Rituximab (RTX) has been proven effective in the treatment of idiopathic nephrotic syndrome (INS). The development of anti-rituximab antibodies (ARA) may compromise its efficacy and safety. However, the incidence and clinical relevance of ARA in pediatric INS remain incompletely defined. This retrospective study involved 90 pediatric patients with INS who were treated with RTX at a dose of 375 mg/m2 at Jinling Hospital, Affiliated Hospital of Medical School of Nanjing University, China, between March 2024 and May 2025. ARA were detected using a paramagnetic particle chemiluminescence immunoassay. ARA were detected in 30 of 90 patients (33.3

BACKGROUND:Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common form of secondary glomerulonephritis in children. Some individuals have acute kidney disease (AKD) early on in their illness. The purpose of this study was to examine the prognosis and clinicopathological characteristics of children with IgAVN complicated by AKD. METHODS:Five medical centers in China provided data on pediatric patients with biopsy-proven IgAVN. The patients were divided into two groups: AKD group and non-AKD group, depending on whether AKD was present at disease onset. Clinical manifestations, laboratory findings, pathological characteristics, and prognostic outcomes were compared between the two groups. RESULTS:Among 1862 children with IgAVN, 213 (11.44%) presented with AKD. Compared to children in the non-AKD group, children in the AKD group had more severe clinical and pathological findings. Kaplan-Meier analysis revealed statistically significant differences in kidney survival among the three stages of AKD (χ² = 15.68, P < 0.0001), and showed that kidney survival in the AKD group was significantly lower than that in the non-AKD group (χ² = 14.75, P < 0.0001) over a median follow-up of 66 months. AKD was identified as an independent risk factor for progression to chronic kidney disease stage 5 (CKD 5) in both short-term (6 months) and long-term (five- and ten-year) follow-ups. CONCLUSIONS:The clinicopathological and pathological features are much more severe in IgAVN children with AKD. AKD is a significant risk factor for unfavorable short- and long-term outcomes in pediatric IgAVN.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) in children refers to the systemic mineral and bone metabolism disorders caused by CKD, including biochemical abnormalities, abnormalities in bone turnover, mineralization, quality, and ectopic calcification. Like the adult patients, mineral metabolism and bone structure abnormalities are universally present in children with CKD. But there have been no guidelines specifically for the children in the past. The medication treatment and clinical practices for children are usually based on those for adults, lacking targeted guidance. On the one hand, the children are in the process of growth and development, and the adult guidelines do not take into account the characteristics of children. On the other hand, the medication range for children is different from that of adults, and new drugs have been verified and tested in children. Hence, based on the developmental characteristics of children, combined with expert opinions from adults, children, kidney, nutrition, and medicine, this guideline was initiated by the Subspecialty Group of Nephrology, the Society of Pediatrics, Chinese Medical Association. It answered 15 important clinical questions related to the diagnosis and treatment of pediatric CKD-MBD, aimed to provide individualized treatment plans considering the clinical characteristics of CKD children and their treatment goals, while also addressing the needs of their growth and development.

