IncRNA XIST Promotes Cardiac Fibrosis in Mice with Diabetic Nephropathy via Sponging miR-106a-5p to Target RUNX1.

Diabetic nephropathy (DN) accompanied by cardiac fibrosis (CF) increases the mortality rate among people with diabetes. This study sought to explore the molecular mechanism of long non-coding RNA X inactive specific transcript (lncRNA XIST) in CF in DN mice. The animal model of DN was established by streptozocin (STZ). The levels of lncRNA XIST, microRNA (miR)-106a-5p, and RUNX family transcription factor 1 (RUNX1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), followed by biochemical analysis, hematoxylin & eosin and Masson staining, echocardiography, and quantification of collagen I, collagen III, α-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1) levels through qRT-PCR and Western blot assay. The subcellular localization of lncRNA XIST was analyzed by nuclear/cytoplasmic fractionation assay and the bindings of miR-106a-5p to lncRNA XIST and RUNX1 were confirmed by RNA immunoprecipitation and dual-luciferase assays. Functional rescue experiments were performed to validate the role of miR-106a-5p/RUNX1 in CF in DN mice. lncRNA XIST and RUNX1 were elevated while miR-106a-5p was decreased in STZ mice. lncRNA XIST inhibition reduced myocardial injury and collagen deposition, along with decreased levels of fasting blood glucose, serum creatinine, blood urea nitrogen, and urinary microalbumin, collagen I, collagen III, α-SMA, and TGF-ß1. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription. miR-106a-5p downregulation or RUXN1 upregulation reversed the protective role of lncRNA XIST inhibition in STZ mice. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription, thereby aggravating renal dysfunction and CF in DN mice.

The Association between Baseline Serum Lipids and Mortality in Peritoneal Dialysis Patients.

INTRODUCTION: Lipid disturbances are common in ESRD patients. In peritoneal dialysis (PD) patients, dyslipidemia is even more common. This study aimed to examine whether serum lipids were associated with prognosis of PD patients. METHODS: Patients from a multicenter retrospective cohort were used for the present study. The primary endpoint was all-cause mortality. Cox regression was used to analyze the association between serum lipids including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, and triglycerides and the prognosis. RESULTS: The results showed that lower total cholesterol and LDL levels at the initiation of PD predicted higher all-cause mortality in PD patients. Multivariate analysis reveal that the association disappeared after adjusting for age, gender, albumin, prealbumin, protein catabolic rate normalized to body weight, C-reactive protein, and residual renal function. Further analysis showed that patients with lower total cholesterol/LDL had a higher mortality only during the first 24 months of follow-up. In the patients who survived >2 years after PD, lower total cholesterol/LDL was not associated with higher long-term all-cause mortality any more. CONCLUSION: Lower total cholesterol/LDL levels at the initiation of PD were associated with overall mortality in PD patients. The association could be potentially modified by malnutrition, inflammation, and residual renal function or disappeared after 24 months.

Sleep Disorders and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Prospective Cohort Study.

BACKGROUND: Patients with chronic kidney disease experience a high burden of sleep disorders, and there are associations between sleep disorders and cognitive impairment. OBJECTIVES: Based on our previous cross-sectional survey on cognitive impairment in peritoneal dialysis, we further explored the relationship between sleep disorders and cognitive impairment, and predictors for declining cognitive function. METHOD: We conducted a multicenter prospective cohort study enrolling 458 clinically stable patients on peritoneal dialysis who were then followed up for 2 years.Demographic data, comorbidities, depression, and biochemistry data were collected at baseline. Sleep disorders including insomnia, restless legs syndrome, sleep apnea syndrome, excessive daytime sleepiness, possible narcolepsy, sleep walking and nightmares, and possible rapid eye movement behavior disorders were assessed using a panel of specific sleep questionnaires at baseline and in a second survey. Global cognitive function was measured at baseline and in a second survey, using the Modified Mini-Mental State Examination. Specific cognitive domains were evaluated using Trail-Making Test Forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status were used to asses immediate and delayed memory, visuospatial skills, and language ability. RESULTS: Sleep disorders were common among peritoneal dialysis patients. The prevalence of cognitive impairment evaluated by the Modified Mini-Mental State Examination (3MS) increased from 19.8 to 23.9%. Possible narcolepsy was associated with decreased Modified Mini-Mental State Examination scores at baseline. During follow-up, sleepwalking and nightmares were associated with higher risks of declined delayed memory in the longitudinal study. CONCLUSIONS: Possible narcolepsy was associated with general cognitive dysfunction, and sleep walking and nightmares were risk factors for impaired delayed memory.

