Proteomic profiling of laser capture microdissection kidneys from diabetic nephropathy patients.

Diabetic nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN. 5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Significantly, the expression of multiple heat shock proteins (HSPs), tubulins, and heterogeneous nuclear ribonucleoproteins (hnRNPs) in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the protein-protein interaction (PPI) analysis of DEPs in both glomeruli and renal tubules. In this study, we delve into the unique proteomic characteristics of each sub-region of renal tissue. This enhances our understanding of the potential pathophysiological changes in DN, particularly the potential involvement of glycolysis metabolic disorder, glomerular cytoskeleton and cell junctions. These insights are crucial for further research into the identification of disease biomarkers and the pathogenesis of DN.

Risk factors and clinical prediction models for osteoporosis in pre-dialysis chronic kidney disease patients.

BACKGROUND: Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied. OBJECTIVE: To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis. METHODS: Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models. RESULTS: In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage. CONCLUSION: Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.

Relationship of serum total cholesterol and triglyceride with risk of mortality in maintenance hemodialysis patients: a multicenter prospective cohort study.

OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.

Blood urea nitrogen to serum albumin ratio as a new prognostic indicator in type 2 diabetes mellitus patients with chronic kidney disease.

Chronic kidney disease (CKD) is often a common comorbidity in critically ill patients with type 2 diabetes mellitus (T2DM). This study explored the relationship between blood urea nitrogen to serum albumin ratio (BAR) and mortality in T2DM patients with CKD in intensive care unit (ICU). Patients were recruited from the Medical Information Mart database, retrospectively. The primary and secondary outcomes were 90-day mortality, the length of ICU stay, hospital mortality and 30-day mortality, respectively. Cox regression model and Kaplan-Meier survival curve were performed to explore the association between BAR and 90-day mortality. Subgroup analyses were performed to determine the consistency of this association. A total of 1920 patients were enrolled and divided into the three groups (BAR < 9.2, 9.2 ≤ BAR ≤ 21.3 and BAR > 21.3). The length of ICU stay, 30-day mortality, and 90-day mortality in the BAR > 21.3 group were significantly higher than other groups. In Cox regression analysis showed that high BAR level was significantly associated with increased greater risk of 90-day mortality. The adjusted HR (95%CIs) for the model 1, model 2, and model 3 were 1.768 (1.409-2.218), 1.934, (1.489-2.511), and 1.864, (1.399-2.487), respectively. Subgroup analysis also showed the consistency of results. The Kaplan-Meier survival curve analysis revealed similar results as well that BAR > 21.3 had lower 90-day survival rate. High BAR was significantly associated with increased risk of 90-day mortality. BAR could be a simple and useful prognostic tool in T2DM patients with CKD in ICU.

Establishment and evaluation of a nomogram prediction model for the risk of vascular calcification in stage 5 chronic kidney disease patients.

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) that has a detrimental effect on patients' survival and prognosis. The aim of this study was to develop and validate a practical and reliable prediction model for VC in CKD5 patients. The medical records of 544 CKD5 patients were reviewed retrospectively. Multivariate logistic regression analysis was used to identify the independent risk factors for vascular calcification in patients with CKD5 and then created a nomogram prediction model. The area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow test, and decision curve analysis (DCA) were used to assess model performance. The patients were split into groups with normal and high serum uric acid levels, and the factors influencing these levels were investigated. Age, BUN, SUA, P and TG were independent risk factors for vascular calcification in CKD5 patients in the modeling group (P < 0.05). In the internal validation, the results of model showed that the AUC was 0.917. No significant divergence between the predicted probability of the nomogram and the actual incidence rate (x2 = 5.406, P = 0.753) was revealed by the calibration plot and HL test, thus confirming that the calibration was satisfactory. The external validation also showed good discrimination (AUC = 0.973). The calibration chart and HL test also demonstrated good consistency. Besides, the correlation analysis of serum uric acid levels in all CKD5 patients revealed that elevated uric acid levels may be related to gender, BUN, P, and TG.

