Higher Urine Albumin-to-creatinine Ratio Research Articles

Normoalbuminuria-is it normal? The association of urinary albumin within the 'normoalbuminuric' range with adverse cardiovascular and mortality outcomes: A systematic review and meta-analysis.

To assess the association between urinary albumin-to-creatinine ratio (UACR) categories within the normal range with mortality and adverse cardiovascular outcomes. PubMed and Embase were systematically searched for real-world evidence studies. Studies were manually evaluated according to predefined eligibility criteria. We included prospective and retrospective cohort studies of the association between UACR categories <30 mg/g and cardiovascular outcomes or mortality. Published information regarding study design, participants, UACR categorization, statistical methods, and results was manually collected. Two UACR categorization approaches were defined: a two-category (UACR <10 mg/g vs. 10-30 mg/g) and a three-category division (UACR <5 mg/g vs. 5-10 and 10-30 mg/g). A random effects meta-analysis was performed on studies eligible for the meta-analysis. In total, 22 manuscripts were identified for the systematic review, 15 of which were eligible for the meta-analysis. The results suggest an association between elevated UACR within the normal to mildly increased range and higher risks of all-cause mortality, cardiovascular death, and coronary heart disease, particularly in the range of 10-30 mg/g. Compared with UACR <10 mg/g, the hazard ratio [HR (95% confidence interval, CI)] for UACR between 10 and 30 mg/g was 1.41 (1.15, 1.74) for all-cause mortality and 1.56 (1.23, 1.98) for coronary heart disease. Compared with UACR <5 mg/g, the risk of cardiovascular mortality for UACR between 10 and 30 mg/g was more than twofold [HR (95% CI): 2.12 (1.61, 2.80)]. Intermediate UACR (5-10 mg/g) was also associated with a higher risk of all-cause mortality [HR (95% CI): 1.14 (1.05, 1.24)] and cardiovascular mortality [HR (95% CI): 1.50 (1.14, 1.99)]. We propose considering higher UACR within the normoalbuminuric range as a prognostic factor for cardiovascular morbidity and mortality. Our findings underscore the clinical significance of even mild increases in albuminuria.

High Urine Albumin-to-Creatinine Ratio is Associated with Increased Arterial Stiffness in Diabetes: A Chinese Cross-Sectional Study.

Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes. From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out. The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p<0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176-0.276, p<0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19-1.33, p<0.001), and 1.16 (1.08-1.25, p<0.001) respectively in diabetic patients before and after adjusting for potential confounders. The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.

Positive Association of Pulse Pressure with Presence of Albuminuria in Chinese Adults with Prediabetes: A Community-Based Study.

Purpose: There has been limited evidence for the association between pulse pressure (PP) and proteinuria in prediabetes. The aim of our study was to explore the association between PP and albuminuria in community-dwelling Chinese adults with prediabetes. Materials and Methods: PP and urinary albumin-to-creatinine ratio (ACR) were measured in 2012 prediabetic patients and 3596 control subjects with normal glucose tolerance. Multivariate logistic regression models were used to evaluate the possible association of PP with the risk of presence of albuminuria. Results: PP was positively associated with the presence of albuminuria, and subjects in the higher PP quartiles had higher urinary ACR and presence of albuminuria as compared with those in the lowest quartile in both prediabetes and control groups (all P < 0.01). Multivariate logistic regression analysis demonstrated that the highest PP quartile was positively associated with increased risk of presence of albuminuria in all prediabetic subjects [odds ratio (OR): 2.289, 95% confidence interval (CI) 1.364-3.842, P < 0.01) and prediabetic subjects without anti-hypertensive drugs (OR: 1.932, 95% CI 1.116-3.343, P < 0.01), whereas higher PP quartile has nothing to do with the risk of presence of albuminuria in control subjects with and without anti-hypertensive drugs after adjustment for potential confounders (all P > 0.01). Consistently, stratified analysis showed that in the prediabetes group, the risks of presence of albuminuria progressively elevated with increasing PP quartiles in men, those aged 60 years or older, and with overweight/obesity, normal high-density lipoprotein cholesterol, and appropriate low-density lipoprotein cholesterol (all P for trend <0.05). Conclusion: Higher PP is independently related to increased risk of presence of albuminuria in community-dwelling Chinese adults with prediabetes.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes

Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Association Between Continuous Glucose Monitoring-Derived Glycemia Risk Index and Albuminuria in Type 2 Diabetes.