Application of miR-193a/WT1/PODXL axis to estimate risk and prognosis of idiopathic membranous nephropathy.

Background: This investigation was managed to explore whether miR-193a in combination with two podocytes, namely, Wilms tumor type 1 (WT1) and podocalyxin (PODXL), were feasible in estimating onset and prognosis of idiopathic membranous nephropathy (IMN). Methods: We recruited a total of 189 healthy controls and 364 IMN patients, whose urine samples were prepared to measure the expression of miR-193a and PODXL. Meanwhile, renal tissues collected from above-mentioned IMN patients (n = 364) and renal cell carcinoma patients (n = 189) were arranged to determine the expression of WT1. Ultimately, receiver operating characteristic curves were constructed to appraise the performance of miR-193a, WT1, and PODXL in predicting renal survival of IMN patients. Results: The IMN patients were measured with up-regulated miR-193a expression and down-regulated WT1/PODXL expression, when compared with healthy controls (p < 0.05). Moreover, highly expressed miR-193a, lowly expressed WT1/PODXL, elevated amounts of proteinuria (>3.79 g/24 h)/serum creatinine (>174.63 µmol/L), and declined GFR (≤68.13 mL/min/1.73 m2) were implicated as prominent biomarkers for the poor renal survival of IMN patients (all p < 0.05). Notably, miR-193a combined with PODXL and WT1 generated optimal effects in differentiating IMN patients from healthy controls (AUC = 0.994) and also in anticipating the renal survival state of IMN patients (AUC = 0.824), when compared with strategies that merely employed ≤2 of the biomarkers. Conclusion: The combination of miR-193a, WT1, and PODXL might serve as a favorable strategy for expecting IMN prognosis.

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study.

RATIONALE & OBJECTIVE: Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 458 PD patients were enrolled and followed up for 2 years. PREDICTORS: Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. OUTCOMES: The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. ANALYTICAL APPROACH: Multivariable linear regression models. RESULTS: The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (ß values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. LIMITATIONS: A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. CONCLUSIONS: In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

BACKGROUND: Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. STUDY DESIGN: Multicenter cross-sectional study. SETTING & PARTICIPANTS: 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. PREDICTOR: Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. OUTCOMES: Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. LIMITATIONS: The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. CONCLUSIONS: Even mild depression is closely associated with global and specific cognitive impairment in PD patients.

High glucose promotes tumor invasion and increases metastasis-associated protein expression in human lung epithelial cells by upregulating heme oxygenase-1 via reactive oxygen species or the TGF-ß1/PI3K/Akt signaling pathway.

BACKGROUND: Growing evidence indicates that heme oxygenase-1 (HO-1) is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG) levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. METHODS: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS) production and TGF-ß1 production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. RESULTS: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS) and transforming growth factor-ß1 (TGF-ß1) in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC) or with phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. CONCLUSION: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-ß1/PI3K/Akt signaling pathway.

SCP, a polysaccharide from Schisandra chinensis, induces apoptosis in human renal cell carcinoma Caki-1 cells through mitochondrial-dependent pathway via inhibition of ERK activation.

This study is the first to investigate the anticancer effect of Schisandra chinensis polysaccharide (SCP) in renal cell carcinoma (RCC) cells. The results revealed that SCP treatment showed high cytotoxic potency in Caki-1 cells by inducing apoptosis, which is associated with the disruption of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol, increase of Bax/Bcl-2 ratio, activation of caspase-3/9, and cleavage of poly(ADP-ribose) polymerase (PARP). Furthermore, pan-caspase inhibitor (z-VAD-fmk) significantly blocked SCP-induced apoptosis and PARP cleavage in Caki-1 cells. As well, we also observed that SCP inhibited the phosphorylation of ERK1/2, whereas it had no significant inhibition effect on the phospho-p38 and phospho-JNK activity. All the above parameters provided scientific evidence that SCP induced mitochondrial-mediated apoptosis in Caki-1 cells through the inactivation of ERK pathways, which may shed further light on its potential application as a cancer chemopreventive agent against RCC.

