The number of valvular insufficiency is a strong predictor of cardiovascular and all-cause mortality in hemodialysis patients.

OBJECTIVES: To investigate the relationship between the number of valvular insufficiency (VI) and emergency hospitalization or mortality in maintenance hemodialysis (HD) patients. METHODS: The maintenance HD patients with cardiac ultrasonography were included. According to the number of VI ≥ 2 or not, the patients were divided into two groups. The difference of emergency hospitalized for acute heart failure, arrhythmia, acute coronary syndrome (ACS) or stroke, cardiovascular mortality, and all-cause mortality between the two groups were compared. RESULTS: Among 217 maintenance HD patients, 81.57% had VI. 121 (55.76%) patients had two or more VI, and 96 (44.24%) with one VI or not. The study subjects were followed up for a median of 47 (3-107) months. At the end of the follow up, 95 patients died (43.78%), of whom 47 (21.66%) patients died because of cardiovascular disease. Age (HR 1.033, 95% CI 1.007-1.061, P = 0.013), number of VI ≥ 2 (HR 2.035, 95% CI 1.083-3.821, P = 0.027) and albumin (HR 0.935, 95% CI 0.881-0.992, P = 0.027) were independent risk factors for cardiovascular mortality. The three parameters were also independent risk factors for all-cause mortality. The patients with number of VI ≥ 2 were more likely to be emergency hospitalized for acute heart failure (56 [46.28%] vs 11 [11.46%], P = 0.001). On the contrary, the number of VI was not associated with emergency hospitalized for arrhythmia, ACS or stroke. Survival analysis results showed that probability of survival was statistically different in the two groups (P < 0.05), no matter based on cardiovascular mortality or all-cause mortality. Based on age, number of VI ≥ 2 and albumin, nomogram models for 5-year cardiovascular and all-cause mortality were built. CONCLUSIONS: In maintenance HD patients, the prevalence of VI is prominently high. The number of VI ≥ 2 is associated with emergency hospitalized for acute heart failure, cardiovascular and all-cause mortality. Combining age, number of VI ≥ 2, and albumin can predict cardiovascular and all-cause mortality.

Total cholesterol to high-density lipoprotein cholesterol ratio is independently associated with CKD progression.

PURPOSE: Although dyslipidemia can cause kidney damage, whether it independently contributes to the progression of chronic kidney disease (CKD) remains controversial. The research aims to evaluate the predictive value of serum lipids and their ratios in the progression of CKD. METHODS: The retrospective, case-control study included 380 adult subjects with CKD stage 3-4 (G3-4) at baseline. The end point of follow-up was the progression of CKD, defined as a composite of renal function rapid decline [an annual estimated glomerular filtration rate (eGFR) decline > 5 mL/min/1.73 m2] or the new-onset end-stage renal disease (ESRD) [eGFR < 15 mL/min/1.73 m2]. Logistic regression analysis was performed to examine the association between CKD progression and lipid parameters. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of lipid parameters in the progression of CKD. RESULTS: Over a median follow-up of 3.0 years, 96 participants (25.3%) developed CKD progression. In multivariable logistic regression analysis, logarithm-transformed urinary albumin-to-creatinine ratio (log ACR) [odds ratio (OR) 1.834;95% confidence interval (CI) 1.253-2.685; P = 0.002] and total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) [OR 1.345; 95% CI 1.079-1.677; P = 0.008] were independently associated with CKD progression. The ROC curve showed the combined predictor of ACR and TC/HDL-C ratio was acceptable for CKD progression diagnosis (area under the ROC curve [AUC] = 0.716, sensitivity 50.0%, specificity 84.2%), and the cut-off value was - 0.98. CONCLUSIONS: The combination of TC/HDL-C ratio and ACR had predictive value in the progression of CKD, and may help identify the high-risk population with CKD.

Correlation between home systolic blood pressure variability and cognitive impairment in maintenance hemodialysis patients.

