The high prevalence and substantial burden of kidney diseases necessitate advanced approaches to elucidate molecular mechanisms and promote precision medicine. Mass spectrometry (MS)-based proteomics has evolved into a widely used analytical platform, delivering high-sensitivity, high-throughput protein profiling capabilities that have contributed substantially to biomarker discovery, mechanistic dissection, and therapeutic target identification across a broad range of kidney diseases. This review provides a comprehensive overview of MS-based proteomics applications in kidney disease research, covering progress in biomarker identification, pathogenic mechanism interrogation, and clinical translation. It highlights methodological advances, emerging trends, and persistent challenges that shape the field. Existing literature has uncovered abundant disease-specific biomarkers and revealed key pathogenic pathways, including podocyte injury-associated protein interaction networks, dysregulated complement activation, and metabolic reprogramming, and have critically assessed their translational potential. Additionally, investigations into posttranslational modifications such as phosphorylation and glycosylation have provided valuable insights for targeted therapies. Collectively, these findings illustrate the contributions of MS-based proteomics to the characterization of disease molecular heterogeneity, the identification of key pathogenic drivers, and the development of precision medicine approaches. This review further addresses current challenges in clinical applications, including sample heterogeneity, data complexity, and standardization issues. We additionally emphasize the critical need for minimum reporting standards and multicenter harmonization to accelerate the clinical translation of renal proteomics. Future research should focus on integrating multiomics and artificial intelligence-driven data mining to enhance precise disease subtyping, dynamic monitoring, and personalized treatment strategies.

Acute kidney injury (AKI) represents a life-threatening condition among hospitalized patients, where early prediction enables prevention. Despite advances in existing models, clinical implementation remains hindered by excessive false positive rates (70%-94%) and lack of actionable clinical insights. We conduct a multi-center retrospective cohort study and develop a two-model large language model framework: AKI-PM (Prediction Model) for predicting AKI occurrence within 24 hours and AKI-RAM (Risk Attribution Model) for providing explainable risk attribution. Using a cohort of 140,637 hospital admissions across four geographically diverse Chinese hospitals, we demonstrate that AKI-PM achieves high predictive performance in internal validation (area under curve 0.95, positive predictive value 0.68) and maintains robust generalizability across external sites after few-shot (area under curve 0.92-0.96, positive predictive value 0.69-0.74). Crucially, AKI-RAM provides structured, clinically actionable risk explanations by distinguishing modifiable from non-modifiable factors and offering tailored recommendations. In a clinical evaluation of 200 cases from four independent hospitals by six nephrologists, AKI-RAM receives high scores across eight dimensions (Likert scale: 4.18-4.88) with moderate to good inter-rater reliability (intraclass correlation coefficients: 0.680-0.803). This integrated framework addresses critical limitations in AI-driven clinical prediction by combining accuracy with interpretability, offering a scalable solution for early AKI prevention in diverse healthcare settings.

AIM:To characterize the epidemiology, clinicopathological features, and renal outcomes in patients with Monoclonal Gammopathy of Renal Significance (MGRS). METHODS:The authors conducted a retrospective analysis of all renal biopsy-confirmed MGRS cases diagnosed between 2010‒2020, with histopathological review by two independent pathologists. Post-hoc power analysis confirmed adequate statistical power (92 %). RESULTS:Among 124 histologically confirmed MGRS cases (median age 64.0-years, IQR 52.5‒68.0), renal amyloidosis predominated (75.8 %), followed by monoclonal immunoglobulin deposition disease (MIDD, 10.5 %), cryoglobulinemic GN (4.8 %), proliferative GN with monoclonal Ig deposits (PGNMID, 2.4 %), light chain proximal tubulopathy (3.2 %), and C3 glomerulopathy with monoclonal gammopathy (1.6 %). Amyloidosis patients primarily presented with nephrotic syndrome (77.7 %), while fewer exhibited acute kidney injury (3.2 %), chronic kidney disease (16.1 %), or ESRD (6.7 %). Compared to other MGRS subtypes, amyloidosis patients demonstrated significantly lower anemia rates (p < 0.001), higher LDH (p = 0.035), preserved eGFR (p < 0.001), greater proteinuria (p = 0.037), and hypoalbuminemia (p < 0.001). The renal response rates were 26.1 % (Amyloidosis-Associated MGRS, MGRS-A) versus 33.3 % (Non-Amyloidosis MGRS, MGRS-NA), while hematologic responses were 8.7 % versus 0 %, respectively. Both hematologic (p = 0.007) and renal responses (p = 0.009) correlated with improved survival. MGRS-A showed inferior renal survival (p = 0.05). Multivariate analysis identified hypotension (p = 0.005), elevated creatinine (p = 0.002), and cardiac involvement (p = 0.022) as independent predictors of ESKD, while age (p < 0.001) and cardiac involvement (p < 0.001) predicted mortality. CONCLUSION:MGRS represents a clinically significant cause of kidney injury in monoclonal gammopathy patients, with amyloidosis being the predominant etiology. MGRS-A portends a worse prognosis than MGRS-NA. Therapeutic responses in both hematologic and renal parameters predict survival benefits. Age and cardiac involvement emerge as key prognostic markers for both renal and patient survival.

