Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study.

BACKGROUND: The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS. METHODS: This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed. RESULTS: A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and mean arterial pressure (MAP) ≤103 mmHg at the beginning of therapy in patients with MN. No serious adverse effects were reported. CONCLUSIONS: RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients.

Exosomal hsa_circ_0125310 promotes cell proliferation and fibrosis in diabetic nephropathy via sponging miR-422a and targeting the IGF1R/p38 axis.

Diabetic nephropathy (DN) is still on the rise worldwide, and millions of patients have to be treated through dialysis or transplant because of kidney failure caused by DN. Recent reports have highlighted circRNAs in the treatment of DN. Herein, we aimed to investigate the mechanism by which high glucose-induced exo-circ_0125310 promotes diabetic nephropathy progression. circ_0125310 is highly expressed in diabetic nephropathy and exosomes isolated from high glucose-induced mesangial cells (MCs). High glucose-induced exosomes promote the proliferation and fibrosis of MCs. However, results showed that the effects of exosomes on MCs can be reversed by the knockdown of circ_0125310. miR-422a, which targets IGF1R, was the direct target of circ_0125310. circ_0125310 regulated IGF1R/p38 axis by sponging miR-422a. Exo-circ_0125310 increased the luciferase activity of the WT-IGF1R reporter in the dual-luciferase reporter gene assays and upregulated the expression level of IGF1R and p38. Finally, in vivo research indicated that the overexpression of circ_0125310 promoted the diabetic nephropathy progression. Above results demonstrated that the high glucose-induced exo-circ_0125310 promoted cell proliferation and fibrosis in diabetic nephropathy via sponging miR-422a and targeting the IGF1R/p38 axis.

A retrospective study of baseline peritoneal transport character and left ventricular hypertrophy in incident peritoneal dialysis patients: interrelationship and prognostic impacts.

BACKGROUND: Left ventricular hypertrophy is associated with adverse outcomes among peritoneal dialysis patients. The aim of this study was to evaluate the prognostic impact of baseline left ventricular hypertrophy and its relationship with baseline peritoneal transfer characteristics in peritoneal dialysis patients. METHODS: We enrolled 151 incident peritoneal dialysis patients to perform a multicentric retrospective cohort study since January 1, 2017 to January 31, 2021. Patients were grouped based on baseline dialysate-to-plasma creatinine ratio at 4 h as follows: low (<0.50), low average (0.5-0.64), high average (0.65-0.80) and high (≥0.81). Echocardiography and clinic data were recorded yearly. The Cox proportional hazards models and competing risk model were used to evaluate patients' survival. Generalized linear mixed models were performed to explore risk factors associated with left ventricular hypertrophy. RESULTS: During a median follow-up period of 33 months (range, 16-48 months), 21 (13.9%) patients died, including 16 (10.60%) cardiovascular deaths. Controlling the competing risks of switching to hemodialysis, kidney transplantation and loss to follow-up, baseline left ventricular hypertrophy was an independent risk factor for all-cause mortality (subdistribution hazard ratio, 2.645; 95% confidence interval, 1.156-6.056; p = 0.021). Baseline high and high average transport status were positively related to left ventricular mass index and left atrium diameter 2 years after PD initiation. CONCLUSION: Baseline fast peritoneal solute transport rate may be an effect factor for aggravating left ventricular hypertrophy which predicted poor outcomes for peritoneal dialysis patients. The findings offered important ideas for further prospective intervention study.

CDKN2B-AS1 participates in high glucose-induced apoptosis and fibrosis via NOTCH2 through functioning as a miR-98-5p decoy in human podocytes and renal tubular cells.

