Application Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells in Renal Diseases.

The high prevalence and complex etiology of renal diseases already impose a heavy disease burden on patients and society. In certain kidney diseases such as acute kidney injury and chronic kidney disease, current treatments are limited to slowing rather than stabilizing or reversing disease progression. Therefore, it is crucial to study the pathological mechanisms of kidney disease and discover new therapeutic targets and effective therapeutic drugs. As cell-free therapeutic strategies are continually being developed, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have emerged as a hot topic for research in the field of renal diseases. Studies have demonstrated that MSC-EVs not only reproduce the therapeutic effects of MSCs but also localize to damaged kidney tissue. Compared to MSCs, MSC-EVs have several advantages, including ease of preservation, low immunogenicity, an inability to directly form tumors, and ease of artificial modification. Exploring the detailed mechanisms of MSC-EVs by developing standardized culture, isolation, purification, and drug delivery strategies will help facilitate their clinical application in kidney diseases. Here, we provide a comprehensive overview of studies about MSC-EVs in kidney diseases and discuss their limitations at the human nephrology level.

Neferine mitigates cisplatin-induced acute kidney injury in mice by regulating autophagy and apoptosis.

PURPOSE: The nephrotoxicity caused by cisplatin severely limits the application and affects related platinum-based therapeutics. Neferine is a dibenzylisoquinoline alkaloid extracted from a Chinese medicinal herb (Nelumbo nucifera Gaertn), which can decrease cisplatin-induced apoptosis of NRK-52E cells by activating autophagy in vitro in our previous study. In this article, we aimed to further investigate the protective effect of neferine, against to the cispltain-induced kidney damage in mice. METHODS: Six groups were designed in our study. Renal index, mice serum creatinine and blood urea nitrogen levels were detected after the mice were killed. HE staining was used to observe the pathological changes of each group. The apoptosis of mouse kidney tissue was detected by TUNEL. Immunofluorescence and Western blot were used to detect the expression of cleaved-caspase3 and LC3. The transmission electron microscope was used to reveal the changes of apoptosis and autophagy of renal tubular epithelial cells in different groups. RESULTS: In our findings, the pathological changes of acute kidney injury were easily observed in cisplatin-treated mice while those in the neferine-pretreated groups were significantly alleviated. The apoptosis induced by cisplatin in mice increased evidently compared with the control group, which was decreased in the mice with neferine pretreatment. What' more, we found that autophagy increased obviously in mice pretreated by neferine contrast to the cisplatin-treated mice. CONCLUSION: In our study, neferine can effectively alleviate cisplatin-induced renal injury in mice, as well act as an autophagy-regulator in kidney protection.

Expression of LRG-1 in mice with hypertensive renal damage and its significance. / LRG-1åœ¨é«˜è¡€åŽ‹è‚¾æŸå®³å°é¼ ä¸­çš„è¡¨è¾¾åŠå ¶æ„ä¹‰.

OBJECTIVES: Long-term elevated blood pressure may lead to kidney damage, yet the pathogenesis of hypertensive kidney damage is still unclear. This study aims to explore the role and significance of leucine-rich alpha-2-glycoprotein-1 (LRG-1) in hypertensive renal damage through detecting the levels of LRG-1 in the serum and kidney of mice with hypertensive renal damage and its relationship with related indexes. METHODS: C57BL/6 mice were used in this study and randomly divided into a control group, an angiotensin II (Ang II) group, and an Ang II+irbesartan group. The control group was gavaged with physiological saline. The Ang II group was pumped subcutaneously at a rate of 1.5 mg/(kg·d) for 28 days to establish the hypertensive renal damage model in mice, and then gavaged with equivalent physiological saline. The Ang II+irbesartan group used the same method to establish the hypertensive renal damage model, and then was gavaged with irbesartan. Immunohistochemistry and Western blotting were used to detect the expression of LRG-1 and fibrosis-related indicators (collagen I and fibronectin) in renal tissues. ELISA was used to evaluate the level of serum LRG-1 and inflammatory cytokines in mice. The urinary protein-creatinine ratio and renal function were determined, and correlation analysis was conducted. RESULTS: Compared with the control group, the levels of serum LRG-1, the expression of LRG-1 protein, collagen I, and fibronectin in kidney in the Ang II group were increased (all P<0.01). After treating with irbesartan, renal damage of hypertensive mice was alleviated, while the levels of LRG-1 in serum and kidney were decreased, and the expression of collagen I and fibronectin was down-regulated (all P<0.01). Correlation analysis showed that the level of serum LRG-1 was positively correlated with urinary protein-creatinine ratio, blood urea nitrogen, and blood creatinine level in hypertensive kidney damage mice. Serum level of LRG-1 was also positively correlated with serum inflammatory factors including TNF-α, IL-1ß, and IL-6. CONCLUSIONS: Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage.

