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Normal-range urinary albumin excretion associates with blood pressure and renal electrolyte handling in pregnancy.
Birukov, A, Andersen, MS, Jørgensen, JS, Kitlen, G, Rakova, N, Nielsen, JH, Andersen, LB, Dechend, R, Jensen, BL
American journal of physiology. Renal physiology. 2020;(1):F1-F7
Abstract
Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na+ reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na+, K+, Cl-, and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na+, K+, and Cl-, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: -0.25 (-0.35 to -0.14), -5.06 (-6.81 to -3.30), and -0.28 (-0.41 to -0.15), respectively. In conclusion, at gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.
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Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses.
Zanetti, D, Bergman, H, Burgess, S, Assimes, TL, Bhalla, V, Ingelsson, E
Hypertension (Dallas, Tex. : 1979). 2020;(3):714-722
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Abstract
Urinary biomarkers are associated with cardiovascular disease, but the nature of these associations is not well understood. We performed multivariable-adjusted regression models to assess associations of random spot measurements of the urine sodium-potassium ratio (UNa/UK) and urine albumin adjusted for creatinine with cardiovascular risk factors, cardiovascular disease, and type 2 diabetes mellitus (T2D) in 478 311 participants of the UK Biobank. Further, we assessed the causal relationships of these kidney biomarkers, used as proxies for kidney function, with cardiovascular outcomes using the 2-sample Mendelian randomization approach. In observational analyses, UNa/UK showed significant inverse associations with atrial fibrillation, coronary artery disease, ischemic stroke, lipid-lowering medication, and T2D. In contrast, urine albumin adjusted for creatinine showed significant positive associations with atrial fibrillation, coronary artery disease, heart failure, hemorrhagic stroke, lipid-lowering medication, and T2D. We found a positive association between UNa/UK and albumin with blood pressure (BP), as well as with adiposity-related measures. After correcting for potential horizontal pleiotropy, we found evidence of causal associations of UNa/UK and albumin with BP (β systolic BP ≥2.63; β diastolic BP ≥0.85 SD increase in BP per SD change in UNa/UK and urine albumin adjusted for creatinine; P≤0.04), and of albumin with T2D (odds ratio=1.33 per SD change in albumin, P=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.
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Frequency of alcohol drinking modifies the association between salt intake and albuminuria: a 1-year observational study.
Yoshimura, R, Yamamoto, R, Shinzawa, M, Tomi, R, Ozaki, S, Fujii, Y, Ito, T, Tanabe, K, Moriguchi, Y, Isaka, Y, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2020;(11):1249-1256
Abstract
Albuminuria is an important risk factor for end-stage kidney disease and cardiovascular mortality. This 1-year observational study aimed to assess the effect modification of alcohol drinking on the association between salt intake and albuminuria. Overall, 448 employees at a pharmaceutical company in Japan who underwent annual health checkups in both 2017 and 2018 were evaluated. The main exposure of interest was drinking frequency at their first checkups categorized as rarely, occasionally, and daily. To assess the association between the changes in salt intake and albuminuria, the differences in salt intake estimated from single-spot urine specimens and the urinary albumin-to-creatinine ratio (UACR) between 2017 and 2018 were calculated for each subject. A multivariable-adjusted linear regression model showed a significant association between ∆salt intake and ∆Log UACR (per 1 g/day of ∆salt intake, adjusted ß 0.16 [95% confidence interval 0.14, 0.19]) and an effect modification between drinking frequency and ∆salt intake (P for interaction = 0.088). The association between ∆salt intake and ∆Log UACR was enhanced by drinking frequency in a dose-dependent manner (per 1 g/day of ∆salt intake, adjusted ß 0.13 [0.06, 0.19], 0.16 [0.12, 0.20], and 0.20 [0.13, 0.27] in rare, occasional, and daily drinkers, respectively). In conclusion, the results of the present study indicated that salt-induced albuminuria was enhanced in subjects with higher drinking frequency, suggesting that salt restriction may have a stronger renoprotective effect in subjects with higher drinking frequency.
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Chronic kidney disease in psoriasis: a cohort study.