BACKGROUND: Diabetic nephropathy (DN) is the most common causes of end-stage renal disease. Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is connected with the development of DN, but the role of CDKN2B-AS1 in DN has not been entirely elucidated. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure CDKN2B-AS1 and miR-98-5p levels. Cell viability, proliferation, and apoptosis were analyzed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or flow cytometry assays. Protein levels were measured by western blotting. The relationship between CDKN2B-AS1 or notch homolog 2 (NOTCH2) and miR-98-5p was verified via dual-luciferase reporter assay. RESULTS: CDKN2B-AS1 and NOTCH2 were upregulated in the serum of DN patients and high glucose-disposed human podocytes (HPCs) and human renal tubular cells (HK-2), whereas miR-98-5p was downregulated. High glucose repressed viability and accelerated apoptosis of HPCs and HK-2 cells. CDKN2B-AS1 knockdown impaired high glucose-induced apoptosis and fibrosis of HPCs and HK-2 cells. Mechanistically, CDKN2B-AS1 sponged miR-98-5p to regulate NOTCH2 expression. Also, CDKN2B-AS1 inhibition-mediated effects on apoptosis and fibrosis of high glucose-disposed HPCs and HK-2 cells were weakened by miR-98-5p inhibitor. Also, NOTCH2 knockdown partly reversed miR-98-5p inhibitor-mediated impacts on apoptosis and fibrosis of high glucose-disposed HPCs and HK-2 cells. CONCLUSION: High glucose-induced CDKN2B-AS1 promoted apoptosis and fibrosis via the TGF-ß1 signaling mediated by the miR-98-5p/NOTCH2 axis in HPCs and HK-2 cells.

hsa-miR-199b-3p Prevents the Epithelial-Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E-cadherin through Targeting KDM6A in Diabetic Nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The association between epithelial-mesenchymal transition (EMT) and fibrosis is quite ascertained, but its link to eventual tubule dysfunction is missing. Here, we show that human microRNA- (hsa-miR-) 199b-3p protects renal tubules from diabetic-induced injury by repressing KDM6A, a histone lysine demethylase regulating E-cadherin expression. Lower E-cadherin expression is related to a higher level of KDM6A, while E-cadherin is promoted upon treatment with the KDM6A inhibitor GSK-J4 in both high glucose- (HG-) induced HK2 cells and the kidneys from streptozotocin- (STZ-) induced type 1 diabetic mice. However, overexpression or RNA silencing of E-cadherin fails to alter KDM6A expression. We also show that the upregulation of KDM6A is associated with the increased methylation level of the E-cadherin promoter. Then, the target prediction results and a dual-luciferase assay show that hsa-miR-199b-3p is a new miRNA that targets KDM6A. Overexpression of hsa-miR-199b-3p increases E-cadherin expression and prevents EMT through repressing KDM6A expression in HG-induced HK2 cells. In contrast, inhibitor-induced hsa-miR-199b-3p knockdown has opposite effects, as it decreases E-cadherin level and worsens EMT, accompanied by increased levels of KDM6A. Besides, Mir199b-knockout mice without mmu-miR-119b-3p expression exhibit more renal tubule dysfunction and more serious kidney tissue damage upon treatment with STZ. These results demonstrate that hsa-miR-199b-3p improves E-cadherin expression and prevents the progression of DN through targeting KDM6A. miR-199b-3p could be a future biomarker or target for the diagnosis or treatment of DN.

FOXO3a Protects against Kidney Injury in Type II Diabetic Nephropathy by Promoting Sirt6 Expression and Inhibiting Smad3 Acetylation.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Although numerous reports have demonstrated a correlation between epithelial-mesenchymal transition (EMT) and renal fibrosis, how these processes lead to tubular dysfunction remains unclear. Here, we show that FOXO3a protects kidneys from injury in type II DN by increasing Sirt6 expression, which deacetylates Smad3 and inhibits its transcriptional activity. The results showed that progressive EMT in the kidneys from db/db mice is associated with Sirt6 downregulation and involved in tubular injury and dysfunction. The reduction of Sirt6 levels in db/db mice resulted in progressive kidney injury, indicating the protective role of Sirt6. Furthermore, Sirt6 was shown to directly bind to Smad3, a key downstream mediator of TGF-ß, and could deacetylate it to inhibit its nuclear accumulation and transcriptional activity in HK2 cells. Besides, we demonstrate that FOXO3a activates Sirt6 expression by binding to its promoter. shRNA-induced FOXO3a knockdown in the kidneys of db/db mice exacerbated tubular injury and renal function loss. Mechanistically, FOXO3a protects against kidney injury in type II DN through the Sirt6/Smad3 axis. Thus, the pharmacological targeting of FOXO3a-mediated Sirt6/Smad3 signaling pathways may provide a novel strategy for treating type II DN.