Physical exercise has been proven to be beneficial for chronic kidney disease (CKD) patients; however, there is a lack of a comprehensive summary of existing literature, especially the results from randomized controlled trials (RCTs). We had conducted a systematic review and meta-analysis to evaluate the benefits of physical exercise in chronic kidney disease. Outcomes were classified into all-cause mortality, cardiovascular, pulmonary, and renal outcomes, inflammatory indices, laboratory tests, and physical indices. The risk of bias was assessed using the Cochrane criteria. Relative risk ratios with 95% confidence intervals (CIs) for categorical variables, and weighted mean difference or standardized mean differences with 95% CIs for continuous variables were pooled using a random-effects model. Publication bias was assessed using Funnel plot analysis and Egger's Test. At last, 82 studies were included, and the results of the meta-analysis show that the physical exercises can significantly reduce all-cause mortality, particularly in dialysis dependent patients. Cardiovascular function, reflected by 6-minute walk test and blood pressure and pulmonary function, reflected by peak oxygen uptake, forced expiratory volume in 1 second, and forced vital capacity, all improved after physical exercise interventions. Physical exercises helped to increase the dialysis adequacy and preserve the residual renal function. C-reactive protein and interleukin-6 levels decreased, and hemoglobin and albumin levels increased upon physical exercise interventions. The fat mass decreased after physical exercise interventions in non-dialysis patients. We concluded that physical exercise is beneficial for CKD patients, independent of the modes or locations of exercise.

Optimal regional citrate anticoagulation (RCA) for hemodialysis (HD) in high-bleeding-risk patients remains undefined. This prospective observational cohort study included 195 high-bleeding-risk patients (481 HD sessions) allocated to three RCA groups: RCA-one (prefilter citrate only, 141 patients/337 sessions), RCA-two (pre- and post-filter citrate, 51 patients/133 sessions), and RCA+saline (prefilter citrate + post-filter saline, 3 patients/11 sessions). Primary outcome: circuit survival time; secondary outcomes: complete dialysis rate, clotting scores, and adverse events. RCA-two had the highest complete dialysis rate (99.7% vs. 97.0% [RCA-one], 97.7% [RCA+saline]; p = .037) and lowest venous expansion chamber serious clotting (score = 3: 5.4% vs. 16.9%, 30.0%; p < .001). Non-severe venous clotting (score < 3) was highest in RCA-two (94.6% vs. 83.1%, 70%; p < .001), with no intergroup differences in dialyzer clotting (score < 3: 96.1% vs. 95.3%, 90%; p = .83). RCA-two had the lowest adverse event rate (1.8% vs. 10.8%, 11.1%; p = .001), including less hypotension (0.9% vs. 7.6%, 2.0%; p = .023) and no muscle cramps. Venous pretreatment calcium in RCA-two decreased at 2 h (p = .03) without serious electrolyte/acid-base imbalances. Circuit survival time did not differ among groups (p > .05). RCA is safe and effective for high-bleeding-risk HD patients. RCA-two (pre- and post-filter citrate) offers advantages in venous anticoagulation and safety but requires confirmation in large randomized trials.

