Publications by authors named "Xiang-Mei Chen"

199 Publications

The relationship between transforming growth factor β superfamily members (GDF11 and BMP4) and lumbar spine bone mineral density in postmenopausal Chinese women.

Arch Gynecol Obstet 2021 Aug 21. Epub 2021 Aug 21.

Department of Nephrology, General Hospital of Chinese People's Liberation Army, Beijing, China.

Purpose: The relationship between transforming growth factor β superfamily members (GDF11 and BMP4) and bone metabolism remains controversial. The aim of this study was to investigate the association between serum GDF11 and BMP4 levels and lumbar spine bone mineral density (LBMD) in a cohort of postmenopausal Chinese women.

Methods: This was a non-prospective cross-sectional study of 350 postmenopausal women with a mean age of 63.13 ± 8.66 years who came from Shenyang, China. LBMD was measured using dual-energy X-ray absorptiometry. Serum GDF11 and BMP4 concentrations were detected using a sandwich enzyme immunoassay kit. Pearson's correlation analysis and regression analyses were carried out to investigate the relationships between LBMD and serum GDF11 and BMP4 levels.

Results: A linear association between LBMD and serum LgGDF11 concentration was observed after adjusting for numerous confounders (P = 0.018). In addition, the osteoporosis (OP) was inversely related to LgGDF11 and the odds ratios for postmenopausal women with lumbar OP in LgGDF11 quartile group 2, group 3, and group 4 were 0.46 (95% CI 0.23-0.90, P < 0.05), 0.41 (95% CI 0.20-0.84, P < 0.05), and 0.30 (95% CI 0.14-0.63, P < 0.01), respectively (P = 0.001 for the trend), when compared to the highest quartile of LgGDF11 after adjustments for many confounding variables in this study.

Conclusions: This study showed that serum GDF11 levels were linearly related to LBMD, and it was also revealed that serum GDF11 levels were significantly associated with lumbar OP in postmenopausal women. However, serum BMP4 levels were not associated with LBMD and lumbar OP.
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http://dx.doi.org/10.1007/s00404-021-06183-8DOI Listing
August 2021

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

Blood Purif 2021 Jun 25:1-11. Epub 2021 Jun 25.

The PLA Medical College, Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients.

Methods: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80.

Results: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010).

Conclusions: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.
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http://dx.doi.org/10.1159/000506536DOI Listing
June 2021

Nomogram prediction model for renal anaemia in IgA nephropathy patients.

Open Med (Wars) 2021 7;16(1):718-727. Epub 2021 May 7.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China.

In this study, we focused on the influencing factors of renal anaemia in patients with IgA nephropathy and constructed a nomogram model. We divided 462 patients with IgA nephropathy diagnosed by renal biopsy into anaemic and non-anaemic groups. Then, the influencing factors of renal anaemia in patients with IgA nephropathy were analysed by least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model for predicting renal anaemia was established. Eventually, nine variables were obtained, which are easy to apply clinically. The areas under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve reached 0.835 and 0.676, respectively, and the C-index reached 0.848. The calibration plot showed that the model had good discrimination, accuracy, and diagnostic efficacy. In addition, the C-index of the model following internal validation reached 0.823. Decision curve analysis suggested that the model had a certain degree of clinical significance. This new nomogram model of renal anaemia combines the basic information, laboratory findings, and renal biopsy results of patients with IgA nephropathy, providing important guidance for predicting and clinically intervening in renal anaemia.
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http://dx.doi.org/10.1515/med-2021-0284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111477PMC
May 2021

Cellular senescence and the senescence-associated secretory phenotype: Potential therapeutic targets for renal fibrosis.

Exp Gerontol 2021 08 11;151:111403. Epub 2021 May 11.

School of Medicine, Nankai University, Tianjin 300071, China; Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China. Electronic address:

Renal fibrosis plays a crucial role in the progression of chronic kidney disease and end-stage renal disease. However, because the aetiology of this pathological process is complex and remains unclear, there is still no effective treatment. Cellular senescence and the senescence-associated secretory phenotype (SASP) have been reported to lead to renal fibrosis. This review first discusses the relationships among cellular senescence, the SASP and renal fibrosis. Then, the key role of the SASP in irreversible renal fibrosis, including fibroblast activation and abnormal extracellular matrix accumulation, is discussed, with the results of studies having indicated that inhibiting cellular senescence and the SASP might be a potential preventive and therapeutic strategy for renal fibrosis. Finally, we summarize promising therapeutic strategies revealed by existing research on senescent cells and the SASP, including emerging interventions targeting the SASP, caloric restriction and mimetics, and novel regeneration therapies with stem cells.
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http://dx.doi.org/10.1016/j.exger.2021.111403DOI Listing
August 2021

Association between age-related kidney function and vascular subclinical state in a healthy Chinese population.

