A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

Health-Related Quality of Life in Sudanese Children with Nephrotic Syndrome: A Comparative Cross-Sectional Study.

Background: Nephrotic syndrome (NS) is an essential chronic disease in children that has a major impact on a child's health-related quality of life (HRQoL). This study aimed to evaluate the HRQoL of Sudanese children with NS and clinical parameters that can influence their HRQoL. Methods: This study was a descriptive cross-sectional of children with NS conducted in Khartoum state hospitals. A standardized PedsQLTM 4.0 Scale Score evaluated the HRQoL of the participants. Patients' socio-demographics, clinical data, and disease complications were collected using a data collection sheet. This study assessed the HRQoL of children with NS and compared it with apparent age and sex-matched to three groups (healthy children, children with chronic diseases, and kidney-transplanted children). Results: 80 children with NS were recruited from April to August 2021. Children over eight years old represented (63.8%) of the study subjects. The total mean HRQoL scores of nephrotic children were significantly lower than those of healthy children (78.46 ± 24.01) (p = 0.001) and those with other chronic diseases (78.45 ± 24.01) (p= 0.006); however, it was not significantly different from those with kidney transplantation. Socio-demographics did not significantly affect the total mean HRQoL scores of children with NS. Clinical parameters such as the duration of illness, "less than one year" (p= 0.006), and the minimum change nephropathy histopathology (p= 0.035) significantly lowered the total mean HRQoL scores of NS children. Regression analysis further confirmed that edema, proteinuria, and hospital admission had a high impact on the total mean HRQoL. Conclusion: The total mean HRQoL scores of children with NS were low and significantly lower than healthy children. Parameters such as the patient's socio-demographics and phenotype of NS had no significant effect on the total mean HRQoL scores of children with NS. However, other clinical parameters significantly lowered their total mean HRQoL scores.

Differences of clinicopathological characteristics and outcomes of IgA nephropathy patients with and without nephrotic syndrome.

PURPOSE: To evaluate the differences in clinicopathological features and outcomes of IgA nephropathy (IgAN) patients with and without nephrotic syndrome. METHODS: In this retrospective cohort study, IgAN patients from January 2006 to December 2011 in the First Affiliated Hospital of Sun Yat-sen University were enrolled and followed up to Dec 31, 2013. Logistic and Cox regression were conducted to evaluate the associated factors of nephrotic syndrome (NS) and its relation with outcomes of creatinine doubling and progression to end-stage kidney disease (ESKD). RESULTS: A total of 1413 patients with IgAN were enrolled in this study, 57 (4.0%) of whom exhibited NS. Meanwhile, 13 (22.8%) of NS IgAN patients had minimal change disease (MCD). Logistic regression showed that more presence of hypertension, less glomerular sclerosis, less tubular atrophy/interstitial fibrosis, and lower density of IgA deposition in mesangial region were significantly associated with NS IgAN that were independent of age and gender. In addition, a total of 921 patients (890 with non-NS IgAN and 31 with NS IgAN) were followed up to Dec 31, 2013. After adjusting for age, sex, baseline estimated glomerular rate, hypertension and hemoglobin, no significant difference was observed in outcomes of serum creatinine doubling and ESKD between patients with or without NS IgAN. CONCLUSIONS: Prevalence of NS IgAN patients was 4.0%, and 22.8% of them had MCD. Patients with NS IgAN had more severe clinical but less severe pathological features. However, outcomes of serum creatinine doubling and ESKD were not significantly different between patients with or without NS IgAN.

Antineutrophil cytoplasmic antibody in children with nephrotic syndrome treated with levamisole: a cross-sectional cohort study.

BACKGROUND: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning. METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA. RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months. CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.

Bullous striae distensae in a nephrotic syndrome patient: First case report from the Middle East of a rare presentation and review of the literature.

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.

[Clinical study on growth impairment induced by oral glucocorticoids based on FGF23/Klotho homeostasis observations]. / 基于FGF23/Klothoç¨³æ€è§‚å¯Ÿå£æœç³–çš®è´¨æ¿€ç´ è‡´ç”Ÿé•¿éšœç¢çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To observe the correlation between growth impairment induced by long-term oral glucocorticoids (GC) therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome (PNS). METHODS: A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022. After monitoring qualitative and quantitative urine protein levels upon admission, the children with proteinuria relapse were treated with GC (GC group; n=29), while those without relapse did not receive GC treatment (non-GC group; n=27). In addition, 29 healthy children aged 3 to prepuberty were selected as the control group. Height, bone age, growth rate, and the FGF23/Klotho ratio were compared among the groups. The correlations of the FGF23/Klotho ratio with height, bone age, and growth rate were analyzed. RESULTS: The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy (P<0.05), and the height and bone age growth rates within 6 months were lower than those in the non-GC group (P<0.05). Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS (r=-0.356 and -0.436, respectively; P<0.05). CONCLUSIONS: The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.