Intradialytic hypotension (IDH) is one of the most common complications of hemodialysis. In order to prevent IDH, Artificial intelligence (AI) was utilized in predicting the onset of IDH. Different variables and different AI methods were used to improve the diagnostic test accuracy but resulted in different findings. We conducted a systematic review and meta-analysis to quantitatively analyze the diagnostic test accuracy of AI models in predicting IDH in HD patients and investigated the factors influencing the diagnostic test accuracy. Medline, Embase, and the Cochrane Library were searched using combined free texts and MeSH terms relating to hemodialysis, hypotension and AI (prior to Sep, 2025 and English-language publications included). Two authors independently screened the studies, and extracted and analyzed the data. A quantitative random-effects meta-analysis using Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model was applied to summarize the SROC curves. Between-study heterogeneity was explored using multiple methods, and funnel plot analysis was used to identify publication bias. A total of 142 articles were identified and 19 studies with 33,214(95%CI: 405.08 to 3065.86) subjects and 4,350,177(95%CI: 0 to 35865.73) sessions met the inclusion criteria. Decision tree, support vector machine, XGBoost, extreme gradient boosting, recurrent neural network, and random forest were used in the studies. The summary area under the SROC curve(AUC) was 0.86(95%CI: 0.83 to 0.89), showing that the sensitivity of AI for prediction of IDH was 0.74(95%CI: 0.66 to 0.82), specificity was 0.85 (95%CI: 0.77to 0.91).These results indicate that it has moderate diagnostic ability for prediction of IDH during hemodialysis and high accuracy in excluding negative patients, although some missed diagnosis remain unavoidable. The Deeks' funnel plot asymmetry test showed no evidence of publication bias (P = 0.68). This comprehensive systematic review and meta-analysis of AI models demonstrates promising accuracy for predicting IDH in hemodialysis patients. However, current limited studies and between-study heterogeneity limit its clinical application. More standardized approaches are needed for the development and validation of prediction models and randomized clinical trials, including unified IDH definition criteria, standardized data collection and model development protocols, and consistent external validation standards, to evaluate the clinical value of IDH prediction models.

Kidney diseases present substantial clinical challenges, with aberrant glycoproteins emerging as key pathogenic drivers. Minor glomerular abnormalities (MGAs), a category of unclassified glomerular lesions defined by subtle structural changes, are commonly detected in patients with persistent, asymptomatic, isolated proteinuria or microhematuria. Still their site-specific N-glycosylation patterns remain unexplored. To address this gap, a laboratory-developed pressure cycling technology-based quantitative glycoproteomics workflow was applied to compare intact N-glycopeptides (IGPs) among distant non-neoplastic tissues (DNTs; n = 24) and trace renal biopsy samples from MGA patients (n = 27). Integrated with high-resolution mass spectrometry, 672 upregulated IGPs (FC > 1.5, p < 0.05) and 573 downregulated IGPs (FC < 0.67, p < 0.05) in MGA tissues were quantified. Compared with DNTs, 24 glycoproteins associated with the PI3K-Akt signaling pathway exhibited broadly elevated IGP abundances in MGA samples. Site-specific N-glycosylation analysis further revealed distinct patterns among IgG subclasses and complement-related markers that distinguish MGA from DNT, offering new mechanistic insights into MGA pathogenesis. These novel glyco-signatures clarify the role of N-glycosylation in renal disease and validate this workflow as a powerful tool for trace-tissue analysis. This study lays the groundwork for translating N-glycosylation findings into clinical applications to improve MGA diagnosis and management.

