PURPOSE:Pediatric Nephrotic syndrome (PNS) is a prevalent major disorder in children. The precise detection of albumin is of crucial significance for the diagnosis, treatment decision-making, and prognosis improvement of PNS. The bromocresol green (BCG) method is a commonly used method for clinical albumin detection. Typically, patients with PNS exhibit disordered lipid metabolism, with altered levels of apolipoprotein B (ApoB), haptoglobin (Hp), α2-macroglobulin (α2MG), and apolipoprotein A1 (ApoA1). The objective of this study was to determine whether these proteins interfere with the detection of serum albumin using the BCG method in PNS, and to evaluate the extent of interference and its clinical implications. METHODS:A total of 134 PNS patients were enrolled in the study. Serum albumin levels were measured simultaneously using both the BCG method (ALB-BCG) and the immunoturbidimetric assay (ALB-ITA). In addition, serum levels of Hp, α2MG, ApoB, and ApoA1 were measured and evaluated for their potential correlation with the discrepancy in albumin measurements between the two methods (ΔALB = ALB-BCG - ALB-ITA). Furthermore, to evaluate the interference of these proteins on albumin detection using the BCG or ITA method, an in vitro interference assay was performed by spiking purified proteins into standard albumin solutions at progressively increasing concentrations, thereby assessing their potential to interfere with albumin measurement. RESULTS:The children were stratified into three groups based on ALB-BCG levels, Group I, ALB-BCG ≥ 25 g/L (n = 43), Group II, 20 g/L ≤ ALB-BCG < 25 g/L (n = 35), Group III, ALB-BCG < 20 g/L (n = 56). Serum albumin concentrations measured by the BCG method were significantly higher than those obtained by the ITA method, with a difference (ΔALB) ranging from 0.2 to 6.9 g/L. ΔALB showed a significant negative correlation with serum albumin levels (P < 0.01). α2MG, ApoB, Hp and ApoA1 levels showed significant differences among the three groups (P < 0.05). ΔALB demonstrated moderate correlations with Hp, α2MG, and ApoB (P < 0.001), and a weak correlation with ApoA1 (P < 0.001). In vitro experiments demonstrated that ApoB caused a dose-dependent positive interference with the serum albumin detection using the BCG method (P < 0.001), but not with the ITA method. Although α2MG can bring about a slight decrease in ALB-BCG results (P = 0.024), it does not lead to a significant alteration in ΔALB. At physiological concentrations, Hp slightly raises ALB-BCG results, thus increasing ΔALB (P = 0.007), but the changes in ΔALB are only minimal. CONCLUSION:Elevated ApoB levels lead to a dose-dependent overestimation of albumin concentration when measured using BCG method. Thus, it is advisable to utilize the ITA method for the accurate determination of serum albumin levels in PNS patients. Meanwhile, when ITA is not readily available, the bromocresol purple (BCP) method can serve as a more practical alternative. This ensures a proper assessment of colloid osmotic pressure and nutritional status, thereby facilitating clinical diagnosis and therapeutic decision-making.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus that affects pediatric patients with significantly greater severity and worse renal outcomes compared to adults. Despite the urgent clinical need, predicting pediatric LN prognosis remains unexplored in computational pathology. Furthermore, the only existing histopathology-based approach for LN relies on multiple costly staining protocols and fails to integrate complementary clinical data. To address these gaps, we propose the first multimodal computational pathology framework for three-class treatment response prediction (complete remission, partial response, and no response) in pediatric LN, utilizing only routine PAS-stained biopsies and structured clinical data. Our framework introduces two key methodological innovations. First, a Clinical-Injection Transformer (CIT) embeds clinical features as condition tokens into patch-level self-attention, facilitating implicit and bidirectional cross-modal interactions within a unified attention space. Second, we design a decoupled representation-knowledge adaptation strategy using a domain-adapted Masked Autoencoder (MAE). This strategy explicitly separates self-supervised morphological feature learning from pathological knowledge extraction. Additionally, we introduce a multi-granularity morphological type injection mechanism to bridge distilled classification knowledge with downstream prognostic predictions at both the instance and patient levels. Evaluated on a cohort of 71 pediatric LN patients with KDIGO-standardized labels, our method achieves a three-class accuracy of 90.1