Chin Med J (Engl) 2021 Mar 31. Epub 2021 Mar 31.

Department of Gerontology and Geriatrics, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519099, China Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China Department of Kidney, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.

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http://dx.doi.org/10.1097/CM9.0000000000001422DOI Listing
March 2021

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

J Integr Med 2021 03 30;19(2):111-119. Epub 2021 Jan 30.

Department of Nephrology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China.

Background: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.

Objective: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.

Design, Setting, Participants And Intervention: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg.

Main Outcome Measures: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.

Results: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.

Conclusion: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.

Trial Registration Number: NCT02063100 on ClinicalTrials.gov.
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http://dx.doi.org/10.1016/j.joim.2021.01.009DOI Listing
March 2021

Identification of Potential Gene and MicroRNA Biomarkers of Acute Kidney Injury.

Biomed Res Int 2021 8;2021:8834578. Epub 2021 Jan 8.

Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China.

Acute kidney injury (AKI) is a disease that seriously endangers human health. At present, AKI lacks effective treatment methods, so it is particularly important to find effective treatment measures and targets. Bioinformatics analysis has become an important method to identify significant processes of disease occurrence and development. In this study, we analyzed the public expression profile with bioinformatics analysis to identify differentially expressed genes (DEGs) in two types of common AKI models (ischemia-reperfusion injury and cisplatin). DEGs were predicted in four commonly used microRNA databases, and it was found that miR-466 and miR-709 may play important roles in AKI. Then, we found key nodes through protein-protein interaction (PPI) network analysis and subnetwork analysis. Finally, by detecting the expression levels in the renal tissues of the two established AKI models, we found that Myc, Mcm5, E2f1, Oip5, Mdm2, E2f8, miR-466, and miR-709 may be important genes and miRNAs in the process of AKI damage repair. The findings of our study reveal some candidate genes, miRNAs, and pathways potentially involved in the molecular mechanisms of AKI. These data improve the current understanding of AKI and provide new insight for AKI research and treatment.
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http://dx.doi.org/10.1155/2021/8834578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810567PMC
May 2021

Method used to establish a large animal model of drug-induced acute kidney injury.

Exp Biol Med (Maywood) 2021 Apr 19;246(8):986-995. Epub 2021 Jan 19.

Department of Nephrology, the First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China.

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.
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http://dx.doi.org/10.1177/1535370220981756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024500PMC
April 2021

Influences of renal anemia on the pathology of IgA nephropathy: a study based on propensity score matching.

Discov Med 2020 Jul-Aug;30(159):7-18

Department of Nephrology, Chinese PLA Institute of Nephrology/State Key Laboratory of Kidney Diseases/National Clinical Research Center for Kidney Diseases/Beijing Key Laboratory of Kidney Disease/Chinese PLA General Hospital, Beijing 100853, China.

Objective: This study aims to investigate the influences of renal anemia on the pathogenesis of IgA nephropathy using propensity score matching (PSM).

Methods: Renal biopsies from 462 patients with IgA nephropathy were enrolled in this study. PSM was used to balance intergroup covariates, and matching results were verified using a dot-plot of standardized mean differences and histograms of the propensity score distribution and distance distribution. The matched data were used to analyze the impact of renal anemia on the pathological indicators of IgA nephropathy by logistic regression.

Results: A total of 132 pairs of patients from the renal anemia group and the non-renal anemia group were matched by PSM; after matching, the standard deviations of 13 covariates were within 0.25. Multivariate logistic regression results suggested that the CKD4-5 stage of IgA nephropathy and tubular atrophy/interstitial fibrosis >50% were independent risk factors for renal anemia.

Conclusions: Via PSM, we demonstrated that decreased eGFR and severe tubular atrophy/interstitial fibrosis are correlated with renal anemia in IgA nephropathy. In clinical practice, renal anemia in patients with IgA nephropathy of CKD3 stage or above should be closely monitored and managed.
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December 2020

Therapeutic effect of intravenous sodium thiosulfate for uremic pruritus in hemodialysis patients.

Ren Fail 2020 Nov;42(1):987-993

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Objectives: This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients.

Methods: This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes.

Results: There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group ( < 0.05). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant ( > 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy.

Conclusions: STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.
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http://dx.doi.org/10.1080/0886022X.2020.1822867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534216PMC
November 2020

Caloric restriction alleviates aging-related fibrosis of kidney through downregulation of miR-21 in extracellular vesicles.

Aging (Albany NY) 2020 Aug 27;12(18):18052-18072. Epub 2020 Aug 27.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China.