The glycemia risk index (GRI) is a new composite metric derived from continuous glucose monitoring (CGM) data to assess the quality of glycemia. This study investigates the association between the GRI and albuminuria. Professional CGM and urinary albumin-to-creatinine ratio (UACR) data from 866 individuals with type 2 diabetes were retrospectively reviewed. Albuminuria and macroalbuminuria were defined as one or more UACR measurements ≥30 mg/g and ≥300 mg/g, respectively. The overall prevalence of albuminuria and macroalbuminuria was 36.6% and 13.9%, respectively. Participants with a higher UACR had a significantly higher hyperglycemia component and GRI score than those with a lower UACR (all p <0.001), although the hypoglycemia component did not differ among the groups. Multiple logistic regression analyses that adjusted for various factors affecting albuminuria revealed that the OR of albuminuria was 1.13 (95% CI: 1.02-1.27, p = 0.039) per increase in the GRI zone. The results were similar for the risk of macroalbuminuria (OR: 1.42 [95% CI: 1.20-1.69], p <0.001), and that association remained after adjusting for HbA1c (OR: 1.31 [95% CI: 1.10-1.58], p = 0.004). GRI is strongly associated with albuminuria, especially macroalbuminuria, in type 2 diabetes.

Chronic Kidney Disease, Heart Failure, and Adverse Cardiac Remodeling in Older Adults: The ARIC Study

BackgroundThe associations of kidney dysfunction and damage with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as adverse cardiac remodeling, in late-life remain incompletely understood. ObjectivesThe authors sought to define the associations between kidney dysfunction and damage and incident HFrEF and HFpEF and cardiac structure and function in late-life. MethodsThis study included 5,170 adults initially free of a heart failure (HF) diagnosis who had estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) measured at visit 5 (2011-2013) of the ARIC (Atherosclerosis Risk In Communities) study. Multivariable Cox proportional hazards models were used to estimate the associations of eGFR and UACR with incident HF, HFrEF, and HFpEF through 2019. Multivariable linear regression models were used to investigate the associations of eGFR and UACR at visit 5 with changes in cardiac structure and function between visits 5 and 7 in 2,313 participants with available echocardiograms. ResultsThe mean age of participants was 76 ± 5 years, and 2,225 (43%) were men. The mean eGFR and median UACR were 66 ± 18 mL/min/1.73 m2 and 11 mg/g (25th, 75th percentile: 6, 22 mg/g), respectively. In fully adjusted models, both lower eGFR and higher UACR were associated with greater risk of any HF, HFrEF, and HFpEF. Lower eGFR was associated with larger increases in left ventricular end-diastolic volume index and worsening of diastolic measures. UACR did not associate with changes in cardiac structure or function. ConclusionsMild to moderate kidney dysfunction and damage associate with incident HF and adverse cardiac remodeling in late-life.

Allometric body shape indices, type 2 diabetes and kidney function: A two-sample Mendelian randomization study.

