Rationale & Objective:Some patients with psoriasis develop lupus erythematosus-like side effects after treatment with interleukin (IL)-17 inhibitors. Whether use of IL-17 inhibitors increases the risk of systemic lupus erythematosus (SLE) remains unclear. This study explores the potential relationship between use of IL-17 inhibitors and the onset of SLE. Study Design:Case reports, cohort study, pharmacovigilance study, and 2-sample Mendelian randomization (MR). Setting & Participants:Two patients with psoriasis who developed SLE and lupus nephritis (LN) after using IL-17 inhibitors, clinical data from 7,367 patients with psoriasis at Jiangsu Province Hospital, adverse drug reaction reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS), and data from genome-wide association studies related to IL-17A/IL-17 receptor A and SLE. Exposures:Use of IL-17 inhibitors. Outcomes:Development of SLE. Analytical Approach:Fisher exact test, reporting odds ratio (ROR), and inverse variance weighting. Results:Two Chinese patients developed SLE and LN symptoms 2-4 months after receiving IL-17 inhibitor treatment for psoriasis. Kidney biopsy confirmed LN in both patients. A single-center cohort study revealed a significantly higher incidence of lupus among psoriasis patients using IL-17 inhibitors compared to non-users (1.626 vs 0.085 per 1,000 person-years; relative risk, 19.10; 95% confidence intervals [CIs], 1.99-183.47). Pharmacovigilance analysis of the FAERS database indicated an elevated reporting risk of SLE-related adverse reactions associated with IL-17 inhibitors (ROR, 1.62; 95% CI, 1.35-1.95). However, a meta-analysis of MR studies showed that IL-17A (OR, 1.06; 95% CI, 0.89-1.26; P = 0.53) and IL-17 receptor A (OR, 0.98; 95% CI, 0.95-1.02; P = 0.38) were not significantly associated with a decreased risk of SLE. Limitations:The case reports and cohort study focus on Asian populations, whereas the FAERS and MR analyses use data from American and European populations. Conclusions:Use of IL-17 inhibitors might be associated with the increased risk of SLE-like side effects.

Calciphylaxis (calcific uremic arteriolopathy, CUA) is a rare, fatal disorder primarily affecting chronic kidney disease patients, characterized by microvascular calcification, thrombosis, and skin necrosis. In a discovery cohort (3 CUA, 10 uremic), plasma proteomics identified Thrombospondin-1 (THBS1) as the top upregulated hub in CUA, significantly reduced after human amnion-derived mesenchymal stem cell (hAMSC) therapy, alongside latent TGF-β binding protein 1, both linked to coagulation and wound healing. In vitro proteomics indicated that THBS1/TGF-β1 blockade impaired CUA serum-induced endothelial adhesion and coagulation. ELISA in combined discovery and validation cohorts (8 CUA, 20 uremic) confirmed this reduction post-treatment (6 patients), independent of systemic inflammation. Multiplex immunofluorescence revealed THBS1 and CD47 co-localized with CD31 and integrin β3 in injured microvessels. A human microvascular chip showed that THBS1 inhibition or hAMSC-conditioned medium alleviates injury. These findings implicate THBS1 as a key factor and potential biomarker in calciphylaxis, suggesting hAMSC therapy as a promising mechanism-based approach. Video Abstract:

Patients undergoing maintenance hemodialysis (HD) face a substantially elevated risk of all-cause mortality, yet robust tools for individualized risk stratification remain limited. This multicenter study developed a predictive model integrating dynamic autonomic nervous system (ANS) markers - heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) - with clinical factors to assess mortality risk. We enrolled 198 HD patients from two Chinese centers between 2021 and 2023, recording HRV/SKNA parameters at baseline, 30 min, and 240 min into dialysis. Over a median follow-up of 34 months, the all-cause mortality rate was 17.7%. Ninety-one baseline features were included in the LASSO-regression model. The final multivariable logistic regression model incorporated six variables (diabetes mellitus, DBP2h, RMSSD240, ΔNnmean30, ΔApEn30 and ΔaSKNA240) into the nomogram. The AUC of the nomogram for predicting one-year, two-year, and three-year survival rates was 0.764, 0.749, and 0.805, respectively. The Kaplan-Meier curves for overall survival stratified by nomogram model showed a significant difference between high- and low- risk groups. Internal validation via bootstrap resampling confirmed model robustness, with optimism-corrected AUCs of 0.758, 0.736, and 0.788 for one-, two-, and three-year mortality, respectively. The model demonstrated superior predictive accuracy for cardiovascular mortality (C-index = 0.881) and consistent performance across age and sex subgroups. The proposed model has the potential to predict all-cause mortality in HD patients and may enable earlier intervention and personalized management.