Glomerulosclerosis and renal interstitial fibrosis occur with the aging kidney. In this study, we examined the expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF-1α) in the kidney of 3-month-old rats fed ad libitum (YAL), 24-month-old rats fed ad libitum (OAL) and 24-month-old rats subjected to a 70% calorie-restricted diet for 8 months (OCR). We found long-term caloric restriction (CR) ameliorated aging and aging-related fibrosis. CR ameliorated the increment of miR-21 and HIF-1α, as well as the decrement of PPARα in old ad libitum group. Human proximal tubular cells (HPTCs) presented phenotypes of senescence and epithelial to mesenchymal transition (EMT) under high-glucose conditions, in which senescence occurred earlier than EMT. Senescent cells secreted extracellular vesicles (EVs) which contained miR-21 into the recipient cells. Inhibiting miR-21 of donor cells prevented the occurrence of EMT in recipient cells. In addition, miR-21 induced EMT through targeting PPARα protein and consequently enhancing HIF-1α expression, although other pathways cannot be ruled out. These findings demonstrated that miR-21-containing EVs derived from the senescent cells could facilitate EMT of HPTCs via PPARα-HIF-1α signaling pathway. Long-term caloric restriction and caloric restriction mimetics alleviated aging-related-fibrosis of kidney through downregulation of miR-21.
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http://dx.doi.org/10.18632/aging.103591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585074PMC
August 2020

Risk factors for mortality in elderly haemodialysis patients: a systematic review and meta-analysis.

BMC Nephrol 2020 08 31;21(1):377. Epub 2020 Aug 31.

Department of Nephrology, Chinese PLA Generl Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.

Background: Older haemodialysis patients accompany a high burden of functional impairment, limited life expectancy, and healthcare utilization. This meta-analysis aimed to evaluate how various risk factors influenced the prognosis of haemodialysis patients in late life, which might contribute to decision making by patients and care providers.

Methods: PubMed, Embase, and Cochrane Central were searched systematically for studies evaluating the risk factors for mortality in elderly haemodialysis patients. Twenty-eight studies were included in the present systematic review. The factors included age, cardiovascular disease, diabetes mellitus, type of vascular access, dialysis initiation time, nutritional status and geriatric impairments. Geriatric impairments included frailty, cognitive or functional impairment and falls. Relative risks with 95% confidence intervals were derived.

Results: Functional impairment (OR = 1.45, 95% CI: 1.20-1.75), cognitive impairment (OR = 1.46, 95% CI: 1.32-1.62) and falls (OR = 1.14, 95% CI: 1.06-1.23) were significantly and independently associated with increased mortality in elderly haemodialysis patients. Low body mass index conferred a mortality risk (OR = 1.43, 95% CI: 1.31-1.56) paralleling that of frailty as a marker of early death. The results also confirmed that the older (OR = 1.43, 95% CI: 1.22-1.68) and sicker (in terms of Charlson comorbidity index) (OR = 1.41, 95% CI: 1.35-1.50) elderly haemodialysis patients were, the more likely they were to die. In addition, increased mortality was associated with early-start dialysis (OR = 1.18, 95% CI: 1.01-1.37) and with the use of a central venous catheter (OR = 1.53, 95% CI: 1.44-1.62).

Conclusions: Multiple factors influence the risk of mortality in elderly patients undergoing haemodialysis. Geriatric impairment is related to poor outcome. Functional/cognitive impairment and falls in elderly dialysis patients are strongly and independently associated with mortality.
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http://dx.doi.org/10.1186/s12882-020-02026-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457491PMC
August 2020

GLA missense and promoter variants co-segregating in a Chinese family with Fabry disease.

Ann Transl Med 2020 Jul;8(14):865

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Background: Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder due to mutations in the GLA gene leading to deficiency of lysosomal α-galactosidase A (α-Gal A) and has a wide range of clinical presentations. Over 900 GLA gene mutations are currently known and of those most are thought not to be clinically significant, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician.

Methods: Whole-exome sequencing (WES) was performed to detect the mutation in family members with Fabry disease. The function of g.1170C>T mutation was confirmed by dual luciferase system.

Results: A total of 1,375 variants were found in a Chinese family with FD. A missense variants c.1025C>T (p.Arg342Gln) which have been previously reported in association with FD and g.1170C>T single-nucleotide polymorphism (SNP) in the GLA gene were found in five patients. The g.1170C>T SNP affects transcription of GLA gene, presumably the transcription start site. Female patients only have hypohidrosis and neuropathic pain, while male patients have severe symptoms with simultaneous renal impairment.

