Fengxian Huang

MicroRNA-21 is overexpressed in renal cell carcinoma

Objective To identify microRNAs (miRNAs) that are overexpressed in renal cell carcinoma (RCC) and characterize the functional role of miR-21. Materials and Methods The miRNA expression profiles between RCC tissue and adjacent normal tissue were compared using microarray analysis. The differential expression of miR-21 was validated by real-time polymerase chain reaction (RT-PCR). 786-O RCC cells were transfected with miR-21 mimic, miR-21 inhibitor, or negative controls and cell proliferation, apoptosis and cell cycle were examined by MTT assay and flow cytometry. The expression of programmed cell death 4 (PDCD4) and tropomyosin 1 (TPM1) was detected by RT-PCR and Western blot analysis. Results Compared to adjacent normal tissue, 10 human miRNAs were significantly upregulated and 7 were downregulated in RCC tissue. RT-PCR confirmed that miR-21 was significantly overexpressed in RCC tissue. In vitro expression of miR-21 mimic promoted the growth of 786-O cells, whereas miR-21 inhibitor inhibited cell growth by inducing apoptosis and cell cycle arrest at S phase. Furthermore, miR-21 mimic or inhibitor significantly reduced or increased the expression of PDCD4 and TPM1. Conclusions MiR-21 is overexpressed in RCC tissue and modulates the growth, apoptosis and cell cycle progression of RCC cells and regulates the expression of PDCD4 and TPM1.

Identification of apolipoprotein E Guangzhou (arginine 150 proline), a new variant associated with lipoprotein glomerulopathy

Background/Aims: Lipoprotein glomerulopathy (LPG) is a rare disease characterized by thrombus-like substances in markedly dilated glomerular capillaries and elevated plasma levels of apolipoprotein E (apoE). Previous studies have shown that genetic disorders of apoE may contribute to the pathogenesis of LPG, but LPG may not be caused by apoE gene mutations in Chinese patients. This study investigated the association of a new variant of apoE with LPG in a Chinese family. Methods: The apoE gene in a family with 4 LPG patients was sequenced. The polymerase chain reaction product of coding region of apoE exon 4 was cloned into pMD 18-T vector and then sequenced. Results: A novel point mutation in exon 4 of the apoE gene was identified in all 4 LPG patients and 1 asymptomatic family member. Sequence analysis confirmed a nucleotide G to C point mutation in exon 4 (base 308) of the apoE gene in all patients and the asymptomatic family member. This missense mutation denotes amino acid substitution of the proline residue for arginine residue at position 150 of apoE. Those patients were all heterozygotes with apoE Guangzhou. One of 2 grandsons was a heterozygous carrier of apoE Guangzhou, although he did not have proteinuria. Conclusion: The results of this study suggest that apoE (arginine 150 proline) is a novel apoE variant that etiologically related to LPG. This variant (apoE Guangzhou) may cause a marked molecular conformational change of the apoE and thus impair its binding ability to lipids.

Alkaline Phosphatase and Mortality in Patients on Peritoneal Dialysis

BACKGROUND AND OBJECTIVESnElevated total serum alkaline phosphatase levels have been associated with higher mortality in the general population, CKD patients, and hemodialysis patients. However, in peritoneal dialysis patients, this association has received little attention. The aim of this study was to evaluate the association between alkaline phosphatase and all-cause and cardiovascular mortality in peritoneal dialysis patients.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnIn this single center retrospective cohort study, 1021 incident peritoneal dialysis patients from January 1, 2006, to December 31, 2010 with baseline serum alkaline phosphatase values were enrolled. Collected baseline data included demographic characteristics and clinical and laboratory measurements. All patients were followed until December 31, 2012. The associations of total serum alkaline phosphatase levels with all-cause and cardiovascular mortality were assessed using multivariable-adjusted Cox models.nnnRESULTSnOf 1021 patients, mean age was 47.5 (± 15.5) years, 59.1% of patients were men, and 22.8% of patients were diabetic. The median serum alkaline phosphatase level was 64 U/L (interquartile range=52-82 U/L). During a median 31-month (interquartile range=19-45 months) follow-up period, 203 patients died, of which 109 deaths were caused by cardiovascular disease. After adjusting for demographics, comorbid conditions, liver function, and bone metabolism parameters, the highest alkaline phosphatase quartile was significantly associated with a hazard ratio for all-cause mortality of 1.70 (95% confidence interval, 1.06 to 2.74, P=0.03) and a hazard ratio for cardiovascular mortality of 1.94 (95% confidence interval, 1.02 to 3.72, P=0.04). Each 10 U/L higher baseline alkaline phosphatase level was associated with 4% (95% confidence interval, 1.00 to 1.08, P=0.04) and 7% (95% confidence interval, 1.02 to 1.11, P=0.003) higher risk of all-cause and cardiovascular mortality, respectively.nnnCONCLUSIONnHigher total serum alkaline phosphatase levels at the commencement of peritoneal dialysis were independently associated with all-cause and cardiovascular mortality in peritoneal dialysis patients.

