IntroductionTargeted-release budesonide (Nefecon) has demonstrated efficacy in IgA nephropathy (IgAN) trials, yet real-world data across disease severity spectrum remains limited.MethodsThis multicenter, retrospective cohort study included 148 biopsy-proven IgAN adults (Nefecon =79; RASi =69). Primary endpoints were 9-month changes in proteinuria and eGFR. Mahalanobis distance matching within propensity score calipers addressed baseline imbalances. Response dynamics and safety were secondarily evaluated.ResultsDespite worse baseline eGFR (median 54.2 vs. 85.3 mL/min/1.73m²; P < 0.001) and more severe pathological lesions in the Nefecon group compared to RASi group, Nefecon was associated with greater proteinuria reduction (-1.25 vs. –0.58 g/24h; P < 0.001) and favorable eGFR trajectories (+2.7 vs. -11.2 mL/min/1.73m²; between-group difference 13.9 mL/min/1.73m2; 95% CI 12.7 to 15.1; P <0.001), findings remained largely consistent after Mahalanobis distance matching adjustment. Complete and partial remission rates were higher (29.1% and 54.2% vs. 10.1% and 23.2%; P < 0.001), with 59.5% achieving ≥50% proteinuria reduction versus 21.7% (RR 2.70, 95% CI 1.62–4.51). Treatment effects varied by baseline disease severity. Enhanced antiproteinuric efficacy was observed in patients with proteinuria >1.5 g/24h (interaction P = 0.003), while kidney function preservation was most pronounced in those with eGFR <60 mL/min/1.73m². Notably, 51.1% of initial non-responders achieved remission by 9 months, with complete remission rates increasing 4.6-fold over time. Adverse events were consistent with corticosteroid exposure; menstrual disturbance occurred in 39.5% of females. Serious adverse events were rare (2.5%).ConclusionThis real-world observational analysis shows Nefecon associated with improved proteinuria and eGFR outcomes across IgAN severity, extending randomized trial evidence to patients with advanced CKD and revealing substantial delayed response.

Nephropathy in nail-patella syndrome (NPS) has limited therapeutic options. Progressive nephrotic-range proteinuria often persists despite maximal renin–angiotensin–aldosterone system inhibitor (RAASi) therapy. Calcineurin inhibitors such as cyclosporine A (CsA) are unexplored in NPS. We therefore evaluated the efficacy and safety of CsA in a patient with NPS. A 15-year-old boy with genetically confirmed NPS (novel LMX1B missense variant, c.796T>G, p. W266G) was studied. Clinical, pathological, and follow-up data were analyzed. Bioinformatic screening (GSE12008 dataset) identified LMX1B-regulated podocyte genes. Functional assays (immunofluorescence, dual luciferase reporter, and molecular dynamics analyses) assessed the mutation’s impact. The patient presented with classical NPS features, including nail dysplasia, limited elbow motion, patellar dysplasia, and proteinuria. Kidney biopsy revealed focal glomeruli immaturity with small foci of foamy cells, diffuse foot process effacement, and heterogeneous glomerular basement membrane (GBM) abnormalities (predominantly thinned with segmental thickening and loosening), demonstrating Alport-like kidney pathology. Despite resistance to RAASi and sodium-glucose cotransporter inhibitor (SGLT2i), CsA therapy for 7 months significantly reduced proteinuria from 3.74 to 0.697 g/24 h, increased serum albumin from 28.8 to 39.4 g/L, and maintained normal serum creatinine (54–63 μmol/L). Immunofluorescence analysis of the patient’s kidney tissue indicated reduced expressions of PTPRO, NPHS2, and COL4A3. The W266G mutation severely impaired LMX1B binding to the promoters, reducing the transcriptional activity of PTPRO, NPHS2, and COL4A3. CsA effectively reduced nephrotic-range proteinuria in genetically confirmed NPS, suggesting the therapeutic potential of calcineurin inhibitors in for NPS-associated nephropathy.