Conclusions: Two simultaneous variants in cis of the GLA gene, c.1025C>T (p.Arg342Gln) and g.1170C>T, were verified in Chinese individuals, and the corresponding clinical symptoms were described. The disease severity in male patients is worse than in female patients. These results may be helpful for genetic counseling, diagnosis and prognosis of patients with FD.
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http://dx.doi.org/10.21037/atm-19-4510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396806PMC
July 2020

Associations of coenzyme Q10 with endothelial function in hemodialysis patients.

Nephrology (Carlton) 2021 Jan 1;26(1):54-61. Epub 2020 Sep 1.

Medical School of Chinese PLA, Beijing, PR China.

Background: Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients.

Methods: Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model.

Results: In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (β = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (β = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels.

Conclusion: Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients.
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http://dx.doi.org/10.1111/nep.13766DOI Listing
January 2021

Cognitive impairment and associated risk factors in older adult hemodialysis patients: a cross-sectional survey.

Sci Rep 2020 07 27;10(1):12542. Epub 2020 Jul 27.

Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Disease, Beijing, 100853, China.

The clinical epidemiological features of cognitive impairment in Chinese older adult patients undergoing hemodialysis are not clear, we aimed to identify the extent and patterns of cognitive impairment among those patients. We conducted a cross-sectional study of 613 hemodialysis patients aged 50 to 80 from 11 centers in Beijing. A neuropsychological battery of 11 tests covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied, patients were classified as none, mild, or major cognitive impairment according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria for cognitive impairment. Compared with Chinese population norms, 37.2% of the participants had mild cognitive impairment, 43.7% had major cognitive impairment. Memory and language were the most severe impaired domains in the mild cognitive impairment group, attention and visuospatial function domains were the most serious impaired domains in the major cognitive impairment group. Concomitant impairment across multiple cognitive domains was common. Factors associated with major cognitive impairment included age, education level, history of stroke and hypertension, dialysis vintage, and single-pool Kt/V. There is a high frequency of cognitive impairment in Chinese older adult hemodialysis patients, with varying severity and concomitant impairment across multiple domains.
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http://dx.doi.org/10.1038/s41598-020-69482-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385128PMC
July 2020

Analysis of the causes of cervical lymphadenopathy using fine-needle aspiration cytology combining cell block in Chinese patients with and without HIV infection.

BMC Infect Dis 2020 Mar 14;20(1):224. Epub 2020 Mar 14.

Department of Pathology, Beijing Ditan Hospital,Captial Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.

Background: Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block.

Methods: A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori's methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section.

Results: The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p < 0.01). Of all patients infected with HIV, 390 (86.1%) were males. This proportion was significantly higher than that of non-HIV-infected patients [65/136 (47.8%)] (p < 0.01). The major causes of cervical lymphadenopathy in HIV positive patients were mycobacterial infection (38.4%), reactive hyperplasia (28.9%), non-specific inflammation (19.9%), and malignant lesions (4.2%). In contrast, the most common causes in HIV negative patients were reactive hyperplasia (37.5%), malignancy (20.6%), non-specific inflammation (19.1%) and mycobacterial infection (12.5%). Opportunistic infections such as non-tuberculous mycobacteria (4.2%), cryptococcosis (1.5%), Talaromyces marneffei (1.5%) and other fungi (0.4%) were found only in HIV-infected individuals. Non-Hodgkin's lymphoma (2.4%) was the most common malignant lesion in patients with HIV infection, followed by Kaposi's sarcoma (0.9%) and metastatic squamous cell carcinomas (0.7%). However, the most common malignancy in non-HIV-infected patients was metastatic carcinomas (14%) including small cell carcinomas, adenocarcinomas, squamous cell carcinomas and hepatocellular carcinoma, which were noticeably greater than the HIV patients (p < 0.01).

Conclusions: There were significantly different causes of cervical lymphadenopathy in HIV infected and non-HIV infected patients. FNAC was a useful diagnostic method for differential diagnosis of cervical lymphadenopathy.
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http://dx.doi.org/10.1186/s12879-020-4951-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071630PMC
March 2020

Single-cell RNA sequencing data suggest a role for angiotensin-converting enzyme 2 in kidney impairment in patients infected with 2019-novel coronavirus.

Chin Med J (Engl) 2020 May;133(9):1129-1131

Department of Nephrology, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100039, China.

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http://dx.doi.org/10.1097/CM9.0000000000000783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213623PMC
May 2020

Relationship between serum C3/C4 ratio and prognosis of immunoglobulin A nephropathy based on propensity score matching.

Chin Med J (Engl) 2020 Mar(6):631-637

Department of Nephrology, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.