Although tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for chronic myeloid leukemia (CML), their renal safety profiles need investigation. Herein, we report a case of flumatinib-associated acute kidney injury (AKI). We also conducted a disproportionality analysis to evaluate TKI-related renal risks using pharmacovigilance data. This report described the case of a patient with CML who developed AKI during flumatinib treatment. A meta-analysis was subsequently performed to assess the incidence of flumatinib-associated renal adverse events. Adverse event reports for TKIs (imatinib, dasatinib, nilotinib, flumatinib, radotinib, bosutinib, and ponatinib) from 2004 to 2024 were retrieved from the FDA Adverse Event Reporting System (FAERS). Reporting odds ratios (RORs) with corresponding 95

Intraoperative guidance plays a pivotal role in enhancing surgical success rates and optimizing patients' prognosis. However, during surgery, the lack of reliable monitoring methods remains a critical challenge. Therefore, we developed an autoencoder-support-vector-machine (SVM)-assisted label-free differential surface-enhanced Raman spectroscopy (dSERS) platform for rapidly intraoperatively assessing parathyroidectomy outcomes. Using only 2 μL of untreated plasma, this platform enables real-time differentiation between complete and partial parathyroid gland resection within 16 min. By leveraging differential spectral analysis (postoperative vs preoperative spectra), our approach effectively minimized individual variability while amplifying surgery-induced molecular changes. The SVM classifier achieved exceptional diagnostic performance, with 95.8% and 79% accuracies in an internal test set and an independent validation cohort (n = 144 and 33 spectra), respectively, suggesting that because of its microliter-scale sample requirements and rapid turnaround time, the label-free dSERS-artificial intelligence platform should become a transformative tool for guiding precision endocrine surgery.

Introduction:This study assessed the safety and efficacy of B cell- and anti-PLA2R antibody-targeted low-dose rituximab therapy in patients with idiopathic membranous nephropathy (IMN). Methods:This was a multicenter, investigator-initiated, open-label, prospective cohort study. Patients were recruited from 10 hospitals in the east coastal region of China between November 1st, 2019 and June 15th, 2023. Enrolled patients were assigned to individualized rituximab therapy (guided by peripheral B cells and anti-PLA2R antibody levels) or standard rituximab therapy (1,000 mg × 2 or 375 mg/m² × 3-4): the individualized group (n = 78) and the standard group (n = 62). Odds ratios (ORs) and 95% confidence intervals (CIs) for response were estimated using multivariate logistic regression models, adjusting for key confounders, with inverse probability of treatment weighting (IPTW) applied to balance demographic and clinical characteristics. The primary outcome was a composite of complete or partial remission of proteinuria. Results:A total of 140 patients were included in the sta tistical analysis, which was completed on June 10th, 2024. After IPTW, baseline characteristics were well balanced between the two groups. Patients were followed every 2 months for 1 year after the first rituximab injection. At 12 months, 57 of 78 patients (73.1%) in the individualized therapy group and 40 of 62 patients (64.5%) in the standard therapy group achieved complete or partial remission [the adjusted risk difference and 95% CI were 0.1 (-0.05 to 0.26); p = 0.001 for noninferiority]. In the weighted cohort, 74.1% in the individualized group and 70.5% in the standard group achieved remission (p = 0.5). The median (interquartile range) total rituximab dose per patient at 1 year was 800 mg (600-1,100 mg), with a total cost of RMB 16,227.5 (13,148-23,536) per unit utility in the individualized group, which was markedly lower than in the standard group. Anti-PLA2R autoantibody negativity at 6 months post-treatment predicted a higher probability of remission. The frequency of adverse events differed significantly between groups (6.4% vs. 12.9%, P = 0.02). Discussion:B cell- and anti-PLA2R antibody-targeted rituximab therapy may be a cost-effective and safe alternative for patients with IMN. Randomized controlled trials with larger samples are needed to confirm these findings. Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=42793, identifier ChiCTR1900026382.