Treatment of established peritoneal fibrosis by gene transfer of Smad7 in a rat model of peritoneal dialysis.

Background/Aims: It has been shown that blockade of TGF-β1 signaling with Smad7 prevents experimental peritoneal fibrosis. The present study investigated whether Smad7 has a therapeutic effect on established peritoneal fibrosis associated with peritoneal dialysis (PD). Methods: A rat model of peritoneal fibrosis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. After peritoneal fibrosis had been established on day 14, groups of 6 rats were treated intraperitoneally with gene transfer of Smad7 or control plasmids using an ultrasound-microbubble-mediated system for 2 weeks until day 28. In addition, a group of 6 diseased rats was euthanized on day 14 before treatment as the basal disease control. Results: Compared to the control-treatment animals on day 28, real-time PCR, Western blot, and confocal microscopy revealed that Smad7 gene transfer significantly attenuated the increased peritoneal fibrosis including the thickening of fibrotic peritoneum, accumulation of α-SMA and collagen I, and an improvement in peritoneal dysfunction (all p < 0.05). Importantly, Smad7 treatment also improved the severity of peritoneal fibrosis and functional impairment when compared to those on day 14 before treatment (all p < 0.05). Inhibition of the established peritoneal fibrosis by Smad7 was associated with an abrogation of TGF-β signaling and upregulation of TGF-β1 and PAI-1. Conclusions: Smad7 gene therapy is able to inhibit established peritoneal fibrosis in a rat model of PD. Results from this study suggest that Smad7 may be a therapeutic agent for the treatment of peritoneal fibrosis associated with PD.

Clinical Outcomes of Remote Peritoneal Dialysis Patients: A Retrospective Cohort Study from a Single Center in China

Background/Aims: To investigate clinical outcomes of remote peritoneal dialysis (PD) patients in Southern China. Methods: In this retrospective cohort study, incident remote PD patients managed with a comprehensive follow-up program in our PD center were included and clinical outcomes were estimated. Results: One thousand and five remote PD patients with mean age 46.1 ± 14.6 years, of which 38.1% were women, were followed-up for a median of 35.7 months. Patient survival rates were 95.4, 84.7 and 71.8% and death-censored technique survival rates were 98.6, 92.3 and 83.4% at 1, 3 and 5 years, respectively. Peritonitis rate was 0.16 episodes per patient-year. Advanced age, diabetes mellitus, shorter peritonitis-free survival time, poor compliance for regular visiting nephrologists and lower hemoglobin predicted all-cause mortality of remote PD patients. Conclusion: The remote PD patients in Southern China managed with comprehensive follow-up program had favorable clinical outcomes, which indicated that home-based PD therapy could be an appropriate treatment option for remote end-stage kidney disease patients.

The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patients

BackgroundResults concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up.MethodsThis retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality.ResultsA total of 1321 patients were included. The mean age was 48.1xa0±xa015.3xa0years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21–48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46–2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28–2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47–9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2xa0years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2xa0years.ConclusionsPeritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.

Platelet index levels and cardiovascular mortality in incident peritoneal dialysis patients: a cohort study