Background: Aberrant activation of the complement system plays an important role in the pathogenesis and development of immunoglobulin A nephropathy (IgAN). The relationship between serum complement and the clinical-histopathological features and outcomes of IgAN is controversial. This retrospective study aimed to examine the relationship between the complement 3/4 (C3/C4) ratio and the clinicopathologic changes and prognosis of patients with IgAN.

Methods: A total of 397 patients with primary IgAN from January 2007 to December 2012 at the Chinese People's Liberation Army General Hospital were included in this study. The correlation test and Chi-square test or one-way analysis of variance test were performed to evaluate the relationship between the C3/C4 ratio and other clinical-pathological factors. Propensity score matching and a multivariate Cox regression model were used to calculate the risk factors of renal outcome.

Results: The median follow-up period was 75 months. During the follow-up period, 62 patients (15.6%) developed into the end-stage renal disease (ESRD). The C3/C4 ratio at baseline was associated with the level of serum creatinine (SCr), 24 h urinary protein excretion (24 h Upre), global glomerular sclerosis, and tubulointerstitial lesion. The level of SCr and 24 h Upre and the degree of chronic kidney injury were statistically different among groups defined by different C3/C4 ratio levels. The survival rates of patients among groups with different C3/C4 ratio levels were different. After propensity score matching, eighty-eight pairs of patients were successfully matched, and the C3/C4 ratio was an influencing factor for the patients' outcome (hazard ratio 0.587, 95% confidence interval 0.329-0.880). Patients with a C3/C4 ratio <3.6 had a poorer outcome compared with the others (P = 0.002).

Conclusions: IgAN patients with decreased C3/C4 ratio displayed significantly more severe clinical symptoms and chronic renal injury than patients with higher ratios. A low C3/C4 ratio could be a risk factor for patients developing to ESRD.
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http://dx.doi.org/10.1097/CM9.0000000000000674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190234PMC
March 2020

Risk Factors For Hyperuricemia In Chinese Centenarians And Near-Centenarians.

Clin Interv Aging 2019 19;14:2239-2247. Epub 2019 Dec 19.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Kidney Diseases, Beijing 100853, People's Republic of China.

Purpose: Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians.

Patients And Methods: In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted.

Results: The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p<0.05). Multivariate logistic regression analysis showed that WC (OR=1.020), eGFR (OR=0.960), TP level (OR=1.038), serum urea level (OR=1.154), passive smoking (OR=2.589), snoring (OR=2.003), meat consumption (OR=2.506), seafood consumption (OR=1.422) and vegetable consumption (OR=0.521) were significantly associated with the risk of hyperuricemia (p<0.05).

Conclusion: Low eGFR and vegetable consumption, high WC, TP, and serum urea levels, passive smoking, snoring, and high meat and seafood consumption were independent risk factors for hyperuricemia. It is recommended that people at high risk for hyperuricemia should actively limit their intake of fried food, alcohol and purine-rich food, increase their intake of fresh vegetables, actively treat sleep apnea syndrome, avoid passive smoking, maintain a healthy WC and seek to improve their kidney and liver function.
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http://dx.doi.org/10.2147/CIA.S223048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927493PMC
March 2020

Association of the malnutrition-inflammation score with anthropometry and body composition measurements in patients with chronic kidney disease.

Ann Palliat Med 2019 Nov 12;8(5):596-603. Epub 2019 Nov 12.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing 100853, China.

Background: The malnutrition-inflammation score (MIS) is a nutritional scoring system that has been validated in chronic kidney disease (CKD) stages III-V, especially in dialysis patients. We aimed to test whether the MIS changed in the early stages of CKD and whether it was associated with anthropometry and body composition measurements (BCMs) in patients with CKD.

Methods: This was a cross-sectional study conducted in the Nephrology Department. A total of 144 patients with CKD were included in the study between May 2017 and December 2017. The MIS was calculated without computing the dialysis vintage in the scoring. Body composition was measured using a portable whole-body bioimpedance spectroscopy device. Anthropometric, laboratory, and other body composition parameters were recorded.

Results: The MIS was increased in patients with CKD. It was negatively correlated with body mass index (BMI), mid-arm muscle circumference (MAMC), handgrip strength, lean tissue index (LTI), fat tissue index (FTI), phase angle (PA), and hemoglobin and albumin concentrations, and it was positively correlated with sex, overhydration, urinary protein excretion and IL-6. A high MIS was significantly correlated with a low LTI (r=-0.274; P=0.001), low FTI (r=-0.179; P=0.032), overhydration (r=0.457; P<0.001) and low PA (r=-0.475; P<0.001). A rather strong correlation was observed between the PA and the MIS. In the multivariate regressions, after adjusting for age, sex, presence of diabetes, handgrip strength, BMI, overhydration, glomerular filtration rate, albumin and IL-6 concentrations, these relationships did not diminish.