High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis. / 血小板/淋巴细胞比率比值升高可能预示中国MPO-ANCAç›¸å ³æ€§è¡€ç®¡ç‚Žæ‚£è€ è¿›å±•è‡³ç»ˆæœ«æœŸè‚¾ç— çš„é£Žé™©è¾ƒä½Ž.

OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7.

INTRODUCTION: Transforming growth factor-ß (TGF-ß), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. OBJECTIVE: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. METHODS: HK-2 cells were induced with 5 ng/mL TGF-ß1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-ß1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-ß1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. RESULTS: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-ß1-induced cells. CONCLUSION: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.

Antiviral treatment and prognosis in patients undergoing maintenance hemodialysis due to hepatitis C virus. / ç»´æŒæ€§è¡€æ¶²é€æžä¸™åž‹è‚ç‚Žç— æ¯’æ„ŸæŸ“æ‚£è€ çš„æŠ—ç— æ¯’æ²»ç–—åŠé¢„åŽ.

OBJECTIVES: Maintenance hemodialysis (MHD) is one of the important renal replacement therapies for patients with end-stage renal disease. Hepatitis C virus (HCV) infection is a serious global public health problem. The proportion of MHD patients complicated with HCV infection and the risk of adverse prognosis are higher than those in the general population. Active antiviral treatment and prevention of reinfection is a combined treatment by nephrology and infection physicians. It is a widely accepted preventive measure to set hemodialysis buffer area for patients in treating HCV infection, but its effectiveness and safety still need to be further explored. Thus, the aim of this study is to explore the antiviral treatment and prognosis of MHD patients with HCV infection during hemodialysis. METHODS: A retrospective analysis for renal disease patients at 10 end-stage with long-term hemodialysis in the HCV area of the Blood Purification Center of Xiangya Hospital, Central South University. After standard antiviral drug treatment, the patient reached the cure standard for HCV infection. The buffer zone was set up in the Blood Purification Center by the Department of Nephrology of Xiangya Hospital since April 2017. Patients cured of HCV infection were transferred from the HCV area to the buffer zone for continuous dialysis, accompanied by monitoring serum HCV-RNA, anti-HCV antibody levels and changes in clinical biochemical indicators following the status of reinfection. RESULTS: Ten patients with HCV infection were finally cured after antiviral treatment, and there were no significant changes in clinical biochemical indicators before and after treatment. In the followed-up period after the transfer, the patient continued to be negative for HCV-RNA and positive for anti-HCV antibody. CONCLUSIONS: Direct antiviral therapy is safe and effective in MHD patients with HCV infection. Active antiviral therapy and transferring to the buffer area for dialysis are new and effective treatment modes for HCV patients during MHD.

The epidemiology and clinical information about COVID-19.

In December 2019, pneumonia of unknown cause occurred in Wuhan, Hubei Province, China. On 7 January 2020, a novel coronavirus, named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was identified in the throat swab sample of one patient. The World Health Organization (WHO) announced the epidemic disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). Currently, COVID-19 has spread widely around the world, affecting more than seventy countries. China, with a huge burden of this disease, has taken strong measures to control the spread and improve the curative rate of COVID-19. In this review, we summarized the epidemiological characteristics, clinical features, diagnosis, treatment, and prognosis of COVID-19. A comprehensive understanding will help to control the disease.

Role of Artificial Intelligence in Kidney Disease.