ObjectiveTo explore the clinical and prognostic characteristics of chronic kidney disease （CKD） patients with Pneumocystis jirovecii pneumonia （PJP）， thus facilitating the diagnosis and treatment of Pneumocystis jirovecii infections.MethodsWe retrospectively analyzed the clinical date of 22 CKD patients with PJP who were hospitalized in the First Affiliated Hospital with Nanjing Medical University and diagnosed by metagenomic next-generation sequencing （mNGS） from October 1， 2019 to October 31， 2023. Based on the prognosis， CKD patients with PJP were divided into the cured group （n=14） and death group （n=8）. The clinical characteristics， laboratory examination indicators， and disease treatment situations of the two groups of patients were compared.ResultsA total of 22 CKD patients were diagnosed with PJP， including 6 males （27.3%） and 16 females （72.7%）. The mean age was （57.1 ± 16.3） years. The primary underlying diseases were membranous nephropathy， immunoglobulin A nephropathy （IgAN）， lupus nephritis，antineutrophil cytoplasmic antibody （ANCA）-associated glomerulonephritis. The median time of PJP was 3 （2， 108） months after the diagnosis of nephropathy. Totally 16 （72.7%） patients developed type Ⅰ respiratory failure. All patients had a history of glucocorticoids or immunosuppressants use 3 months prior to PJP. CT findings included mixed ground-glass opacities type and nodular type （81.8%）. Lactate dehydrogenase （LDH） was elevated in all patients. The 1，3-β-glucan test was positive in 18 patients （81.8%）. Lymphocyte count was low in 16 patients （72.7%）. The cluster of differentiation 4 receptors （CD4） cell count averaged at 292.3 cells/μL， and 60.0% of the patients had CD4 cell count<200 cells/μL. The mean serum creatinine on admission was （232.0 ± 216.6）μmol/L， among which 15 patients （68.2%） developed acute kidney injury and 12 patients （54.5%） required dialysis. All patients received anti-PJP therapy and 16 patients （72.7%） adjusted their medication based on mNGS results. The mean dose of compound sulfamethoxazole was （11.0 ± 5.8）mg·kg-1·d-1 （base on trimethoprim）. Totally 10 patients （45.5%） required mechanical ventilation. Compared with the cured group， the death group had higher oral glucocorticoid dose ［（28.6 ± 12.2）mg vs （18.1 ± 8.8）mg，P=0.039］， more patients required dialysis （7 cases vs 5 cases， P=0.031）， and more patients required mechanical ventilation （7 cases vs 3 cases， P=0.006）.ConclusionClinical symptoms， radiological findings， and laboratory testing should be combined to identify PJP in patients with CKD. The mNGS method is useful for etiological diagnosis of PJP and so facilitate the treatment of PJP. Long-term high-dose oral glucocorticoids， dialysis and mechanical ventilation may be risk factors for poor prognosis in PJP patients.

Background:Membranous nephropathy (MN) is a frequent cause of nephrotic syndrome in adults with variable response to rituximab (RTX) therapy. While traditional markers like proteinuria and anti-phospholipase A2 receptor (PLA2R) antibodies exhibit predictive value, their limitations necessitate more robust biomarkers. Methods:We prospectively analysed 149 MN patients receiving RTX over 12 months. Inflammatory indices such as neutrophil:lymphocyte ratio (NLR), monocyte:lymphocyte ratio (MLR) and systemic inflammation response index (SIRI) together with B cell levels were measured alongside conventional markers at baseline, 3 months and 6 months. Predictive models for 6- and 12-month remission (complete/partial) were developed using multivariate regression and receiver operating characteristics (ROC) analysis. Results:Non-responders exhibited persistently elevated inflammatory markers (NLR, MLR, SIRI) throughout the entire observation period. Among the three, only SIRI can independently predict the remission of MN. At 3 months, SIRI ≤1.25 {odds ratio [OR] 3.68 [95% confidence interval (CI) 1.39-9.72]} and B cell proportion ≤0.2% [OR 2.90 (95% CI 1.00-8.35)] independently predicted 6-month response. Incorporating these two newly added indicators into the traditional variable model, which includes the levels of proteinuria, albumin and anti-PLA2R antibody at 3 months, markedly enhances prediction accuracy [area under the curve (AUC) 0.86 versus 0.81]. By 6 months, only SIRI ≤0.9 [OR 4.84 (95% CI 1.43-16.40)] and albumin change [OR 1.11 (95% CI 1.03-1.19)] predicted 12-month prognosis, as B cell and anti-PLA2R antibody levels lost significance. The prediction model incorporating SIRI also had better performance (AUC 0.82 versus 0.79). Conclusions:B lymphocyte levels constitute a robust predictive biomarker for assessing short-term therapeutic response in patients with MN receiving RTX therapy. Furthermore, SIRI emerges as a valuable prognostic indicator capable of predicting both short-term efficacy and long-term renal outcomes. These findings suggest that concurrent monitoring of B lymphocyte levels and SIRI values warrants integration into standardized monitoring frameworks within clinical management protocols.