Conti, A, Giovannini, L, Mandel, VD, Odorici, G, Lasagni, C, Bigi, L, Pellacani, G, Cappelli, G
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2020;(5):438-445
Abstract
BACKGROUND Psoriasis is a chronic, relapsing disease often associated with comorbidities. While its associations with cardiovascular and metabolic factors have been investigated, little is known about its association with impairment of renal function. MATERIALS AND METHODS We performed a cohort study of 219 psoriatic patients in which we evaluated chronic kidney disease (CKD) and eGFR as well as albuminuria according to their KDIGO stratification risk criteria. We also evaluated circulating immunoglobulins (IgG, IgA, IgM), C3-C4 levels and the urinary albumin-to-creatinine ratio. We divided the patients into two groups, according to the presence or absence of known and established CKD risk factors. RESULTS In our population, the risk of CKD was moderate in 17.35 % of patients, high in 5.02 % and very high in 3.66 %. The risk prevalence for CKD was slightly greater in the group without established risk factors than the risk prevalence reported in NHANES 1999-2006. The presence of psoriatic arthritis, duration of psoriasis (≥ 21 years) and magnitude of the PASI score showed a positive correlation with the urinary albumin-to-creatinine ratio. CONCLUSIONS We found an association between microalbuminuria and the duration of psoriasis, as well as with psoriatic arthritis. Moreover, patients with microalbuminuria exhibited a higher Kidney Disease Improving Global Outcome stratification risk.
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The Effect of Antioxidant Vitamins on Patients With Diabetes and Albuminuria: A Meta-Analysis of Randomized Controlled Trials.
Chen, J, Wu, J, Kong, D, Yang, C, Yu, H, Pan, Q, Liu, W, Ding, Y, Liu, H
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(2):101-110
Abstract
OBJECTIVE This study aimed to investigate the effect of antioxidant vitamins, including vitamins E and C, on patients with diabetes and albuminuria by conducting a meta-analysis of randomized controlled trials. DESIGN The PubMed, Embase, CENTRAL (the Cochrane Central Register of Controlled Trials at the Cochrane Library), Web of Science, OVID, and www.clinicaltrials.gov (latest search: December 10, 2018) databases were searched. This study was limited to randomized controlled trials. Patients with diabetes and albuminuria were included regardless of diabetic type, and patients must have received treatment with vitamins C or E. RESULTS Ten studies, representing 445 participants, were identified for analysis. Antioxidant vitamins had significant effects on serum creatinine levels (mean difference = -0.11 mg/dL, 95% confidence interval -0.19 to -0.03, P = .007) and systolic pressure (mean difference = -6.02 mm Hg, 95% confidence interval -9.65 to -2.40, P = .001) with low heterogeneity. Antioxidant vitamins had no effect on albuminuria or proteinuria, diastolic blood pressure, glucose, or lipid metabolism. CONCLUSION This meta-analysis indicated that antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria. Further studies with larger sample sizes and longer follow-up are needed to completely understand the effect of antioxidant vitamins in these patients.
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Association of smoking and cardiometabolic parameters with albuminuria in people with type 2 diabetes mellitus: a systematic review and meta-analysis.
Kar, D, Gillies, C, Nath, M, Khunti, K, Davies, MJ, Seidu, S
Acta diabetologica. 2019;(8):839-850
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Abstract
AIMS: Smoking is a strong risk factor for albuminuria in people with type 2 diabetes mellitus (T2DM). However, it is unclear whether this sequela of smoking is brought about by its action on cardiometabolic parameters or the relationship is independent. The aim of this systematic review is to explore this relationship. METHODS Electronic databases on cross-sectional and prospective studies in Medline and Embase were searched from January 1946 to May 2018. Adult smokers with T2DM were included, and other types of diabetes were excluded. RESULTS A random effects meta-analysis of 20,056 participants from 13 studies found that the odds ratio (OR) of smokers developing albuminuria compared to non-smokers was 2.13 (95% CI 1.32, 3.45). Apart from smoking, the odds ratio of other risk factors associated with albuminuria were: age 1.24 (95% CI 0.84, 1.64), male sex 1.39 (95% CI 1.16, 1.67), duration of diabetes 1.78 (95% CI 1.32, 2.23), HbA1c 0.63 (95% CI 0.45, 0.81), SBP 6.03 (95% CI 4.10, 7.97), DBP 1.85 (95% CI 1.08, 2.62), total cholesterol 0.06 (95% CI - 0.05, 0.17) and HDL cholesterol - 0.01 (95% CI - 0.04, 0.02), triglyceride 0.22 (95% CI 0.12, 0.33) and BMI 0.40 (95% CI 0.00-0.80). When the smoking status was adjusted in a mixed effect meta-regression model, the duration of diabetes was the only statistically significant factor that influenced the prevalence of albuminuria. In smokers, each year's increase in the duration of T2DM was associated with an increased risk of albuminuria of 0.19 units (95% CI 0.07, 0.31) on the log odds scale or increased the odds approximately by 23%, compared to non-smokers. Prediction from the meta-regression model also suggested that the odds ratios of albuminuria in smokers after a diabetes duration of 9 years and 16 years were 1.53 (95% CI 1.10, 2.13) and 5.94 (95% CI 2.53, 13.95), respectively. CONCLUSIONS Continuing to smoke and the duration of diabetes are two strong predictors of albuminuria in smokers with T2DM. With a global surge in younger smokers developing T2DM, smoking cessation interventions at an early stage of disease trajectory should be promoted.