Ameliorative effects of miR-186 on cisplatin-triggered acute kidney injury via targeting ZEB1.

Cisplatin is a commonly used chemotherapy drug in cancers, which can lead to acute kidney injury (AKI). AKI can occur in almost one third of tumor patients, who receive cisplatin treatment. microRNAs (miRNAs) are significant tools in regulating the expression of crucial factors in multiple diseases, but little is known about their biological roles in AKI. As exhibited, miR-186 has been observed to be down-regulated in tumors. Our study concentrated on the function of miR-186 in cisplatin-triggered AKI. Here, we reported miR-186 was considerably decreased in the serum samples from AKI patients compared with those from the healthy controls. Additionally, we found in NRK-52E cells exposed to 6 mM cisplatin, miR-186 was greatly decreased time-dependently. Meanwhile, an AKI model in rats was successfully set in our study. Levels of serum creatinine and blood urea nitrogen were significantly induced by cisplatin exposure. In AKI rat models, miR-186 exhibited a rapid decrease in both the serum and the kidney tissues. Then, miR-186 overexpression improved NRK-52E cell proliferation and protected NRK-52E cells against cisplatin-triggered apoptosis. Furthermore, ZEB1 was identified and confirmed as a target gene of miR-186. It has been demonstrated that ZEB1 exerts crucial roles in the development of AKI. As evidenced in our current study, ZEB1 was remarkably elevated in AKI patients and AKI rat models. Moreover, ZEB1 was induced by indicated doses of cisplatin in different time periods in NRK-52E cells. ZEB1 inhibition rescued the reduced proliferation and increased apoptosis of NRK-52E cells. In conclusion, loss miR-186 expression contributed to cisplatin-induced AKI, partly through targeting ZEB1. miR-186 might be provided as an effective biomarker for AKI via targeting ZEB1.

Circ_LARP4 regulates high glucose-induced cell proliferation, apoptosis, and fibrosis in mouse mesangial cells.

The current study aimed to investigate the role and underlying mechanisms of circ_LARP4 in diabetic nephropathy (DN). Here, mouse mesangial cells (SV40-MES13) were cultured with 30 mM glucose to establish a DN cellular model. The qRT-PCR results indicated that circ_LARP4 expression was downregulated in the DN cellular model compared to that in the control cells. As determined by an MTT assay, circ_LARP4 overexpression via the circ_LARP4 overexpression (OE) plasmids inhibited the cell proliferation rate. As determined by an Annexin V/PI kit and flow cytometry, circ_LARP4 overexpression increased the cell apoptosis rate. As measured by Western blot, circ_LARP4 overexpression enhanced BAX expression but reduced Bcl-2 expression, also suggesting an enhancement of cell apoptosis. Moreover, regarding cell fibrosis, circ_LARP4 overexpression reduced the mRNA levels of fibrosis markers, including fibronectin, collagen I and collagen IV. Interestingly, miR-424 was found to be reduced in the DN cellular model after transfection with the circ_LARP4 OE plasmids. In addition, restoration of miR-424 expression with the miR-424 mimics reversed the negative effects of circ_LARP4 overexpression on cell proliferation and fibrosis. In conclusion, circ_LARP4 was lower in the DN cellular model than in normal cells, and circ_LARP4 overexpression resulted in decreased cell proliferation and cell fibrosis but increased cell apoptosis in the DN cellular model by sponging miR-424.

LINC00052 ameliorates acute kidney injury by sponging miR-532-3p and activating the Wnt signaling pathway.