Conclusions: The MIS was strongly linked with indicators of nutrition. As a simple and practical tool for assessing nutritional status, the MIS should be calculated in the early stages of CKD.
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http://dx.doi.org/10.21037/apm.2019.10.12DOI Listing
November 2019

Diagnostic efficacy of serum anti-phospholipase A2 receptor antibodies for idiopathic membranous nephropathy in patients with diabetic kidney disease.

Clin Chim Acta 2020 Mar 13;502:222-226. Epub 2019 Nov 13.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China. Electronic address:

Aim: Serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies are highly accurate in diagnosing idiopathic membranous nephropathy (IMN) in populations with kidney disease. However, the diagnostic value of anti-PLA2R antibodies for IMN in diabetic kidney disease (DKD) is unclear. The objective of this study is to determine the diagnostic efficacy and the optimal cut-off value of this marker in populations with DKD.

Methods: This study included 227 patients with type 2 diabetes who were admitted to the Department of Nephrology of the Chinese People's Liberation Army General Hospital from May 2016 to January 2018 and underwent pathological diagnosis by renal biopsy. Anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay in this population. According to the pathological results, the participants were divided into an IMN group and non-membranous nephropathy (non-MN) group. The clinical characteristics were analyzed, the diagnostic ability of anti-PLA2R antibodies was evaluated, and the receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value.

Results: There were 45 patients in the IMN group, accounting for 19.8% of the study sample. The patients in this group were older at the time of renal biopsy than the non-MN group and presented a shorter duration of diabetes, better glycemic control, lower blood pressure and uric acid, and better renal function; in addition, their clinical symptoms indicated nephrotic syndrome. The optimal cut-off value for anti-PLA2R antibodies for the diagnosis of IMN in DKD was 2.71 Ru/ml, sensitivity was 0.800, specificity was 0.951, positive predictive value was 0.800, negative predictive value was 0.951, accuracy was 0.921, and the Yoden index was 0.750. The area under the ROC curve was 0.87 (95% CI, 0.788-0.952) (p < 0.001).

Conclusions: Patients in the IMN group were older, had better renal function and general condition, and the clinical symptoms indicated nephrotic syndrome. Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD, and the optimal cut-off value was 2.71.
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http://dx.doi.org/10.1016/j.cca.2019.11.004DOI Listing
March 2020

miRNAs in stem cell-derived extracellular vesicles for acute kidney injury treatment: comprehensive review of preclinical studies.

Stem Cell Res Ther 2019 09 3;10(1):281. Epub 2019 Sep 3.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, 100853, China.

Stem cell therapy has been applied in many fields. Basic and clinical studies on stem cell therapy for acute kidney injury (AKI) have been conducted. Stem cells have been found to exert renal protection through a variety of mechanisms, such as regulating the immune system and secreting growth factors, cytokines, and extracellular vesicles (EVs). Among them, EVs are considered to be important mediators for stem cell protection because they contain various biological components, including microRNAs (miRNAs). miRNAs are a class of small RNAs that function in posttranscriptional gene regulation. A number of studies have confirmed that miRNAs in stem cell-derived EVs can protect from AKI. miRNAs can enter the injured renal tissue through EVs released from stem cells, thereby exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenesis effects on AKI. However, the stem cell sources and AKI models used in these studies have differed. This article will summarize the miRNAs that play a role in kidney protection in stem cell EVs and clarifies the treatment characteristics and mechanisms of different miRNAs. This may provide a reference for clinical practice for acute and chronic kidney diseases.
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http://dx.doi.org/10.1186/s13287-019-1371-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724288PMC
September 2019

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy.

Kidney Blood Press Res 2019 28;44(5):928-941. Epub 2019 Aug 28.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background/aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification.

Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]).

Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21-0.74; Oxford classification 0.48, 95% CI 0.28-0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23-0.92; Oxford classification 0.59, 95% CI 0.10-0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification.

Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.
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http://dx.doi.org/10.1159/000500459DOI Listing
March 2020

Can we predict who will develop postoperative hyperkalaemia after parathyroidectomy in dialysis patients with secondary hyperparathyroidism?

BMC Nephrol 2019 06 20;20(1):225. Epub 2019 Jun 20.

Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.

Background: Hyperkalaemia occurs frequently in many maintenance haemodialysis (MHD) patients after parathyroidectomy (PTX) with secondary hyperparathyroidism (SHPT). However, the clinical risk factors that predict postoperative hyperkalaemia are uncertain.