Artificial intelligence (AI), as an advanced science technology, has been widely used in medical fields to promote medical development, mainly applied to early detections, disease diagnoses, and management. Owing to the huge number of patients, kidney disease remains a global health problem. Challenges remain in its diagnosis and treatment. AI could take individual conditions into account, produce suitable decisions and promise to make great strides in kidney disease management. Here, we review the current studies of AI applications in kidney disease in alerting systems, diagnostic assistance, guiding treatment and evaluating prognosis. Although the number of studies related to AI applications in kidney disease is small, the potential of AI in the management of kidney disease is well recognized by clinicians; AI will greatly enhance clinicians' capacity in their clinical practice in the future.

Development of prognostic model for patients at CKD stage 3a and 3b in South Central China using computational intelligence.

BACKGROUND: Chronic kidney disease (CKD) stage 3 was divided into two subgroups by eGFR (45 mL/ min 1.73 m2). There is difference in prevalence of CKD, racial differences, economic development, genetic, and environmental backgrounds between China and Western countries. METHODS: We used a computational intelligence model (CKD stage 3 Modeling, CSM) to distinguish CKD stage 3 with CKD stage 3a/3b by data distribution rules, pearson correlation coefficient (PCC), spearman correlation (SCC) analysis, logistic regression (LR), random forest (RF), support vector machine (SVM), and neural network (Nnet) to develop Prognostic Model for patients with CKD stage 3a/3b in South Central China. Furthermore, we used RF to discover risk factors of progression of CKD stage 3a and 3b to CKD stage 5. 1090 cases of CKD stage 3 patients in Xiangya Hospital were collected. Among them, 455 patients progressed to CKD stage 5 in a median follow-up of 4 years (IQR 4.295, 4.489). RESULTS: We found that the common risk factors for progression of CKD stage 3a/3b to CKD stage 5 included albumin, creatinine, total protein, etc. Proteinuria, direct bilirubin, hemoglobin, etc. accounted for the progression from stage CKD stage 3a to stage 5. The risk factors for CKD stage 3b progression to stage 5 included low-density lipoprotein cholesterol, diabetes, eosinophil percentage, etc. CONCLUSIONS: CSM could be used as a point-of-care test to screen patients at high risk for disease progression, might allowing individualized therapeutic management.

Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-ß1 through Notch1 signaling pathway.

Transforming growth factor-ß1 (TGF-ß1) is a crucial factor implicated in the development of renal inflammation and tubulointerstitial fibrosis (TIF). The cytokine interleukin 22 (IL-22) was previously reported to involve in the pathogenesis of chronic inflammatory diseases, however recent studies showed that IL-22 could reduced inflammatory responses and tissue damage. In the present study, we aim to investigate the role and mechanisms of IL-22 in renal tubular cells inflammation and fibrosis induced by TGF-ß1. HK-2 cells were treated with TGF-ß1 in the presence of IL-22 or the Notch pathway inhibitor dibenzazepine (DBZ) for 48 h. Collagen I (Col I), fibronectin (FN), α-smooth muscle actin (α-SMA), vimentin and E-Cadherin were detected by western blot, proinflammatory factors (TNF-α, IL-6) and chemokines (MCP-1, RANTES) were evaluated by ELISA. Jagged1, Notch1, NICD1, and Hes1 were also detected by western blot. We found TGF-ß1 increased the levels of Col I, FN, α-SMA and vimentin in HK-2 cells compared with control, and decreased E-Cadherin level, however, IL-22 restored their expressions partly. IL-22 reduced overexpression of proinflammatory factors (TNF-α, IL-6) and chemokines (MCP-1, RANTES) levels induced by TGF-ß1, along with down-regulation of Jagged1, Notch, NICD1 and Hes1. Fibrosis and inflammation in renal tubular cells induced by TGF-ß1 could be attenuated by IL-22, and the effects were similar to DBZ treatment. Collectively, our study shows that IL-22 exerts a protective role in renal fibrotic and inflammatory responses induced by TGF-ß1 in vitro, which may be through inhibiting Jagged1/Notch1 signaling pathway activation.