Proximal tubule cells in blood and urine as potential biomarkers for kidney disease biopsy.

Early diagnosis and treatment are crucial for managing kidney disease, yet there remains a need to further explore pathological mechanisms and develop minimally invasive diagnostic methods. In this study, we employed single-cell RNA sequencing (scRNA-seq) to assess the cellular heterogeneity of kidney diseases. We analyzed gene expression profiles from renal tissue, peripheral blood mononuclear cells (PBMCs), and urine of four patients with nephritis. Our findings identified 12 distinct cell subsets in renal tissues and leukocytes. These subsets encompassed fibroblast cells, mesangial cells, epithelial cells, proximal tubule cells (PTCs), and six immune cell types: CD8+ T cells, macrophages, natural killer cells, dendritic cells, B cells, and neutrophils. Interestingly, PTCs were present in both PBMCs and urine samples but absent in healthy blood samples. Furthermore, several populations of fibroblast cells, mesangial cells, and PTCs exhibited pro-inflammatory or pro-apoptotic behaviors. Our gene expression analysis highlighted the critical role of inflammatory PTCs and fibroblasts in nephritis development and progression. These cells showed high expression of pro-inflammatory genes, which could have chemotactic and activating effect on neutrophils. This was substantiated by the widespread in these cells. Notably, the gene expression profiles of inflammatory PTCs in PBMCs, urine, and kidney tissues had high similarity. This suggests that PTCs in urine and PBMCs hold significant potential as alternative markers to invasive kidney biopsies.

Proteomic analysis of glomeruli, tubules and renal interstitium in idiopathic membranous nephropathy (IMN): A statistically observational study.

Idiopathic membranous nephropathy (IMN) is a common type of primary glomerulonephritis, which pathogenesis are highly involved protein and immune regulation. Therefore, we investigated protein expression in different microregions of the IMN kidney tissue. We used laser capture microdissection and mass spectrometry to identify the proteins in the kidney tissue. Using MSstats software to identify the differently expressed protein (DEP). Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to predict and enrich the potential functions of the DEPs, and DEPs were compared to the Public data in the gene expression omnibus (GEO) database for screening biomarkers of IMN. Immune infiltration analysis was used to analyze the immune proportion in IMN. Three significantly up-regulated proteins were identified in the glomeruli of patients with IMN; 9 significantly up-regulated and 6 significantly down-regulated proteins were identified in the interstitium of patients with IMN. Gene ontology analysis showed that the DEPs in the glomerulus and interstitium were mostly enriched in "biological regulation, the immune system, and metabolic processes." Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEPs in the glomerulus and interstitium were mostly enriched in the "immune system" and the "complement and coagulation cascades. " According to the public information of the GEO database, DEPs in our study, Coatomer subunit delta Archain 1, Laminin subunit alpha-5, and Galectin-1 were highly expressed in the IMN samples from the GEO database; in the immune infiltration analysis, the proportion of resting memory CD4 T cells and activated NK cells in IMN were significantly higher than in the normal group. This study confirmed that there were significant differences in protein expression in different micro-regions of patients with IMN, The protein Coatomer subunit delta Archain 1, Laminin subunit alpha 5, Galectin-1 are potential biomarkers of IMN, the memory T cells CD4 and NK cells, maybe involved in the immunologic mechanism in the development of IMN.

Proteomic analysis of lysine 2-hydroxyisobutyryl in SLE reveals protein modification alteration in complement and coagulation cascades and platelet activation Pathways.