Background Pediatric focal segmental glomerulosclerosis (FSGS) is a heterogeneous disease. Childhood is a dynamic developmental period, and age-related differences may influence disease presentation and progression. However, age-specific clinicopathological features and outcomes remain unclear. Methods We conducted a retrospective cohort study including 305 children with biopsy-proven primary FSGS from Jinling Hospital. Patients were classified into three groups based on age at onset and biopsy, using adolescence as the cutoff: childhood-onset and childhood-diagnosed (COCD-FSGS), childhood-onset and adolescent-diagnosed (COAD-FSGS), and adolescent-onset and adolescent-diagnosed (AOAD-FSGS). Baseline clinical and histopathological characteristics were compared across groups at the time of biopsy. The estimated glomerular filtration rate (eGFR) slope was calculated using a linear mixed-effects model. Renal survival was assessed using Kaplan–Meier analysis, and risk factors for poor renal outcomes were evaluated using Cox proportional hazards regression. Results Three distinct trajectories were identified. The COCD-FSGS group showed early onset, high steroid resistance, and rapid eGFR decline, consistent with an aggressive course. The COAD-FSGS group exhibited the most severe chronic histopathology but had relatively favorable outcomes and slower progression, suggesting a chronic, slowly progressive course. The AOAD-FSGS group presented with more severe baseline clinical features but showed slower decline and better prognosis, consistent with a late-onset, slowly progressive disease course. Conclusions Pediatric FSGS comprises distinct disease trajectories not fully explained by conventional factors. Age may play a key role in shaping disease course. These findings have implications for risk stratification and clinical trial design.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) in children refers to the systemic mineral and bone metabolism disorders caused by CKD, including biochemical abnormalities, abnormalities in bone turnover, mineralization, quality, and ectopic calcification. Like adult patients, mineral metabolism and bone structure abnormalities are universally present in children with CKD. However, there have been no guidelines specifically for children in the past. The medication treatment and clinical practices for children are usually based on those for adults, thus lacking targeted guidance. Children are in the process of growth and development, and adult guidelines do not take into account the characteristics of children. In addition, the medication range for children is different from that of adults, and new drugs have been verified and tested in children. Therefore, based on the developmental characteristics of children, combined with expert opinions about adults, children, kidney, nutrition, and medicine, this guideline was initiated by the Subspecialty Group of Nephrology, the Society of Pediatrics, Chinese Medical Association. It answers many important clinical questions related to the diagnosis and treatment of pediatric CKD-MBD, aims to provide individualized treatment plans considering the clinical characteristics of children with CKD and their treatment goals, while addressing the needs of their growth and development.

OBJECTIVES:To study the significance of serum 25-hydroxyvitamin D3 [25-(OH)D3] level in the clinicopathological characteristics and prognosis of children with immunoglobulin A vasculitis nephritis (IgAVN). METHODS:A retrospective analysis was conducted on the clinical data of children with IgAVN who underwent renal biopsy at Suzhou Hospital Affiliated to Anhui Medical University and Jinling Hospital of the Medical School of Nanjing University from June 2015 to June 2020. Based on serum 25-(OH)D3 level, the patients were divided into a normal group and a lower group. The clinicopathological characteristics and follow-up data of the two groups were collected and compared. RESULTS:A total of 359 children with IgAVN were included. Compared to the normal group (62 cases), the lower group (297 cases) exhibited higher incidences of hematochezia and gross hematuria, higher levels of serum creatinine, blood urea nitrogen, urinary retinol protein, urinary N-acetyl-β-D-glucosaminidase, and quantitative urinary protein, and a longer duration from renal biopsy to urinary protein becoming negative, as well as lower estimated glomerular filtration rate and albumin level (P<0.05). Renal pathology in the lower group showed a higher occurrence of tubular interstitial injury, crescent formation, segmental sclerosis in glomeruli, and inflammatory cell infiltration in the renal interstitium compared to the normal group (P<0.05). Survival analysis indicated that the cumulative renal survival rate was lower in the lower group (P<0.05). Multivariate Cox regression analysis revealed that low serum 25-(OH)D3 level is an independent risk factor for poor prognosis in children with IgAVN. CONCLUSIONS:Children with IgAVN and low serum 25-(OH)D3 level have relatively severe clinicopathological manifestations. Low serum 25-(OH)D3 level is an independent risk factor for poor prognosis in children with IgAVN.