Clinical characteristics and prognosis in 269 patients with antineutrophil cytoplasimc antibody associated vasculitis. / 269ä¾‹æŠ—ä¸­æ€§ç²’ç»†èƒžèƒžæµ†æŠ—ä½“ç›¸å ³æ€§è¡€ç®¡ç‚Žæ‚£è€ çš„ä¸´åºŠç— ç†ç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To investigate the clinic-pathological characteristics, prognosis and its risk factors for antineutrophil cytoplasimc antibody (ANCA)-associated vasculitis (AAV). METHODS: The basic information and clinic-pathological characteristics of AAV patients, who was diagnosed from January 2010 to January 2018 in Xiangya Hospital, Central South University, were retrospectively collected. The renal survival and patient survival were regular followed up, and their clinical pathological, prognosis data and risk factors for renal were analyzed. RESULTS: Among 269 AAV patients, 225 patients (83.64%) were microscopic polyangiitis (MPA), 33 patients (12.27%) were granulomatosis with polyangiitis (GPA), and 11 patients (4.09%) were eosinophilic granulomatosis with polyangiitis (EGPA). Male-to-female ratio was almost 1∶1 for MPA (147/122), but GPA and EGPA was more frequent among man. The medium time from disease onset to diagnosis was 64.0 (32.5, 148.5) days, 65 patients (24.16%) were diagnosed within 30 days. A total of 94.67% patients had kidney involvement in MPA patients, which was significantly higher than that in patients with GPA (63.63%), but ear, nose, and throat manifestations were more frequent in GPA patients. The 1-year kidney survival rates of GPA and MPA patients in this study were 75% and 59.3%, respectively. The 1-year death rates were 16.7% and 16.9%, respectively. The multivariable logistic regression analysis revealed that the low platelet level, low globulin level, low immunoglobin G, and high serum creatinine level were independent risk factors for the 1-year renal survival rate in AAV patients. Multiple factor logistic regression analysis showed that the serum creatinine level was an independent risk factor for all-cause mortality. CONCLUSIONS: MPA is the priority in the AAV patients. The proportion of patients with advanced end-stage renal disease and mortality is still high, and the early diagnosis and treatment in time is crucial for the improvement of prognosis for AAV.

LncRNA ENST00000453774.1 contributes to oxidative stress defense dependent on autophagy mediation to reduce extracellular matrix and alleviate renal fibrosis.

Although long noncoding RNA (LncRNA) are important players in the initiation and progression of many pathological processes, the role of LncRNAENST00000453774.1 (LncRNA 74.1) in renal fibrosis still remains unclear. Lentivirus mediated LncRNA 74.1 overexpressing HK2 cells and overexpression mice models were constructed. HK2 cells induced by transforming growth factor-ß (TGF-ß) in vitro, and the mice UUO model in vivo were used to simulate renal fibrosis. The expression of LncRNA 74.1 was significantly downregulated in the TGF-ß-induced HK-2 cell fibrosis and clinical renal fibrosis specimens. LncRNA 74.1 overexpression obviously attenuated renal fibrosis in vitro and unilateral ureteral obstruction-induced renal fibrosis in vivo. LncRNA 74.1 promoted reactive oxygen species defense by activating prosurvival autophagy then decreased ECM-related proteins fibronectin and collagen I involved in renal fibrosis. We also found that Nrf2-keap1 signaling played important roles in the remission of ECM mediated by LncRNA 74.1. This study indicates that LncRNA 74.1 downregulation would contribute to renal fibrosis and its overexpression might represent a novel anti-fibrotic treatment in renal diseases.

Bile salt (glycochenodeoxycholate acid) induces cell survival and chemoresistance in hepatocellular carcinoma.

