| 1. |
- Waikar, Sushrut S, et al.
(författare)
-
Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies
- 2016
-
Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 31:9, s. 1460-1470
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ∼90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD.METHODS: We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values.RESULTS: In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {β = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [β = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15-0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.CONCLUSION: Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.
|
|
| 2. |
- Hansson, Jonas, et al.
(författare)
-
Biomarkers of Extracellular Matrix Metabolism (MMP-9 and TIMP-1) and Risk of Stroke, Myocardial Infarction, and Cause-Specific Mortality : Cohort Study
- 2011
-
Ingår i: PLoS ONE. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. e16185-
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991-1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03-1.19; and 1.11, 1.02-1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09-1.37; and 1.18, 1.04-1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.
|
|
| 3. |
- Ingelsson, Erik, et al.
(författare)
-
Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity
- 2009
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:3, s. 953-957
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Skeletal muscle morphology and function are strongly associated with insulin sensitivity. OBJECTIVE: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. DESIGN, SETTINGS, AND PARTICIPANTS: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. MAIN OUTCOME MEASURES: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. RESULTS: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, -0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. CONCLUSIONS: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.
|
|
| 4. |
- Ingelsson, Erik, et al.
(författare)
-
Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly
- 2009
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 206:1, s. 239-244
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly. METHODS: We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD. RESULTS: RBP4 concentrations were positively correlated with serum triglycerides (r=0.30; P<0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% confidence interval (CI), 0.99-1.37 and 1.05-1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction. CONCLUSION: In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.
|
|