Background:This study sought to explore the bone metabolism clinical features of pediatric nephrotic syndrome (NS) patients receiving glucocorticoid (GC) therapy and evaluate the bone-protective and renal-protective efficacy of alfacalcidol in this cohort. Methods:A prospective randomized cohort study was conducted at the Department of Nephrology, Guangzhou Women and Children's Medical Center, enrolling 86 children from January 2021 to June 2022. Participants were randomized into two groups (n = 43 each): the alfacalcidol group administered 0.05 µg/kg alfacalcidol plus 300 mg calcium daily, and the control group given 400 IU vitamin D3 plus 300 mg calcium daily. Primary outcomes included bone mineral density (BMD) and cumulative GC dose, measured at baseline, 3 months, 6 months and study endpoint. Secondary outcomes covered bone metabolism biomarkers (type I collagen C-terminal telopeptide and type I procollagen N-terminal propeptide), urine protein-to-creatinine ratio and proteinuria remission status. Results:Multivariate regression identified cumulative GC dose as a risk factor for BMD reduction, while alfacalcidol treatment correlated with BMD improvement. Lumbar spine BMD increased by 0.028 ± 0.008 g/cm² in the alfacalcidol group versus 0.002 ± 0.008 g/cm² decrease in the control group (P = .035). Alfacalcidol recipients had lower cumulative GC doses, shorter time to initial urinary protein negativity (7 vs 11 days, P = .004), higher 1-year GC discontinuation rate (67.9% vs 38.7%, P = .025), lower proteinuria relapse rate (7.9% vs 41.9%, P = .045) and more favorable proteinuria remission survival curves (P = .035). Conclusions:Alfacalcidol may have potential bone-protective and renal-protective effects in pediatric NS patients undergoing GC therapy (Trial registration: ChiCTR2200055790).

The primary cause of branchio-oto-renal syndrome (BORS) is mutations in the EYA1 gene. The aim of this study was to investigate the clinical characteristics associated with induced podocyte reappearance in children with BORS and EYA1 mutations. We collected clinical and genetic data from a 4-year-old girl diagnosed with BORS and her family. Induced pluripotent stem cells (iPSC) were derived from peripheral blood mononuclear cells of both the patient and healthy individuals, which were differentiated into podocytes in vitro. RNA-seq was used to analyze differentially expressed genes in both groups. Here, the proband, along with his brother and mother, exhibited symptoms of BORS. WES analysis identified a heterozygous splicing variant at the EYA1 locus: c.1050 + 5G > A, inherited from his mother. The proband was initially glucocorticoid-resistant. After tacrolimus treatment, his urine protein/creatinine ratio significantly improved. Compared to healthy individuals, patient-derived podocytes displayed increased motility and pronounced cytoskeletal rearrangement. RNA-Seq results indicated significant downregulation of cell adhesion molecule and cytoskeletal rearrangement signaling pathway expression in patient-derived podocytes. Dexamethasone was ineffective in ameliorating the pathological damage induced by puromycin aminonucleoside in patient-derived podocytes. In BORS patients, podocytes exhibit cytoskeletal reorganization and enhanced motility in vitro while showing resistance to steroid treatment. These findings were consistent with the clinical features observed in the patient, suggesting that this unique cellular disease model merits further investigation.

Rare diseases affect hundreds of millions worldwide, yet diagnosis often spans years. Convectional pipelines decouple noisy evidence extraction from downstream inferential diagnosis, and general/medical large language models (LLMs) face scarce real world electronic health records (EHRs), stale domain knowledge, and hallucinations. We assemble a large, domain specialized clinical corpus and a clinician validated reasoning set, and develop RareSeek R1 via staged instruction tuning, chain of thought learning, and graph grounded retrieval. Across multicenter EHR narratives and public benchmarks, RareSeek R1 attains state of the art accuracy, robust generalization, and stability under noisy or overlapping phenotypes. Augmented retrieval yields the largest gains when narratives pair with prioritized variants by resolving ambiguity and aligning candidates to mechanisms. Human studies show performance on par with experienced physicians and consistent gains in assistive use. Notably, transparent reasoning highlights decisive non phenotypic evidence (median 23.1