INTRODUCTION: To investigate the correlation between home blood pressure variability and cognitive function in maintenance hemodialysis (MHD) patients. METHODS: Patients who received MHD were included. Their home blood pressure on nondialysis days within 1 week was collected. All patients were assessed with the Montreal Cognitive Assessment scale, according to which the patients were divided into cognitive impairment (CI) group and non-CI group, and the differences between two groups were compared. RESULTS: A total of 224 patients were included in the study, of which 168 had CI (75%). Compared with non-CI group, patients in CI group had larger variability of systolic blood pressure (SBPV) (8.4 [6.7, 10.6]% vs. 6.9 [4.9, 8.8]%, P < 0.001). The smooth fitting curve (OR = 1.2, 95% CI [1.1-1.4], P < 0.001) and trend test (P for trend = 0.004) showed that the risk of CI raised with the increase of SBPV. The patients were further divided into tertiles according to the SBPV. We also found a gradual increase in the proportion of incident CI in the three tertiles. Multiple logistic regression analysis showed that age, shorter years of education, less frequency of hemodialysis, and greater SBPV were the dependent risk of CI. CONCLUSION: In conclusion, greater SBPV indicates higher risk of cognitive impairment in MHD patients.

Acute Kidney Injury in Hospitalized Patients Infected with COVID-19 from Wuhan, China: A Retrospective Study.

BACKGROUND: Since the first diagnosed case of infection with the novel coronavirus (SARS-CoV-2), there has been a rapid spread of the disease with an increasing number of cases confirmed every day, as well as a rising death toll. An association has been reported between acute kidney injury (AKI) and mortality in patients infected with SARS-CoV-2. Therefore, our study was conducted to explore possible risk factors of AKI as well as whether AKI was a risk factor for worse outcome, especially mortality among patients with coronavirus disease (COVID-19). METHODS: We included all hospital admissions with confirmed or clinically diagnosed COVID-19 from January 29 to February 25, 2020. We collected demographic and epidemiological information, past medical history, symptoms, laboratory tests, treatments, and outcome data from electronic medical records. A total of 492 patients with diagnosed or clinically diagnosed COVID-19 were included in this study. RESULTS: The prevalence rate of AKI was 7.32%. Among the factors associated with AKI, males versus females (aOR 2.73), chronic kidney disease (aOR 42.2), hypertension (aOR 2.82), increased leucocytes (aOR 6.08), and diuretic use (aOR 7.89) were identified as independent risk factors for AKI among patients infected by SARS-CoV-2. There was a significant difference in hospital fees and death in patients with and without AKI (p < 0.05). The mortality rate in patients with AKI was 63.9%. CONCLUSIONS: AKI was widespread among patients with COVID-19. The risk factors of AKI in COVID-19 patients included sex, chronic kidney disease, hypertension, infection, and diuretic use. AKI may be associated with a worse outcome, especially mortality in COVID-19 patients.

Clinical features of patients undergoing hemodialysis with COVID-19.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.

Prevalence of kidney damage in Chinese elderly: a large-scale population-based study.

BACKGROUND: In China, both population aging and kidney damage has become emerging public health challenges. Despite the number of elders is huge, data on kidney damage in this population are scarce. The present study aimed to describe the prevalence of kidney damage among older adults in Wuhan, China. METHODS: To describe the prevalence of kidney damage among Chinese elderly, the health screening data of 350,881 adults older than 65 years in Wuhan, China were collected and analyzed. Kidney damage was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of proteinuria. Decreased renal function was defined as an eGFR < 60 mL/min/1.73 m2. Proteinuria was defined as urine protein ≥1+ and without urine WBC or nitrite positive. The associated risk factors of eGFR decline and kidney damage were analyzed by multivariate logistic regression. RESULTS: The age-standardized prevalence of kidney damage, decreased renal function and proteinuria was 17.2, 13.5 and 5.3%. Among the patients, up to 74.4% was stage 3. The prevalence of kidney damage and eGFR decline were higher in suburbs than in urban (18.3% vs 16.0 and 14.6% vs 12.4%). Factors independently associated with kidney damage were age, female, BMI, abdominal circumference, hypertension, diabetes, stroke and coronary heart disease. CONCLUSIONS: Kidney damage has become an important public health problem in Chinese elderly. More attention should be paid to elderly lived in suburbs or rural area in our further work.

