| 1. |
- Carlsson, Axel C, et al.
(author)
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High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis
- 2015
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In: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:2, s. 89-95
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Journal article (peer-reviewed)abstract
- Objective: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and 5TNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients. Research Design and Methods: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.Results: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha. Conclusions:Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.
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| 2. |
- Carlsson, Axel C, et al.
(author)
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Soluble tumor necrosis factor receptor 1 is associated with glomerular filtration rate progression and incidence of chronic kidney disease in two community-based cohorts of elderly individuals
- 2015
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In: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:4, s. 278-288
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Journal article (peer-reviewed)abstract
- Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes.Research design and methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and <30 ml/min/1.73 m(2).Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR >= 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes.Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.
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| 3. |
- Feldreich, T., et al.
(author)
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Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men
- 2017
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In: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 7:3, s. 245-254
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Journal article (peer-reviewed)abstract
- Background and Objectives: The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.Design, Setting, Participants, and Measurements: A community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.Results: There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman Ï = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002).Conclusions: Higher urinary osteopontin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.
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| 4. |
- Kamran, Haroon, et al.
(author)
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Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis.
- 2018
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In: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 8:2, s. 105-112
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Journal article (peer-reviewed)abstract
- Statins have long been prescribed for the primary and secondary prevention of cardiovascular disease (CVD) and kidney disease. Their benefits and efficacy are widely accepted in current clinical practice, but like any other therapeutic agents, they have adverse effects. One of the emerging concerns with statin therapy is the development of new-onset diabetes mellitus (NODM), a dreaded risk factor for CVD and kidney disease and widely viewed as CVD equivalent. Accumulating evidence indicates that NODM is a consequence of statin use.We conducted a meta-analysis of studies reporting on associations between NODM and statin use. Based on strict exclusion criteria, a total of 11 studies were selected. Their data were analyzed using Comprehensive Meta-Analysis® statistical software and reported as odds ratios (OR) with 95% confidence intervals (CI).The cumulative fixed effect for use of statin therapy and incident NODM was an OR of 1.61 (95% CI 1.55-1.68, p < 0.001). Our results suggest that statin therapy is associated with NODM, such that there is a small but significant risk of NODM among patients receiving statin for CVD prevention therapy. However, this high-risk population also has other diabetes risk factors (such as obesity and hypertension) contributing to the development of NODM.It is imperative that patients on statin therapy be monitored carefully for NODM. However, it can be argued that the risk of statin therapy is offset by the multitude of cardiovascular and kidney-protective effects provided by such an important and highly effective therapeutic agent.
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| 5. |
- Kashioulis, Pavlos, 1980, et al.
(author)
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High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels
- 2016
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In: Cardiorenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 6:4, s. 317-327
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Journal article (peer-reviewed)abstract
- Aims: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). Methods: Male Sprague-Dawley rats either received chow containing adenine or were pair-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. Results: Rats with ACRF showed statistically significant increases (p < 0.001) in arterial pressure (AP), LV weight and fibrosis, and serum cTnT levels compared to controls. Two weeks of high-NaCl intake augmented the increases in AP, LV weight and fibrosis, and serum cTnT concentrations only in ACRF rats (p < 0.05 for group x NaCl intake interaction). Compared to group C-NNa, cTnT levels were elevated approximately 6-fold in group ACRF-NNa and 24-fold in group ACRF-HNa. Focal LV injury with cardiomyocyte necrosis, scarring, and fibrinoid necrosis of small arteries were only detected in group ACRF-HNa. There was a strong correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p < 0.01). Conclusion: Two weeks of high-NaCl diet in rats with ACRF produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading to myocardial ischemia. This model may be suitable for studying pathophysiological mechanisms in chronic renicardiac syndromes. (C) 2016 S. Karger AG, Basel
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| 6. |
- Kocyigit, I, et al.
(author)
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Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension
- 2019
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In: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 9:6, s. 370-381
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Journal article (peer-reviewed)abstract
- <b><i>Background and Objectives:</i></b> Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via <i>IL-1β</i> activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, <i>HIF-1α</i> gene expression from whole blood and urine samples and <i>IL-1β</i>gene expression from whole blood were measured. <b><i>Methods:</i></b> One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for <i>HIF-1α</i> and <i>IL-1β</i> gene<i></i>expression by using quantitative real-time PCR. <b><i>Results:</i></b> There were significant differences in whole blood <i>HIF-1α</i>,<i> IL-1β</i> gene<i></i>expression, and serum<i></i>succinate levels between the ADPKD patients and the control subjects. Whole blood <i>HIF-1α</i>gene expression,<i> IL-1β</i> gene<i></i>expression, and serum<i></i>succinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (<i>p</i> < 0.05). Serum succinate levels and blood<i> IL-1β</i> gene<i></i>expression were increased in ADPKD patients with high levels of <i>HIF-1α gene</i>expression (<i>p</i> = 0.018 and <i>p</i> = 0.029, respectively). <b><i>Conclusions:</i></b> Increased age,<i></i>low eGFR, and <i>HIF-1α</i> and <i>IL-1β</i> gene<i></i>expressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.