The renal histopathology of nonproteinuric kidney impairment: a three center experience.

Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of  three university teaching hospitals in Shenzhen city of Southern  China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria  (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases  showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity,  glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting.

Protein-energy wasting and peritoneal function in elderly peritoneal dialysis patients.

BACKGROUND: Nutritional status is important in peritoneal dialysis (PD) patients. We aimed to compare the peritoneal transport (PT) characteristics and indicators of nutritional status in elderly and non-elderly PD patients. METHODS: One-hundred and four consecutive patients were divided into either the elderly (>65 years old; n = 44) or the non-elderly (≤65 years old; n = 60) group. PT was assessed via the peritoneal equilibration test, Kt/V (K dialyzer clearance of urea, t dialysis time, V volume of distribution of urea), total creatinine clearance (CrCl), and glomerular filtration rate. Subjective global assessment (SGA), serum albumin (ALB), hemoglobin, prealbumin (PA), transferrin (TF), fat-free edema-free body mass (fat-free edema-free BM), and normalized protein intake (nPNA) were determined, and were used to indicate nutritional status. RESULTS: Elderly PD patients had higher dialysate to plasma creatinine ratios (D/P Cr) and CrCl, but lower serum creatinine body weights, ALB, PA, TF, fat-free edema-free BM, SGA, and nPNA than the non-elderly group. Multivariate analysis indicated that, after adjusting for PD time, body weight, diabetes mellitus, age, and sex, SGA negatively correlated with D/P Cr, whereas after adjusting for PD time, diabetes mellitus, and sex, D/P Cr positively correlated with age in all patients. CONCLUSIONS: Protein-energy wasting and a high PT are more common in elderly than non-elderly PD patients. Nutritional status should be carefully considered when prescribing the PD dose and frequency, especially in elderly patients.

Overexpression of NR4A2 alleviates renal and myocardial injury in diabetes nephropathy rats through the HDAC11/SPRY1 pathway.

BACKGROUND: Diabetic nephropathy (DN) remains the most prevalent cause of end-stage renal disease. Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a nuclear receptor with unique physiological characteristics. OBJECTIVE: This study explored the molecular mechanism of NR4A2 in renal and cardiac functions of DN rats. METHODS: A rat model of DN was established by intraperitoneal injection of streptozocin. NR4A2, histone deacetylase 11 (HDAC11), and sprouty 1 (SPRY1) expressions were detected. The fasting blood glucose (FBG), urinary albumin (UAlb), serum creatinine (Cr), and blood urea nitrogen (BUN) were determined. The pathological injury of renal and myocardial tissues was evaluated. The mitral early to late diastolic flow velocity ratio (E/A ratio), left ventricular ejection fraction (LVEF), left ventricular systolic function (LVSF), left ventricular internal dimension systole (LVIDs), and left ventricular internal diameter diastole (LVIDd) were tested, and the levels of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined. The enrichment of NR4A2 in HDAC11 promoter and enrichment of H3K27 acetylation in SPRY1 promoter were measured. RESULTS: NR4A2 and SPRY1 were downregulated while HDAC11 was upregulated in renal and myocardial tissues of DN rats. NR4A2 overexpression reduced FBG, UAlb, Cr, and BUN, alleviated pathological injury of renal and myocardial tissues, elevated the E/A ratio, LVEF, and LVFS, but reduced LVIDs, and decreased serum cTnI and CK-MB. NR4A2 depressed HDAC11 expression by binding to the HDAC11 promoter. HDAC11 repressed SPRY1 transcription by suppressing the H3K27ac level. HDAC11 overexpression or SPRY1 inhibition reversed the alleviating effect of NR4A2 overexpression on DN rats. CONCLUSION: NR4A2 was poorly expressed in DN rats. NR4A2 overexpression suppressed HDAC11 expression by binding to the HDAC11 promoter and enhanced SPRY1 transcription by enhancing H3K27 acetylation, thereby alleviating the renal and myocardial injury of DN rats.