Background Immunoglobulin A vasculitis nephritis (IgAVN) is a common childhood vasculitis with heterogeneous clinical and pathological manifestations. Repeat kidney biopsy may help assess pathological evolution and guide treatment, but its role in pediatric IgAVN remains underexplored. This study aimed to evaluate the clinicopathological changes between initial and repeat biopsies and their association with treatment response and outcomes in children with IgAVN. Methods This single-center retrospective analysis included 19 pediatric IgAVN patients who underwent two kidney biopsies. Clinical, laboratory, and pathological data were compared between biopsies. Pathological evaluation used ISKDC, semiquantitative classification (SQC), and Oxford Classification (MEST-C) systems. Correlations between changes in proteinuria (Δ24hUP), eGFR slope, and pathological scores (ΔSQC, ΔActivity Index, ΔChronicity Index) were analyzed. Outcomes were classified as good (A/B) or poor (C/D) based on modified Counahan criteria. Results A total of 19 pediatric patients with IgAVN were included in this study. The cohort consisted of 12 males (63.2%) and 7 females (36.8%), with a mean age at disease onset of 10.6 ± 3.6 years. The median time from symptom onset to initial kidney biopsy was 155 days (IQR: 36, 364). A repeat kidney biopsy was performed at a median interval of 38 months (IQR: 18, 51) after the first biopsy, with the primary indications being disease recurrence (52.6%) and suboptimal treatment response (47.4%). Recurrent palpable purpura was observed in 31.6% of the patients at the time of repeat biopsy. Prior to the initial biopsy, 47.4% of the patients had received glucocorticoid therapy. The median follow-up duration for the entire cohort was 57 months (IQR: 38, 81). Microscopic hematuria improved significantly at the second biopsy ( p = 0.012), while 24-hour proteinuria did not change significantly. Pathological scores (SQC, MEST-C) also showed no significant change. A strong positive correlation was found between Δ24hUP and ΔActivity Index (r = 0.718, p < 0.001). 10 patients had good outcomes and 9 had poor outcomes, but no baseline or evolution parameters significantly predicted outcome. Treatment intensity increased after repeat biopsy, with more patients receiving pulse steroids and immunosuppressants. Conclusions Repeat kidney biopsy in pediatric IgAVN reveals discordance between clinical and pathological changes and supports its utility in guiding therapy adjustments. Proteinuria change strongly correlates with active pathological lesions, reinforcing its role in monitoring disease activity.

Background: Recent developments indicated that Bowman capsule rupture (BCR) is observed in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). We aimed to explore the relationship between BCR and clinical manifestations, pathological changes, and prognosis in children with myeloperoxidase (MPO)-AAGN. Methods: A total of 56 children with MPO-AAGN were divided into BCR (+) and BCR (-) groups according to the status of Bowman's capsule. Results: After retrospective analysis of the data, 24 children (42.9%) were found to have BCR. The results showed that BCR positively correlated with intrarenal immune cell infiltrates, obsolescence and crescents in glomeruli, tubulointerstitial inflammation, tubulitis, and tubular atrophy negatively correlated with normal glomeruli and immunoglobulin G deposition in the kidney. The clinical features and kidney pathological changes were more severe in the BCR (+) group than BCR (-) group, and the renal survival rate was significantly poorer in the BCR (+) group than BCR (-) group (chi 2 = 5.45, p = 0.02). Moreover, estimated glomerular filtration rate (<= 15 mL/ min/1.73 m2), BCR and ANCA renal risk score (ARRS) were independent risk factors for the development of end-stage kidney disease (ESKD) in children with MPO-AAGN. After combining BCR with the Berden classification and ARRS, our data suggested that the Berden classification + BCR and ARRS + BCR showed better predictive values for ESKD than those of the Berden classification and ARRS, respectively. Conclusion: BCR is an important pathological lesion that correlates with severe clinical manifestations, pathological changes, and poor prognosis in children with MPO-AAGN.