Methods: This retrospective cohort study included 90 maintenance haemodialysis patients aged ≥18 years who underwent PTX between April 2011 and April 2016 at Aerospace Center Hospital (Peking University Aerospace School of Clinical Medicine). Pre- and post-PTX surgery venous samples were measured in quadruplicate. We examined univariate associations with demographics, dialysis characteristics, laboratory values and medications. Hyperkalaemia was defined as serum potassium >5.3 mmol/L.

Results: Out of nighty patients, twenty-two (24.4%) developed postoperative hyperkalaemia, of whom sixteen (18.1%) developed hyperkalaemia on postoperative day 3. The univariate analysis showed that weight, dialysis duration, preoperative serum potassium, alkaline phosphate, triglyceride, and postoperative alkaline phosphate were independently associated with hyperkalaemia after parathyroidectomy. The univariate logistic regression model showed that preoperative serum potassium was the only independent factor that could predict hyperkalaemia after parathyroidectomy (odds ratio, 1.59; 95% confidence interval, 1.24-2.05). The optimal cut-off for pre-operative K was 3.9 mmol/L according to the receiver operating characteristic (ROC) curve. A higher incidence of postoperative hyperkalaemia was found in male and younger patients, but the difference was not statistically significant (p>0.05).

Conclusions: Pre-operative serum potassium less than 3.9 mmol/L was associated with less hyperkalaemia post-operatively in end-stage renal disease (ESRD) patients undergoing PTX.
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http://dx.doi.org/10.1186/s12882-019-1416-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585140PMC
June 2019

The prevalence of depression and the association between depression and kidney function and health-related quality of life in elderly patients with chronic kidney disease: a multicenter cross-sectional study.

Clin Interv Aging 2019 15;14:905-913. Epub 2019 May 15.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, People's Republic of China.

The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL. In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument. The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=-0.097, =0.001) or as a continuous variable (r=-0.100, =0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1-2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; =0.031) and CKD 5 (odds ratio [OR] =5.171; <0.001), respectively. We observed negative and significant correlations with the GDS score for the following components: PCS (r=-0.370, <0.001), MCS (r=-0.412, <0.001), burden of kidney disease (r=-0.403, <0.001), symptoms and problems of kidney disease (r=-0.360, <0.001) and effects of kidney disease (r=-0.355, <0.001). Depression was an independent and significant predictor of all the subcomponents of the HRQOL. The prevalence of depression in elderly patients with CKD was high and was negatively correlated with kidney function. Depression had a major negative impact on HRQOL.
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http://dx.doi.org/10.2147/CIA.S203186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526925PMC
September 2019

Methionine restriction delays senescence and suppresses the senescence-associated secretory phenotype in the kidney through endogenous hydrogen sulfide.

Cell Cycle 2019 07 5;18(14):1573-1587. Epub 2019 Jun 5.

a Department of Nephrology, Chinese PLA General Hospital , Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases , Beijing , China.

Aging is a risk factor for various acute and chronic kidney injuries. Kidney aging is accompanied by the secretion of growth factors, proteases, and inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). These factors accelerate the aging process and senescence-associated changes. Delaying kidney senescence may prevent acute and chronic kidney injury. Methionine restriction (MR) was found to be an effective intervention for delaying senescence. However, the mechanism of MR remains unclear. In this study, we investigated the effect of MR on the survival rate and renal aging of C57BL/6 mice and examined the relevant mechanisms. MR increased the survival rate and decreased the levels of senescence markers in the aging kidney. Both in vivo and in vitro, MR upregulated the transsulfuration pathway to increase HS production, downregulated senescence markers and the SASP, and activated AMPK. The ability of MR to delay aging was reduced when AMPK was inhibited. These results suggest that MR may slow animal aging and kidney senescence through HS production and AMPK pathway activation. : DR: diet restriction; MR: methionine restriction; SASP: senescence-associated secretory phenotype; AL: ad libitum; CKD, chronic kidney disease; AKI: acute kidney disease; TSP: transsulfuration pathway; CGL: cystathionine g-lyase; HS: hydrogen sulfide; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; IS: indoxyl sulfate; CC: compound C.
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http://dx.doi.org/10.1080/15384101.2019.1618124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619995PMC
July 2019

Association between ventricular repolarization variables and cardiac diastolic function: A cross-sectional study of a healthy Chinese population.

World J Clin Cases 2019 Apr;7(8):940-950

Department of Kidney, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.

Background: Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population.

Aim: To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals.

Methods: This was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography (ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity (E) and late diastolic inflow velocity (A), E-wave deceleration time, left atrial volume (LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.