Long noncoding RNA X-inactive specific transcript regulates NLR family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy.

BACKGROUND: NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology. Long noncoding RNAs (lncRNAs) are active participators of diabetic nephropathy (DN). X inactive specific transcript (XIST) expression has been reported to be elevated in the serum of DN patients. AIM: To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell (RTEC) pyroptosis in DN. METHODS: A DN rat model was established through streptozotocin injection, and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST. Renal metabolic and biochemical indices were detected, and pathological changes in the renal tissue were assessed. The expression of indicators related to inflammation and pyroptosis was also detected. High glucose (HG) was used to treat HK2 cells, and cell viability and lactate dehydrogenase (LDH) activity were detected after silencing XIST. The subcellular localization and downstream mechanism of XIST were investigated. Finally, a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3 (NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p (miR-15b-5p)/Toll-like receptor 4 (TLR4) axis. RESULTS: XIST was highly expressed in the DN models. XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury. The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells; cell viability was decreased and LDH activity was increased after HG treatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically, XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promoting miR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect of silencing XIST on HG-induced RTEC pyroptosis. CONCLUSION: Silencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury in DN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.

Promising Epigenetic Biomarkers Associated With Cancer-Associated-Fibroblasts for Progression of Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common malignant kidney tumor as its characterization of highly metastatic potential. Patients with KIRC are associated with poor clinical outcomes with limited treatment options. Up to date, the underlying molecular mechanisms of KIRC pathogenesis and progression are still poorly understood. Instead, particular features of Cancer-Associated Fibroblasts (CAFs) are highly associated with adverse outcomes of patients with KIRC, while the precise regulatory mechanisms at the epigenetic level of KIRC in governing CAFs remain poorly defined. Therefore, explore the correlations between epigenetic regulation and CAFs infiltration may help us better understand the molecular mechanisms behind KIRC progression, which may improve clinical outcomes and patients quality of life. In the present study, we identified a set of clinically relevant CAFs-related methylation-driven genes, NAT8, TINAG, and SLC17A1 in KIRC. Our comprehensive in silico analysis revealed that the expression levels of NAT8, TINAG, and SLC17A1 are highly associated with outcomes of patients with KIRC. Meanwhile, their methylation levels are highly correlates with the severity of KIRC. We suggest that the biomarkers might contribute to CAFs infiltration in KIRC. Taken together, our study provides a set of promising biomarkers which could predict the progression and prognosis of KIRC. Our findings could have potential prognosis and therapeutic significance in the progression of KIRC.

Rapamycin protects against aristolochic acid nephropathy in mice by potentiating mammalian target of rapamycin­mediated autophagy.

Autophagy serves a crucial role in the etiology of kidney diseases, including drug­induced renal impairment, inherited kidney disease, diabetic nephropathy and aristolochic acid nephropathy (AAN) and is, therefore, a potential target for treatment. We previously demonstrated that rapamycin could attenuate AAN in mice; however, the underlying mechanism remains to be elucidated. Therefore, whether the renal protective effect of rapamycin (an autophagy activator) is related to autophagy in aristolochic acid (AA)­treated mice was of particular interest. The pathophysiological roles of rapamycin were investigated in AA­induced nephrotoxicity in mice and the mechanisms of rapamycin action were explored by evaluating the modulation of autophagy in rapamycin­treated mice and cultured renal tubular epithelial cells. Supplementation with rapamycin reversed AA­induced kidney injury in mice and improved AA­induced autophagy damage in vivo and in vitro. Mechanistically, rapamycin inhibited the renal expression of phosphorylated (p­)mammalian target of rapamycin (mTOR) and p­ribosomal S6 protein kinase 1, which in turn activated renal autophagy and decreased apoptosis, probably by removing AA­elicited damaged mitochondria and misfolded proteins. The findings of the present study demonstrated that rapamycin protects against AA­induced nephropathy by activating the mTOR­autophagy axis and suggested that rapamycin may be a promising pharmacological target for the treatment of AAN.