Acute kidney injury (AKI) is a complex renal disease. Long non-coding RNAs (lncRNAs) have frequently been associated with AKI. In the present study, we aimed to investigate the molecular mechanism(s) of LINC00052 in AKI. We found that LINC00052 expression was significantly decreased in AKI patient serum. In addition, in a hypoxic AKI cell model, LINC00052 expression was strongly elevated. In an I/R-triggered AKI rat model, the expression of TNF-α, IL-6 and IL-1ß mRNA was strongly elevated. Moreover, we predicted miR-532-3p to be targeted by LINC00052 in AKI. Overexpression of LINC00052 increased hypoxia-induced inhibition of NRK-52E cell proliferation and reversed hypoxia-triggered apoptosis. Furthermore, we found that induction of TNF-α, IL-6 and IL-1ß was repressed by overexpression of LINC00052. LINC00052 decreased hypoxia-induced ROS and MDA accumulation in vitro and increased SOD activity. Decreased levels of c-myc and cyclin D1 were observed in renal tissues of AKI rats. Lastly, Wnt/ß-catenin signaling was inactivated in NRK-52E cells experiencing hypoxia, and LINC00052 upregulation reactivated Wnt/ß-catenin signaling by sponging miR-532-3p. Taken together, these results suggest that LINC00052 ameliorates AKI by sponging miR-532-3p and activating Wnt signaling.

Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3/NF-κB/MMP-2 axis.

Diabetic kidney disease (DKD) is closely associated with the high risk of cardiovascular disease and mortality. Exosomal circRNAs can exert significant roles in the pathology of various diseases. Nevertheless, the role of exosomal circRNAs in DKD progression remains barely known. Circular RNA DLGAP4 has been reported to be in involved in acute ischemic stroke. In our study, we found exosomal circ_DLGAP4 was increased in the exosomes isolated from HG-treated mesangial cells (MCs), DKD patients, and DKD rat models compared with the corresponding normal subjects. Then, we observed that exo-circ_DLGAP4 significantly promoted proliferation and fibrosis of MCs cells. Moreover, to study the underlying mechanism of circ_DLGAP4 in regulating DKD, bioinformatics method was consulted and miR-143 was predicted as its target. The direct correlation between miR-143 and circ_DLGAP4 was validated in MCs. MCs proliferation and fibrosis were increased by circ_DLGAP4, which could be decreased by mimic-miR-143. Next, elevated expression of Erb-b2 receptor tyrosine kinase 3 (ERBB3) is involved in various diseases. However, the function of ERBB3 in DKD development remains poorly known. Next, ERBB3 was predicted as the downstream target for miR-143. It was displayed that circ_DLGAP4 promoted proliferation and fibrosis of MCs by sponging miR-143 and regulating ERBB3/NF-κB/MMP-2 axis. Meanwhile, the loss of exo-circ_DLGAP4 induced miR-143 and repressed ERBB3/NF-κB/MMP-2 expression in MCs. Subsequently, in vivo assays were performed and it was proved that overexpression of circ_DLGAP4 markedly promoted DKD progression in vivo via modulating miR-143/ERBB3/NF-κB/MMP-2. In conclusion, we indicated that exosomal circ_DLGAP4 could prove a novel insight for DKD development.

Loss of lncRNA MIAT ameliorates proliferation and fibrosis of diabetic nephropathy through reducing E2F3 expression.

Diabetic nephropathy (DN) is a serious kidney disease resulted from diabetes. Dys-regulated proliferation and extracellular matrix (ECM) accumulation in mesangial cells contribute to DN progression. In this study, we tested expression level of MIAT in DN patients and mesangial cells treated by high glucose (HG). Up-regulation of MIAT was observed in DN. Then, functional assays displayed that silence of MIAT by siRNA significantly repressed the proliferation and cycle progression in mesangial cells induced by HG. Meanwhile, we found that collagen IV, fibronectin and TGF-ß1 protein expression was obviously triggered by HG, which could be rescued by loss of MIAT. Then, further assessment indicated that MIAT served as sponge harbouring miR-147a. Moreover, miR-147a was decreased in DN, which exhibited an antagonistic effect of MIAT on modulating mesangial cell proliferation and fibrosis. Moreover, bioinformatics analysis displayed that E2F transcription factor 3 (E2F3) could act as direct target of miR-147a. We demonstrated that E2F3 was greatly increased in DN and the direct binding association between miR-147a and E2F3 was evidenced using luciferase reporter assay. In summary, our data explored the underlying mechanism of DN pathogenesis validated that MIAT induced mesangial cell proliferation and fibrosis via sponging miR-147a and regulating E2F3.

Correlation of TNF-α and IL-10 gene polymorphisms with primary nephrotic syndrome.