ABSTRACT Background The presence of sarcopenia in patients with chronic kidney disease (CKD) is associated with poor prognosis. The mechanism underlying CKD‐induced muscle wasting has not yet been fully explored. This study investigates the influence of renal secretions on muscles using multiomics sequencing. Methods The kidney transcriptome analysis by RNA‐seq and protein profiling by tandem mass tag (TMT), serum TMT and muscle TMT were performed in CKD established using 0.2% adenine and control mice. Spp1 recombinant protein was used to study its effect on myotube atrophy in vitro. In animal experiments on CKD, pharmacological inhibition of Spp1 was used to explore the role of Spp1 in skeletal muscle wasting. Transcriptome analysis was performed to identify differentially expressed genes (DEGs) in the gastrocnemius muscle following Spp1 pharmacological inhibition. Results In the renal transcriptome and TMT, 503 and 377 proteins/genes respectively were co‐upregulated and co‐downregulated. In the serum TMT of CKD and normal control (NC) mice, 22 upregulated and 7 downregulated differentially expressed proteins (DEPs) showed the same expression patterns as those in the kidney transcriptome and TMT analysis. Based on bioinformatics analysis and reported studies, we selected Spp1 for further validation. Spp1 recombinant protein was added to C2C12 myotubes in vitro, and the results indicated that Spp1 significantly increased the protein levels of the muscle atrophy marker (Murf‐1) and promoted the smaller myotubes (all p < 0.05). Compared with NC mice, Spp1 mRNA and protein levels were significantly upregulated in the kidneys of CKD mice, and the serum concentration of Spp1 was also markedly increased (all p < 0.05). In animal experiments, pharmacological inhibition of Spp1 increased the weights of gastrocnemius and tibialis anterior muscles (p < 0.05) and improved muscle atrophy phenotype. Transcriptome analysis showed that DEGs in the gastrocnemius muscle following Spp1 pharmacological inhibition were enriched in protein digestion and absorption, glucagon signalling pathway, apelin signalling pathway and ECM‐receptor interaction pathway. Conclusions Our study is the first to establish a regulatory network of kidney‐muscle crosstalk to explore the potential mechanism of CKD‐related sarcopenia. Employing multiomics analysis, cellular assessment and animal experiments, we have identified that Spp1 could potentialy serve as a promising therapeutic target for CKD patients with sarcopenia.

Belimumab is approved for treating systemic lupus erythematosus (SLE) in children over 5 years old; however, its efficacy and safety in pediatric SLE patients require further validation. This study aimed to evaluate the impact of belimumab on the long-term cumulative probability of sustained renal response and disease flare in children with lupus nephritis (LN), to inform clinical decision-making. We included a total of 96 children with LN in our study. The patients were part of a prospective cohort study and were divided into two groups: belimumab group (68 cases) and standard treatment (group (28 cases). We compared remission rates, flare rates, and adverse event incidence between these two groups. After 152 weeks of follow-up, belimumab increased the renal response and complete renal response rates by 16.7

Anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare autoimmune disease that often progresses to end-stage renal disease (ESRD). Complement activation and anti-GBM GN are closely related, as evidenced by the renal pathological characteristics of patients with anti-GBM GN, which include the linear deposition of immunoglobulin G (IgG) and C3 along the GBM. Increasing evidence suggests that all three pathways of complement activation may be involved in the pathogenesis and progression of anti-GBM GN. Anti-GBM GN’s clinical symptoms are linked to complement-related proteins, which are risk factors that impact the disease’s prognosis. This suggests that complement activation and activity may be the primary causes of renal damage in anti-GBM GN. Therefore, biomarkers of complement activation can identify anti-GBM GN cases that may progress to severe renal damage, and complement inhibition may become a new strategy for the clinical treatment of anti-GBM GN.

Kidney stone disease (KSD) is one of the most common urological disorders, and oxalate-induced tubular epithelial cell injury plays a crucial role in stone-related renal damage. However, the mechanisms linking oxalate exposure to mitochondrial dysfunction remain unclear. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is recognized for its antioxidant and mitophagy-promoting properties. This study investigated the renoprotective effects and mechanisms of UA in calcium oxalate (CaOx) crystal-induced renal injury. In mice, UA markedly reduced renal CaOx deposition, improved renal function, and alleviated kidney injury. Consistently, both in vivo and in vitro experiments demonstrated that UA restored oxalate-suppressed mitophagy while also alleviating oxidative stress, apoptosis, and mitochondrial dysfunction. Transcriptomic and molecular docking analyses identified phosphoenolpyruvate carboxykinase 1 (PCK1) as a downstream target of UA. UA restored PCK1 expression under oxalate stress both in vivo and in vitro, whereas pharmacological inhibition of PCK1 weakened the renal protective and mitophagy-promoting effects. Conversely, PCK1 overexpression enhanced mitophagy under high-oxalate conditions. These findings indicate that UA alleviates CaOx-induced renal injury by activating PCK1-dependent mitophagy and restoring mitochondrial homeostasis. Given its natural origin and favorable safety profile, UA represents a promising candidate for preventing or treating calcium oxalate-associated renal injury.