BACKGROUND: Post-translational modifications (PTMs) are considered to be an important factor in the pathogenesis of Systemic lupus erythematosus (SLE). Lysine 2-hydroxyisobutyryl (Khib), as an emerging post-translational modification of proteins, is involved in some important biological metabolic activities. However, there are poor studies on its correlation with diseases, especially SLE. OBJECTIVE: We performed quantitative, comparative, and bioinformatic analysis of Khib proteins in Peripheral blood mononuclear cells (PBMCs) of SLE patients and PBMCs of healthy controls. Searching for pathways related to SLE disease progression and exploring the role of Khib in SLE. METHODS: Khib levels in SLE patients and healthy controls were compared based on liquid chromatography tandem mass spectrometry, then proteomic analysis was conducted. RESULTS: Compared with healthy controls, Khib in SLE patients was up-regulated at 865 sites of 416 proteins and down-regulated at 630 sites of 349 proteins. The site abundance, distribution and function of Khib protein were investigated further. Bioinformatics analysis showed that Complement and coagulation cascades and Platelet activation in immune-related pathways were significantly enriched, suggesting that differentially modified proteins among them may affect SLE. CONCLUSION: Khib in PBMCs of SLE patients was significantly up- or down-regulated compared with healthy controls. Khib modification of key proteins in the Complement and coagulation cascades and Platelet activation pathways affects platelet activation and aggregation, coagulation functions in SLE patients. This result provides a new direction for the possible significance of Khib in the pathogenesis of SLE patients.

The impact of statin use before intensive care unit admission on patients with acute kidney injury after cardiac surgery.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery. The influence of statin use before surgery on the renal outcome of patients undergoing cardiac surgery is controversial. The purpose of this study was to evaluate the effect of statins on postoperative renal outcomes in patients undergoing cardiac surgery. Methods: We included CSA-AKI patients in the Medical Information Mart for Intensive Care (MIMIC)-IV database and were divided into statin group and non-statin group according to whether they used statins before entering intensive care units (ICU). The main outcomes were hospitalization and 30-day mortality, and the secondary outcomes were 60-day mortality and 90-day mortality. We used propensity score matching (PSM) to adjust for confounding factors. The 95% confidence interval (CI) and risk ratio (RO) were calculated by the COX proportional regression model. At the same time, stratified analysis was used to explore whether the relationship between the statins use before intensive care units and mortality was different in each subgroup and whether the relationship between different doses of Atorvastatin and mortality was different. Result: We identified 675 pre-ICU statin users and 2095 non-statin users. In the COX proportional regression model, pre-ICU statin use was associated with decreased in-hospital (HR = 0.407, 95%confidence interval 0.278-0.595, p < 0.001) and 30-day mortality (HR = 0.407, 95%CI 0.279-0.595, p < 0.001). The survival rate of patients who took statins before entering ICU was significantly higher than that of those who did not use statins at 30 days, 60 days and 90 days. There is a significant interaction between patients with aged>65 years (HR = 0.373, 95%CI 0.240-0.581, p < 0.001), Acute kidney injury grade I (HR = 0.244, 95%CI 0.118-0.428, p < 0.001), and without post-myocardial infarction syndrome (HR = 0.344, 95%CI 0.218-0.542, p < 0.001). The mortality in hospital and 60 days of CSA-AKI patients treated with ≥80 mg Atorvastatin before operation was significantly reduced (p < 0.05). Conclusion: The pre-ICU statin use was significantly associated with decreased risk in hospital and 30-day mortality. The preoperative use of ≥80 mg Atorvastatin may improve the prognosis of CSA-AKI.

Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma.

PURPOSE: Oral adenoid cystic carcinoma (OACC) has high rates of both local-regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. EXPERIMENTAL DESIGN: We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC-MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein-protein interaction networks) to illustrate how Khib modification interfere with OACC evolution. RESULTS: Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression. CONCLUSIONS AND CLINICAL RELEVANCE: Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

Corrigendum to "The novel putative methyltransferase METTL7A as one prognostic biomarker potentially associated with immune infiltration in human renal cancer".

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15371.].

Aspirin reduces the mortality risk of sepsis-associated acute kidney injury: an observational study using the MIMIC IV database.