Background: Chronic kidney disease (CKD) associated vascular calcification (VC) is a leading cause of cardiovascular mortality, partially driven by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation cellular process. However, the precise role and mechanism of CMA in CKD-associated vascular calcification remain unknown. Methods: We studied calcified arteries from CKD patients and rats fed on a high-phosphate diet using histological and ultrastructural methods. VSMCs’ calcification was induced by a calcification medium containing high phosphate and calcium. CMA activity was measured by a KFERQ reporter and lysosomal staining. The expression of LAMP2a and HSP90AA1 was knocked down by siRNA, overexpressed by plasmid, and activated by QX77.1. Bioinformatic analysis, protein interaction studies, immunofluorescence and co-immunoprecipitation were performed to investigate the potential mechanism of CMA in VC. Results: The expression of LAMP2a was increased in human calcified radial artery tissues (n = 3, p < 0.05) and rats’ calcified aortic tissues (n = 3, p < 0.01), accompanied by lysosomal abnormalities. The activity of CMA was increased during the osteogenic transdifferentiation of VSMCs, as indicated by increased expression of RUNX2 and reduced expression of SM22α (p < 0.05). LAMP2a knockdown attenuated VSMCs’ calcification (p < 0.05), whereas pharmacological activation of CMA aggravated calcification in VSMCs (p < 0.01). Bioinformatic screening identified HSP90AA1 as a candidate involved in CMA in vascular calcification. Elevated HSP90AA1 expression was observed in human calcified radial artery tissues (n = 3, p < 0.01) and rat calcified aortic tissues (n = 3, p < 0.01), which promoted osteogenic transdifferentiation of VSMCs (p < 0.05). HSP90AA1 interacted with LAMP2a and positively regulated its expression (p < 0.01). Conclusions: These findings support an association between CMA activation and CKD vascular calcification. It suggests that HSP90AA1 facilitates vascular calcification in chronic kidney disease involving chaperone-mediated autophagy.

Background:Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. Methods:We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010-2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated. Results:PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, P = 0.003), with better renal function and more frequent C1q deposition (38.1% vs. 13.5%, P = 0.016). Serum anti-PLA2R antibodies were detected in 55.3% of patients and strongly correlated with tissue PLA2R positivity (AUC = 0.851; optimal cutoff ≥17.47 RU/mL). Baseline antibody titers were not associated with remission (P = 0.573). During 5-years follow-up, 42.4% achieved CR, 36.4% PR, and 21.2% had NR, with an estimated 5-year renal survival rate of 81.95%. No malignancy events were observed among the seven THSD7A-positive patients or the single NELL-1-positive patient in this cohort. Statistical power for rare antigen subgroups was limited. Conclusions:This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN.

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.

Rituximab is effective for primary membranous nephropathy (PMN), yet infectious complications remain a critical safety concern with poorly characterized risk factors and prognostic implications. This retrospective study analyzed 88 biopsy-proven PMN patients receiving rituximab at a tertiary center from January to December 2022. Patients were categorized based on the occurrence of severe infection (necessitating hospitalization, intravenous antibiotics, or causing death) over 24 months. Primary outcomes included cumulative probabilities of complete remission (CR) and clinical remission (CR plus partial remission, PR). Infections occurred in 18 patients (20.5

ObjectiveTo assess the screening status of high-risk individuals for chronic kidney disease （CKD） in a community in Chengdu and to identify the main factors associated with incident CKD， thereby providing evidence for community-based CKD prevention and control strategies.MethodsClinical data were collected from high-risk individuals for CKD who visited the Chengdu Wuhou South Railway Station Community Health Service Center between April 17， 2014， and April 16， 2023. CKD was diagnosed based on the criterion of two consecutive abnormal findings of the same kidney damage marker persisting for at least 3 months. A Cox proportional hazards regression model was used to analyze risk factors for newly diagnosed CKD. Kaplan-Meier survival curves were applied to evaluate the effect of different numbers of risk factors on patient CKD-free survival time.ResultsA total of 7，599 high-risk individuals were included， among whom 33.12% underwent combined screening for estimated glomerular filtration rate （eGFR） and urinary microalbuminuria （MAlb）. During follow-up， 357 cases of CKD were diagnosed， with an overall annual incidence rate of 4684.83 per 100，000. Cox regression analysis showed that hypertension （HR=1.85， 95%CI： 1.28-2.69）， diabetes mellitus （HR=4.16， 95%CI： 3.02-5.74）， and obesity （HR=2.03， 95%CI： 1.62-2.54） were independent risk factors for CKD. Kaplan-Meier survival analysis showed that individuals with two or more high-risk factors had a significantly lower CKD-free survival rate （P<0.001）.ConclusionA substantial number of individuals in the community are at potential risk for CKD. Diabetes mellitus， hypertension， and obesity are the main contributing factors. The implementation rate of combined eGFR and urine MAlb screening remains low and should be further promoted. The number of individual risk factors is significantly negatively correlated with CKD-free survival time.