Objectives: Skeletal muscle loss and abnormal fat distribution are predictors of poor clinical outcomes in adults with chronic kidney disease (CKD). However, the relationship between body composition (muscle mass and adipose tissue) and prognosis in children with CKD has not been well elucidated. Methods: The retrospective single-center study enrolled children with CKD and healthy group who underwent an abdominal computerized tomography examination and compared the body composition of the third lumbar spine (L3) between the 2 groups. We defined the primary outcome as hemodialysis, peritoneal dialysis, kidney transplantation, or death. Logistic regression analysis was applied to assess the connection between low skeletal muscle density (SMD) and clinical and demographic variables. Multivariate Cox regression analysis was used to evaluate the risk factors for progression to the primary outcome. Kaplan-Meier survival analysis was performed to compare the effect of different body composition on event-free survival rate. Results: Thirty-two patients with CKD [estimated glomerular filtration rate: 14.89 (8.86, 29.88) (mL/min/1.73 m2)] and 66 heathy subjects [estimated glomerular filtration rate: 135.72 (121.70, 161.29) (mL/min/1.73 m2)] were recruited in our study. From the assessment of body composition assessed by computerized tomography, skeletal muscle area, SMD, and skeletal muscle index in the CKD group was lower than those in the healthy group (P < .05). On the other hand, visceral fat area and visceral fat index in the CKD group were significantly higher than those in the healthy group (P < .05). In logistic regression analysis, triglyceride (odds ratio: 8.635, 95% confidence interval (CI): 1.153-64.687) was independently associated with low SMD. After adjusting clinical data and body composition, high serum albumin (hazard ratio: 0.873, 95% CI: 0.798-0.955) and high SMD (hazard ratio: 0.895, 95% CI: 0.822-0.974) were protective factors for delaying renal failure. Based on the Kaplan-Meier analysis, only the group with low SMD had lower event-free survival in comparison to the reference group (P < .05). Conclusions: These findings suggest that there is significant skeletal muscle loss and decrease in SMD in CKD children. Notably, low SMD is indicative of poor prognosis in CKD children. (c) 2024 by the National Kidney Foundation, Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

To study the significance of serum 25-hydroxyvitamin D3 [25-(OH)D3] level in the clinicopathological characteristics and prognosis of children with immunoglobulin A vasculitis nephritis (IgAVN). A retrospective analysis was conducted on the clinical data of children with IgAVN who underwent renal biopsy at Suzhou Hospital Affiliated to Anhui Medical University and Jinling Hospital of the Medical School of Nanjing University from June 2015 to June 2020. Based on serum 25-(OH)D3 level, the patients were divided into a normal group and a lower group. The clinicopathological characteristics and follow-up data of the two groups were collected and compared. A total of 359 children with IgAVN were included. Compared to the normal group (62 cases), the lower group (297 cases) exhibited higher incidences of hematochezia and gross hematuria, higher levels of serum creatinine, blood urea nitrogen, urinary retinol protein, urinary N-acetyl-β-D-glucosaminidase, and quantitative urinary protein, and a longer duration from renal biopsy to urinary protein becoming negative, as well as lower estimated glomerular filtration rate and albumin level (P<0.05). Renal pathology in the lower group showed a higher occurrence of tubular interstitial injury, crescent formation, segmental sclerosis in glomeruli, and inflammatory cell infiltration in the renal interstitium compared to the normal group (P<0.05). Survival analysis indicated that the cumulative renal survival rate was lower in the lower group (P<0.05). Multivariate Cox regression analysis revealed that low serum 25-(OH)D3 level is an independent risk factor for poor prognosis in children with IgAVN. Children with IgAVN and low serum 25-(OH)D3 level have relatively severe clinicopathological manifestations. Low serum 25-(OH)D3 level is an independent risk factor for poor prognosis in children with IgAVN.

