Dataset Information

Increased Circulating Visfatin Is Associated With Progression of Kidney Disease in Non-Diabetic Hypertensive Patients.

ABSTRACT:

Backgroud

Declining renal function is an independent risk factor for all-cause mortality in cardiovascular disease. Visfatin has been described as a marker of inflammation and endothelial dysfunction, but whether circulating visfatin levels are predictive to a subsequent decline in renal function remains unclear.

Methods

In total, 200 nondiabetic, non-proteinuric hypertensive outpatients with initial serum creatinine (Scr) ?1.5 mg/dl were enrolled. Plasma visfatin concentration and endothelial function estimated by brachial artery flow-mediated dilatation (FMD) were determined in the study subjects. The primary endpoints were the occurrence of renal events including doubling of Scr, 25% loss of glomerular filtration rate (GFR) from baseline values, and the occurrence of end-stage renal disease during follow-up.

Results

The mean annual rate of GFR decline (?GFR/y) was -1.26±2.76 ml/min/1.73 m(2) per year during follow-up (8.6±2.5 years). At baseline, plasma visfatin was negatively correlated with estimated GFR. In longitudinal analysis, the ?GFR/y was correlated with visfatin, baseline GFR, FMD, systolic blood pressure, and fasting blood glucose (FBG). Multivariate analysis indicated that increased visfatin (r = -0.331, P <0.001), baseline GFR (r = -0.234, P = 0.001), FMD (r = 0.163, P = 0.015), and FBG (r = -0.160, P = 0.015) are independent predictors of ?eGFR/y. Cox regression model analysis showed that visfatin (hazard ratio (HR), 1.09; 95% confidence interval (CI), 1.05-1.13, P <0.001), FBG (HR, 1.01; 95% CI, 1.00-1.02, P = 0.020), and FMD (HR, 0.87; 95% CI, 0.76-1.00, P = 0.049) were independently associated with the risk of developing future renal events.

Conclusions

Increased circulating visfatin are associated with subsequent decline in renal function in nondiabetic hypertensive patients.

SUBMITTER: Hsu CY

PROVIDER: S-EPMC4886489 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Increased Circulating Visfatin Is Associated With Progression of Kidney Disease in Non-Diabetic Hypertensive Patients.

Hsu Chien-Yi CY Huang Po-Hsun PH Chen Tz-Heng TH Chiang Chia-Hung CH Leu Hsin-Bang HB Huang Chin-Chou CC Chen Jaw-Wen JW Lin Shing-Jong SJ

American journal of hypertension 20150822 4

<h4>Backgroud</h4>Declining renal function is an independent risk factor for all-cause mortality in cardiovascular disease. Visfatin has been described as a marker of inflammation and endothelial dysfunction, but whether circulating visfatin levels are predictive to a subsequent decline in renal function remains unclear.<h4>Methods</h4>In total, 200 nondiabetic, non-proteinuric hypertensive outpatients with initial serum creatinine (Scr) ≤1.5 mg/dl were enrolled. Plasma visfatin concentration an ...[more]

PMID: 26298010

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Project description:BackgroundCirculating matrix metalloproteinase (MMP)-2, -3 and -9 are well recognized in predicting cardiovascular outcome in coronary artery disease (CAD), but their risks for chronic kidney disease (CKD) are lacking. Therefore, the present study aimed to investigate whether circulating MMP levels could independently predict future kidney disease progression in non-diabetic CAD patients.MethodsThe prospective study enrolled 251 non-diabetic subjects referred for coronary angiography, containing normal coronary artery (n?=?30) and CAD with insignificant (n?=?95) and significant (n?=?126) stenosis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. eGFR decline rate was calculated and the primary endpoint was a decline in eGFR over 25% from baseline.ResultsThe eGFR decline rate (ml/min/1.73 m(2) per year) in patients with CAD (1.22 [-1.27, 1.05]) was greater than that in those with normal coronary artery (0.21 [-2.63, 0.47], P<0.01). The circulating MMP-2, -3 and -9 were independently associated with faster eGFR decline among CAD patients. The mean follow-up period was 8.5±2.4 years, and 39 patients reached the primary endpoint. In multivariate Cox regression model, the adjusted hazard ratios of MMP-2 ?861 ng/mL, MMP-3 ?227 ng/mL and MMP-9 ?49 ng/mL for predicting CKD progression were 2.47 (95% CI, 1.21 to 5.07), 2.15 (1.12 to 4.18), and 4.71 (2.14 to 10.4), respectively. While added to a model of conventional risk factors and baseline eGFR, MMP-2, -3 and -9 further significantly improved the model predictability for CKD progression (c statistic, 0.817). In the sensitivity analyses, the results were similar no matter if we changed the endpoints of a decline of >20% in eGFR from baseline or final eGFR < 60 mL/min/1.73 m(2).ConclusionCirculating MMP-2, -3 and -9 are independently associated with kidney disease progression in non-diabetic CAD patients and add incremental predictive power to conventional risk factors.

Project description:AimsGlomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling.Materials and methodsUrinary steroid hormone profiles of patients with diabetic kidney disease were analyzed by gas chromatography-mass spectrometry and compared to an age and gender matched healthy control group taken out of a population study. In both cohorts, the activity of the MR pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), which inactivates cortisol to prevent it from binding to the MR, was assessed to define a change in MR selectivity. Expression of HSD11B2, MR and GR was quantified in HRMC and primary human renal glomerular endothelial cells (HRGEC). Activity of MR and GR was explored in HRMC by measuring the MR/GR down-stream signal SGK1 and the pro-fibrotic genes TGFB1, FN1 and COL1A1 in normal and high glucose conditions with the MR/GR agonists aldosterone/cortisol and the MR/GR antagonists spironolactone/RU486.ResultsPatients with diabetic kidney disease excreted more tetrahydroaldosterone than the control group reaching significance in men. The excretion of MR-agonistic steroid hormones was only increased for 18-hydroxytetrahydrocorticosterone in diabetic women. The excretion of most glucocorticoids was higher in the diabetic cohort. Higher apparent systemic HSD11B2 activity suggested less activation of the MR by cortisol in diabetic patients. Both cell types, HRMC and HRGEC, lacked expression of HSD11B2. Hyperglycemic conditions did not change MR and GR expression and activity. Stimulation with both aldosterone and cortisol promoted upregulation of pro-fibrotic genes in HRMC. This effect of MR and/or GR activation was more pronounced in high glucose conditions and partially inhibited by MRAs and GR antagonists.ConclusionsIn patients with diabetic kidney disease alternative MR activation is conceivable as cortisol and cortisone metabolites are increased. Systemic availability of active metabolites is counteracted via an increased HSD11B2 activity. As this cortisol deactivation is absent in HRMC and HRGEC, cortisol binding to the MR is enabled. Both, cortisol and aldosterone stimulation led to an increased expression of pro-fibrotic genes in HRMC. This mechanism was related to the MR as well as the GR and more marked in high glucose conditions linking the benefit of MRAs in diabetic kidney disease to these findings.

Dataset Information

Increased Circulating Visfatin Is Associated With Progression of Kidney Disease in Non-Diabetic Hypertensive Patients.

Backgroud

Methods

Results

Conclusions

Publications

Increased Circulating Visfatin Is Associated With Progression of Kidney Disease in Non-Diabetic Hypertensive Patients.

Similar Datasets

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