BACKGROUND:Calciphylaxis, also termed calcific uremic arteriolopathy (CUA) in patients with end-stage kidney disease (ESKD), is a rare and fatal condition characterized by cutaneous ischemic necrosis. METHODS:Three patients with calciphylaxis and metastatic pulmonary calcification (MPC) were treated with human amnion-derived mesenchymal stem cells (hAMSCs). Effects were evaluated using the Visual Analogue Scale (VAS), modified Bates-Jensen Wound Assessment Tool for CUA (BWAT-CUA), wound quality of life questionnaire (Wound-QoL), and histological analysis. MPC was assessed by high-resolution CT (HRCT) and 99ᵐTc-methylene diphosphonate (99ᵐTc-MDP) bone scans.99ᵐTc-labeled macroaggregated albumin (99ᵐTc-MAA) pulmonary perfusion imaging was conducted for the first time in patients with MPC. RESULTS:Three patients exhibited wound healing and improvement in skin symptoms. Two months before CUA, asymptomatic MPC was detected in Patient 1, who was treated with hAMSCs for 15 months. The condition progressed to chest pain and dyspnea. HRCT and 99ᵐTc-MDP bone scans showed worsening calcification, particularly in the upper and mid-thoracic lobes.99ᵐTc-MAA pulmonary perfusion imaging revealed impaired or absent blood perfusion in the areas of metastatic calcification. Patient 1 died from respiratory failure. Patients 2 and 3 had asymptomatic MPC at calciphylaxis diagnosis. After 2 months of treatment, Patient 2, showed no significant imaging improvement and passed away 6 months after discontinuing hAMSC treatment. Patient 3 has shown no significant progression of pulmonary lesions and continues hAMSC therapy. CONCLUSION:We reported personalized early, noninvasive diagnosis and regenerative treatments for calciphylaxis patients with MPC. Although the current hAMSC treatment regimen is effective for skin lesions, its impact on MPC requires further investigation.

Calciphylaxis is a rare, progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications, microthrombi, and endothelial damage. It mainly affects patients with chronic kidney disease (CKD), which is also known as calcific uremic arteriolopathy. Skin biopsy is the gold standard for diagnosis, but it is an invasive procedure. Calciphylaxis frequently results in ischemic and nonhealing ulcerations with a high mortality rate. A multidisciplinary targeted approach is the primary treatment method. Vascular calcification, which is a common complication in patients with CKD, cannot completely explain the rapid progression of calciphylaxis. This article reviews the advances in the epidemiological characteristics, risk factors, and diagnosis, including non-uremic calciphylaxis and visceral calciphylaxis, pathogenesis, associated animal models, and treatment of calciphylaxis. The scarcity of animal models that mimic the clinical presentation of calciphylaxis hampers the understanding of its pathogenesis. The acute effects on progressive vascular injury, including the induction of severe ischemia and inflammatory responses, have been emphasized. Actively listening to the voices of patients and their families and building a multidimensional research system with artificial intelligence technologies based on the specific molecular makeup of calciphylaxis patients will help tailor regenerative treatment strategies. Mesenchymal stem cells (MSCs) may represent a novel therapy for calciphylaxis because of their regenerative effects, inhibition of vascular calcification, anti-infection and immunomodulation properties, and improvement of hypercoagulability. Safe, effective, accessible, and economical MSC strategies guided by biomarkers deserve consideration for the treatment of this devastating disease.

