Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis ... more Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis is based on increased serum creatinin, most often several days after the initial renal injury. Several novel biomarkers are being studied and validated in clinical settings. Cystatin C, NGAL, KIM-1, IL-18 or L-FABP are the most promising. Their elevation in serum or urine is specifically associated with kidney injury. They seem also to predict mortality and the need of dialysis. In the near future, these biomarkers could affect the way we treat patients with acute kidney injury, as well as their evolution. However, the real challenge will be in using the best combination of biomarkers and in the correct interpretation of their results.
Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular... more Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33–1.70) for cSBP, 1.36 (95% CI, 1.19–1.54) for cPP, 1.49 (95% CI, 1.33–1.67) for pSBP, and 1.34 (95% CI, 1.19–1...
BACKGROUND AND AIM Blood pressure displays a seasonal pattern. Whether this pattern is related to... more BACKGROUND AND AIM Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.
Background Previous investigations have reported that adverse socioeconomic circumstances across ... more Background Previous investigations have reported that adverse socioeconomic circumstances across the life-course lead to the alteration of major biological processes, eventually resulting in a higher disease risk and premature death. In particular, a low life-course socioeconomic position (SEP) has been associated with a modified epigenetic signature of loci involved in inflammation, the physiological response to stress, and other regulatory processes. Methods In this study, we investigated the association between nine indicators of SEP across the life-course and the differential methylation of 451'000 genome-wide CpG markers, using data from 690 adults included in a Swiss population-based study. We further examined the interrelations between the SEP-related CpGs, and the biological pathways in which the identified markers are involved. Results Three SEP indicators in adulthood were associated the differential methylation of 161 genome-wide CpG markers, whereby 156 CpGs were les...
Background Chronic intake of caffeinated beverages might be associated with plasma lipids via dis... more Background Chronic intake of caffeinated beverages might be associated with plasma lipids via disturbed lipid metabolism. Previous investigations have been limited by the use of self-reported caffeine intake instead of measured caffeine, whereas the associations between plasma lipids and other methylxanthines (paraxanthine, theobromine, theophylline) are unknown. Here, we investigated the associations of plasma lipids with caffeine and its metabolites in plasma and urine in two European populations. Methods Individuals were selected from the general population of North Belgium (FLEMENGHO) and Switzerland (SKIPOGH). Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured in plasma using standard enzymatic methods. Plasma and 24h urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured using ultra-high performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of methylxanthine...
Journal of endocrinological investigation, Jan 12, 2017
Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycoge... more Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11β-hydroxysteroid-dehydrogenase-type 2 (11β-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11β-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11β-HSD2 activity were presented as appropriat...
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2016
Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointersti... more Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and...
Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI... more Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple ...
Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis b... more Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates ...
Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor ... more Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7...
Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis ... more Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis is based on increased serum creatinin, most often several days after the initial renal injury. Several novel biomarkers are being studied and validated in clinical settings. Cystatin C, NGAL, KIM-1, IL-18 or L-FABP are the most promising. Their elevation in serum or urine is specifically associated with kidney injury. They seem also to predict mortality and the need of dialysis. In the near future, these biomarkers could affect the way we treat patients with acute kidney injury, as well as their evolution. However, the real challenge will be in using the best combination of biomarkers and in the correct interpretation of their results.
Prevention of Contrast Media induced acute renal failure is of importance, especially in patients... more Prevention of Contrast Media induced acute renal failure is of importance, especially in patients with chronic renal failure. Vasodilatators such as fenoldopam and prophylactic hemodialysis have been reported to procure disappointing results. Hydratation prior to and post- exposure to contrast media remains the cornerstone of prevention. Urine alcalinisation with sodium bicarbonate may bring additional renoprotection. Use of a small quantity of contrast media and Acetylcysteine concomitantly to hydratation are also recommended.
Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis ... more Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis is based on increased serum creatinin, most often several days after the initial renal injury. Several novel biomarkers are being studied and validated in clinical settings. Cystatin C, NGAL, KIM-1, IL-18 or L-FABP are the most promising. Their elevation in serum or urine is specifically associated with kidney injury. They seem also to predict mortality and the need of dialysis. In the near future, these biomarkers could affect the way we treat patients with acute kidney injury, as well as their evolution. However, the real challenge will be in using the best combination of biomarkers and in the correct interpretation of their results.
Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular... more Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33–1.70) for cSBP, 1.36 (95% CI, 1.19–1.54) for cPP, 1.49 (95% CI, 1.33–1.67) for pSBP, and 1.34 (95% CI, 1.19–1...
BACKGROUND AND AIM Blood pressure displays a seasonal pattern. Whether this pattern is related to... more BACKGROUND AND AIM Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.
Background Previous investigations have reported that adverse socioeconomic circumstances across ... more Background Previous investigations have reported that adverse socioeconomic circumstances across the life-course lead to the alteration of major biological processes, eventually resulting in a higher disease risk and premature death. In particular, a low life-course socioeconomic position (SEP) has been associated with a modified epigenetic signature of loci involved in inflammation, the physiological response to stress, and other regulatory processes. Methods In this study, we investigated the association between nine indicators of SEP across the life-course and the differential methylation of 451'000 genome-wide CpG markers, using data from 690 adults included in a Swiss population-based study. We further examined the interrelations between the SEP-related CpGs, and the biological pathways in which the identified markers are involved. Results Three SEP indicators in adulthood were associated the differential methylation of 161 genome-wide CpG markers, whereby 156 CpGs were les...
Background Chronic intake of caffeinated beverages might be associated with plasma lipids via dis... more Background Chronic intake of caffeinated beverages might be associated with plasma lipids via disturbed lipid metabolism. Previous investigations have been limited by the use of self-reported caffeine intake instead of measured caffeine, whereas the associations between plasma lipids and other methylxanthines (paraxanthine, theobromine, theophylline) are unknown. Here, we investigated the associations of plasma lipids with caffeine and its metabolites in plasma and urine in two European populations. Methods Individuals were selected from the general population of North Belgium (FLEMENGHO) and Switzerland (SKIPOGH). Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured in plasma using standard enzymatic methods. Plasma and 24h urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured using ultra-high performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of methylxanthine...
Journal of endocrinological investigation, Jan 12, 2017
Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycoge... more Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11β-hydroxysteroid-dehydrogenase-type 2 (11β-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11β-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11β-HSD2 activity were presented as appropriat...
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2016
Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointersti... more Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and...
Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI... more Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple ...
Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis b... more Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates ...
Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor ... more Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7...
Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis ... more Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis is based on increased serum creatinin, most often several days after the initial renal injury. Several novel biomarkers are being studied and validated in clinical settings. Cystatin C, NGAL, KIM-1, IL-18 or L-FABP are the most promising. Their elevation in serum or urine is specifically associated with kidney injury. They seem also to predict mortality and the need of dialysis. In the near future, these biomarkers could affect the way we treat patients with acute kidney injury, as well as their evolution. However, the real challenge will be in using the best combination of biomarkers and in the correct interpretation of their results.
Prevention of Contrast Media induced acute renal failure is of importance, especially in patients... more Prevention of Contrast Media induced acute renal failure is of importance, especially in patients with chronic renal failure. Vasodilatators such as fenoldopam and prophylactic hemodialysis have been reported to procure disappointing results. Hydratation prior to and post- exposure to contrast media remains the cornerstone of prevention. Urine alcalinisation with sodium bicarbonate may bring additional renoprotection. Use of a small quantity of contrast media and Acetylcysteine concomitantly to hydratation are also recommended.
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