Serum Klotho, a biomarker associated with anti-aging, has been implicated in kidney disease. However, there is a lack of robust evidence for the relationship between the serum Klotho and diabetic kidney disease (DKD). This study aimed to investigate the association of the serum Klotho levels with DKD and assess the relationship between serum Klotho and all-cause mortality in individuals with DKD. We utilized data from the 2007–2016 National Health and Nutrition Examination Survey (NHANES), incorporating both cross-sectional and cohort study designs. The association between the serum Klotho and DKD was examined using weighted logistic regression models. To estimate the hazard ratios (HRs) and 95

Chronic kidney disease (CKD) is a global health challenge, but invasive renal biopsies, the gold standard for diagnosis and prognosis, are often clinically constrained. To address this, we developed the kidney intelligent diagnosis system (KIDS), a noninvasive model for renal biopsy prediction using 13,144 retinal images from 6773 participants. The KIDS achieves an area under the receiver operating characteristic curve (AUC) of 0.839-0.993 for CKD screening and accurately identifies the five most common pathological types (AUC: 0.790-0.932) in a multicenter and multi-ethnic validation, outperforming nephrologists by 26.98% in accuracy. Additionally, the KIDS further predicts disease progression based on pathological classification. Given its flexible strategy, the KIDS can be adapted to local conditions to provide a tailored tool for patients. This noninvasive model has the potential to improve CKD clinical management, particularly for those who are ineligible for biopsies.

Sarcopenia is a progressive skeletal muscle disorder that contributes to disability, chronic disease burden, and mortality. While the roles of metabolic, cardiovascular, and kidney dysfunction are individually recognized, the collective influence of cardiovascular-kidney-metabolic (CKM) syndrome on sarcopenia remains uncharacterized. Furthermore, it is unclear whether physical inactivity amplifies this risk. This study is the first to apply the recently defined CKM staging framework to investigate sarcopenia risk, thereby offering an integrated, multisystem perspective. A cross-sectional analysis was conducted using 4,193 adults from the National Health and Nutrition Examination Survey 2011–2018 dataset. Sarcopenia was defined using the Foundation for the National Institutes of Health criteria. CKM syndrome was classified into five progressive stages (0–4), and physical activity was quantified using metabolic equivalent of task scores. Multivariable logistic regression models assessed the independent and combined associations of CKM stage and physical inactivity with sarcopenia, adjusting for demographic and clinical confounders. Subgroup and interaction analyses explored effect modification. The overall prevalence of sarcopenia was 7.2

OBJECTIVE:Glomerular immune complex deposition plays a central role in lupus nephritis (LN), but the prognostic relevance of individual immunoglobulin components remains unclear. This study aimed to investigate the clinical impact of glomerular immunoglobulin M (IgM) deposition intensity on patient outcomes. METHODS:This retrospective cohort study analysed 952 biopsy-proven LN patients (1996-2019) from the First Affiliated Hospital of Sun Yat-sen University. A semiquantitative scoring system stratified glomerular immunoglobulin G (IgG), immunoglobulin A (IgA), IgM, complement 3 (C3) and complement component 1q (C1q) deposition into low (-/+) and high (++ to ++++) groups. The primary outcome was a composite of doubling of serum creatinine from baseline or the development of end-stage renal disease (ESRD). The secondary outcome was all-cause mortality. A multivariable Cox regression model was used to adjust for baseline clinical and pathological factors. RESULTS:Among the studied immune complexes, only high glomerular IgM deposition was significantly associated with adverse renal outcomes (p=0.025). These patients had higher baseline Systemic Lupus Erythematosus Disease Activity Index scores (SLEDAI) (16 (12-20) vs 15 (12-18), p<0.001), more severe histopathological features (including proliferative glomerulonephritis, endocapillary hypercellularity, leucocyte infiltration and microthrombi), and profound complement activation (lower median serum C3 and complement 4 (C4) levels, both p<0.05). High glomerular IgM deposition also correlated with high IgA (r=0.48) and C3 (r=0.40) deposition (both p<0.01). Multivariable analysis revealed that high glomerular IgM deposition remained an independent predictor of renal progression (adjusted HR=1.485, 95% CI 1.040 to 2.119, p=0.029). CONCLUSION:High glomerular IgM deposition emerged as an independent prognostic marker for adverse renal outcomes in LN, potentially outperforming other individual immune complexes. These findings highlight the pathogenic significance of IgM in LN and support its value in risk stratification and treatment guidance.