BACKGROUND:The clinical significance of immunoglobulin M (IgM) deposition in the glomeruli of children with immunoglobulin A vasculitis (IgAV) nephritis remains unclear. This study aimed to analyze the clinical and pathological characteristics and prognoses of this population. METHODS:Patients were divided into three groups according to histopathological IgM deposition intensity: grade A (204 cases); grade B (101 cases); and grade C + D (54 cases). The clinicopathological characteristics and follow-up information of the three groups of patients were collected and compared. RESULTS:This study included 359 children with IgAV nephritis and found that 44.9% of them had IgM deposition in the kidney glomerulus. Children with IgM deposition and IgAV nephritis have relatively severe clinicopathological features. A total of 39 children (10.9%) had entered the end-stage kidney disease stage. Kaplan-Meier analysis showed that cumulative renal survival was significantly lower in children with higher glomerular IgM deposition (log-rank test chi-square = 55.341, p < 0.001). Multivariable Cox regression analysis found that IgM deposition (grade C + D: hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.67-3.93; p = 0.04; grade B: HR, 2.59; 95% CI, 1.08-4.23; p = 0.03) and S1 (HR, 1.76; 95% CI, 0.42-2.98; p = 0.03) were independent risk factors for poor prognoses in children with IgAV nephritis. The receiver operating characteristic curve indicated that IgM deposition presented significant predictive capability. CONCLUSION:There are differences in the clinicopathological features of IgAV nephritis with different degrees of mesangial IgM deposition. IgM deposition and S1 are independent risk factors for poor prognoses of IgAV nephritis in children.

Mucormycosis is a highly invasive and rare opportunistic infection caused by mucor fungi, characterized by challenging diagnosis and rapid disease progression. It predominantly affects patients with compromised immune systems due to various reasons, such as kidney failure, long-term use of antibiotics or corticosteroids. We recently successfully treated a pediatric patient with rapidly progressive glomerulonephritis accompanied by severe cutaneous mucormycosis. To our knowledge, this is the first reported case of rapidly progressive glomerulonephritis nephritis accompanied by dermatophytosis in a pediatric patient. In this case, we share our management experience, including special nursing experience. Cutaneous mucormycosis progresses quickly and is difficult to diagnose and treat, especially in children with compromised immune function, warranting high vigilance from clinicians and nursing staff. Early diagnosis and targeted treatment are crucial for improving the prognosis of patients. Therefore, once there is a suspicion of a mucormycosis infection, we recommend the early application of various testing methods such as fungal culture, skin biopsy and genetic testing in order to to promptly confirm the diagnosis.

This study aimed to comprehensively evaluate the diagnostic potential of urinary exosomal microRNA (miRNA) in IgA vasculitis (IgAV) kidney injury by meticulously comparing the miRNA expression profiles in urine exosomes between children diagnosed with IgAV and those with IgA vasculitis nephritis (IgAVN). Urine samples were obtained from children with IgAV who were treated at our hospital from October 2022 to October 2023. These samples were then categorized into the IgAV group and the IgAVN group. High-throughput sequencing and bioinformatics analysis techniques were employed to conduct a thorough analysis of the differentially expressed miRNAs between the two groups. Additionally, the correlation between urinary exosomal miRNA and clinical parameters was evaluated. A total of 57 urinary exosomal miRNAs exhibited differential expression between the IgAV and IgAVN groups. Specifically, in the IgAVN group, 42 miRNAs were upregulated, while 15 were downregulated. Lasso regression analysis and ROC analysis identified five candidate urinary exosomal miRNAs with high diagnostic accuracy. A prediction of 95 target genes related to the candidate miRNAs led to the construction of an exosomal miRNA-mRNA regulatory network consisting of four key miRNAs and ten hub genes. Gene function and metabolic pathway analyses indicated that these ten hub genes were predominantly enriched in pro-fibrotic and inflammatory pathways. The analysis incorporating clinical parameters demonstrated a significant correlation between hsa-miR-383-5p and urinary protein levels. This research identified exosomal miRNAs and mRNAs with differential expression patterns associated with IgAVN and constructed the corresponding exosomal miRNA-mRNA network. It was determined that hsa-miR-3065-5p, hsa-miR-383-5p, hsa-miR-25-3p, and hsa-miR-450b-5p might mediate the pathogenesis of IgAVN by targeting pro-fibrotic and inflammatory pathways. Among them, exosomal hsa-miR-383-5p is highly likely to serve as a novel non-invasive biomarker for assessing the disease status of IgAVN, thereby offering new perspectives on the non-invasive diagnosis and treatment of IgAVN.