The study explored the correlations of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) gene polymorphisms with susceptibility and the condition of primary nephrotic syndrome. A total of 200 patients with primary nephrotic syndrome in Qilu hospital were collected as disease group, and 200 healthy people were selected as control group. Genomic deoxyribonucleic acids (DNAs) of nucleated cells in the peripheral blood were extracted to detect the gene polymorphisms of TNF-α (rs1799724 and rs1800629) and IL-10 (rs1800872 and rs141219090). Allele distributions at rs1799724 (P=0.003) and rs1800629 (P=0.011) of TNF-α gene and at rs1800872 (P=0.033) of IL-10 gene in disease group were different from those in control group. In the disease group, allele C frequency at rs1799724 and allele A frequency at rs1800629 of TNF-α gene and allele T frequency at rs1800872 of IL-10 gene were higher. There were differences between rs1799724 (P=0.007) and rs1800629 (P=0.002) of TNF-α gene. In addition, there was a difference in the frequency of the dominant model of TNF-α gene rs1800629 between disease group and control group (P=0.035), and the frequency of dominant model GG+GA was remarkably lower in the disease group. Additionally, TT genotype at rs1799724 of TNF-α gene was obviously related to the plasma TNF-α level (P<0.05), and the plasma TNF-α level was significantly increased in disease group. AA genotype at rs141219090 of IL-10 gene had a notable correlation with the plasma IL-10 level (P<0.05), and the plasma IL-10 level in disease group was markedly raised. Additionally, CT genotype at rs1799724 of TNF-α gene was related to the 24-h urine protein level (P=0.035), GG genotype at rs1800872 of IL-10 gene was associated with the plasma albumin level (P=0.031), and GG genotype at rs141219090 was related to the serum creatinine level (P=0.047). TNF-α and IL-10 gene polymorphisms are predominantly correlated with the susceptibility and the condition of primary nephrotic syndrome.

Circ-AKT3 inhibits the accumulation of extracellular matrix of mesangial cells in diabetic nephropathy via modulating miR-296-3p/E-cadherin signals.

Diabetic nephropathy is a leading cause of end-stage renal disease globally. The vital role of circular RNAs (circRNAs) has been reported in diabetic nephropathy progression, but the molecular mechanism linking diabetic nephropathy to circRNAs remains elusive. In this study, we investigated the significant function of circ-AKT3/miR-296-3p/E-cadherin regulatory network on the extracellular matrix accumulation in mesangial cells in diabetic nephropathy. The expression of circ-AKT3 and fibrosis-associated proteins, including fibronectin, collagen type I and collagen type IV, was assessed via RT-PCR and Western blot analysis in diabetic nephropathy animal model and mouse mesangial SV40-MES13 cells. Luciferase reporter assays were used to investigate interactions among E-cadherin, circ-AKT3 and miR-296-3p in mouse mesangial SV40-MES13 cells. Cell apoptosis was evaluated via flow cytometry. The level of circ-AKT3 was significantly lower in diabetic nephropathy mice model group and mouse mesangial SV40-MES13 cells treated with high-concentration (25 mmol/L) glucose. In addition, circ-AKT3 overexpression inhibited the level of fibrosis-associated protein, such as fibronectin, collagen type I and collagen type IV. Circ-AKT3 overexpression also inhibited the apoptosis of mouse mesangial SV40-MES13 cells treated with high glucose. Luciferase reporter assay and bioinformatics tools identified that circ-AKT3 could act as a sponge of miR-296-3p and E-cadherin was the miR-296-3p direct target. Moreover, circ-AKT3/miR-296-3p/E-cadherin modulated the extracellular matrix of mouse mesangial cells in high-concentration (25 mmol/L) glucose, inhibiting the synthesis of related extracellular matrix protein. In conclusion, circ-AKT3 inhibited the extracellular matrix accumulation in diabetic nephropathy mesangial cells through modulating miR-296-3p/E-cadherin signals, which might offer novel potential opportunities for clinical diagnosis targets and therapeutic biomarkers for diabetic nephropathy.

Downregulation of XIST ameliorates acute kidney injury by sponging miR-142-5p and targeting PDCD4.