Most studies focused on glomerular lesions in lupus nephritis (LN). However, the predictive value for tubulointerstitial lesions remains less well understood and controversial. Here, we assessed the impact of tubulointerstitial lesions, quantified by Total Tubulointerstitial Lesions Score (TTS), on long-term renal outcomes and mortality in LN. We conducted a cohort study of 832 patients with LN diagnosed from 1996 to 2018 at the First Affiliated Hospital of Sun Yat-sen University. Patients were stratified by the median of TTS (TTS ≤2 vs TTS >2 groups), which included the total score of tubulointerstitial inflammation, tubular atrophy and interstitial fibrosis by the 2018 ISN/RPS (International Society of Nephrology and Renal Pathology Society) classification semi-score. We used Kaplan-Meier survival curves and Cox regression models to analyse the associations between TTS and patient outcomes. Pearson's correlation analysis revealed that TTS was negatively correlated with estimated glomerular filtration rate, haemoglobin and serum albumin levels, while positively correlated with proteinuria levels. TTS was significantly higher in patients with proliferative LN. Kaplan-Meier analysis showed that patients with higher TTS had a higher risk of all-cause mortality and adverse renal outcomes. Multivariate Cox analysis identified TTS >2 (HR=1.50, 95% CI=1.02 to 2.22, p=0.039) and higher tubulointerstitial inflammation and tubular atrophy as the independent predictor of all-cause mortality, and TTS >2 (HR=1.63, 95% CI=1.05 to 2.52, p=0.030) and severer tubulointerstitial inflammation, tubular atrophy and interstitial fibrosis were independently associated with adverse renal outcomes. TTS provides a comprehensive assessment of renal tubulointerstitial lesions and is a simple and effective predictor of long-term mortality and adverse renal outcomes in LN.

While both cardiovascular health (CVH) and urinary albumin-to-creatinine ratio (UACR) are individually associated with mortality, their combined prognostic significance and potential mechanistic interplay in adults with hypertension remain unclear. This cohort study analyzed data from 9154 hypertensive adults in the National Health and Nutrition Examination Survey 2007-2018. CVH was assessed using the American Heart Association's Life's Essential 8 score, and UACR was measured from spot urine samples. Multivariable Cox proportional hazards models, restricted cubic spline analyses, joint exposure modeling, and causal mediation analysis were used to evaluate the independent, combined, and mediating effects of UACR and CVH on all-cause mortality. Both lower CVH scores and higher UACR levels were independently associated with increased mortality. A nonlinear association was observed for each. Individuals with severely elevated UACR and poor CVH had the highest mortality risk (HR = 6.61; 95% CI, 3.72-11.74), while those with normal UACR (<10 mg/g) showed no significant mortality difference across CVH strata. Notably, even mildly elevated UACR (10-29.9 mg/g), considered within the conventional "normal" range, was associated with significantly increased mortality. Mediation analysis revealed that UACR explained 4.01% (95% CI, 2.83%-6.40%; p < 0.001) of the association between CVH and mortality. This study is the first to demonstrate that UACR not only modifies but also mediates the association between CVH and mortality in individuals with hypertension. These findings underscore the prognostic value of integrating renal and cardiovascular metrics and suggest that even low-grade albuminuria has clinical relevance.

