1.Relationships of Inflammatory Factors and Risk Factors with Different Target Organ Damage in Essential Hypertension Patients.
Chun-Lin LAI ; Jin-Ping XING ; Xiao-Hong LIU ; Jie QI ; Jian-Qiang ZHAO ; You-Rui JI ; Wu-Xiao YANG ; Pu-Juan YAN ; Chun-Yan LUO ; Lu-Fang RUAN
Chinese Medical Journal 2017;130(11):1296-1302
BACKGROUNDAtherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance.
METHODSA total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed.
RESULTSFibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026.
CONCLUSIONSFbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.
1-Alkyl-2-acetylglycerophosphocholine Esterase ; Aged ; Antihypertensive Agents ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Essential Hypertension ; blood ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Kidney Diseases ; blood ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; etiology ; physiopathology ; Risk Factors ; Serum Amyloid A Protein ; metabolism ; Stroke ; blood ; etiology ; physiopathology ; Tryptases ; blood
2.BM-MSCs from Wuzhishan mini-pigs delay the progress of renal fibrosis induced by chronic kidney disease through autocrine hepatocyte growth factor in vitro.
Yang XIANG ; Jiale LONG ; Jiansheng XING ; Yuanhui GAO ; Qing CHENG ; Yong CAI ; Zhenxiang LIU ; Shufang ZHANG ; Lie CHEN ; Chao YANG ; Zhiming BAI
Journal of Central South University(Medical Sciences) 2016;41(12):1260-1269
To isolate bone marrow mesenchymal stem cells (BM-MSCs) and establish the model of chronic kidney disease (CKD) of Wuzhishan (WZS) mini-pig, and to study the repairment effect of BM-MSCs on CKD-induced renal fibrosis in vitro.
Methods: Density gradient method was used to isolate and culture BM-MSCs. The cells were verified by morphology, phenotype, differentiation and so on. The left partial ureteral obstruction (LPUUO) was used to establish the CKD model, which was evaluated by B-ultrasound, single-photon emission computed tomography (SPECT), HE and Masson staining. The cells were divided into 3 groups, the tissue plus BM-MSCs group, the tissue group, and the BM-MSCs group, respectively. Seven days later, the supernatants were collected to observe the changes of hepatocyte growth factor (HGF) cumulative release. HE and Masson staining was used to observe the changes of renal tissue.
Results: The isolated BM-MSCs possessed the features as follow: fibroblast-like adherent growth; positive in CD29 and CD90 expression while negative in CD45 expression; osteogenic induction and alizarin red staining were positive; alcian blue staining were positive after chondrogenic induction. Twelve weeks after the operation of LPUUO, B-ultrasound showed the thin renal cortical with pelvis effusion; SPETCT showed the left kidney delayed filling and renal impairment. The accumulation of HGF in the tissue plus BM-MSCs group was significantly higher than that in the tissue alone group at the 1st, 5th, 6th, 7th day, respectively (P<0.05). HE staining showed the different degree of renal lesions between the tissue plus BM-MSCs+CKD group and the tissue alone group, which was aggravated with the time going. Masson staining showed that the cumulative optical density of blue-stained collagen fibers in tissue plus BM-MSCs group was significantly lower than that in the tissue group at the 5th to 7th day (P<0.05).
Conclusion: BM-MSCs from WZS mini-pig can inhibit or delay the progress of CKD-induced renal fibrosis through autocrine HGF in vitro.
Animals
;
Autocrine Communication
;
physiology
;
Bone Marrow Cells
;
Cells, Cultured
;
Fibrosis
;
physiopathology
;
prevention & control
;
Hepatocyte Growth Factor
;
metabolism
;
Kidney
;
drug effects
;
pathology
;
physiopathology
;
Mesenchymal Stem Cells
;
drug effects
;
Renal Insufficiency, Chronic
;
complications
;
physiopathology
;
Swine
;
Swine, Miniature
;
Ureteral Obstruction
;
complications
3.Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy.
Ga Young PARK ; Chung Hoon YU ; Jun Seop KIM ; Yun Jeong KANG ; Owen KWON ; Ji Young CHOI ; Jang Hee CHO ; Chan Duck KIM ; Yong Lim KIM ; Sun Hee PARK
The Korean Journal of Internal Medicine 2015;30(3):345-353
BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.