The decidual endometrial stromal cells play a critical role in the establishment of uterine receptivity and pregnancy in human. Our previous studies demonstrate that protein tyrosine phosphatase 2 SHP2 is highly expressed in decidualized cells and governs the decidualization progress. However, the role and mechanism of SHP2 in the function of decidual cells remain unclear. Here, we screened proteins interacting with SHP2 in decidual hTERT-immortalized human endometrial stromal cells (T-HESCs) and identified Hypoxia-inducible factor-1 (HIF-1) signaling pathway as a potential SHP2-mediated signaling pathway through proximity-dependent biotinylation (BioID) analysis. Immunoprecipitation (Co-IP) revealed an interaction between SHP2 and HIF-1α, which colocalized to the nucleus in decidual cells. Furthermore, the SHP2 expression correlated with the transcriptional activation of HIF-1α and its downstream genes Beta-enolase (Eno3), Pyruvate kinase 2 (Pkm2), Aldolase C (Aldoc), and Facilitative glucose transporter 1 (Glut1). Knockdown or inhibition of SHP2 significantly reduced the mRNA and protein levels of HIF-1α and its downstream genes, as well as lactate production in decidual cells. We also established a hypoxia model of T-HESCs and 293 T cells and found that hypoxic treatment induced the expression of SHP2 and HIF-1α, which colocalized in the nucleus. SHP2 forced-expression rescued the inhibitory effects of SHP2 deficiency on HIF-1α expression and lactate production. Finally, SHP2 binds to the promoter regions of HIF-1α and its target genes (Eno3, Pkm2, Aldoc, and Glut1). Collectively, our results suggest that SHP2 influences the function of decidual cells by HIF-1α signaling and provide a novel function mechanism of decidual stromal cells.

Alport syndrome is a hereditary kidney disease with significant variations in onset and prognosis. While 80-85% of cases are due to pathogenic variants in the COL4A5 gene, there is a notable lack of mouse models with Col4a5 mutations for basic research. Our research presents an 8-year-old child with Alport syndrome, exhibiting facial edema and abnormal urine. Next-generation sequencing revealed a c.1517-1G > T mutation in the intron sequence of the COL4A5 gene. Minigene experiments confirmed that this intronic mutation affects mRNA splicing. Using the CRISPR/Cas9 system, we developed a Col4a5-c.1517-1G > T mutant mouse model. Col4α5-deficient mice exhibited growth retardation and reduced lifespan. Renal function analysis indicated progressive deterioration, with high levels of BUN and creatinine. Histological and ultrastructural analyses revealed abnormalities such as mesangial sclerosis, interstitial fibrosis and severe irregularity in membrane thickness. Additionally, significant immune cell infiltration was observed in the renal interstitium. This mouse model provides a valuable tool for studying the role of immune cells in the pathogenesis and treatment of XLAS. It is also the first reported X-linked Alport syndrome mouse model caused by a splicing mutation.

Background:The package insert is a key reference and legal basis for clinical medication. However, in the field of rare diseases, advances in diagnosis and treatment often outpace updates to drug labels, resulting in widespread off-label drug use-a practice that is particularly common and often unavoidable in pediatric populations. Inappropriate off-label use, however, carries significant clinical and safety risks. Methods:Under the guidance of the Rare Disease Expert Committee of the Guangdong Pharmaceutical Association, a multidisciplinary panel of experts from clinical medicine, pharmacy, and related specialties developed the "Expert consensus on the off-label use of drugs for pediatric rare diseases in China (2025 edition)". The consensus integrates available evidence, clinical experience, evidence quality, and medication safety profiles, and was finalized after several rounds of rigorous iterative review. Results:The consensus presents 73 recommendations on off-label drug use across 21 rare diseases, organized in a tabular format for clarity and ease of reference. Conclusions:This consensus aims to standardize the management of off-label drug use in pediatric rare diseases. It supports medical institutions in developing off-label drug formularies, promotes rational drug use, and helps address the diagnostic and therapeutic needs of pediatric rare disease patients. Furthermore, it contributes to the establishment of a structured evaluation and management framework for off-label drug use in this clinical context.

Steroid-sensitive nephrotic syndrome is a prevalent glomerular disease in children. The 2021 guidelines for glomerular disease management by Kidney Disease: Improving Global Outcomes and the 2023 recommendations for steroid-sensitive nephrotic syndrome management by International Pediatric Nephrology Association recommend rituximab for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome in children. However, there is considerable variation in rituximab application, including administration timing, dose, frequency, concomitant medications, and follow-up schedules. In addition, rituximab use for nephrotic syndrome remains off-label in most countries. The “Pediatric Nephrology Committee of the Chinese Medical Doctor Association”, the “Pediatric Nephrology Society of the Chinese Medical Association”, and the “Fudan University GRADE Center” collaborated to develop a clinical practice guideline for rituximab in pediatric steroid-sensitive nephrotic syndrome. Databases and starting/ending time for retrieval were as follows. Databases in English: PubMed, Embase, Cochrane, and Scopus; database in Chinese: Chinese Biomedical Literature Service provided by SinoMed. The publication dates were limited to those from 2004 to June 26, 2022. Through systematic reviews and meta-analyses covering nine clinically relevant patient or population covered, intervention, comparator, and outcome questions, seven recommendations were formulated and formally graded according to these guidelines. This guideline aspires to serve as a pivotal resource for healthcare providers, offering guidance on administration timing, dosage, frequency, concomitant medications, and follow-up protocols.