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Association between Sodium Intake and Urinary Fractional Albumin and Immunoglobulin G Excretion in Chronic Nondialytic Renal Disease: A Prospective Longitudinal Study.
Martinez, MG, Dos Santos Silva, V, do Valle, AP, de Oliveira, RC, Banin, VB, Hokama, NK, Martin, LC
Nephron. 2019;(1):62-67
Abstract
BACKGROUND/AIMS: Previous studies reported that fractional clearance of urinary proteins is better than total proteinuria in predicting chronic kidney disease (CKD) progression. However, the role of sodium in the fractional excretion of proteins has not been established. We aimed to evaluate the association between sodium intake and fractional albumin and immunoglobulin G (IgG) excretion in nondialytic CKD. METHODS We did a longitudinal, observational, and prospective study that included CKD patients aged 18-80. Included patients performed basal routine laboratory evaluations, urinary sodium excretion, and fractional albumin and IgG excretion that were repeated after 6-month of follow-up. RESULTS We evaluated 84 patients, mean age 55 ± 15.6 years, 40 women, and 74 whites. The change of estimated sodium intake had an association with the change of fractional albumin (R = 0.54; p < 0.001) and IgG (R = 0.56; p < 0.001) excretion in univariate analysis (increases in sodium intake were paralleled by increases in albumin and IgG excretion fractions). This association was maintained in a multiple generalized linear model even after adjusting for age and for changes in blood pressure, urinary potassium, protein intake, and blood glucose. CONCLUSION In CKD patients, changes in estimated sodium intake were associated with changes in the fractional albumin and IgG excretion regardless of confounding factors. Findings of this study support the idea that reducing salt intake, and consequently, albumin and IgG fractional excretions could help to slow CKD progression. This hypothesis must be tested in long-term interventional studies.
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The effect of SGLT-2 inhibitors on albuminuria and proteinuria in diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.
Piperidou, A, Sarafidis, P, Boutou, A, Thomopoulos, C, Loutradis, C, Alexandrou, ME, Tsapas, A, Karagiannis, A
Journal of hypertension. 2019;(7):1334-1343
Abstract
: Diabetic kidney disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease in western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may have renoprotective effects. Our aim was to systematically review the effect of SGLT-2 inhibitors on albuminuria and proteinuria in patients with diabetes mellitus. Studies were identified by search in major electronic databases, clinical trial registers, and sources of gray literature. We included randomized controlled trials of currently approved SGLT-2 inhibitors with a duration of at least 12 weeks. The primary outcome was the between-groups difference in the proportional (%) change of albuminuria or proteinuria between baseline and end of treatment. SGLT-2 inhibitors were associated with statistically significant reduction in albuminuria compared to placebo or active control [weighted mean difference (WMD) -25.39%, 95% confidence interval (CI) -34.17 to -16.62] (15 studies, N = 17 540 patients). When trials were stratified according to the level of baseline albuminuria, reduction in urine albumin-to-creatinine ratio was more prominent in randomized controlled trials in patients with moderately (WMD -40.78%, 95% CI -63.21 to -18.34) or severely increased albuminuria (WMD -36.40%, 95% CI -51.53 to -21.26). Only one study reported data for urine protein-to-creatinine ratio. Finally, SGLT-2 inhibitors reduced systolic and diastolic blood pressure by 4.43 mmHg (95% CI -5.24 to -3.63) and 1.81 mmHg (95% CI -2.38 to -1.23), respectively.