Background:Nephrotic syndrome, a prevalent childhood glomerular disorder, manifests with proteinuria, hypoalbuminemia, edema, and hypercholesteremia. Hypercalcemia, though rare, occasionally complicates these cases. Familial hypocalciuric hypercalcemia, an autosomal dominant disorder, is characterized by lifelong hypercalcemia, hypocalciuria, and normal or elevated parathyroid hormone levels due to loss-of-function mutations. Case Presentation:We detail a 2-year-old girl with nephrotic syndrome whose proteinuria responded effectively to steroid therapy without side effects. Hypercalcemia emerged after one month, prompting a familial history investigation, revealing a predisposition to hypercalcemia. Genetic analysis identified a heterozygous mutation c.1394G>A (p.R465Q) in the calcium-sensing receptor gene, shared among the patient, her grandmother, her father, and one sister. Notably, hypercalcemia required no intervention. Conclusions:This case report is the first documenting familial hypocalciuric hypercalcemia in a child with primary nephrotic syndrome and delineates the familial pedigree. While familial hypocalciuric hypercalcemia is infrequent, our findings affirm its generally benign nature. A critical aspect of patient care involves monitoring for potential complications, including acute pancreatitis or chondrocalcinosis. The indispensability of genetic studies in both diagnosis and the differentiation of related conditions is underscored, emphasizing their pivotal role in enhancing our understanding of this rare yet clinically significant disease. Continued research is imperative for advancing knowledge and improving clinical management.

Podocyte injury plays a vital role in focal segmental glomerulosclerosis (FSGS), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is highly expressed in podocytes and mutations mediate podocyte injury. We found TRPC6 gene mutation (N110S) was a new mutation and pathogenic in the preliminary clinical work. The purpose of this study was to investigate the potential mechanism of mutation in TRPC6 (TRPC6-N110S) in the knock-in gene mouse model and in immortalized mouse podocytes (MPC5). Transmission electron microscopy was used to evaluate renal injury morphology. We measured 24-hour urinary albumin-to-creatinine ratios and major biochemical parameters such as serum albumin, urea nitrogen, and total cholesterol. The results of CCK-8 assay and apoptosis experiments showed that the TRPC6-N110S overexpression group had slower proliferative activity and increased apoptosis than the control group. FluO-3 assay revealed increased calcium influx in the TRPC6-N110S overexpression group. Podocin level was decreased in TRPC6-N110S group, while TRPC6 and desmin levels were increased in TRPC6-N110S group. The 24 h uACR at 6 weeks was significantly higher in the pure-zygotes group than in the WT and heterozygotes groups, and this difference was found at 8 and 10 weeks.TRPC6 levels showed no significant difference between homozygote and WT mice. Compared to homozygote group, expression of podocin and nephrin were increased in WT, but levels of desmin was decreased in WT. Our results suggest that this new mutation causes podocyte injury probably by enhancing calcium influx and podocyte apoptosis, accompanied by increased proteinuria and decreased expression of nephrin and podocin.

The aim of this study was to evaluate the clinical features, pathological characteristics, and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) with renal arteritis. The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A−, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups was evaluated. In contrast to the AAGN-A− group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine, interleukin-6, urinary neutrophil gelatinase-associated lipocalin, negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A− group (χ 2 = 4.278, p = 0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition, ANCA renal risk score and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.