To examine the association between body mass index (BMI)-independent allometric body shape indices and kidney function. We performed a two-sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM. BMI-independent allometric body shape indices were: A Body Shape Index (ABSI), Waist-Hip Index (WHI) and Hip Index (HI). Kidney function outcomes were: urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate and blood urea nitrogen. Furthermore, we investigated type 2 diabetes (T2D) as a potential mediator on the pathway to albuminuria. The main analysis was inverse variance-weighted random-effects MR in participants of European ancestry. We also performed several sensitivity MR analyses. A 1-standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (β= 0.039 [95% confidence interval: 0.016, 0.063] log [UACR], P= 0.001 for ABSI, and β= 0.028 [0.012, 0.044] log [UACR], P= 6 x 10-4 for WHI) in women, but not in men. Meanwhile, a 1-SD increase in genetically predicted HI was associated with lower UACR in women (β= -0.021 [-0.041, 0.000] log [UACR], P= 0.05) and in men (β= -0.026 [-0.058, 0.005] log [UACR], P= 0.10). Corresponding estimates in individuals with diabetes were substantially augmented. Risk of T2D increased for genetically high ABSI and WHI in women (P< 6 x 10-19 ) only, but decreased for genetically high HI in both sexes (P< 9 x 10-3 ). No other associations were observed. Genetically high HI was associated with decreased risk of albuminuria, mediated through decreased T2D risk in both sexes. Opposite associations applied to genetically high ABSI and WHI in women only.

Factors Associated with the Antihypertensive Effect of Esaxerenone and Serum Potassium Elevation: A Pooled Analysis of Seven PhaseIII Studies.

This study investigated factors associated with the antihypertensive effects of esaxerenone and theincidence of serum potassium elevation in patients with hypertension. Using pooled data from seven phaseIII studies, the study analyzed factors associated with changes in office systolic (SBP) and diastolic (DBP) blood pressure from baseline to 12weeks, and factors associated with incidence of serum potassium levels ≥ 5.5mEq/L in esaxerenone-treated patients. Overall, 1466 and 1472 patients were included in the fullanalysis and safety analysis sets, respectively. Male sex (4.02/2.40mmHg), weight ≥ 78.4kg (4.62/2.09mmHg), hypertension duration ≥ 10years (2.66/1.71mmHg), prior antihypertensive treatment (2.38/1.40mmHg), plasma aldosterone concentration ≥ 120pg/mL (1.66/1.17mmHg), urinary albumin-to-creatinine ratio (UACR) ≥ 300mg/gCr (8.94/4.85mmHg) or 30-299mg/gCr (5.17/4.15mmHg), and smoking (2.62/1.27mmHg)were associated with mean changes in SBP andDBP. Fasting blood glucose ≥ 126mg/dL (- 2.73mmHg) was associated with the mean change in SBP only, and older age (65-74years, - 2.12mmHg; and ≥ 75years, - 3.06mmHg) with mean change in DBP only. Factors significantly associated with incidence of serum potassium levels ≥ 5.5mEq/L were higher baseline serum potassium (≥ 4.5mEq/L, odds ratio [OR] 6.702); lower estimated glomerular filtration rate (≥ 90mL/min/1.73m2, OR 0.148; 60-89mL/min/1.73m2, OR 0.331 vs 30-59mL/min/1.73m2, respectively); higher UACR (30-299mg/gCr, OR 7.317); higher DBP (≥ 100mmHg, OR 3.248); and gradeI hypertension (OR 2.168). Esaxerenone is effective in patients with a broad range of backgrounds, though some factors may predict increased benefit. Regarding elevated serum potassium, careful therapeutic management is recommended for patients with higher baseline serum potassium and reduced renal function. UMIN000047026.

Association of kidney function and brain health: A systematic review and meta-analysis of cohort studies.