Acute kidney injury (AKI) is a common kidney disease that markedly affects public health. To date, the roles of long noncoding RNA XIST in AKI are poorly understood. Here, we investigated the biological functions of XIST in AKI. We observed that XIST expression increased in patients with AKI and HK-2 cells stimulated by CoCl2 . In addition, a rat AKI model induced by ischemia-reperfusion was established. Tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 messenger RNA expression were induced in vivo; moreover, XIST expression was upregulated. Knockdown of XIST significantly repressed CoCl2 -triggered injury in HK-2 cells. However, microRNA (miR)-142-5p, a downstream target of XIST, was downregulated in AKI. miR-142-5p was repressed by XIST and miR-142-5p could inhibit CoCl2 -induced injury in HK-2 cells. Moreover, PDCD4 expression was significantly increased in AKI. PDCD4 was predicted to be the target of miR-142-5p. Subsequently, loss of PDCD4 was able to retard injury in HK-2 cells exposed to CoCl2. Thus, we suggest that XIST regulates miR-142-5p and PDCD4, and it has the potential to function as a biomarker in therapeutic strategies for AKI.

miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy.

Recently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-98-5p in the modulation of EMT and renal fibrosis during DN remains barely investigated. Hence, identifying the mechanisms of miR-98-5p in regulating EMT and fibrosis is of huge significance. In our present research, decreased miR-98-5p was demonstrated in db/db mice and mice mesangial cells treated with the high dose of glucose. Meanwhile, activated EMT and increased fibrosis was accompanied with the decrease of miR-98-5p in vitro and in vivo. Additionally, to further find out the roles of miR-98-5p in DN development, overexpression of miR-98-5p was applied. Firstly, in vivo investigation exhibited that elevation of miR-98-5p restrained proteinuria, serum creatinine, BUN, the EMT process, and fibrosis. Furthermore, high glucose was able to promote mice mesangial cell proliferation, EMT process, and induced renal fibrosis, which could be prevented by overexpression of miR-98-5p. Moreover, high mobility group A (HMGA2) can exhibit an important role in diverse biological processes. Here, HMGA2 was investigated as a target of miR-98-5p currently. Luciferase reporter assay was conducted and the correlation of miR-98-5p and HMGA2 was validated. Moreover, it was displayed that HMGA2 was remarkably elevated in db/db mice and mice mesangial cells. Furthermore, miR-98-5p strongly depressed HMGA2 protein and mRNA levels in mice mesangial cells. Overall, these revealed miR-98-5p could suppress the EMT process and renal fibrosis through targeting HMGA2 in DN.

A Telemedicine-Based Registration System for the Management of Renal Anemia in Patients on Maintenance Hemodialysis: Multicenter Study.

BACKGROUND: Renal anemia is one of the most important complications in patients on maintenance hemodialysis (MHD). Telehealth-based dialysis registration systems have the advantage of real-time monitoring and have gradually been applied to the management of chronic diseases. OBJECTIVE: The objective of our study was to evaluate the impact of a telehealth-based dialysis registration system on patients on MHD in terms of renal anemia control. METHODS: The Red China project aimed to develop a dialysis registration system based on the WeChat mobile platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, and baseline creatinine levels were recorded using this system. In addition, the hemoglobin and hematocrit levels were recorded monthly. The platform then generated a hemoglobin and hematocrit statistics report for each hemodialysis center monthly, including the detection rate, target rate, and distribution of hemoglobin and released it to physicians via the WeChat mobile phone app. The physicians were then able to treat the individual's anemia appropriately by changing the doses of erythropoiesis-stimulating agents or iron use on the basis of this report. We analyzed the demographic and baseline laboratory parameters, detection rate, target rate, and average level and distribution of hemoglobin 28 months after the launch of the project. RESULTS: A total of 8392 patients on MHD from 28 hemodialysis centers in Shanghai were enrolled from June 2015 to October 2017. The detection rate of hemoglobin increased from 54.18% to 73.61% (P<.001), the target rate of hemoglobin increased from 47.55% to 56.07% (P<.001), and the mean level of hemoglobin increased from 10.83 (SD 1. 60) g/dL to 11.07 (SD 1.60) g/dL (P<.001). In addition, the proportion of patients with hemoglobin levels ≥11 g/dL but <13 g/dL increased from 40.40% to 47.48%. CONCLUSIONS: This telehealth-based dialysis registration system can provide timely reporting of the anemia status in patients on MHD, which may improve the awareness of anemia and the attention to and compliance with anemia monitoring.