Acute-Phase Proteins
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Adolescent
;
Adult
;
Aged
;
Biomarkers/blood
;
Biopsy
;
Chi-Square Distribution
;
Creatinine/blood
;
Disease Progression
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Glomerular Filtration Rate
;
Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology
;
Humans
;
Kidney/*metabolism/pathology/physiopathology
;
Linear Models
;
Lipocalins/*blood
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Predictive Value of Tests
;
Prognosis
;
Proportional Hazards Models
;
Proto-Oncogene Proteins/*blood
;
Renal Insufficiency, Chronic/blood/etiology
;
Republic of Korea
;
Retrospective Studies
;
Risk Factors
;
Time Factors
;
Young Adult
4.Comparison of the renal function after partial nephrectomy and radical nephrectomy for T1a renal cell carcinoma.
Chengyuan GU ; Hailiang ZHANG ; Bo DAI ; Yao ZHU ; Guohai SHI ; Yijun SHEN ; Yuanyuan QU ; Fangning WAN ; Guiming ZHANG ; Dingwei YE ; Email: DWYE@SHCA.ORG.CN.
Chinese Journal of Oncology 2015;37(6):441-444
OBJECTIVETo evaluate the alterations in renal function after radical nephrectomy (RN) and partial nephrectomy (PN) for renal cell carcinoma (RCC) and to determine the risk factors for the onset of postoperative renal function impairment.
METHODSWe assessed the renal function of 429 T1a RCC patients by investigating the time-dependent changes of the estimated glomerular filtration rate (eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR < 60 ml · min⁻¹ · 1.73 m⁻² function, and to evaluate the prognosis for the two groups.
RESULTSThe mean eGFR values (ml · min⁻¹ · 1.73 m⁻²) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51.4 ± 12.6, 52.1 ± 17.8, 53.2 ± 19.5, 54.6 ± 20.2, 53.8 ± 16.6, 52.7 ± 22.3 and 51.5 ± 18.4 in the RN group and 69.6 ± 18.3, 70.3 ± 19.5, 71.5 ± 21.4, 76.2 ± 22.8, 75.4 ± 19.7, 74.3 ± 16.3 and 73.1 ± 23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group (P < 0.05). Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction.
CONCLUSIONSRenal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR < 60 ml · min⁻¹ · 1.73 m⁻² impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.
Age Factors ; Carcinoma, Renal Cell ; pathology ; physiopathology ; surgery ; Glomerular Filtration Rate ; Humans ; Kidney Neoplasms ; pathology ; physiopathology ; surgery ; Nephrectomy ; adverse effects ; methods ; Postoperative Complications ; physiopathology ; Postoperative Period ; Renal Insufficiency, Chronic ; etiology ; physiopathology ; Risk Factors
5.Association of Demographic and Socioeconomic Factors With Risk Factors for Chronic Kidney Disease.
Tae Hyun KIM ; Min Jee LEE ; Ki Bong YOO ; Euna HAN ; Jae Woo CHOI
Journal of Preventive Medicine and Public Health 2015;48(3):170-177
OBJECTIVES: The goal of this study was to examine the association of various demographic and socioeconomic factors with risk factors for chronic kidney disease (CKD). METHODS: We used nationally representative pooled data from the Korea National Health and Nutrition Examination Survey (KNHANES), 2007-2013. We estimated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease equation. We defined CKD as a GFR <60 mL/min/1.73 m2, and 1304 of the 45 208 individuals included in the KNHANES were found to have CKD by this definition. The outcome variable was whether individual subjects adhered to the CKD prevention and management guidelines recommended by the Korea Centers for Disease Control and Prevention. The guidelines suggest that individuals maintain a normal weight, abstain from alcohol consumption and smoking, manage diabetes and hypertension, and engage in regular exercise in order to prevent and manage CKD. RESULTS: This study found that individuals with CKD were more likely to be obese and have hypertension or diabetes than individuals without CKD. In particular, male and less-educated CKD patients were less likely to adhere to the guidelines. CONCLUSIONS: Although the prevalence of CKD, as indicated by the KNHANES data, decreased from 2007 to 2013, the prevalence of most risk factors associated with CKD fluctuated over the same time period. Since a variety of demographic and socioeconomic factors are related to the successful implementation of guidelines for preventing and managing CKD, individually tailored prevention activities should be developed.
