-up visit 3 months after the operation. Conclusion: Chronic subdural hematomas are rarely caused by nephrotic syndrome. Trepanation and drainage may be considered for patients confirmed to have adequate hematoma liquefaction on imaging and who can tolerate craniotomy. Atorvastatin should be supplemented as prophylactic treatment after the operation. Nephrotic syndrome should be treated as soon as the patient's neurological condition is stable. [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.