Long non-coding RNA MEG3 promotes fibrosis and inflammatory response in diabetic nephropathy via miR-181a/Egr-1/TLR4 axis.

Long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). This research aimed to study the potential role and underlying molecular mechanisms of long non-coding RNA MEG3 in DN. We found that MEG3 was upregulated in DN in vivo and in vitro and could enhance cell fibrosis and inflammatory response in DN. MEG3 functioned as an endogenous sponge for miR-181a in mesangial cells (MCs) via direct targeting and in an Ago2-dependent manner. MiR-181a inhibition promoted MC fibrosis and inflammatory response. In addition, Egr-1 was confirmed as a target gene of miR-181a. Further investigations verified that MEG3 promotes fibrosis and inflammatory response via the miR-181a/Egr-1/TLR4 axis in vitro and in vivo. These results provide new insights into the regulation between MEG3 and the miR-181a/Egr-1/TLR4 signaling pathway during DN progression.

MicroRNA-503 contributes to podocyte injury via targeting E2F3 in diabetic nephropathy.

Diabetic nephropathy (DN) is serious diabetic complication with capillary injury. Podocyte injury exerts a crucial effect on DN pathogenesis. MicroRNA-503 (miR-503) has been reported in various diseases including DN. Here, we investigated the detailed mechanism of miR-503 in the podocyte injury of DN. The functional role of miR-503 was investigated in cultured podocytes and diabetic rats. Podocyte injury was evaluated by migration and apoptosis experiments in podocytes and we observed that high glucose elevated miR-503 in a time and dose-dependent manner. Meanwhile, E2F transcription factor 3 (E2F3), as a crucial regulator in multiple diseases, was predicted as a potential target of miR-503 here. It was shown that E2F3 was greatly decreased in podocytes incubated with high glucose and miR-503 modulated its expression negatively. In addition, downregulation of E2F3 contributed to podocyte injury, which was reversed by miR-503 inhibitors in vitro. Furthermore, we proved that increase of miR-503 resulted in an unfavorable renal function in diabetic rats via targeting E2F3. These revealed for the first time that the overexpression of miR-503 promoted podocyte injury via targeting E2F3 in diabetic nephropathy and miR-503/E2F3 axis might represent a pathological mechanism of diabetic nephropathy progression.

Association of vaspin rs2236242 gene variants with type 2 diabetes and obesity in a Chinese population: A prospective, single-center study.

AIM: Vaspin is an adipokine separated from visceral fat tissues of obese diabetic rats. This study was to investigate the association between vaspin rs2236242 gene polymorphism and type 2 diabetes mellitus (T2DM) or obesity in a Chinese population. MATERIALS AND METHODS: T2DM patients and nondiabetic controls were recruited from Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University (Shanghai, China) from May 1, 2015 to June 30, 2017. Clinicopathologic characteristics were recorded and their blood samples were collected. Serum vaspin levels were detected by enzyme-linked immunosorbent assay and vaspin rs2236242 genotypes by tetra-amplification refractory mutation system-polymerase chain reaction. RESULTS: Two hundred and ninety-nine patients with T2DM and 311 controls were recruited at last. The vaspin genotypes of diabetic patients were distinct from nondiabetic controls (χ 2 = 54.611, p < 0.0001). Genotyping revealed that T2DM patients have a greater prevalence of A allele compared with controls (61.9% vs. 42.1%, p < 0.0001). A allele was associated with an increased risk of T2DM (odds ratio = 2.23, 95% confidence interval = 1.773-2.804, p < 0.0001) compared with T allele. The genotype distribution did not differ among nondiabetic subjects with or without obesity. The serum vaspin levels were higher in T2DM patients and obese controls than the nonobese controls, however, the rs2236242 was not found to be significantly related to serum vaspin levels. CONCLUSIONS: Our findings showed the association between vaspin rs2236242 gene variants with obesity and T2DM in a Chinese population. People with rs2236242 A allele had a 2.23-fold increased risk of T2DM. These findings suggest that vaspin rs2236242 may serve as a potential diagnostic and/or therapeutic targets for T2DM.