This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities. Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate (eGFR) ranges. PubMed, Embase database, Cochrane library and Web of Science (up to Dec. 2021). Longitudinal studies that provided evidence of the impact of kidney function estimated from eGFR and urine albumin-to-creatinine ratio (UACR) or chronic kidney disease (CKD) on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under 18 years old were excluded. Two independent reviewers screened the included studies, extracted the data, and assessed the risk of bias. We performed a random-effects meta-analysis and a network meta-analysis for outcomes with compatible data. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale criteria (NOS). Subgroup and sensitivity analyses were conducted to explore heterogeneity in the meta-analyses. Inconsistency analyses using the node-splitting method were performed to confirm the results of network meta-analysis. A total of 53 studies with 3037,357 participants were included in the current systematic review. Among these, 16 provided evidence of structural brain abnormalities, and 38 provided evidence of cognitive impairment and dementia. Analysis of evidence of categorical kidney function showed a positive association between kidney dysfunction and cerebral small vessel disease (cSVD) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.40-2.24, I2 =0.0%), but such results were not found in the analyses of evidence where the kidney function was measured as a continuous variable. Meanwhile, analysis of 28 prior longitudinal studies with 194 compatible sets of data showed that the worse kidney function as categorical variables was related to a greater risk of global brain cognitive disorder (RR 1.28, 95% CI 1.20-1.36, I2 = 82.5%). In this systematic review and meta-analysis, we found a positive association between CKD and functional brain disorders. However, the relationship between the kidney dysfunction and structural abnormalities in the brain remains controversial. As for the opposite relationship, structural brain abnormalities, especially cerebral microbleeds and silent infarction, but not functional brain abnormalities, are associated with worse renal function. In addition, a higher UACR, but not a lower eGFR, was associated with a higher risk of Alzheimer's disease and vascular dementia.

Blood oxygen saturation is lower in persons with pre-diabetes and screen-detected diabetes compared with non-diabetic individuals: A population-based study of the Lolland-Falster Health Study cohort.

Low blood oxygen saturation is associated with increased mortality and persons with diabetes have sub-clinical hypoxemia. We aimed to confirm the presence of sub-clinical hypoxemia in pre-diabetes, screen-detected diabetes and known diabetes. Pre-diabetes was defined as hemoglobin A1C (HbA1C) ≥ 42 mmol/mol and <48 mmol/mol; known diabetes as history or treatment of diabetes; screen-detected diabetes as no history or treatment of diabetes and HbA1C ≥ 48 mmol/mol. Blood oxygen saturation was measured with pulse oximetry. Urine albumin-to creatinine ratio (UACR) was measured on a single spot urine. The study included 829 adults (≥18 years) with diabetes (713 (86%) with known diabetes; 116 (14%) with screen-detected diabetes) and 12,747 without diabetes (11,981 (94%) healthy controls; 766 (6%) with pre-diabetes). Mean (95% CI) blood oxygen saturation was 96.3% (96.3% to 96.4%) in diabetes which was lower than in non-diabetes [97.3% (97.2-97.3%)] after adjustment for age, gender, and smoking (p < 0.001), but significance was lost after adjustment for BMI (p = 0.25). Sub-groups with pre-diabetes and screen-detected diabetes had lower blood oxygen saturations than healthy controls (p-values < 0.01). Lower blood oxygen saturation was associated with higher UACR. Persons with pre-diabetes and screen-detected diabetes have sub-clinical hypoxemia, which is associated with albuminuria.

Estimated GFR, Albuminuria, and Physical Function: The Brain in Kidney Disease (BRINK) Cohort Study