Introduction: Sepsis-associated acute kidney injury (SA-AKI) is a complication of sepsis and is characterized by high mortality. Aspirin affects cyclooxygenases which play a significant role in inflammation, hemostasis, and immunological regulation. Sepsis is an uncontrolled inflammatory and procoagulant response to a pathogen, but aspirin can inhibit platelet function to attenuate the inflammatory response, thus improving outcomes. Several studies have generated contradictory evidence regarding the effect of aspirin on patients with sepsis-associated acute kidney injury (SA-AKI). We conducted an analysis of the MIMIC IV database to investigate the correlation between aspirin utilization and the outcomes of patients with SA-AKI, as well as to determine the most effective dosage for aspirin therapy. Materials and methods: SA-AKI patients' clinical data were extracted from MIMIC-IV2.1. Propensity score matching was applied to balance the baseline characteristics between the aspirin group and the non-user group. Subsequently, the relationship between aspirin and patient death was analyzed by Kaplan-Meier method and Cox proportional hazard regression models. Results: 12,091 patients with SA-AKI were extracted from the MIMIC IV database. In the propensity score-matched sample of 7,694 individuals, lower 90-day mortality risks were observed in the aspirin group compared to the non-users group (adjusted HR: 0.722; 95%CI: 0.666, 0.783) by multivariable cox proportional hazards analysis. In addition, the Kaplan-Meier survival curves indicated a superior 90-day survival rate for aspirin users compared to non-users (the log-rank test p-value was 0.001). And the median survival time of patients receiving aspirin treatment was significantly longer than those not receiving (46.47 days vs. 24.26 days). In the aspirin group, the average ICU stay length was shorter than non-users group. (5.19 days vs. 5.58 days, p = 0.006). There was no significant association between aspirin and an increased risk of gastrointestinal hemorrhage (p = 0.144). Conclusion: Aspirin might reduce the average ICU stay duration and the 30-day or 90-day mortality risks of SA-AKI patients. No statistically significant difference in the risk of gastrointestinal hemorrhage was found between the aspirin group and the control group.

Prognostic value of monocyte-to-lymphocyte ratio for 90-day all-cause mortality in type 2 diabetes mellitus patients with chronic kidney disease.

The role of inflammation and the correlation between inflammatory markers and type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) have been studied. In clinical work, a large number of T2DM patients complicated with CKD, but the cause of CKD was not clear. Our study aimed to evaluate the relationship between monocyte-to-lymphocyte ratio (MLR) and mortality in T2DM patients with CKD. The data from Medical Information Mart for Intensive Care III was analyzed. The primary outcome was 90-day all-cause mortality; the secondary outcomes were the length of ICU stay, hospital mortality and 30-day all-cause mortality. Cox regression was used to evaluate the association between MLR and 90-day mortality. We performed subgroup analyses to determine the consistency of this association, and used Kaplan-Meier survival curve to analysis the survival of different levels of MLR. A total of 1830 patients were included in study retrospectively. The length of ICU stay, 30-day all-cause mortality, and 90-day all-cause mortality in the MLR > 0.71 group were significantly higher than those in the MLR < 0.28 and 0.28 ≤ MLR ≤ 0.71 group. In Cox regression analysis, high MLR level was significantly associated with increased greater risk of 90-day all-cause mortality. The adjusted HR (95%CIs) for the model 1, model 2, and model 3 were 2.429 (1.905-3.098), 2.070 (1.619-2.647), and 1.898 (1.478-2.437), respectively. Subgroup analyses also showed the consistency of association between MLR and 90-day all-cause mortality. The Kaplan-Meier survival curve analysis revealed that MLR > 0.71 had worst prognosis. In T2DM patients with CKD in the intensive care unit, high MLR was significantly associated with increased risk 90-day all-cause mortality.

Urinary microbiota and serum metabolite analysis in patients with diabetic kidney disease.