Background:Immunoglobulin A (IgA) nephropathy is a progressive immune-mediated chronic kidney disease with a high prevalence and disease burden in East Asia, including China. In a prespecified interim analysis (IA) of the global phase 3 VISIONARY trial, treatment with sibeprenlimab led to significant placebo-adjusted reduction in 24-hour urine protein-to-creatinine ratio (uPCR-24h) of 51.2% (P < .0001) at 9 months. Here, we report the interim efficacy and safety findings for sibeprenlimab for patients with IgA nephropathy enrolled from mainland China as part of the main global population. Methods:Patients (N = 102) were randomized 1:1 to receive sibeprenlimab 400 mg or placebo subcutaneously Q4W for 26 doses. Patients who completed the 9-month uPCR-24h assessment were included. The primary endpoint was change in uPCR-24h from baseline at 9 months. The key secondary endpoint of annualized estimated glomerular filtration rate slope over 24 months will be reported at trial completion. Other secondary and exploratory endpoints included spot urine protein-to-creatinine ratio (spot uPCR), proteinuria remission, haematuria resolution, reduction in biomarker levels [including galactose-deficient IgA1 (Gd-IgA1) and a proliferation-inducing ligand (APRIL)], and safety. Results:By the China IA data cutoff (January 2025), 42 patients from mainland China completed the 9-month uPCR-24h assessment (sibeprenlimab, n = 25; placebo, n = 17) and were included in the efficacy analysis. At 9 months, a reduction from baseline in uPCR-24h of 63.1% was observed in sibeprenlimab-treated patients versus a decrease of 3.1% in the placebo group, corresponding to a placebo-adjusted reduction of 61.9% (95% confidence interval 43.2%-74.5%). Spot uPCR declined by week 4 and was sustained through month 12. Sibeprenlimab reduced Gd-IgA1 (67.3%) and suppressed APRIL levels (97.7%) from baseline at week 48. The incidence of treatment-emergent adverse events was similar between treatment groups. Conclusions:Interim efficacy and safety results for the mainland China cohort were consistent with the IA of the global cohort of the VISIONARY trial (ClinicalTrials.gov: NCT05248646).

IntroductionThe complement system is increasingly recognized as a contributor to the pathogenesis of focal segmental glomerulosclerosis (FSGS). However, a comprehensive, tissue-based characterization of complement dysregulation in human FSGS kidneys remains lacking.MethodsWe performed an integrative multi-omics analysis combined with histological validation. Proteomic (LC-MS/MS) profiling was conducted on renal cortical tissues from 11 patients with FSGS and 12 healthy controls from our institution, while transcriptomic (RNA-seq) analysis was performed using publicly available datasets comprising 100 FSGS and 30 normal samples. In situ deposition of key complement components (C1q, C3c, C5a, C7, CFB, CFH, MBL) was assessed using multiplex immunofluorescence confocal microscopy. Correlations between complement deposition and clinical outcomes were analyzed.ResultsMulti-omics analyses consistently identified the complement and coagulation cascades among the most significantly enriched pathways in FSGS. Transcriptomic data revealed upregulation of C1QB, C1R, C1S, C2, C3, and CFB mRNA, whereas proteomic profiling showed upregulation of C4BPA, C5, C8B, C8G, and CFHR5, along with downregulation of C1R, C1S, C2, CFB, and CFH. In Tmem30a knocked down mouse podocytes, complement pathway enrichment was observed, but core components including C3, C1r, C1s, and CFB were downregulated. Immunofluorescence confirmed frequent glomerular C3c deposition (43.75%), with lower positivity rates for C1q (15.63%), CFB (12.5%), and CFH (12.5%); MBL deposition was rare. Patients with glomerular deposition of C3c, C1q, CFB, or CFH exhibited significantly lower probabilities of achieving complete remission.ConclusionsThis study systematically demonstrates concurrent dysregulation of the classical and alternative complement pathways in FSGS. The deposition of specific complement components in renal tissue strongly correlates with disease activity, treatment resistance, and poor prognosis, suggesting their potential as pathological biomarkers and therapeutic targets. These findings enhance the understanding of FSGS immunopathogenesis and support the strategy of complement-targeted therapies.