Serum klotho: a potential predictor of cerebrovascular disease in hemodialysis patients.

BACKGROUND: Hemodialysis patients suffer from a serious threat of cerebrovascular disease. Klotho, as an aging-suppressor gene, contributes to protect on vascular calcification and oxidative stress, which are the risk factors of cerebrovascular disease. The purpose of the present study is to determine the relationship between serum klotho and cerebrovascular disease in patients receiving hemodialysis. METHODS: Serum klotho levels of hemodialysis patients were measured by ELISA. Cerebrovascular diseases were diagnosed by CT or MRI scans. The cognitive function of hemodialysis patients with cerebrovascular disease were evaluated with a neuropsychological battery assessing domains of global cognition verbal memory, spatial memory, executive function and verbal fluency. RESULTS: Eighty-eight patients were included, 57 ± 14 years, 63.64% male, 52.27% older than 60 years. Twenty-eight participants had cerebrovascular disease (23 cases had cerebral infarction, 5 cases had cerebral hemorrhage). The average level of serum klotho of all participants was 119.10 ± 47.29 pg/ml. The serum klotho level was significantly associated with cerebrovascular disease in hemodialysis patients (HR(95%CI) = 0.975(0.960-0.990), p = 0.001). The optimal cut-off value of serum klotho for predicting cerebrovascular disease in hemodialysis patients was 137.22 pg/ml, with a specificity of 96.4% and a sensitivity of 46.7%. But serum klotho was not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease (HR((95%CI) = 1.002(0.986-1.018), p = 0.776) or with cerebral infarction (HR(95%CI) = 1.005(0.987-1.023), p = 0.576). CONCLUSIONS: The serum klotho level is a potential predictor of cerebrovascular disease in hemodialysis patients, but it is not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease.

Prevalence of pulmonary hypertension in patients with chronic kidney disease without dialysis: a meta-analysis.

PURPOSE: Recent epidemiological evidence attempts to demonstrate the risk of pulmonary hypertension (PH) among patients with chronic kidney disease (CKD) without dialysis, but prevalence estimates of PH in CKD without dialysis vary widely in the existing studies. This meta-analysis was to summarize the point prevalence of PH in adults with CKD without dialysis. METHODS: PubMed, EMBASE, the Cochrane Collaboration, and the reference lists of relevant articles were searched to identify eligible studies. We used a random-effect meta-analysis model to estimate the prevalence of PH. Associations were tested in subgroups and meta-regression analyses. We also performed sensitivity analyses and assessments of publishing bias. RESULTS: Twenty-one observational studies (n = 8012 participants) were included in this meta-analysis. The result of analysis in random-effect model showed that the pooled prevalence was 32% (95% CI 23-42%), with significant heterogeneity between these studies (I2 = 98%, P < 0.01). Stratified analyses found that the study design, region, sample size, year of publication, and definition of PH based on PASP ≥ 35 mmHg may explain the variation between studies. Sensitivity analysis further demonstrated the results to be robust. There was no evidence of publication bias. CONCLUSIONS: PH is highly prevalent in patients with CKD without dialysis. Owing to the high heterogeneity, future well-designed and large prospective studies are encouraged to confirm the findings and definitively clarify the potential biological mechanisms.

Collagen type III glomerulopathy: A case report and review of 20 cases.

Collagen type III glomerulopathy is a non-immune-mediated glomerular disease, characterized by abnormal accumulation of type III collagen fibrils within the mesangial matrix and subendothelial space. The clinical manifestations of this disease are proteinuria, peripheral edema, hypertension and occasional progression to end-stage renal disease. Collagen type III glomerulopathy is extremely rare, and its etiology and pathogenesis remain elusive. To date, only case reports are available and the majority of these are from Japan. To investigate the idiographic features of collagen type III glomerulopathy in China, we report a case of collagen type III glomerulopathy with two differing renal biopsies and review 20 cases in China. The majority of the Chinese patients were adults. Thirty percent of the patients had nephrotic syndrome, and hypertension was observed in 75% of cases. Elevated creatinine was present in 45% of patients. The pathology of collagen type III glomerulopathy in the Chinese cases was similar to that observed in other ethnicities, although certain cases were IgA-positive by immunofluorescence microscopy, and electron-dense material could be observed in the mesangial area. The onset age, clinical manifestations and pathological features of the disease are not exactly the same in China as worldwide.