Transglutaminase 2 (TGase2) has been shown to contribute to the mesangial IgA1 deposition in a humanized mouse model of IgA nephropathy (IgAN), but the mechanism is not fully understood. In this study, we found that inhibition of TGase2 activity could dramatically decrease the amount of polymeric IgA1 (pIgA1) isolated from patients with IgAN that interacts with human mesangial cells (HMC). TGase2 was expressed both in the cytosol and on the membrane of HMC. Upon treatment with pIgA1, there were more TGase2 recruited to the membrane. Using a cell model of mesangial deposition of pIgA1, we identified 253 potential TGase2-associated proteins in the cytosolic fraction and observed a higher concentration of cellular vesicles and increased expression of Ras homolog family member A (RhoA) in HMC after pIgA1 stimulation. Both the amount of pIgA1 deposited on HMC and membrane TGase2 level were decreased by inhibition of the vesicle trafficking pathway. Mechanistically, TGase2 was found to be coprecipitated with RhoA in the cellular vesicles. Membrane TGase2 expression was greatly increased by overexpression of RhoA, while it was reduced by knockdown of RhoA. Our in vitro approach demonstrated that TGase2 was transported from the cytosol to the membrane through a RhoA-mediated vesicle-trafficking pathway that can facilitate pIgA1 interaction with mesangium in IgAN.

Purposes This study was conducted to identify the frequent mutations from reported Chinese Gitelman syndrome (GS) patients, to predict the three-dimensional structure change of human Na–Cl co-transporter (hNCC), and to test the activity of these mutations and some novel mutations in vitro and in vivo. Methods SLC12A3 gene mutations in Chinese GS patients previously reported in the PubMed, China National Knowledge Infrastructure, and Wanfang database were summarized. Predicted configurations of wild type (WT) and mutant proteins were achieved using the I-TASSER workplace. Six missense mutations (T60M, L215F, D486N, N534K, Q617R, and R928C) were generated by site-directed mutagenesis. 22Na+ uptake experiment was carried out in the Xenopus laevisoocyte expression system. In the study, 35 GS patients and 20 healthy volunteers underwent the thiazide test. Results T60M, T163M, D486N, R913Q, R928C, and R959frameshift were frequent SLC12A3 gene mutations (mutated frequency >3%) in 310 Chinese GS families. The protein’s three-dimensional structure was predicted to be altered in all mutations. Compared with WT hNCC, the thiazide-sensitive 22Na+ uptake was significantly diminished for all six mutations: T60M 22 ± 9.2%, R928C 29 ± 12%, L215F 38 ± 14%, N534K 41 ± 15.5%, Q617R 63 ± 22.1%, and D486N 77 ± 20.4%. In thiazide test, the net increase in chloride fractional excretion in 20 healthy controls was significantly higher than GS patients with or without T60M or D486N mutations. Conclusions Frequent mutations (T60M, D486N, and R928C) and novel mutations (L215F, N534K, and Q617R) lead to protein structure alternation and protein dysfunction verified by 22Na+ uptake experiment in vitro and thiazide test on the patients.

[This corrects the article DOI: 10.1155/2020/2078279.].

目的 探讨合并交通性脑积水的ANCA相关性血管炎(AAV)的发病机制、诊治方法,提高临床医师对AAV罕见类型的认识水平.方法 收集1例以交通性脑积水为首发症状的AAV病例的临床资料,以"ANCA相关性血管炎""脑积水"为关键词(包括中英文)对PubMed和CNKI收录的论文进行检索,结合文献分析病例特点、实验室检查、影像学检查、肾脏活组织检查(活检)和诊治方法.结果 该例71岁男性患者,因头晕伴行走不稳半年余在门诊行CT检查提示交通性脑积水,拟行手术治疗.术前检查发现血清肌酐635μmol/L,核周型-抗中性粒细胞胞质抗体(p-ANCA)(+),MPO 293 U/L,尿红细胞位相示畸形红细胞240000/μL,经肾脏活组织检查(活检)证实存在AAV肾损害.随访30个月,经糖皮质激素(激素)联合环磷酰胺治疗后,患者血清肌酐降至335μmol/L并脱离透析,头晕、行走不稳、智力减退症状逐渐好转,后多次复查颅脑MRI,交通性脑积水较前无明显变化.检索数据库后共收集5篇相关病例报道,患者年龄33～76岁,临床表现为脑积水和AAV,予激素联合免疫抑制剂、脑室-腹膜分流术等治疗,随访期间1例患者死亡,另外4例患者症状缓解.结论 以脑积水起病的AAV罕见且血管炎症状隐匿,易被误诊或漏诊,对不明原因伴肾衰竭的神经系统受累病变进行ANCA筛查十分必要,肾穿刺活检有助于明确诊断,及时正规治疗可缓解脑积水症状,有助改善患者预后.