Background: Diabetic kidney disease (DKD) is a common and potentially fatal consequence of diabetes. Chronic renal failure or end-stage renal disease may result over time. Numerous studies have demonstrated the function of the microbiota in health and disease. The use of advanced urine culture techniques revealed the presence of resident microbiota in the urinary tract, undermining the idea of urine sterility. Studies have demonstrated that the urine microbiota is related with urological illnesses; nevertheless, the fundamental mechanisms by which the urinary microbiota influences the incidence and progression of DKD remain unclear. The purpose of this research was to describe key characteristics of the patients with DKD urinary microbiota in order to facilitate the development of diagnostic and therapeutic for DKD. Methods: We evaluated the structure and composition of the microbiota extracted from urine samples taken from DKD patients (n = 19) and matched healthy controls (n = 15) using 16S rRNA gene sequencing. Meanwhile, serum metabolite profiles were compared using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Associations between clinical characteristics, urine microbiota, and serum metabolites were also examined. Finally, the interaction between urine microbiota and serum metabolites was clarified based on differential metabolite abundance analysis. Results: The findings indicated that the DKD had a distinct urinary microbiota from the healthy controls (HC). Taxonomic investigations indicated that the DKD microbiome had less alpha diversity than a control group. Proteobacteria and Acidobacteria phyla increased in the DKD, while Firmicutes and Bacteroidetes decreased significantly (P < 0.05). Acidobacteria was the most prevalent microbiota in the DKD, as determined by the Linear discriminant analysis Effect Size (LEfSe) plot. Changes in the urinary microbiota of DKD also had an effect on the makeup of metabolites. Short-chain fatty acids (SCFAs) and protein-bound uremic toxins (PBUTs) were shown to be specific. Then we discovered that arginine and proline metabolism was the primary mechanism involved in the regulation of diabetic kidney disease. Conclusions: This study placed the urinary microbiota and serum metabolite of DKD patients into a functional framework and identified the most abundant microbiota in DKD (Proteobacteria and Acidobacteria). Arginine metabolites may have a major effect on DKD patients, which correlated with the progression of DKD.

The novel putative methyltransferase METTL7A as one prognostic biomarker potentially associated with immune infiltration in human renal cancer.

Among urological cancers, renal cancer has the highest fatality rate. In a previous pan-cancer study of the METTL family, we observed a stronger association between the METTL family members and the risk of renal cancer compared to other cancers. Among these members, METTL7A, a potential methyltransferase, was identified as a protective factor, although its role and mechanism in renal cancer remain unclear. In this study, we utilized public databases to examine the expression of METTL7A in renal cancer tissues and normal tissues and found that METTL7A expression was much lower in renal cancer tissues. We also noticed a link between low METTL7A expression and poor prognosis for patients. According to the results of our functional enrichment analysis, METTL7A may have a role in immunological functions in renal cancer. METTL7A expression was strongly linked with the degrees of immune cell infiltration and expression of numerous immunological components. METTL7A had significantly different effects on the survival times of renal cancer patients with high or low immune infiltration. Our findings suggest that METTL7A may be used as both a prognostic biomarker and an immunological target for kidney cancer. In conclusion, our study sheds light on the importance of METTL7A in renal cancer and emphasizes the potential of targeting METTL7A as a novel therapeutic strategy for kidney cancer.

Correlation of Serum FGF23 and Chronic Kidney Disease-Mineral and Bone Abnormality Markers With Cardiac Structure Changes in Maintenance Hemodialysis Patients.