The Role of TNF-α in the Pathogenesis of Idiopathic Nephrotic Syndrome and Its Usefulness as a Marker of the Disease Course.

Background: The pathogenesis of idiopathic nephrotic syndrome (INS) has not been fully explained. Among the likely factors, tumor necrosis factor - alpha (TNF-α) is considered. We aimed to evaluate the TNF-α (sTNF-α, uTNF-α) levels in the serum and urine of INS children, with the aim of determining its association with proteinuria, and of determining its usefulness as a marker of the disease severity. Methods: Fifty-one examined patients were divided into subgroups depending on the number of relapses as follows: group IA-first episode; group IB-more than two relapses, and according to treatment modality; group IIA-glucocorticosteroids (GS) alone; and group IIB-GS with immunosuppressants. Healthy age-matched children served as the control group. Results: sTNF-α and uTNF-α levels were significantly increased in active phases in the whole INS group compared to the control group. They decreased in remission, but remained significantly higher when compared to the control group. During remission in the IB group, sTNF-α levels were significantly higher than in IA, whereas, in the relapse phase, these values were similar. In the IA group, a positive correlation between proteinuria and sTNF-α was demonstrated. Conclusions: Our findings suggest that TNF-α plays a role in the development of INS, and may be used as a prognostic marker, as well as an indicator for the continuation of therapy. Additional research is required to verify this statement.

Role of Palliative Care in the Supportive Management of AL Amyloidosis-A Review.

Light chain amyloidosis is a plasma-cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients' quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis.

Cerebral Venous Sinus Thrombosis as an Initial Presentation of Nephrotic Syndrome: A Case Report.

Cerebral sinovenous thrombosis (CSVT) encompasses a spectrum of disorders involving thrombosis of the cerebral venous system. As shown by previous epidemiological studies, the prevalence of cerebral sinovenous thrombosis is 4-7 cases per million people. Nephrotic syndrome was very rarely associated with thrombosis cerebral veins or sinuses. Hypercoagulability and thrombotic complications in nephrotic syndrome are most commonly seen in deep veins of the lower extremities and renal veins. Our case highlights a unique scenario in which cerebral sinovenous thrombosis was the initial presentation of nephrotic syndrome in a patient that was not an important past medical or surgical problem. The patient was brought to the emergency department with severe headache, vomiting, altered mental status, and generalized body swelling. Laboratory results showed proteinuria, hypoalbuminemia and hyperlipidemia. Non-contrast brain CT demonstrated hemorrhagic venous infarct associated with vasogenic edema. A subsequent brain MR venogram demonstrated occlusion of superior sagittal and right transverse sinuses. She was managed with low molecular weight heparin and intervenous corticosteroids then shifted to rivaroxaban and oral steroids, respectively, which resulted in massive clinical improvement and resolution of thrombus.

Managing venous thrombosis in a pediatric patient with short bowel and congenital nephrotic syndromes: a case report emphasizing rivaroxaban level monitoring.

Direct Oral Anticoagulants (DOACs) typically exhibit a predictable pharmacokinetic and pharmacodynamic response at a fixed dose, not necessitating monitoring under standard conditions. Yet, in specific clinical scenarios that can impair it, like Congenital Nephrotic Syndrome (CNS) or Short Bowel Syndrome (SBS) due to absorption issues, anti-thrombin III (AT-III) deficiency and non-selective proteinuria, adjusting the dosage to achieve appropriate plasma concentrations could prove beneficial. We report a 3-month-old female with catheter-related jugular thrombosis affected by CNS concomitant to SBS and failure of both treatments with heparin and warfarin, that was switched to dose-adjusted pediatric rivaroxaban. Rivaroxaban was adjusted to reach peak levels between 189 and 419 ng/ml and the lower trough levels between 6 and 87 ng/ml. Increasing doses were needed due to SBS related malabsorption but a complete permeabilization of the vein was achieved without bleeding complications. The use of anti-Xa adjusted rivaroxaban could be an alternative to improve anticoagulation and secondary thromboprophylaxis in pediatric patients SBS and an option to children with CNS.

Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

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.

Comprehensive mapping of saliva by multiomics in children with idiopathic nephrotic syndrome.

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".

The Impact of Spironolactone Co-administration on Cyclosporin Initial Dosage Optimization for Pediatric Refractory Nephrotic Syndrome.

OBJECTIVES: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration. METHODS: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen. RESULTS: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively. CONCLUSION: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time.

Spontaneous Remission of Minimal Change Disease in a Colon Cancer Patient: A Case Report.