Background In the first year of dialysis, patients are vulnerable to cardiovascular disease (CVD) hospitalization, but knowledge regarding the risk factors and long-term outcomes of cardiovascular readmission within the first year after dialysis in incident continuous ambulatory peritoneal dialysis (CAPD) patients is limited.Methods This retrospective cohort study was conducted in incident CAPD patients. The demographic characteristics, laboratory parameters, and CVD readmission were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included CVD mortality, infection-related mortality and technique failure. A logistic regression was used to identify the risk factors associated with CVD readmission within the first year after dialysis. Cox proportional hazards models were used to evaluate the association between CVD readmission and the outcomes.Results In total, 1589 peritoneal dialysis (PD) patients were included in this study, of whom 120 (7.6%) patients had at least one episode of CVD readmission within the first year after dialysis initiation. Advanced age, CVD history, and a lower level of serum albumin were independently associated with CVD readmission. CVD readmission within the first year after dialysis was significantly associated with all-cause (HR 2.66, 95%CI 1.91–3.70, p < 0.001) and CVD (HR 3.42, 95%CI 2.20–5.31, p < 0.001) mortality, but not infection-related mortality or technique failure, after adjusting for confounders.Conclusions Our findings suggest that an advanced age, a history of CVD, and a lower level of serum albumin were independently associated with CVD readmission. Moreover, CVD readmission was associated with all-cause and cardiovascular mortality in incident CAPD patients.

A practical method for the synthesis of N-(2-carbonylaryl) benzenesulfonamides via an iron-catalyzed electrophilic amination of sodium sulfinates with anthranils is described. This redox-neutral transformation has high atom efficiency and is achieved under simple and mild reaction conditions. A wide range of anthranils and sodium sulfinates were compatible in this transformation. Moreover, the synthetic potential of this methodology was further demonstrated by the synthesis of various useful N-heterocycles and derivatives.

It has been proven that vitamin D was decreased and function of circulating endothelial progenitor cells (EPCs) was injured in systemic lupus erythematosus (SLE) patients. However, the effect of vitamin D on the function of EPCs in vitro and its mechanism need further study. Therefore, we investigated whether vitamin D improved the function of EPCs in vitro. The peripheral blood mononuclear cells of the participants were isolated from SLE patients and control subjects and cultured to EPCs. After the EPCs were treated with vitamin D (1,25-(OH)2D3), we evaluated the number, migratory and proliferative activities, and nitric oxide (NO) production of EPCs in vitro and detected vascular endothelial function by flow-mediated dilatation (FMD). We found that vitamin D in a dose-dependent manner improved number and migratory and proliferative activities of EPCs from SLE patients. Additionally, vitamin D upregulated NO production from EPCs in vitro. A significant correlation between the FMD and plasma NO level was found. There was also a correlation between number, migration, and proliferation of EPCs and NO production. Thus, the present findings indicated that vitamin D improved the function of EPCs from SLE patients via NO secretion.