BackgroundVitamin D (VD) deficiency has been found to be common and associated with a higher risk of adverse outcomes in chronic kidney disease (CKD), according to certain studies. However, whether it is associated with the progression of IgA nephropathy (IgAN) and the efficacy of supplementation remains a topic of debate.MethodsA total of 866 patients with IgAN were included. Identification of the baseline and time-weighted average (TWA) serum 25-hydroxyvitamin D (25(OH)D) levels associated with the major adverse kidney events (MAKE) was performed using Kaplan–Meier survival analysis, receiver operating characteristic (ROC) curves, and multivariate logistic regression analysis. Furthermore, the dataset was divided into derivation and validation cohorts using a 6:4 ratio. Internal validation was performed to assess the added value of TWA 25(OH)D levels to clinical variables using ROC curves, decision curve analysis, and Net Reclassification Improvement (NRI). An integrative analysis combining genomic, single-cell RNA sequencing (scRNA-seq), and molecular docking analysis was employed to elucidate the potential mechanism of VD supplementation on the progression of IgAN.ResultsDuring a median follow-up of 4.3 years (interquartile range (IQR): 3.3–5.9 years), a total of 92 (10.6%) patients experienced MAKE. Cumulative renal outcomes were significantly higher in patients with lower baseline and TWA 25(OH)D levels. The multivariate Cox regression analyses indicated that TWA 25(OH)D level was an independent determinant for MAKE in IgAN after adjusting for important confounders. Moreover, it showed reliable predictive performance in risk stratification of MAKE, with the optimal predictive cut-off value of 44.8 nmol/L. Accordingly, a significant linear association was observed between TWA 25(OH)D and the risk of MAKE. Reclassification further confirmed the consistency of the overall findings. Furthermore, in addition to routinely used clinical parameters, the TWA 25(OH)D-based model demonstrated strong risk-prediction power, verified internally, and showed satisfactory efficacy and significant net advantages. Moreover, VD treatment may improve prognosis by regulating the processes of cell chemotaxis, inflammatory response, and defense response through targeting the expressions OF NFKB1 and NR4A1 in proximal tubule cells in IgAN.ConclusionOur findings provide a more comprehensive insight into VD in IgAN and strengthen the efficacy of VD supplementation in IgAN. The long-term maintenance of optimal VD levels from early in life might be associated with reduced future risk of kidney progression in IgAN.

The Agatston coronary artery calcification score (CACS) is utilized as an index to assess coronary artery calcification (CAC). The objective of this study was to investigate the characteristics of CACS in patients with end-stage kidney disease (ESKD) and establish a predictive model to evaluate the risk of severe CAC in these patients.

Objective To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA). Methods We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival. Results A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) μmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 μmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group. Conclusions DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival.

Background: Calciphylaxis, which mostly affects individuals with end stage kidney disease (ESKD), is also known as calcific uremic arteriolopathy (CUA). It is a rare and fatal disease that manifests with calcification and thrombosis of microvessels, ischemia, and necrosis in skin tissues(ORPHA:280062). Histopathological features of extracutaneous tissues of CUA patients undergoing human amnion derived mesenchymal stem cell (hAMSC) treatment remain unknown. Methods: A female CUA patient, treated with hAMSCs for 20 months, passed away due to stroke. Histopathological features of her extracutaneous tissues were compared with those of ESKD patients (n = 7). Raman spectroscopy was applied to identify the composition of calcifications. The distribution of hAMSCs, derived from the amnion of a male fetus, in tissues of the CUA patient was determined by detecting the Y chromosome using reverse-transcription polymerase chain reaction. Results: Microvessel lesions were more prevalent in the extracutaneous tissues of the CUA patient than in those of ESKD patients, although the regenerated skin showed normal histological characteristics. The CUA patient exhibited calcifications of microvessel media, including the microvessels in the lungs, kidneys, spleen, pancreas, and uterus. Her mitral valve and kidney displayed severe calcification, identified as calcium phosphate with some calcium carbonate. hAMSCs were not detected in the tissues of the CUA patient. Conclusion: Under the treatment strategy with hAMSCs, based on the effects of skin regeneration, microvascular lesions in the extracutaneous tissues of the CUA patient were more severe than those in ESKD patients. CUA should be considered a systemic disease when identifying treatment targets. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement The National Natural Science Foundation of China (81270408, 81570666, 81730041, and 81671447), the International Society of Nephrology (ISN) Clinical Research Program (18-01-0247), Construction Program of Jiangsu Provincial Clinical Research Center Support System (BL2014084), Jiangsu Province Key Medical Personnel Project (ZDRCA2016002), CKD Anemia Research Foundation from China International Medical Foundation (Z-2017-24-2037), Outstanding Young and Middle-Aged Talents Support Program of The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), the National Key Research and Development Program of China (2017YFC1001303), the Program of Jiangsu Province Clinical Medical Center (YXZXB2016001, BL2012009), the State Key Laboratory of Reproductive Medicine Program (SKLRM-GC201803), and the Program of Jiangsu Commission of Health (H201605), Jiangsu Province Hospital (the First Affiliated Hospital with Nanjing Medical University) Clinical Capacity Enhancement Project (JSPH-MA-2023-7), Jiangsu Provincial Medical Key Discipline(Laboratory) Cultivation Unit(JSDW202206). All authors declared no competing interests. The study was supported by the ISN Mentorship Program and the authors thank Professor Marcello Tonelli (University of Calgary, Canada) for his helpful comments on the draft of the manuscript. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee of the First Affiliated Hospital with Nanjing Medical University in China gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript

Introduction The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients. Methods CACS of ESKD patients was assessed using an electrocardiogram-gated coronary computed tomography (CT) scan with the Agatston scoring method. A predictive nomogram model was established based on stepwise regression. An independent validation cohort comprised of patients with ESKD from multicentres. Results 369 ESKD patients were enrolled in the training set, and 127 patients were included in the validation set. In the training set, the patients were divided into three subgroups: no calcification (CACS = 0, n = 98), mild calcification (0 < CACS ≤ 400, n = 141) and severe calcification (CACS > 400, n = 130). Among the four coronary branches, the left anterior descending branch (LAD) accounted for the highest proportion of calcification. Stepwise regression analysis showed that age, dialysis vintage, β-receptor blocker, calcium-phosphorus product (Ca × P), and alkaline phosphatase (ALP) level were independent risk factors for severe CAC. A nomogram that predicts the risk of severe CAC in ESKD patients has been internally and externally validated, demonstrating high sensitivity and specificity. Conclusion CAC is both prevalent and severe in ESKD patients. In the four branches of the coronary arteries, LAD calcification is the most common. Our validated nomogram model, based on clinical risk factors, can help predict the risk of severe coronary calcification in ESKD patients who cannot undergo coronary CT analysis.

OBJECTIVES:To explore the association of the cortico-medullary difference in apparent diffusion coefficient (ΔADC) with clinicopathological parameters of disease activity at the time of biopsy, and with the prognositic risk stratification in IgA nephropathy (IgAN) patients. METHODS:We included 112 patients with biopsy-proven IgAN who measured ΔADC. Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of the biopsy. Clinicopathological characteristics were compared according to different ΔADC levels. The effect of ΔADC on eGFR and kidney fibrosis was explored using multivariate regression and ROC analysis. An individual's 5-year risk probability of progressing to ESKD or decreasing of eGFR > 50% was calculated by the guidelines-recommended international risk-prediction tool in IgAN. The effect of ΔADC on prognostic risk stratification was assessed. Net reclassification improvement (NRI) was used to evaluate the model performance. RESULTS:The average ΔADC was 168.89 ± 85.1 x10-6 mm2/s. ΔADC levels decreased significantly with increasing chronic kidney disease (CKD) stages (p = 0.0038). Spearman correlation analysis revealed that ΔADC was positively correlated with eGFR, hemoglobin, serum albumin, while negatively correlated with levels of serum creatine (Scr), blood urea nitrogen (BUN), T score of Oxford classification and Lee grades (p < 0.05). Moreover, we showed that ΔADC was independently associated with eGFR (β = 0.04, 95% CI = [0.003, 0.077], p = 0.033) demonstrated by a backward stepwise multivariate linear regression analysis. Besides, ΔADC, a combination of ΔADC and eGFR showed an AUC of 0.776 (60% sensitivity and 85.3% specificity) and an AUC of 0.875 (100% sensitivity and 69.6% specificity) respectively for evaluating kidney interstitial fibrosis (IF) severity. Furthermore, ΔADC showed an AUC of 0.792 (95% CI 0.677-0.906) for differentiating higher progression risk categories from lower categories (specificity = 91.6%, sensitivity = 58.8%). The low-ΔADC group (≤ median value 167.1 × 10-6 mm2/s) was associated with 7.509-fold higher likelihood of higher progression risk compared to the high-ΔADC group (>167.1 × 10-6 mm2/s) in a fully-adjusted model. And reclassification analyses confirmed that the final adjusted model improved NRI. CONCLUSIONS:ΔADC was significantly associated with kidney function and enabled a reliable evaluation of kidney IF severity in IgAN patients. Low ΔADC can predict a high 5-year kidney progression risk in IgAN, independent of important clinical factors. Moreover, the predictive ability to identify patients at high risk of severe kidney fibrosis and adverse progression estimates with satisfactory accuracy, facilitating ΔADC a promising and noninvasive tool in complementarily evaluating disease activity and the prognostic risk stratification in patients with IgAN.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is an orphan disease without proven therapies, we rescued it with human amnion-derived mesenchymal stem cells (hAMSCs). In a discovery cohort of 10 uremic patients and 3 CUA patients, plasma proteomic analysis showed core differentially expressed proteins (DEPs) Thrombospondin 1 (THBS1) and Latent transforming growth factor (TGF)-β binding protein 1 (LTBP1) decreased significantly after 3 days of hAMSC treatment. Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMCs) indicated megakaryocytes were the source of THBS1 in CUA patient. Same as the discovery cohort, plasma THBS1 and TGF-β1 levels were increased in seven CUA patients compared to the uremic group (n=20), as measured by enzyme-linked immunosorbent assay (ELISA) in the validation cohort. They can be inhibited after hAMSC treatment and increased as the frequency of therapy decreased. THBS1 and its receptor, CD47, were increased in the CUA skin. THBS1 and TGF-β1 are biomarker candidates for calciphylaxis.