Adult
;
Aged
;
Demography
;
Diabetes Mellitus, Type 2/complications
;
Female
;
Glomerular Filtration Rate
;
Humans
;
Hypertension/complications
;
Male
;
Middle Aged
;
Nutrition Surveys
;
Obesity/complications
;
Prevalence
;
Renal Insufficiency, Chronic/complications/epidemiology/*physiopathology
;
Republic of Korea/epidemiology
;
Risk Factors
;
Socioeconomic Factors
6.The Clinical Association of the Blood Pressure Variability with the Target Organ Damage in Hypertensive Patients with Chronic Kidney Disease.
Jiwon RYU ; Ran Hui CHA ; Dong Ki KIM ; Ju Hyun LEE ; Sun Ae YOON ; Dong Ryeol RYU ; Ji Eun OH ; Sejoong KIM ; Sang Youb HAN ; Eun Young LEE ; Yon Su KIM
Journal of Korean Medical Science 2014;29(7):957-964
It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score > or =4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 and proteinuria).The mean BPV of the subjects was 15.9+/-4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients.
Adult
;
Aged
;
Blood Pressure/*physiology
;
Blood Pressure Monitoring, Ambulatory
;
Cross-Sectional Studies
;
Electrocardiography
;
Female
;
Glomerular Filtration Rate
;
Humans
;
Hypertension/*complications/*diagnosis
;
Hypertrophy, Left Ventricular/*physiopathology
;
Kidney/injuries
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Male
;
Middle Aged
;
Odds Ratio
;
Proteinuria/complications
;
Renal Insufficiency, Chronic/*complications/*diagnosis
7.Long-Term Outcomes of Complete Versus Incomplete Revascularization for Patients with Multivessel Coronary Artery Disease and Left Ventricular Systolic Dysfunction in Drug-Eluting Stent Era.
Gwan Hyeop SOHN ; Jeong Hoon YANG ; Seung Hyuk CHOI ; Young Bin SONG ; Joo Yong HAHN ; Jin Ho CHOI ; Hyeon Cheol GWON ; Sang Hoon LEE
Journal of Korean Medical Science 2014;29(11):1501-1506
We aimed to investigate that complete revascularization (CR) would be associated with a decreased mortality in patients with multivessel disease (MVD) and reduced left ventricular ejection fraction (LVEF). We enrolled a total of 263 patients with MVD and LVEF <50% who had undergone percutaneous coronary intervention with drug-eluting stent between March 2003 and December 2010. We compared major adverse cardiac and cerebrovascular accident (MACCE) including all-cause death, myocardial infarction, any revascularization, and cerebrovascular accident between CR and incomplete revascularization (IR). CR was achieved in 150 patients. During median follow-up of 40 months, MACCE occurred in 52 (34.7%) patients in the CR group versus 51 (45.1%) patients in the IR group (P=0.06). After a Cox regression model with inverse-probability-of-treatment-weighting using propensity score, the incidence of MACCE of the CR group were lower than those of the IR group (34.7% vs. 45.1%; adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.95, P=0.03). The rate of all-cause death was significantly lower in patients with CR than in those with IR (adjusted HR, 0.48; 95% CI, 0.29-0.80, P<0.01). In conclusion, the achievement of CR with drug-eluting stent reduces long-term MACCE in patients with MVD and reduced LVEF.
Age Factors
;
Aged
;
Coronary Artery Disease/*drug therapy/mortality/physiopathology
;
Diabetes Mellitus, Type 2/complications
;
*Drug-Eluting Stents
;
Female
;
Follow-Up Studies
;
Humans
;
Kaplan-Meier Estimate
;
Male
;
Middle Aged
;
Myocardial Infarction/etiology
;
Myocardial Revascularization
;
Percutaneous Coronary Intervention/adverse effects
;
Proportional Hazards Models
;
Renal Insufficiency, Chronic/complications
;
Retrospective Studies
;
Sex Factors
;
Treatment Outcome
;
Ventricular Dysfunction, Left/physiopathology
8.Serum osteoprotegerin is associated with vascular stiffness and the onset of new cardiovascular events in hemodialysis patients.