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| 7. |
- Olsson, DP, et al.
(author)
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Acute kidney injury after valvular heart surgery and early changes in cardiac function and structure
- 2014
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In: Cardiorenal medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 4:3-4, s. 201-209
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Acute kidney injury (AKI) following heart surgery is associated with long-term risk of heart failure. It is not known if AKI following valvular heart surgery is associated with early changes in cardiac function or structure. <b><i>Methods:</i></b> A cohort study was conducted on 201 patients with AKI and 201 patients without AKI after valvular heart surgery, who were matched for age, sex, left ventricular function, and estimated glomerular filtration rate. AKI was defined as an increase in postoperative serum creatinine of ≥26 Vmol/l (≥0.3 mg/dl) or a relative increase of ≥50%. The two primary outcomes were changes in post- compared with preoperative left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) assessed by echocardiography. <b><i>Results:</i></b> The mean age was 72 years, and 33% were female. Aortic valve surgery was the most frequent procedure. The mean time from surgery to the postoperative echocardiographic examination was 4.9 days (SD 3.7). There was no significant change in postoperative mean LVEF (-3.6 vs. -4.3%; p = 0.58) or mean LVEDD (-4.7 vs. -3.9 mm; p = 0.31) in patients with AKI compared to those without AKI. <b><i>Conclusion:</i></b> We found no acute changes in cardiac function or structure assessed by echocardiography in patients with AKI compared to those without AKI after valvular heart surgery. i 2014 S. Karger AG, Basel
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| 8. |
- Rhee, CM, et al.
(author)
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Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients
- 2022
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In: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 12:3, s. 106-116
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. <b><i>Methods:</i></b> In secondary analyses of patients from the <i>Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients</i> trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm<sup>3</sup> and >100 Houndsfield Units, respectively) using multivariable logistic regression. <b><i>Results:</i></b> Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. <b><i>Conclusions:</i></b> In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.
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| 9. |
- Rhee, CM, et al.
(author)
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Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients
- 2022
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In: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 12:3, s. 106-116
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. <b><i>Methods:</i></b> In secondary analyses of patients from the <i>Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients</i> trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm<sup>3</sup> and >100 Houndsfield Units, respectively) using multivariable logistic regression. <b><i>Results:</i></b> Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. <b><i>Conclusions:</i></b> In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.
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| 10. |
- Sendic, Senka, et al.
(author)
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Soluble CD14 and Osteoprotegerin Associate with Ankle-Brachial Index as a Measure of Arterial Stiffness in Patients with Mild-to-Moderate Chronic Kidney Disease in a Five-Year Prospective Study
- 2023
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In: CardioRenal Medicine. - : Karger. - 1664-3828 .- 1664-5502. ; 13:1, s. 189-201
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Journal article (peer-reviewed)abstract
- Introduction: Vascular lesions and arterial stiffness appear at early stages of chronic kidney disease (CKD) and follow an accelerated course with disease progression, contributing to high cardiovascular mortality. There are limited prospective data on mechanisms contributing to progression of arterial stiffness in mild-to-moderate CKD (stages 2-3). Methods: We applied an affinity proteomics approach to identify candidates of circulating biomarkers with potential impact on vascular lesions in CKD and selected soluble cluster of differentiation 14 (sCD14), angiogenin (ANG), and osteoprotegerin (OPG) for further analysis. We studied their association with ankle-brachial index (ABI) and carotid intima-media thickness, as measures of arteriosclerosis and atherosclerosis, respectively, in 48 patients with CKD stages 2-3, who were prospectively followed and intensively treated for 5 years, and 44 healthy controls. Results: Concentrations of sCD14 (p < 0.001), ANG (p < 0.001), and OPG (p < 0.05) were higher in patients with CKD 2-3 at baseline, and sCD14 (p < 0.001) and ANG (p < 0.001) remained elevated in CKD patients at follow-up. There were positive correlations between ABI and sCD14 levels (r = 0.36, p = 0.01) and between ABI and OPG (r = 0.31, p = 0.03) at 5 years. The changes in sCD14 during follow-up correlated to changes in ABI from baseline to 5 years (r = 0.41, p = 0.004). Conclusion: Elevated levels of circulating sCD14 and OPG in patients with CKD 2-3 were significantly associated with ABI, a measure of arterial stiffness. An increase in sCD14 over time in CKD 2-3 patients was associated with a corresponding increase in ABI. Further studies are needed to examine if early intensive multifactorial medication to align with international treatment targets may influence cardiovascular outcomes.
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