DJ-1 knockdown inhibits growth and xenograft­induced tumor generation of human hepatocellular carcinoma cells.

The aim of this study was to identify potential downstream effectors of the oncogene DJ-1 in hepatocellular carcinoma (HCC) cell lines, and examine its role in the Akt signaling pathway and HCC oncogenesis. Expression of the DJ-1 protein was assessed by immunoblotting in several human HCC cell lines. Knockdown of DJ-1 was achieved by transfecting DJ-1-specific short hairpin RNAs into the HepG2 HCC cell line. The effect of DJ-1 downregulation on phosphatase and tensin homolog (PTEN) and phosphorylated Akt was evaluated. In addition, cell cycle, proliferation, adhesion and invasion were analyzed in the DJ-1 knockdown of HepG2 cells. The growth of HepG2­induced tumor was evaluated in a nude mouse model after DJ-1 silencing. Stable DJ-1 knockdown was achieved in HepG2 cells using a shRNA eukaryotic expression vector. Downregulation of DJ-1 increased PTEN expression but decreased phosphorylation of Akt in HepG2 cells. In addition, DJ-1 knockdown resulted in the decreased proliferation, adhesion and invasion of HepG2 cells in vitro, and inhibited the growth of HepG2-induced tumor in vivo. DJ-1 knockdown altered the malignant behavior of HepG2 cells, potentially through the Akt signaling pathway, suggesting a crucial role for DJ-1 in the oncogenesis of HCC.

Renal tuberculosis and iliopsoas abscess: Two case reports.

The urinary system is the second most commonly affected site of extrapulmonary tuberculosis (TB). Due to the diverse and atypical clinical manifestations of urinary TB, the disease is easy to misdiagnose. In the present study, two cases of renal TB are reported, which had completely different clinical manifestations. The first case is a female who presented with loin pain and fever. Purified protein derivative (PPD) and TB antibody tests were negative and computed tomography (CT) scans showed a low density focus in the right kidney with an iliopsoas abscess. The typical CT findings indicated renal tuberculosis. Anti-TB drugs were effective proved the diagnosis. The second case is a male who presented with intermittent gross hematuria. Acid-fast bacilli in urine and TB antibody tests were positive. CT scans revealed a low density focus in the unilateral kidney with a slight expansion of the pelvis, calices and ureter. The patients were treated with the anti-TB drugs and the clinical manifestations disappeared. The diagnosis of urinary TB is challenging in certain cases; when there is no response to the usual antibiotics in patients with fever or gross hematuria, TB should be suspected. CT is the mainstay for investigating possible urinary TB.

Upregulated DJ-1 promotes renal tubular EMT by suppressing cytoplasmic PTEN expression and Akt activation.

Recently, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is suggested as a new agent in the fighting against fibrogenesis. In tumor, DJ-1 is identified as a negative regulator of PTEN. But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear. Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model. Human proximal tubular epithelial cells (HKC) were treated with transforming growth factor-beta 1 (TGF-ß1), or transfected with DJ-1 or PTEN. Confocal microscope was used to investigate the localization of DJ-1 and PTEN. The selective phosphoinositide-3 kinase (PI3K) inhibitor, LY294002, was administered to inhibit PI3K pathway. The DJ-1 and PTEN expression, markers of epithelial-mesenchymal transition (EMT) and Akt phosphorylation were measured by RT-PCR, Western blotting or immunocytochemistry. In vitro, after HKC cells were stimulated with 10 ng/mL TGF-ß1 for 72 h, the expression of DJ-1 was increased, and that of PTEN was decreased. In vivo, the same results were identified in 5/6-nephrectomized rats. In normal HKC cells, most of DJ-1 protein localized in cytoplasm, and little in nucleus. TGF-ß1 upregulated DJ-1 expression in both cytoplasma and nuclei. In contrary, TGF-ß1 emptied cytoplasmic PTEN protein into nucleus. Overexpression of DJ-1 decreased the expression of PTEN, promoted the activation of Akt and the expression of vimentin, and also led to the loss of cytoplasmic PTEN. Contrarily, overexpression of PTEN protected HKC cells from TGF-ß1-induced EMT. In conclusion, DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.