Infectious episodes contribute to morbidity and mortality in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Renal involvement, also known as ANCA-associated glomerulonephritis (AGN), is frequently observed in AAV. Little is known about whether co-infection at initial diagnosis is associated with renal outcome and prognosis in children with AGN. Clinical and prognostic data for children admitted to our center with AAV from January 2001 to August 2023 were analyzed retrospectively. We compared the incidence of end-stage renal disease (ESRD) and mortality according to infection status at initial diagnosis. A total of 33 children with AGN were included in this study, 22 had an infection at the time of AGN diagnosis. A trend toward higher levels of proteinuria in the infected group than in the non-infected group was observed (p = 0.42). Patients in the infected group had higher creatinine and lower eGFR values than those in the non-infected group (p = 0.09). A significant decrease in HGB was observed in the infected group (p < 0.05). There were no significant differences in the baseline values of ALB and complement c3 between the two groups. A similar proportion of patients in both groups required dialysis at the time of diagnosis (27.3

Fibrosis is the final common pathway leading to end-stage chronic kidney disease (CI(D). However, the function of protein palmitoylation in renal fibrosis and the underlying mechanisms remain unclear. In this study, we observed that expression of the palmitoyltransferase ZDHHC18 was significantly elevated in unilateral ureteral obstruction (UUO) and folic acid-induced (FA-induced) renal fibrosis mouse models and was significantly upregulated in fibrotic kidneys of patients with CI(D. Functionally, tubule-specific deletion of ZDHHC18 attenuated tubular epithelial cells' partial epithelial-mesenchymal transition (EMT) and then reduced the production of profibrotic cytokines and alleviated tubulointerstitial fibrosis. In contrast, ZDHHC18 overexpression exacerbated progressive renal fibrosis. Mechanistically, ZDHHC18 catalyzed the palmitoylation of HRAS, which was pivotal for its translocation to the plasma membrane and subsequent activation. HRAS palmitoylation promoted downstream phosphorylation of MEI(/ERI( and further activated Ras-responsive element-binding protein 1 (RREB1), enhancing SMAD binding to the Snai1 cis-regulatory regions. Taken together, our findings suggest that ZDHHC18 plays a crucial role in renal fibrogenesis and represents a potential therapeutic target for combating kidney fibrosis.

Background:The use of tacrolimus (TAC) in clinical settings is hindered by its nephrotoxic effects, which can vary significantly among individuals. Urine retinol-binding protein (RP), as a novel biochemical marker, is a potential indicator for early detection of renal tubular injury caused by TAC. The objective was to develop and validate a machine learning model that combines clinical features with genetic markers for predicting TAC nephrotoxicity in children with nephrotic syndrome (NS). Methods:A retrospective cohort of 203 children diagnosed with NS who were admitted between June 2013 and December 2018 was used for model development, while 12 children were prospectively recruited for external validation. The model incorporated 38 clinical features and 80 genetic variables, with changes in urine RP levels pre- and post-TAC administration indicating renal tubular toxicity. Five machine learning algorithms were employed: Extra Random Trees (ET), Gradient Boosting Decision Tree (GBDT), random forests (RF), and eXtreme Gradient Boosting (XGBoost), and logistic regression (LR). Results:The LR model, including six genetic markers (CYP3A5*3 rs776746_*3/*3, NFATC1 rs1660144_AA, NFKB1 rs230526_AG, NFKBIA rs696_TC, CD2AP rs12664637_CT and PLCE1 rs2274223_AG), exhibited the best performance with a sensitivity of 78.6%, specificity of 63.8%, accuracy of 67.2%, and area under the curve (AUC) of 76.1%. Conclusions:By employing RP as a marker of renal toxicity, we established and validated the renal tubular toxicity prediction model for the use of TAC using machine learning incorporating genetic factors of NS patients. This model allows physicians to evaluate the risk of nephrotoxic effects and adjust treatment plans accordingly to prevent kidney injury.

Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P < 0.001). The cut-offs we calculated for hypoalbuminemia and severe hypoalbuminemia based on the IN were 25 and 15 g/L, which were 5 g/L lower than the cut-offs recommended by KIDGO, respectively. A pair of historical control samples (206 vs. 216) with ALB-B or ALB-I showed that the proportion of severe hypoalbuminemia was 14.60% greater in IN group (75.20% vs. 60.60%, P < 0.001). The misdiagnosis rate of severe hypoalbuminemia by IN was 33.77% when 20 g/L rather than 15 g/L was used as the cut-off. Furthermore, the proportion of patients receiving albumin injections increased by 10.20%, and the average consumption increased by 97.06% (P = 0.01) along with the use of IN. So, our results suggested that the difference between ALB-B and ALB-I led to misdiagnosis and prescription abuse in PNS children.