Background: CKD-MBD is a mineral and bone metabolism syndrome caused by chronic kidney disease. FGF23 is an important factor regulating phosphorus and is the main influencer in the CKD-MBD process. In this study, we observed the correlation among serum FGF23 and calcium, phosphorus and parathyroid hormone, and the correlation between FGF23 levels and cardiac structural changes in MHD patients. Methods: We examined serum FGF23 concentrations in 107 cases of MHD patients using the ELISA method, recorded demographic information and biochemical data, and analyzed the correlation between serum FGF23 levels and blood calcium and blood phosphorus and PTH levels. All patients were evaluated by cardiac color ultrasound, and we finally analyzed the association between the FGF23 level and cardiac structural changes. Results: In 107 cases of MHD patients, serum FGF23 levels were linearly associated with serum calcium (r = 0.27 P < 0.01) and parathyroid hormone levels (r = 0.25, P < 0.05). FGF 23 was negatively correlated with age (r = -0.44, P < 0.01).Serum FGF23 levels were correlated with right atrial hypertrophy in HD patients (P < 0.05). No correlation was found among FGF23, left ventricular hypertrophy/enlargement, and valve calcification stenosis (P > 0.05). Conclusion: Serum FGF23 showed a positive correlation among blood calcium levels and PTH levels in hemodialysis patients, and FGF23 levels can affect the incidence of right atrial hypertrophy in MHD patients.

Global-feature of autoimmune glomerulonephritis using proteomic analysis of laser capture microdissected glomeruli.

Background: IgA nephropathy (IgAN), (LN), membranous nephropathy (MN), and minimal change nephropathy (MCN) are all belonged to autoimmune glomerulonephritis. This study aimed to identify the specific proteomic characteristics of the four GNs diseases in order to provide frameworks for developing the appropriate drug for patients diagnosed with GNs disease. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to investigate proteomic features of glomerular tissues obtained by laser capture microdissection (LCM). 8 normal control cases, 11 IgAN cases, 19 LN cases, 5 MN cases, and 3 MCN cases in this study were selected for bioinformatics analyses. Results: The shared overlapping proteins among the top 100 DEPs of each GNs type were mostly downregulated, in which only FLII was significantly downregulated in the four GNs diseases. A2M was significantly upregulated in MN, IgAN, and LN subgroups. The pathway of complement and coagulation cascades was notably activated with NES value ranging 2.77 to 3.39 among MCN, MN, IgAN, and LN diseases, but the pattern of protein expression level were significantly different. In LN patients, the increased activity of complement and coagulation cascades was contributed by the high expression of multiple complements (C1QB, C3, C4A, C4B, C6, C8B, C8G, C9). Meanwhile, both C1QC and C4B were remarkably upregulated in MN patients. On the contrary, complement-regulating proteins (CD59) was substantially decreased in MCN and IgAN subgroup. Conclusions: The integrative proteomics analysis of the four GNs diseases provide insights into unique characteristics of GNs diseases and further serve as frameworks for precision medicine diagnosis and provide novel targets for drug development.

Serum metabolomics analysis reveals metabolite profile and key biomarkers of idiopathic membranous nephropathy.

Background: Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease with multiple and complex pathogenic mechanisms. Currently, renal biopsy is considered the gold standard for diagnosing membranous nephropathy. However, there were limitations to the renal puncture biopsy, such as the relatively high cost, longer time consuming, and the risk of invasive procedures. We investigated the profile of serum metabolites in IMN patients based on the UHPLC-QE-MS metabolomics technique for exploring the potential disease biomarkers and clinical implementation. Methods: In our research, we collected serum samples from healthy control (n = 15) and IMN patients (n = 25) to perform metabolomics analysis based on the UHPLC-QE-MS technique. Result: We identified 215 differentially expressed metabolites (DEMs) between the IMN and healthy control (HC) groups. Furthermore, these DEMs were significantly identified in histidine metabolism, arginine and proline metabolism, pyrimidine metabolism, purine metabolism, and steroid hormone biosynthesis. Several key DEMs were significantly correlated with the level of clinical parameters, such as serum albumin, IgG, UTP, and cholesterol. Among them, dehydroepiandrosterone sulfate (DHEAS) was considered the reliable diagnostic biomarker in the IMN group. There was an increased abundance of actinobacteria, phylum proteobacteria, and class gammaproteobacterial in IMN patients for host-microbiome origin analysis. Conclusion: Our study revealed the profiles of DEMs from the IMN and HC groups. The result demonstrated that there were disorders of amino acids, nucleotides, and steroids hormones metabolism in IMN patients. The down-regulation of DHEAS may be associated with the imbalance of the immune environment in IMN patients. In host-microbiome origin analysis, the gut microbiota and metabolite disturbances were present in IMN patients.