Abstract Prior studies have shown that the levels of some platelet (PLT) indices were associated with mortality in patients undergoing hemodialysis. We aimed to investigate whether the changes in PLT indices associated with mortality in patients on peritoneal dialysis (PD). A single-center, retrospective observational cohort study was conducted in incident PD patients from 1 January 2006 to 31 December 2012, and followed up until 31 December 2014. Cox proportional hazard models were used to examine the relationships between the levels of PLT indices including PLT, plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), and mortality. Of 1324 patients, 276 (20.8%) died during follow-up (median, 37; IQR, 3–107.4 months), among which 134 were due to cardiovascular diseases (CVD). The highest tertile of PLT levels at baseline was associated with increased risk for cardiovascular mortality after adjustment for demographic, clinical characteristics, and laboratory variables (hazard ratio [HR]:1.93; 95% confidence interval [CI]: 1.16–3.20). The similar treads were also observed in the middle and the highest tertile of the PCT level (HR: 1.68, 95%CI: 1.00–2.81 and HR: 1.89, 95%CI: 1.14–3.14, respectively). In addition, the highest tertile of PCT was associated with increased all-cause mortality (HR: 1.41, 95%CI: 1.01–1.96). However, none of the associations in MPV, PDW, and PLCR analyses reached statistical significance (HR: 0.71, 95%CI: 0.43–1.16; HR: 0.72, 95%CI: 0.45–1.18 and HR: 0.74, 95%CI: 0.46–1.19, respectively). These results suggest that higher PLT and PCT may be associated with higher risk for cardiovascular mortality in incident PD patients. Additional studies are needed to investigate whether correction of these two PLT indices reduces the risk.

Association of Serum Uric Acid with Arterial Stiffness in Peritoneal Dialysis Patients

Background/Aims: Serum uric acid (SUA) has been proposed as a mediator associated with increased cardiovascular risk and arterial stiffness. However, evidence on the association between SUA and arterial stiffness in peritoneal dialysis (PD) patients is lacking. The aim of this study was to examine the relationship between SUA and arterial stiffness in PD patients. Methods: The patients who performed vascular profiler test from January 1, 2014 to October 31, 2016, and with SUA values were enrolled. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). The relationship between SUA and baPWV was tested by multiple linear regression models. Results: Of 645 PD patients, mean SUA was 6.80 (±1.29) mg/dL, mean baPWV was 1713 (±505) cm/s. In fully adjusted linear regression models, higher SUA was significantly associated with higher baPWV in young [standardized coefficients (β), 0.085; 95% confidence interval (95% CI), 0.013 to 0.130; P=0.02] but not in elderly (β, -0.194; 95% CI, -0.774 to 0.093; P=0.1) PD patients. In gender-stratified models of young patients, there was a significant association between SUA and baPWV in male (β, 0.115; 95% CI, 0.015 to 0.182; P=0.02) but not in female. Male in the highest gender-specific SUA quartile had a higher baPWV than those in the lowest quartile (β, 0.132; 95% CI, 0.011 to 0.209; P=0.03). This gender difference was reversed when selecting male patients with lower SUA levels (quartile 1 and 2) and female patients with higher SUA levels (quartile 3 and 4). Conclusion: SUA was positively associated with baPWV in young PD patients, and this association was significant in males but not in females, which is possibly explained by the higher SUA level in males than in females.

Nomogram for Predicting Cardiovascular Mortality in Incident Peritoneal Dialysis Patients: An Observational Study.

Cardiovascular mortality risk is high for peritoneal dialysis (PD) patients but it varies considerably among individuals. There is no clinical tool to predict cardiovascular mortality for PD patients yet. Therefore, we developed a cardiovascular mortality risk nomogram in a PD patient cohort. We derived and internally validated the nomogram in incident adult PD patients randomly assigned to a training (Nu2009=u2009918) or a validation (Nu2009=u2009460) dataset. The nomogram was built using the LASSO Cox regression model. Increasing age, history of cardiovascular disease or diabetes were consistent predictors of cardiovascular mortality. Low hemoglobin and serum albumin, high hypersensitive C-reactive protein and decreasing 24u2009hours urine output were identified as non-traditional cardiovascular risk predictors. In the validation dataset, the above nomogram performed good discrimination (1 year c-statisticu2009=u20090.83; 3 year c-statisticu2009=u20090.78) and calibration. This tool can classify patients between those at high risk of cardiovascular mortality (high-risk group) and those of low risk (low-risk group). Cardiovascular mortality was significantly different in the internal validation set of patients for the high-risk group compared to the low-risk group (HR 3.77, 2.14–6.64; pu2009<u20090.001). This novel nomogram can accurately predict cardiovascular mortality risk in incident PD patients.

Association of TNFSF13 polymorphisms with IgA nephropathy in Chinese Han population

Our previous genome‐wide association study of IgA nephropathy (IgAN) in a Chinese Han population suggested that the TNFSF13 gene may be a novel susceptibility gene for IgAN. In the present study, we aimed to further evaluate the associations of single‐nucleotide polymorphisms (SNPs) and expression level of the TNFSF13 gene with the risk and clinical parameters of IgAN.