Jung Eun LEE ; Hyung Jong KIM ; Sung Jin MOON ; Ji Sun NAM ; Jwa Kyung KIM ; Seung Kyu KIM ; Gi Young YUN ; Sung Kyu HA ; Hyeong Cheon PARK
The Korean Journal of Internal Medicine 2013;28(6):668-677
BACKGROUND/AIMS: Osteoprotegerin (OPG) and fetuin-A are vascular calcification regulators that may be related to high cardiovascular (CV) mortality in hemodialysis (HD) patients. We evaluated the relationship between OPG, fetuin-A, and pulse wave velocity (PWV), a marker of vascular stiffness, and determined whether OPG and fetuin-A were independent predictors of CV events in HD patients. METHODS: We conducted a prospective observational study in 97 HD patients. OPG and fetuin-A were measured at baseline and arterial stiffness was evaluated by PWV. All patients were stratified into tertiles according to serum OPG levels. RESULTS: A significant trend was observed across increasing serum OPG concentration tertiles for age, HD duration, systolic blood pressure, cholesterol, triglycerides, and PWV. Multiple linear regression analysis revealed that diabetes (beta = 0.430, p = 0.000) and OPG levels (beta = 0.308, p = 0.003) were independently associated with PWV. The frequency of new CV events was significantly higher in the upper OPG tertiles compared with those in the lower OPG tertiles. In Cox proportional hazards analysis, upper tertiles of OPG levels were significantly associated with CV events (hazard ratio = 4.536, p = 0.011). CONCLUSIONS: Serum OPG, but not fetuin-A, levels were closely associated with increased vascular stiffness, and higher OPG levels may be independent predictors of new CV events in HD patients.
Adult
;
Aged
;
Biological Markers/blood
;
Cardiovascular Diseases/blood/diagnosis/*etiology/mortality/physiopathology
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
Linear Models
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Osteoprotegerin/*blood
;
Predictive Value of Tests
;
Prognosis
;
Proportional Hazards Models
;
Prospective Studies
;
Pulse Wave Analysis
;
*Renal Dialysis/adverse effects/mortality
;
Renal Insufficiency, Chronic/complications/diagnosis/mortality/*therapy
;
Risk Factors
;
Up-Regulation
;
*Vascular Stiffness
;
alpha-2-HS-Glycoprotein/analysis
9.Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population.
Dong-Wei LIU ; Jia WAN ; Zhang-Suo LIU ; Pei WANG ; Gen-Yang CHENG ; Xue-Zhong SHI
Chinese Medical Journal 2013;126(7):1207-1212
BACKGROUNDDyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD.
METHODSA total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, < 60 ml×min(-1)×1.73 m(-2)). Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR.
RESULTSParticipants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively.
CONCLUSIONSOur findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.
Aged ; Albuminuria ; epidemiology ; etiology ; physiopathology ; Cross-Sectional Studies ; Dyslipidemias ; complications ; epidemiology ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; epidemiology ; etiology ; physiopathology
10.Relations of fetuin-A with estimated glomerular filtration rate and carotid artery calcification in patients with chronic kidney disease.
Junlin ZHAN ; Jianbo LIANG ; Zebin WANG
Journal of Southern Medical University 2013;33(11):1689-1691
OBJECTIVETo investigate the association of fetuin-A with residual renal function and carotid artery calcification in patients with chronic kidney disease (CKD).
METHODSBlood examples were collected form 60 CKD patients in stages CKD3 to CKD5 (20 patients per stage) for measurement of serum fetuin-A, albumin, calcium, phosphorus and parathyroid hormone, cholesterol, triglycercide, low-density lipoprotein, and high-density lipoprotein. MDRD equation was used to calculate the estimated glomerular filtration rate (eGFR), and ELISA was used to detect serum fetuin-A. Color Doppler ultrasound was performed to measure carotid intima-media thickness (CIMT).
RESULTSAs the eGFR decreased, serum fetuin-A significantly decreased in CKD5 stage compared with that in CKD4 stage (P<0.05); compared with that in CKD3 stage, serum fetuin-A level was significantly lowered in CKD4 stage (P<0.05). Linear regression analysis suggested a significant positive correlation between fetuin-A and eGFR. The rate of carotid artery calcification was the highest in CKD5 stage. Rank correlation analysis showed a negative correlation between fetuin-A and cIMT, and logistic regression analysis identified decreased serum Fetuin-A as a risk factor of carotid artery calcification.
CONCLUSIONSerum fetuin-A decreases following the decrease in eGFR, and decreased serum Fetuin-A level is a risk factor of carotid artery calcification in CKD patients.
Adult ; Calcinosis ; etiology ; Carotid Artery Diseases ; etiology ; Carotid Intima-Media Thickness ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; complications ; physiopathology ; Risk Factors ; alpha-2-HS-Glycoprotein ; metabolism

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