Deletion of Smad3 protects against C-reactive protein-induced renal fibrosis and inflammation in obstructive nephropathy.

Introduction and Aims: Elevated plasma levels of C-reactive protein (CRP) are closely associated with progressive renal injury in patients with chronic kidney disease (CKD). Here, we tested a hypothesis that CRP may promote renal fibrosis and inflammation via a TGF-ß/Smad3-dependent mechanism. Methods: Role and mechanisms of TGF-ß/Smad3 in CRP-induced renal fibrosis and inflammation were examined in a mouse model of unilateral ureteral obstruction (UUO) induced in CRP Tg/Smad3 KO mice and in a rat tubular epithelial cell line in which Smad3 gene is stably knocked down (S3KD-NRK52E). Results: We found that mice overexpressing the human CRP gene were largely promoted renal inflammation and fibrosis as evidenced by increasing IL-1ß, TNF-α, MCP-1 expression, F4/80+ macrophages infiltration, and marked accumulation of α-smooth muscle actin (α-SMA), collagen I and fibronectin in the UUO kidney, which were blunted when Smad3 gene was deleted in CRPtg-Smad3KO. Mechanistically, we found that the protection of renal inflammation and fibrosis in the UUO kidney of CRPtg-Smad3KO mice was associated with the inactivation of CD32-NF-κB and TGF-ß/Smad3 signaling. Conclusion: In conclusion, Smad3 deficiency protects against CRP-mediated renal inflammation and fibrosis in the UUO kidney by inactivating CD32-NF-κB and TGF-ß/Smad3 signaling.

The Association of Cognitive Impairment with Peritoneal Dialysis-Related Peritonitis.

Background:Research on the association between cognitive impairment (CI) and peritoneal dialysis (PD)-related peritonitis is limited. Therefore, we investigated whether CI contributed to the risk of PD-related peritonitis.Methods:This prospective cohort study enrolled 458 patients from 5 PD centers between 1 March 2013, and 30 November 2013, and continued until 31 May 2016. We used the Modified Mini-Mental State Examination (3MS) to assess general cognition, the Trail-Making Test to assess executive function, and subtests of the Battery for the Assessment of Neuropsychological Status to assess immediate and delayed memory, visuospatial skills, and language ability. Patients were assigned to CI and non-CI groups based on their 3MS scores. The first episode of peritonitis was the primary endpoint event. Treatment failure of peritonitis was defined as peritonitis-associated death or transfer to hemodialysis. We used competing risk models to analyze the association between CI and the risk of peritonitis. The association of CI with treatment failure after peritonitis was analyzed using logistic regression models.Results:Ninety-four first episodes of peritonitis were recorded during a median follow-up of 31.4 months, 18.1% of which led to treatment failure. No significant group differences were observed for the occurrence, distribution of pathogenic bacteria, or outcomes of first-episode peritonitis. Immediate memory dysfunction was independently associated with a higher risk of PD-related peritonitis (hazard ratio [HR] 1.736, 95% confidence interval [CI] 1.064 - 2.834, p < 0.05), adjusting for confounders.Conclusions:Immediate memory dysfunction was a significant, independent predictor of PD-related peritonitis. Neither general nor specific domains of CI predicted treatment failure of peritonitis.

Depression at Baseline Is an Independent Risk Factor for Cognitive Decline in Patients on Peritoneal Dialysis: A Multicenter Prospective Cohort Study.