Results: Ventricular repolarization variables, such as the QTc interval (393.59 26.74 403.86 33.56; 0.001), Tpe interval (72.68 12.41 77.26 17.86; 0.01), Tpe interval (76.36 13.53 83.32 21.25; 0.001) and Tpe/QT ratio (0.19 0.03 0.20 0.04; 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function. After adjusting for all other possible confounders, the QTc and Tpe intervals were significantly associated with the E/A ratio ( = 0.008; 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertile, in the second QTc tertile, the odds ratio was 0.257 (95%CI: 0.102-0.649; = 0.004).

Conclusion: Repolarization variables are associated with cardiac diastolic function even in healthy people. Moderate levels of the QTc interval exert a protective effect on diastolic dysfunction in men.
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http://dx.doi.org/10.12998/wjcc.v7.i8.940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509266PMC
April 2019

A simplified lung ultrasound for the diagnosis of interstitial lung disease in connective tissue disease: a meta-analysis.

Arthritis Res Ther 2019 04 11;21(1):93. Epub 2019 Apr 11.

Department of Ultrasound, Peking University Shenzhen Hospital, Lianhua Road 1120, FuTian District, Shenzhen, 518036, Guangdong, China.

Background: Interstitial lung disease (ILD) is a common complication of connective tissue disease (CTD) and a leading cause of morbidity and mortality. There are various lung ultrasound (LUS) scoring systems with different lung intercostal spaces (LIS). The purpose of this meta-analysis was to find a simplified LUS method for the assessment of CTD-ILD.

Methods: We systematically retrieved lung ultrasound diagnostic studies on CTD-ILD in PubMed, Embase, and Web of Science databases. Summary diagnostic accuracy, including sensitivity, specificity, and area under the curve (AUC), was analyzed. Subgroup analysis was conducted according to different LIS and diseases.

Results: The 11 studies included in this meta-analysis comprised a total of 487 patients with CTD. The pooled sensitivity and specificity of the LUS were 0.859 (95% confidence interval (CI) 0.812-0.898) and 0.839 (95% CI 0.782-0.886), respectively, illustrating its great value for CTD-ILD diagnosis. In addition, there were six methods to evaluate LIS, including 72, 65, 50, 14, 10, and all LIS. The pooled sensitivity and specificity of 14 LIS were 0.982 (95% CI 0.904-1.000) and 0.875 (95% CI 0.710-0.965), respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odd ratio (DOR) of 14 LIS were 7.297 (95% CI 6.050-17.45), 0.029 (95% CI 0.006-0.147), and 292.30 (95% CI 35.53-2403.8), respectively. Moreover, the AUC for systemic sclerosis (SSc) and rheumatoid arthritis (RA) was 0.929 and 0.981, respectively; the DOR for SSc and RA was 42.93 (95% CI 17.75-103.79) and 80.24 (95% CI 8.107-796.09), respectively.

Conclusions: We found a modified and simplified method of LUS, by scanning 14 LIS in a short time, which had a very high sensitivity and specificity.
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http://dx.doi.org/10.1186/s13075-019-1888-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460810PMC
April 2019

Urinary angiostatin: a novel biomarker of kidney disease associated with disease severity and progression.

BMC Nephrol 2019 04 3;20(1):118. Epub 2019 Apr 3.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, 100853, China.

Background: This study aimed to evaluate the value of urinary angiostatin levels for assessing disease severity and progression of IgA nephropathy (IgAN).

Methods: Urinary angiostatin was identified as one of the distinct proteins in samples of patients with IgAN analyzed by Raybiotech protein array, and further confirmed by enzyme-linked immunosorbent assay (ELISA).

Results: Urinary angiostatin levels were significantly higher in IgAN patients than that in healthy controls (HC) subjects and lower than in disease controls (DC) patients. The concentrations of angiostatin in urine normalized to urinary creatinine (angiostatin/Cr) were positively associated with proteinuria level. With advancing chronic kidney disease (CKD) stage, urinary angiostatin/Cr levels were gradually increased. Urinary angiostatin/Cr levels in patients with Lee's grade IV-V were significantly higher than those in Lee's grade I-II and III. We further compared urinary angiostatin/Cr levels by using Oxford classification and found the expression in patients with mesangial proliferative score 1(M1) was significantly higher than that in M0 (P < 0.001). In addition, the levels of urinary angiostatin/Cr in patients with tubular atrophy/interstitial fibrosis score 1(T1) and T2 were significantly higher than those in T0 (P < 0.01, P < 0.001, respectively). After follow-up, renal survival was significantly worse in patients with higher levels of urinary angiostatin (P < 0.05).

Conclusions: Urinary angiostatin may be a useful novel noninvasive biomarker to evaluate disease severity and progression of IgAN.
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http://dx.doi.org/10.1186/s12882-019-1305-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446319PMC
April 2019
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