OBJECTIVE: Glycochenodeoxycholate acid (GCDA) is a toxic component in bile salts. It plays an important role in the development and progression of liver cancer. In this study, we investigated the underlying mechanism of GCDA in hepatocarcinogenesis and chemotherapy resistance. MATERIALS AND METHODS: Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clonality by Ki-67 and colony-formation assay. Apoptosis was examined by flow cytometry. Real-time polymerase chain reaction (PCR) and western blot analysis were used to measure messenger RNA and protein levels, respectively. Short hairpin RNA was used to silence signal transducer and activator of transcription 3 (Stat3) expression. RESULTS: Bile salts (GCDA) promoted the proliferation of hepatocellular carcinoma (HCC) cells (HepG2 and QGY-7703), and GCDA treatment reduced the chemosensitivity of 5-fluorouracil (5FU) in HepG2 and QGY-7703 cells. GCDA upregulated the expression of antiapoptosis proteins Mcl-1/Survivin/Bcl-2. GCDA had no discernible effect on basal protein level or subcellular localization of phosphorylated Stat3. 5FU increased the apoptosis of HepG2 cells with silenced Stat3 expression, but GCDA-induced chemoresistance was not reversed. CONCLUSIONS: GCDA-reduced HCC cell chemosensitivity may occur by upregulating antiapoptosis proteins Mcl-1/Survivin/Bcl-2. Stat3 may be a target for enhancing the chemosensitivity of hepatocellular carcinoma cells, but GCDA-induced chemoresistance is independent of Stat3.

Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

BACKGROUND: Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1-4 CKD. METHODS: Patients with stages 1-4 CKD (18-74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. RESULTS: Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52-5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. CONCLUSION: Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 ).

NLRC5: potential novel non-invasive biomarker for predicting and reflecting the progression of IgA nephritis.

BACKGROUND: The nucleotide oligomerization domain-like receptor subfamily C5 (NLRC5) is primarily expressed in the adaptive and innate immune systems. NLRC5 was recently discovered to regulate immunity and inflammatory responses. Abnormal immune and inflammatory responses are considered critical pathogenesis in IgA nephritis (IgAN). However, the role of NLRC5 in IgAN is unknown. We previously showed that NLRC5 can be detected in patients with IgAN; herein, we further examined the pathophysiological significance of NLRC5 in the serum and renal deposits of patients with IgAN. This study is the first to find that NLRC5 is closely correlated with IgAN. METHODS: IgAN patients (n = 50) who were diagnosed by renal biopsy provided blood and renal biopsy tissue, and age-matched healthy control subjects (blood donators n = 22; tissue donators n = 5) were included. Renal biopsies were diagnosed, and blood biochemical parameters were tested. Serum creatinine, urea, proteinuria, haematuria, albumin, and immunoglobulin A levels were recorded. Serum NLRC5 concentrations were detected by enzyme-linked immunosorbent assay, and tissue NLRC5 expression in kidney tissue was detected by immunohistochemical analysis. ROC curve analysis was used to evaluate the diagnostic value of the serum NLRC5 concentration in IgAN. RESULTS: Serum NLRC5 concentration was significantly decreased in the IgAN group compared to that in the healthy control group (P < 0.0001), especially in S1 (Oxford classification) patients (P < 0.0001). Furthermore, serum NLRC5 concentration had a negative correlation with Lee's grade (r = 0.3526, P = 0.0060) and proteinuria levels (r = 0.4571, P = 0.0004). Tissue NLRC5 expression was significantly increased in the IgAN group compared to that in the healthy control group (P < 0.0001); a more significant increase was identified in the S1 group (P < 0.05) and had a positive correlation with Lee's grade (r = 0.497, P < 0.0001). We proposed a cut-off value of 1415 pg/ml for serum NLRC5 concentration, which was able to predict IgAN with 77.27% sensitivity and 87.5% specificity. CONCLUSIONS: Serum NLRC5 concentrations in IgAN are significantly decreased, and tissue NLRC5 expression is significantly increased in IgAN renal tissue, which is consistent with pathological severity. This finding suggests that NLRC5 could potentially be a diagnostic index and represents a prognostic factor in IgAN patients.

Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway.

Cisplatin is one of the most effective chemotherapeutic agents; however, its clinical use is limited by serious side effects of which nephrotoxicity is the most important. Nephrotoxicity induced by cisplatin is closely associated with autophagy reduction and caspase activation. In this study, we investigated whether neferine, an autophagy inducer, had a protective effect against cisplatin-induced nephrotoxicity. In an in vitro cisplatin-induced nephrotoxicity model, we determined that neferine was able to induce autophagy and that pretreatment with neferine not only attenuated cisplatin-induced cell apoptosis but further activated cell autophagy. This pro-survival effect was abolished by the autophagic flux inhibitor chloroquine. Furthermore, neferine pretreatment activated the AMPK/mTOR pathway; however, pharmacological inhibition of AMPK abolished neferine-mediated autophagy and nephroprotection against cisplatin-induced apoptosis. Collectively, our findings suggest for the first time the possible protective mechanism of neferine, which is crucial for its further development as a potential therapeutic agent for cisplatin-induced nephrotoxicity.