Low BMI and high waist-to-hip ratio are associated with mortality risk among hemodialysis patients: a multicenter prospective cohort study.

Background: Data are limited on the relationship between waist-to-hip ratio (WHR) and mortality risk among maintenance hemodialysis (MHD) patients. Moreover, the combined association of body mass index (BMI) and WHR with mortality remains uncertain. Therefore, we aimed to explore the individual and combined association of BMI and WHR with the all-cause and cardiovascular disease (CVD) mortality. Methods: In this multicenter prospective cohort study, we enrolled 1034 MHD patients. The primary outcome was all-cause mortality and secondary outcome was CVD mortality. Multivariable Cox proportional hazards models were used to evaluate the individual and combined association of BMI and WHR with the risk of mortality. Results: A nonlinear inverse relationship was found between BMI and risk of all-cause mortality (P for nonlinearity <.05). Being underweight (<18.5 kg/m2) was associated with higher all-cause mortality risk (HR 1.45; 95% CI 1.08-1.94) compared with normal weight (18.5-23.9 kg/m2), while being overweight (24-27.9 kg/m2; HR 0.96; 95% CI 0.70-1.31) and obese (≥28 kg/m2; HR 1.19; 95% CI 0.62-2.26) showed no significant differences. Of note, WHR was independently and positively associated with all-cause mortality (per standard deviation increase, HR 1.13; 95% CI 1.00-1.27). When analyzed jointly, patients with low BMI (<18.5 kg/m2) and high WHR (≥0.95) had the highest risk of all-cause mortality. Similar results were obtained for CVD mortality. Conclusions: In patients undergoing hemodialysis from China, low BMI and high WHR were individually and jointly associated with higher risk of mortality. Our results emphasize that BMI and WHR may jointly affect the prognosis of MHD patients.

A nomogram for predicting the mortality of patients with type 2 diabetes mellitus complicated with acute kidney injury in the intensive care unit.

BACKGROUND: There is no predictive tool for type 2 diabetes mellitus (T2DM) patients with acute kidney injury (AKI). Our study aimed to establish an effective nomogram model for predicting mortality in T2DM patients with AKI. METHOD: Data on T2DM patients with AKI were obtained from the Medical Information Mart for Intensive Care III. 70% and 30% of the patients were randomly selected as the training and validation cohorts, respectively. Univariate and multivariate logistic regression analyses were used to identify factors associated with death in T2DM patients with AKI. Factors significantly associated with survival outcomes were used to construct a nomogram predicting 90-day mortality. The nomogram effect was evaluated by receiver operating characteristic curve analysis, Hosmer‒Lemeshow test, calibration curve, and decision curve analysis (DCA). RESULTS: There were 4375 patients in the training cohort and 1879 in the validation cohort. Multivariate logistic regression analysis showed that age, BMI, chronic heart failure, coronary artery disease, malignancy, stages of AKI, white blood cell count, blood urea nitrogen, arterial partial pressure of oxygen and partial thromboplastin time were independent predictors of patient survival. The results showed that the nomogram had a higher area under the curve value than the sequential organ failure assessment score and simplified acute physiology score II. The Hosmer‒Lemeshow test and calibration curve suggested that the nomogram had a good calibration effect. The DCA curve showed that the nomogram model had good clinical application value. CONCLUSION: The nomogram model accurately predicted 90-day mortality in T2DM patients with AKI. It may provide assistance for clinical decision-making and treatment, thereby reducing the medical burden.