Introduction: Minimal change disease (MCD) is most often primary but may occur secondary to other systemic diseases such as malignancy. In secondary MCD, spontaneous remission of nephrotic syndrome after the treatment of related diseases without steroid therapy is rare. Case Presentation: A 78-year-old man visited the outpatient clinic with foamy urine and generalized edema that had persisted for 2 months. The patient had nephrotic syndrome. Before a kidney biopsy, he underwent several tests to determine the secondary cause of the nephrotic syndrome. The serum CEA was slightly elevated, and colon cancer was detected in the sigmoid colon. MCD was diagnosed from a kidney biopsy. He immediately underwent surgery for colon cancer. Complete remission of the MCD was achieved within 2 weeks after surgery. Conclusion: Here, we report a rare case of a patient with secondary MCD who successfully achieved spontaneous remission after colon cancer surgery.

Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury.

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 µg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

Nephrotic Syndrome and Posterior Reversible Encephalopathy Syndrome as Clinical Presentations of Gemcitabine-Induced Thrombotic Micro-Angiopathy.

Gemcitabine-induced thrombotic micro-angiopathy (GiTMA) is a very rare pathology of micro-vascular occlusion with a poor prognosis. In this case report, we present a young male with pancreatic carcinoma who received gemcitabine as adjuvant chemotherapy and developed thrombotic micro-angiopathy (TMA) manifesting as nephrotic syndrome with renal dysfunction and posterior reversible encephalopathy syndrome (PRES). The case was successfully managed with discontinuation of the drug and conservative management. The pathogenesis of GiTMA might be direct endothelial dysfunction with consequent activation of the clotting system. The role of plasma exchanges and monoclonal antibodies is unclear in drug-induced TMA.

Collapsing Glomerulopathy in a Patient with Tuberculosis and Poncet's Disease.

A 39-year-old woman presented with inflammatory polyarthritis, low-grade fever, progressive pedal edema, and frothy urination of three weeks duration. She had nephrotic range proteinuria and elevated creatinine. Kidney biopsy showed collapse of capillary tuft in the glomeruli and proliferation, hyperplasia, and hypertrophy of the overlying podocytes suggestive of collapsing glomerulopathy. Histology of the cervical lymph node showed necrotizing granulomatous inflammation suggestive of tuberculosis. With all other possible causes of polyarthritis ruled out, a diagnosis of Poncet's disease-a form of polyarthritis observed in patients suffering from an active form of extrapulmonary tuberculosis (TB)-was considered. Association between TB lymphadenitis and collapsing glomerulopathy (CG) is very rare, and the patient had partial remission of the disease after being started on anti-tuberculosis therapy (ATT) along with steroids.

A Case of Acute Kidney Injury, Proteinuria, and Thrombotic Microangiopathy Associated With Sunitinib Therapy in Metastatic Pancreatic Neuroendocrine Tumor.

There have been rare reports of patients developing nephrotic syndrome and thrombotic microangiopathy (TMA) with tyrosine kinase inhibitors (TKIs). We present the case of a patient with a history of metastatic pancreatic neuroendocrine tumor (pNET), treated with sunitinib, who rapidly developed TMA and acute kidney injury. The patient was successfully treated with cessation of sunitinib and administration of steroids. This case report contributes to the growing body of literature surrounding the rare side effects of TKIs and our experience with the management of these adverse events.

Effect of proteinuria at relapse on shear wave velocity assessed using ultrasound elastography in children with idiopathic nephrotic syndrome.

PURPOSE: Shear wave velocity (SWV) is an ultrasound elastography technique that provides much information for kidney disease assessment. However, the factors that alter SWV are not fully understood; it is unclear whether the variation in SWV seen in proteinuria associated with disease progression is due to tissue or proteinuria. This study investigated the effect of proteinuria on SWV. METHODS: This prospective observational study compared SWV at remission with SWV at relapse in children treated for idiopathic nephrotic syndrome (INS) between April 2020 and December 2023. All relapses without oral steroids during the observation period were measured. SWV at remission was defined as the date closest to relapse during which repeated measurements were taken approximately every 3 months after steroid discontinuation. RESULTS: Eight patients were treated for INS with a median observation period of 21.9 months (11.8-27.1). Of the 15 relapses, five that met the definition were considered for the study. The median interval between the measurement at relapse and remission was 40 days (11-55). SWV was significantly lower at relapse than remission (2.40 ± 0.20 m/s vs. 2.14 ± 0.15 m/s, P < 0.01). CONCLUSIONS: SWV decreased in the presence of severe proteinuria at relapse compared to the remission measurements. Although more cases need to be studied, the decrease in SWV may reflect the mechanism by which protein leaks into the urine, not just a direct change caused by the presence of proteinuria.