BackgroundHigh sodium intake and fluid overhydration are common factors of and strongly associated with adverse outcomes in chronic kidney disease (CKD) patients. Yet, their effects on cardiac dysfunction remain unclear.AimsThe study aimed to explore the impact of salt and volume overload on cardiac alterations in non-dialysis CKD.MethodsIn all, 409 patients with CKD stages 1–4 (G1–G4) were enrolled. Daily salt intake (DSI) was estimated by 24-h urinary sodium excretion. Volume status was evaluated by the ratio of extracellular water (ECW) to total body water (TBW) measured by body composition monitor. Recruited patients were categorized into four groups according to DSI (6 g/day) and median ECW/TBW (0.439). Echocardiographic and body composition parameters and clinical indicators were compared. Associations between echocardiographic findings and basic characteristics were performed by Spearman’s correlations. Univariate and multivariate binary logistic regression analysis were used to determine the associations between DSI and ECW/TBW in the study groups and the incidence of left ventricular hypertrophy (LVH) and elevated left ventricular filling pressure (ELVFP). In addition, the subgroup effects of DSI and ECW/TBW on cardiac abnormalities were estimated using Cox regression.ResultsOf the enrolled patients with CKD, the median urinary protein was 0.94 (0.28–3.14) g/d and estimated glomerular filtration rate (eGFR) was 92.05 (IQR: 64.52–110.99) mL/min/1.73 m2. The distributions of CKD stages G1–G4 in the four groups was significantly different (p = 0.020). Furthermore, compared to group 1 (low DSI and low ECW/TBW), group 4 (high DSI and high ECW/TBW) showed a 2.396-fold (95%CI: 1.171–4.902; p = 0.017) excess risk of LVH and/or ELVFP incidence after adjusting for important CKD and cardiovascular disease risk factors. Moreover, combined with eGFR, DSI and ECW/TBW could identify patients with higher cardiac dysfunction risk estimates with an AUC of 0.704 (sensitivity: 75.2%, specificity: 61.0%). The specificity increased to 85.7% in those with nephrotic proteinuria (AUC = 0.713). The magnitude of these associations was consistent across subgroups analyses.ConclusionThe combination of high DSI (>6 g/d) and high ECW/TBW (>0.439) independently predicted a greater risk of LVH or ELVFP incidence in non-dialysis CKD patients. Moreover, the inclusion of eGFR and proteinuria improved the risk stratification ability of DSI and ECW/TBW in cardiac impairments in CKD.