Upregulated DJ-1 Promotes Renal Tubular EMT by Suppressing Cytoplasmic PTEN Expression and Akt Activation / 华中科技大学学报（医学）（英德文版）

Recently,phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells (HKC) were treated with transforming growth factor-beta 1 (TGF-β1),or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase (PI3K) inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition (EMT) and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of D J-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.

Increased DJ-1 and its prognostic significance in hepatocellular carcinoma.

BACKGROUND/AIMS: To investigate the expression profile of DJ-1 gene and its clinical relevance and prognostic value in hepatocellular carcinoma (HCC). METHODOLOGY: Specimens from 149 HCC patients were applied for DJ-1 expression through immunohistochemistry. The correlation of DJ-1 levels with clinicopathologic variables and prognosis was analyzed. 32 paired HCC and para-carcinomatous liver tissue (PCLT) specimens from 149 HCC patients plus 10 hepatic cirrhosis specimens and 10 normal liver specimens were detected by semi-quantitative polymerase chain reaction (PCR) and Western blot. RESULTS: DJ-1 was up-regulated significantly in HCC by semi-quantitative PCR and Western blot. DJ-1 expression closely correlated with preoperative AFP, liver cirrhosis, vein invasion, differentiation and Edmondson grade in HCCs by Pearson Chi-square test. Both of tumor-free survival time and overall survival time in the DJ-1 high expression group were shorter than those in the low expression group. DJ-1 was adopted as an independent prognostic factor for overall survival of HCC patients through multivariate Cox proportional hazard model analysis (HR, 2.568; p = 0.003). Additionally, immunohistochemistry analysis revealed that expression of DJ-1 negatively correlated with expression of tumor suppressor gene phosphatase and tensin homolog deleted on chromosome ten (PTEN) in HCC (r = -0.836; p < 0.001). CONCLUSIONS: DJ-1 expression is significantly upregulated in HCC, and its expression level correlates with clinicopathological variables and prognosis of HCC patients, which suggests that DJ-1 maybe a candidate prognostic biomarker of HCC.

Role of protein kinase C in advanced glycation end products-induced epithelial-mesenchymal transition in renal proximal tubular epithelial cells.

The role of protein kinase C (PKC) activation in advanced glycation end products (AGEs)-induced epithelial-mesenchymal transition in renal proximal tubular epithelial cells was investigated. HKC cells were divided into three groups: normal group, AGE-BSA group (100 mg/L AGE-BSA) and AGE-BSA+PKC inhibitor (10 mumol/L chelerythrine chloride) group. PKC activity was measured by PKC assay kit. The expression of Vimentin, and phosphorylated beta-catenin was detected by using Western blotting, and the content of TGF-beta1 was examined by ELISA method. The intracellular disposition of Vimentin was observed by fluorescence microscopy. As compared with normal group, PKC activity was increased significantly in AGE-BSA group. The expression of Vimentin, phosphorylated beta-catenin, and TGF-beta1 was enhanced significantly in AGE-BSA group. The expression of Vimentin, phosphorylated beta-catenin, and TGF-beta1 was significantly blocked by chelerythrine chloride. High expression of Vimentin, phosphorylated beta-catenin, and TGF-beta1 induced by AGE-BSA may be mediated via the activation of PKC signal transduction pathway.

Role of Protein Kinase Cin Advanced Glycation End Products-induced Epithelial-Mesenchymal Transition in Renal Proximal Tubular Epithelial Cells / 华中科技大学学报（医学）（英德文版）

d by AGE-BSA may be mediated via the activation of PKC signal transduction pathway.