Purpose. It was reported that gut-kidney axis may play an important role in IgA nephropathy (IgAN). Previous five GWASs of different populations for IgAN have discovered several genes related to intestinal immunity, including DEFA gene. However, the roles of the encoded proteins of DEFA5/6 which were called intestinal antimicrobial peptides HD5 and HD6 were not clear in kidney disease, such as IgAN. The purpose of this study was to clarify the association of HD5 and HD6 with IgAN. Methods. We measured HD5 and HD6 in serum, urine, and kidney of IgAN patients and normal controls by ELISA, Western blot, and immunofluorescence. The association of HD5 or HD6 levels with clinical and pathologic phenotypes was analyzed. Results. Serum levels of HD5 and HD6 were significantly higher in IgAN patients than those in normal controls. Baseline serum HD5 levels were significantly associated with eGFR (P=0.002) and tubular atrophy/interstitial fibrosis (P=0.004) by stepwise multivariate regression analysis. Compared to the patients with serum HD5 below the median level, patients with elevated serum HD5 above the median level had a significantly worse renal outcome (log-rank test, P=0.009) by Kaplan-Meier analysis. A Cox regression model showed that serum HD5 was an independent prognostic factor (HR=1.239, P=0.029) after adjusting for the well-known predictors of outcome in IgAN patients. In renal biopsies of IgAN patients, HD5 was significantly expressed in the damaged proximal tubules, while no immunoreactive HD6 was found. Interestingly, the serum HD6 level of IgAN patients was significantly associated with gender. Conclusions. In IgAN patients, an elevated serum HD5 level at the time of renal biopsy was associated with poor renal outcomes. HD5 rather than HD6 was probably associated with renal function of IgAN patients.

Aim of Study To investigate podocyte density in aging diabetic Ins2± and Ins2±, A1AR-/- mouse models in C57Bl/6 background. Methods Ins2± mice and especially Ins2±, adenosine A1 receptor knockout mice (Ins2±, A1AR-/-) are mouse models with a phenotype of diabetic nephropathy. Aged mice (at ~40 weeks) were assessed for glomerular filtration barrier function by measuring albuminuria, glomerular filtration, glomerular damage by electron microscopy, and podocyte numbers by Wilms Tumor protein (WT-1) staining. Results Compared to healthy wild-type mice, both diabetic mouse models developed diabetic nephropathy, including hyperfiltration (p<0.01) and albuminuria (p<0.05). Typical diabetic structural glomerular and podocyte damage was visualized by electron microscopy. Podocyte count per glomerular area (podocyte density) was significantly decreased in both diabetic mouse models (p<0.01). In contrast, no significant correlation was detected between albuminuria and absolute podocyte count per glomerulus. Conclusion The amount of albuminuria as marker of diabetic nephropathy does not correlate with the podocytes density; however, a relative podocyte deficiency became evident with an increase in glomerular area in the diabetic animals, suggesting a relative podocytopenia.

Introduction The prevalence of hyperuricaemia in peritoneal dialysis patients is quite high. Studies have demonstrated a correlation between hyperuricaemia and cardiovascular disease and treatment of hyperuricaemia reportedly reduces cardiovascular risk in patients with chronic kidney disease. However, whether hyperuricaemia treatment benefits cardiovascular outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is not yet known.Methods and analyses This prospective, multicentre, double-blind, randomised controlled trial was designed to evaluate the effects of hyperuricaemia treatment on cardiovascular event risk in CAPD patients. Based on a power of 80%, with type I error α=0.05, two-sided test and 1:1 parallel control study, considering a dropout rate of 20%, a total of 548 eligible patients are expected to be randomly assigned to either the hyperuricaemia treatment group (febuxostat) or control group (placebo).Ethics and dissemination This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University and the ethics committees of other participating institutions. Written informed consent will be obtained from potential trial participants or authorised surrogates.The findings of the study will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.Trial registration number NCT03200210. 25 June 2017. The trial was started on 13 July 2017, and is expected to end by 31 December 2022. Till 20 Jan 2020, a total of 548 patients have been recruited.Protocol version The protocol version number and date are YLT-1604-V2.0 and 15 December 2016.