Abstract Objective: To describe and explore the clinical characteristics and associated factors of growth in children after kidney transplantation (KT). Method: Retrospective study was performed on the clinical data of 111 children who underwent allogeneic KT and met the inclusion criteria (provided by Guangzhou Women and Children’s Medical Center and the Sun Yat-sen University First Affiliated Hospital). Catch-up growth was defined as present if the increment of height standard deviation score (∆Ht-SDS) was ≥0.5 per year. Described the clinical characteristics and compared possible associated factors between children with catch-up growth and no catch-up growth groups. Result: The median age at KT was 9(6,12) years, and 54.1% (60/111) are females. Mean height-SDS before KT was -2.14±1.29, 55.9% (62/111) showed growth retardation. Catch-up growth within the first years post-KT was present in 47.7% (53/111) recipients, the mean ∆Ht-SDS was 0.53±0.71. The Ht-SDS before KT was positively associated with last follow-up Ht-SDS (R=0.78, P<0.001). The baseline Ht-SDS, transplantation age, serum creatinine, and GC dose were significantly lower in the chase group (all P≤0.05), multivariate logistic regression analysis indicated that lower baseline Ht-SDS and serum creatinine were the protect factors for catch-up growth on the 1st year of post-transplantation (OR=0.62, 0.97, respectively, P<0.05). The last follow-up Ht-SDS affected by baseline Ht-SDS and ∆Ht-SDS. HtSDS was no statistical difference among different age groups (patient age at KT: <6years,6-9 years,9-12years,>12years), but ∆Ht-SDS showed significant difference between groups (0.74±0.80, 0.82±0.73, 0.28±0.67, 0.32±0.47, respectively, P<0.05). Younger Children showed significant catch-up rate after KT(<9years:68%,>9years:31%), however the ∆Ht-SDS was decrease in the second year (P<0.05). Conclusion: Growth assessment and management should be performed in any pediatric KT recipients. Even in younger children with more catch-up potential, ∆Ht-SDS decreased significantly at second year, growth continues to be suboptimal after KT. Given that baseline ∆Ht-SDS is a significantly associated factor, it is important for children with severe growth retardation need early identification and plan interventions in terms of growth improvement. We expected the children recipients achieved the ideal target height of post-transplantation.

Introduction:This study aimed to analyze the clinical characteristics of nephropathy associated with WT1 gene mutations in Chinese children and explore the relationship between genotype and clinical phenotype.Methods:Cases diagnosed at the Guangzhou Women and Children's Medical Center, were combined with those retrieved from PubMed and China National Knowledge Infrastructure (CNKI) databases from January 2015 to June 2022 and integrated into a study cohort; grouped according to gene mutation sites, clinical phenotype, and renal pathological types. The clinical characteristics between groups were compared, and the relationship between genotype and age of onset, clinical phenotype, and pathological type were retrospectively analyzed.Results:The center enrolled 15 confirmed children: seven cases of non-simple nephropathy, including Denys-Drash syndrome (DDS) and Frasier syndrome (FS); eight cases of isolated steroid-resistant nephrotic syndrome (ISRNS); and 13 cases (86.7%) that progressed to end-stage renal disease (ESRD). The initial hemoglobin and bicarbonate levels of patients with clinical non-simple nephropathy were significantly lower than those with simple nephropathy, whereas the serum creatinine levels were higher than those of patients with simple nephropathy. A total of 75 cases of nephropathy associated with WT1 mutations in the study cohort met the inclusion and exclusion criteria. The most common clinical manifestations of WT1 mutations in this cohort were DDS (29/75, 38.7%) and ISRNS (37/75, 49.3%). A renal biopsy was performed in 43 patients, and the common types of renal pathology were focal segmental glomerulosclerosis (23/43, 53.5%) and DMS (13/43, 30.2%). Within the cohort, there were 12 cases (16.0%) in the exon 8 mutation group, 32 (42.6%) in the exon 9 group, 19 (25.3%) in the intron 9 group, and 12 (16.0%) in other gene site mutation groups. Common sites of WT1 mutations in Chinese children were exons 9 and intron 9. Exon 8 mutations were uniquely correlated with the age of onset within three months [5/7; 71.4%; Adjusted standardized residual (AR) = 4.2]. The renal survival time in the exon 8 mutation group was the shortest (P = 0.003).Discussion:The molecular and biological characteristics of WT1 mutation-related nephropathy determine the clinical type, pathological features, and renal survival time of the disease; and there was a strong correlation between the genotype and clinical phenotype.