Clinical features and CKD-related quality of life in patients with CKD G3a and CKD G3b in China: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

BACKGROUND: This study aimed to compare clinical features and health-related quality of life (HRQoL) in the Chinese chronic kidney disease (CKD) 3 population and determined the necessity of the subdivision of CKD3 in Chinese patients with CKD. METHODS: Participants with stage 3 CKD (18-74 years of age) were recruited at 39 clinical centers located at 28 cities in 22 provinces of China. The sociodemographic status, medical history, anthropometric measurements, and lifestyle behaviors were documented at entry, and blood and urine samples were collected. The estimated glomerular filtration rate was calculated using the CKD-EPI creatinine equation. The HRQoL was evaluated using the kidney disease quality-of-life instrument. A linear regression model was used to estimate the association between HRQoL and CKD stages (G3b vs G3a). RESULTS: The levels of intact parathyroid hormone, systolic blood pressure, uric acid, and high-density lipoprotein cholesterol were statistically significantly higher, whereas the levels of serum bicarbonate and hemoglobin were statistically significantly lower in the G3b group compared with the G3a group. Compared with CKD G3a group, the proportions of subjects with hyperuricemia and anemia were significantly higher in CKD G3b group (61.4% vs. 52.0% and 26.4% vs. 17.9%, respectively, P< 0.01). The HRQoL scores in "physical functioning (PCS)", "symptoms and problems", "effects of the kidney disease" and "burden of the kidney disease" were statistically significantly lower in the CKD G3b group compared with the CKD G3a group (90.88 ± 11.05 vs. 89.30 ± 11.52, 88.29 ± 11.94 vs. 86.49 ± 13.45, 55.86 ± 26.40 vs. 52.10 ± 27.64, 46.56 ± 8.16 vs. 44.51 ± 9.22, respectively, P< 0.01). Further, CKD G3b was associated with a lower score of physical functioning compared with G3a (regression coefficient =-1.12 [95%CI: -2.23, -0.16]). CONCLUSIONS: The preliminary results of this study suggested that modest differences existed in many important clinical features and KDQoL between patients with G3a and G3b CKD in a Chinese population. Also, a significant association between CKD3 subdivision of the disease and PCS was detected. Although further work is needed, we can speculate based on these results the CKD3 subdivision may be clinically meaningful for Chinese patients with CKD.

[Investigation of status for vascular access in hemodialysis patients at Xiangya Hospital of Central South University].

OBJECTIVE: To investigate the status of vascular access in hemodialysis patients in our center.
 Methods: The general information of hemodialysis patients and types and complications of vascular access at Xiangya Hospital of Central South University from April 2015 to April 2016, were retrospectively analyzed.
 Results: Among 258 prevalent patients, 87.60% of them had arteriovenous fistula (AVF), while 12.40% showed tunneled cuffed catheter. Of the 61 incident patients, 80.33% of them initiated dialysis with a non-tunneled and non-cuffed catheter, 8.19% with an AVF, 9.84% with a tunneled cuffed catheter, and 1.64% with needle puncture. The types of AVF access included 76.55% of wrist radiocephalic fistula, 7.08% of mid-forearm cephalic fistula, 11.06% of elbow brachiocephalic fistula, and 5.31% of antecubital fistula and transposed basilic fistula. Seventy-seven (34.07%) patients with AVF suffered complications and wherein aneurysms accounted for 24.34%.
 Conclusion: In maintenance hemodialysis patients, autologous AVF is the prevalent vascular access. In the beginners for dialysis, non-tunneled and non-cuffed catheter are their choice. Additional efforts and incentives may be necessary to improve vascular access during the initiation of hemodialysis.

Acute interstitial nephritis caused by ANCA-associated vasculitis: a case based review.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).