Background:Depression has been recognized as a risk factor for cognitive impairment (CI) from cross-sectional datasets. This multicenter prospective study investigated the association between depression and cognitive decline in peritoneal dialysis (PD) patients.Methods:This multicenter prospective cohort study included 458 PD patients who were followed up for 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function, Trail-Making Tests A and B for executive function, subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skill, and language ability. Depression was assessed using Zung's Self-Rating Depression Scale.Results:During the 2-year follow-up, patients with moderate/severe depression at baseline showed a significant decline in global cognitive function (80.5 ± 15.2 vs 76.6 ± 15.5, p = 0.008), while patients without depression or with mild depression kept a stable global cognitive function. In the meantime, patients without depression showed significant improvements in immediate memory, visuospatial skill, and language ability. However, no significant improvement in these parameters was shown in depression groups. In multivariable linear regression analysis, depression at baseline was a significant predictor of worsening global cognitive function, whether depression was analyzed as a continuous variable (odds ratio [OR] = -0.14, 95% confidence interval [CI] -0.27, -0.01, p = 0.031) or a rank variable (OR = -1.88, 95% CI -3.30, -0.45, p = 0.010). Moreover, higher depression score or more severe depression degradation was significantly associated with decline of immediate memory, delayed memory, and language skill.Conclusion:Depression was a significant risk factor for worsening of CI in PD patients.

[Parathyroid hormone 1-34 induce cardiac myocytes hypertrophy via extracellular regulated protein kinase 1/2 pathway].

OBJECTIVE: To investigate the role of mitogen activated protein kinase kinase 1 (MAPKK, MEK1) and regulated kinase1/2 (ERK1/2) on cardiac hypertrophy induced by rat parathyroid hormone1-34 (rPTH1-34). METHOD: Neonatal rat cardiomyocytes was treated with or without 10(-7) mol/L rPTH1-34 in the absence or presence 2 x 10(-5) mol/L PD98059, a MEK1 inhibitor. Cellular diameter was measured by Motic Images Advanced 3.0 software and the synthetic rate of protein in cardiac myocytes was detected by 3H-leucine incorporation, mRNA expression of atrial natriuretic peptide (ANP) was measured by RT-PCR and protein expression of ERK1/2 and p-ERK1/2 was measured by Western blot. RESULTS: rPTH1-34 (10(-7) mol/L) significantly increase cellular diameter (+13.6 microm), 3H-leucine incorporation (+898 cpm/well), ANP mRNA expression (+73.9%), and p-ERK1/2 protein expression (+15%) compared to control cells (all P < 0.05) and these effects could be significantly attenuated by PD98059: cellular diameter (-7.1 microm), 3H-leucin e incorporation (-644 cpm/well), ANP mRNA expression (-52.2%), and protein expression of p-ERK1/2 (-18%) (all P < 0.05 vs. PTH group). PD98059 did not affect control cells without PTH treatment (all P > 0.05). CONCLUSIONS: PD98059 attenuates PTH induced cardiac hypertrophy in vitro via inhibiting the expression of ERK1/2 and p-ERK1/2.

Association of Social Support and Family Environment with Cognitive Function in Peritoneal Dialysis Patients.

♦ BACKGROUND: Cognitive impairment (CI) is a common phenomenon and predictive of high mortality in peritoneal dialysis (PD) patients. This study aimed to analyze the association of social support and family environment with cognitive function in PD patients. ♦ METHODS: This is a cross-sectional study of PD patients from Peking University First Hospital and the Second Affiliated Hospital of Harbin Medical University. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), executive function was measured by the A and B trail-making tests, and other cognitive functions were measured by the Repeatable Battery for the Assessment of Neuropsychological Status. Social support was measured with the Social Support Scale developed by Xiaoshuiyuan and family environment was measured with the Chinese Version of the Family Environment Scale (FES-CV). ♦ RESULTS: The prevalence of CI and executive dysfunction among the 173 patients in the study was, respectively, 16.8% and 26.3%. Logistic regression found that higher global social support (odds ratio [OR] = 1.09, 1.01 - 1.17, p = 0.027) and subjective social support predicted higher prevalence of CI (OR = 1.13, 1.02 - 1.25, p = 0.022), adjusting for covariates. Analyses of the FES-CV dimensions found that greater independence was significantly associated with better immediate memory and delayed memory. Moreover, higher scores on achievement orientation were significantly associated with poorer language skills. ♦ CONCLUSIONS: Our findings indicate that social support is negatively associated with the cognitive function of PD patients and that some dimensions of the family environment are significantly associated with several domains of cognitive function.

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

BACKGROUND: Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). METHODS: In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). CONCLUSIONS: Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.