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Association of microalbuminuria and high-normal 24-hour urinary albumin excretion with metabolic syndrome and its components in the general Chinese population: cross-sectional study.
Xu, J, Ma, J, Chen, X, Yan, L, Cai, X, Guo, X, Zhang, Y, Wu, J
BMJ open. 2019;(11):e031443
Abstract
OBJECTIVE Microalbuminuria (MAU) has been described as a risk factor for metabolic syndrome (MetS). However, the association between MetS components with MAU and 24-hour urinary albumin excretion (UAE) has not been clearly explained in the general Chinese population. We aimed to analyse the associations between MAU and high-normal 24-hour UAE with MetS and its components. DESIGN Cross-sectional observational study. SETTING Four selected counties/districts in China's Shandong and Jiangsu Provinces. PARTICIPANTS A total of 2261 participants aged 18-69 years were included in this study. Participants with missing physical examination data or incomplete urine collection were not included in the analysis. RESULTS The prevalence of MAU was 9%, and the mean 24-hour UAE was 18 mg/d. The prevalence of MAU was significantly higher for the MetS, high blood pressure (BP), high triglyceride (TG) levels, low high-density lipoprotein cholesterol (HDL-C) and hyperglycaemia groups but not for the central obesity group. Both MAU and mean 24-hour UAE were significantly increased in association with a number of MetS components. The adjusted prevalence OR (POR) for MetS with MAU was 2.95 (95% CI 2.15 to 4.04) compared with those without MAU. MAU was significantly associated with three components of MetS: high BP (POR=1.86, 95% CI 1.31 to 2.64), high TG levels (POR=1.80, 95% CI 1.31 to 2.46) and hyperglycaemia (POR=1.84, 95% CI 1.34 to 2.53). No significant association between MAU and central obesity or low HDL-C was found. The presence of MetS gradually increased according to the normal-range 24-hour UAE quartiles: POR=1.00, POR=1.22, POR=1.14 and POR=2.02, respectively. Hyperglycaemia also increased significantly according to the normal-range 24-hour UAE quartiles. CONCLUSIONS MAU and elevated 24-hour UAE within the normal range were closely associated with MetS in the Chinese population, which may provide a basis for the development of early interventions to decrease the effects of MetS.
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Associations between serum apolipoproteins, urinary albumin excretion rate, estimated glomerular filtration rate, and diabetic retinopathy in individuals with type 2 diabetes.
Chung, JO, Park, SY, Cho, DH, Chung, DJ, Chung, MY
Medicine. 2019;(20):e15703
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The published data regarding the role of serum apolipoprotein (apo) A-I, apoB, and the apoB/A-I ratio in the risk of diabetic retinopathy remain inconsistent, and there is limited information about the effect of renal status on their associations in individuals with type 2 diabetes. The aim of this study was to investigate whether serum apoA-I, apoB, and the apoB/A-I ratio are associated with the presence of diabetic retinopathy in type 2 diabetes and to explore whether the relationships between these apolipoproteins and diabetic retinopathy are modified by urinary albumin excretion rate (UACR) and estimated glomerular filtration rate (eGFR).In total, 1215 individuals with type 2 diabetes were included in this cross-sectional study. Serum levels of apoA-I and apoB and the apoB/apoA-I ratio were measured. A logistic regression model was performed to explore associations of apolipoproteins with retinopathy.Individuals with diabetic retinopathy had significantly lower levels of serum apoA-I and higher apoB/apoA-I ratio than those without diabetic retinopathy. In the multivariable analyses, the associations between apoA-I and diabetic retinopathy and between the apoB/apoA-I ratio and diabetic retinopathy were statistically significant after adjustment for the traditional risk factors (odds ratio [OR] per standard deviation [SD] increase in the log-transformed value; 0.55, 95% confidence interval (CI); 0.32 to 0.97, P = .038; OR per SD increase in the log-transformed value; 2.83, 95% CI; 1.18 to 6.76, P = .019; respectively). Additional adjustments for UACR or eGFR removed the significant associations.In individuals with type 2 diabetes, serum apoA-I and the apoB/apoA-I ratio are associated with presence of diabetic retinopathy, which might be attributable to the correlated changes in UACR and eGFR.