Rationale & ObjectiveChronic kidney disease (CKD) is associated with impaired physical performance. However, the association between albuminuria, a marker of vascular endothelial dysfunction, and physical performance has not been fully characterized. We hypothesized that estimated glomerular filtration rate (eGFR) and albuminuria would be independently associated with physical performance.Study DesignCross-sectional analysis.Setting & ParticipantsA total of 571 adults with and without CKD.PredictorsCreatinine-based eGFR (eGFRCr) and cystatin C-based eGFR (eGFRCysC) and urine albumin to creatinine ratio (UACR).OutcomeShort Physical Performance Battery (SPPB).Analytical ApproachUnivariate and multivariable logistic regression models were used to examine associations of eGFR and UACR with impaired physical performance.ResultsOf the 571 participants (mean age, 69.3 years), 157 (27.5%) had eGFRCr (mL/min/1.73m2) <30, 276 (48.3%) had eGFRCr 30-<60, and 138 (24.2%) had eGFRCr ≥60; 303 (55.3%) participants had eGFRcysC <30, 141 (25.7%) had eGFRcysC 30-<60, and 104 (19.0%) had eGFRcysC ≥60. Impaired physical performance was observed in 222 (38.9%) participants. Separate univariate analyses showed that lower eGFRCr, lower eGFRCysC, and higher UACR were associated with higher odds of impaired physical performance. In the adjusted model with eGFRCr or eGFRCysC, UACR, and covariates, UACR retained a statistically significant association with impaired physical performance (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 1.21-3.47 for UACR from 30-300 mg/g vs <30 mg/g and adjusted OR, 1.93; 95% CI, 1.01-3.69 for UACR >300 mg/g vs <30 mg/g), but eGFRCr and eGFRCysC did not.LimitationsCross-sectional analysis, estimated rather than measured GFR.ConclusionsOnly UACR was associated with worse physical performance in the fully adjusted model, suggesting that vascular endothelial function and inflammation may be important mechanisms of decreased physical function. Similar results were found using eGFRCr or eGFRCysC, suggesting that confounding based on muscle mass does not explain the lack of an association between eGFRCr and physical performance.

Association of osteopontin with kidney function and kidney failure in chronic kidney disease patients: the GCKD study.

Osteopontin (OPN), synthesized in the thick ascending limb of Henle's loop and in the distal tubule, is involved in the pathogenesis of kidney fibrosis, a hallmark of kidney failure (KF). In a cohort of chronic kidney disease (CKD) patients, we evaluated OPN's association with kidney markers and KF. OPN was measured from baseline serum samples of German Chronic Kidney Disease study participants. Cross-sectional regression models for estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) as well as Cox regression models for all-cause mortality and KF were evaluated to estimate the OPN effect. Additionally, the predictive ability of OPN and time-dependent population-attributable fraction were evaluated. Over a median follow-up of 6.5 years, 471 KF events and 629 deaths occurred among 4950 CKD patients. One-unit higher log(OPN) was associated with 5.5mL/min/1.73 m2 lower eGFR [95% confidence interval (95% CI) -6.4 to -4.6] and 1% change in OPN with 0.7% higher UACR (estimated effect 0.7, 95% CI 0.6-0.8). Moreover, higher OPN levels were associated with a higher risk of KF [hazard ratio (HR) 1.4, 95% CI 1.2-1.7] and all-cause mortality (HR 1.5, 95% CI 1.3-1.8). After 6 years, 31% of the KF events could be attributed to higher OPN levels (95% CI 3%-56%). In this study, higher OPN levels were associated with kidney function markers worsening and a higher risk for adverse outcomes. A larger proportion of KF could be attributed to higher OPN levels, warranting further research on OPN with regards to its role in CKD progression and possible treatment options.

Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Women With a History of Gestational Diabetes

Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease as their age‐matched counterparts. GDM is associated with endothelial dysfunction and elevated oxidative stress during pregnancy, and vascular dysfunction postpartum. However, the mechanism(s) mediating this postpartum dysfunction are unknown. Using the cutaneous circulation as a model, we examined if oxidative stress contributes to microvascular dysfunction in healthy women with a history of GDM (GDM). We hypothesized that: 1) endothelium‐ and nitric oxide (NO)‐dependent dilation would be attenuated in GDM compared to women with a history of normal pregnancy (NP), and 2) local antioxidant (L‐ascorbate) administration would augment endothelium‐ and NO‐dependent dilation in GDM. Ten NP (35±1yrs) and 10 GDM (34±1yrs) underwent a standard local heating protocol (42°C; 0.1°C·s‐1). Two intradermal microdialysis fibers were placed in the ventral forearm for local delivery of lactated Ringer’s (control), or 5mM ascorbate. After full expression of the local heating response, 15mM NG‐nitro‐L‐arginine methyl ester (L‐NAME; NO synthase‐inhibition) was perfused. Red cell flux was measured continuously by laser‐Doppler flowmetry and cutaneous vascular conductance (CVC=flux/MAP) was standardized to maximum (%CVCmax; 28mM SNP + 43°C). Urine albumin to creatinine ratio (ACR) and plasma concentrations of oxidized LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) were measured. Women with history of GDM had attenuated endothelium‐dependent (GDM: 67±7 vs. NP: 90±4%CVCmax; p&lt;0.001) and NO‐dependent (GDM: 54±7 vs. NP: 71±3%; p=0.001) dilation at the control site and tended to have higher urine ACR (p=0.06). Both endothelium‐dependent (r2=0.53, p=0.02) and NO‐dependent (r2=0.56, p=0.01) dilation were related to urine ACR in GDM. Local ascorbate perfusion improved endothelium‐dependent (82±5%CVCmax; p=0.03 vs. control) and NO‐dependent (68±5%; p=0.02 vs. control) dilation in those with history of GDM but had no effect in HC (p&gt;0.05). There were no differences in plasma oxLDL (hxGDM:60.5 vs hxNP:50.9 U/L; p=0.18) or TBARS (hxGDM: 0.3 vs hxNP: 0.2 μM; p=0.26) concentrations between groups. These data suggest that otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and that this dysfunction is mediated, in part, by oxidative stress at the level of the vasculature.

Kidney disease parameters, metabolic goal achievement, and arterial stiffness risk in Chinese adult people with type 2 diabetes.

BackgroundTo investigate the arterial stiffness (AS) risk within urinary albumin‐to‐creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) categories and the joint effect between kidney disease parameters and metabolic goal achievement on AS risk in adult people with type 2 diabetes (T2D).MethodsA total of 27 439 Chinese participants with T2D from 10 National Metabolic Management Centers (MMC) were categorized into four albuminuria/decreased eGFR groups. The criteria for decreased eGFR and AS were eGFR <90 ml/min/1.73 m2 and brachial‐ankle pulse wave velocity value >the 75th percentile (1770.0 cm/s). Three metabolic goals were defined as glycated hemoglobin <7%, BP <130/80 mmHg, andlow‐density lipoprotein cholesterol <2.6 mmol/L.ResultsAfter full adjustment, odds ratios (ORs) for AS were highest for albuminuria and decreased eGFR (2.23 [1.98–2.52]) and were higher for albuminuria and normal eGFR (1.52 [1.39–1.67]) than for those with nonalbuminuria and decreased eGFR (1.17 [1.04–1.32]). Both UACR and eGFR in the subgroup or overall population independently correlated with AS risk. The achievement of ≥2 metabolic goals counteracted the association between albuminuria and AS risk (OR: 0.93; 95% CI: 0.80–1.07; p = .311). When the metabolic goals added up to ≥2 for patients with decreased eGFR, they showed significantly lower AS risk (OR: 0.65; 95% CI: 0.56–0.74; p < .001).ConclusionsBoth higher UACR and lower eGFR are determinants of AS risk, with UACR more strongly related to AS than eGFR in adults with T2D. The correlation between albuminuria/decreased eGFR and AS was modified by the achievement of multiple metabolic elements.

Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes

BackgroundData on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes.MethodsParticipants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories.ResultsA total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR < 30 mg/g, moderate albuminuria and severe albuminuria were associated with increasing hazards for stroke (HR 1.61 [95% CI 1.12–2.32] and 2.29 [95% CI 1.39–3.80], respectively). Compared to eGFR of ≥ 60 mL/min/1.73 m2, decreased eGFR (eGFR < 60 mL/min/1.73 m2) was associated with higher risk of stroke (HR 1.50, 95% CI 0.98–2.29). Compared to no CKD, worsening CKD stage was associated with an increasing risk of stroke (HRs of 1.76 [95% CI 1.10–2.83] for CKD G1, 1.77 [95% CI 1.13–2.75] for CKD G2, and 2.03 [95% CI 1.27–3.24] for CKD G3).ConclusionsIn a large sample of adults with type 2 diabetes, increasing albuminuria and worsening stages of early CKD were independently associated with higher risk of incident stroke.Trial registrationClinicalTrials.gov. Identifier: NCT00000620.

The association between serum activin A levels and albuminuria among community-dwelling middle-aged and older adults in Taiwan

Activin A, a cytokine belonging to the transforming growth factor-β family, has been shown to play pivotal roles in tissue remodeling after renal injury and is present in elevated levels in diabetic patients. However, the association between activin A and albuminuria remains unclear. We aimed to evaluate their association by using cross-sectional data from community-dwelling middle-aged and older adults in Taiwan. We assessed 466 participants (67% male; mean age 71 ± 13 years) from the I-Lan Longitudinal Aging study for whom data pertaining to serum activin A level and urine albumin-to-creatinine ratio (UACR) were available. Of these, 323 (69%) had normal albuminuria, 123 (26%) had microalbuminuria, and 20 (4%) had overt albuminuria. Patients with overt albuminuria and microalbuminuria had significantly higher activin A concentrations than those in the normal albuminuria group (p < 0.001). Circulating activin A was significantly correlated with multiple risk factors, including higher systolic blood pressure and higher UACR. Univariate and multivariate results indicated that activin A level was an independent variable for albuminuria. The cutoff value of 602 pg/mL of activin A demonstrated a sensitivity of 70.6% and specificity of 75.7% (AUC 0.774) in diagnosing overt albuminuria. In conclusion, middle-aged and older adults with elevated activin A levels were associated with a higher incidence of albuminuria.

Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial

Dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease with and without type 2 diabetes in the DAPA-CKD trial. In this pre-specified analysis, we assessed the effect of dapagliflozin on the rate of change in estimated glomerular filtration rate (eGFR)-ie, the eGFR slope. DAPA-CKD was a randomised controlled trial that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73m2. Participants were randomly assigned (1:1) to oral dapagliflozin 10 mg once daily or placebo, added to standard care. In this pre-specified analysis, we analysed eGFR slope using mixed-effect models with different slopes from baseline to week 2 (acute eGFR decline), week 2 to end of treatment (chronic eGFR slope), and baseline to end of treatment (total eGFR slope). DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150, and is now complete. Between Feb 2, 2017, and April 3, 2020, 4304 participants were recruited, of whom 2152 (50%) were assigned to dapagliflozin and 2152 (50%) were assigned to placebo. At baseline, the mean age was 62 years (SD 12), 1425 (33·1%) participants were women, 2906 (67·5%) participants had type 2 diabetes. The median on-treatment follow-up was 2·3 years (IQR 1·8-2·6). From baseline to the end of treatment, dapagliflozin compared with placebo slowed eGFR decline by 0·95 mL/min per 1·73 m2 per year (95% CI 0·63 to 1·27) in the overall cohort. Between baseline and week 2, dapagliflozin compared with placebo resulted in an acute eGFR decline of 2·61 mL/min per 1·73 m2 (2·16 to 3·06) in patients with type 2 diabetes and 2·01 mL/min per 1·73 m2 (1·36 to 2·66) in those without type 2 diabetes. Between week 2 and end of treatment, dapagliflozin compared with placebo reduced the mean rate of eGFR decline by a greater amount in patients with type 2 diabetes (mean difference in chronic eGFR slope 2·26 mL/min per 1·73 m2 per year [1·88 to 2·64]) than in those without type 2 diabetes (1·29 mL/min per 1·73 m2 per year [0·73 to 1·85]; pinteraction=0·0049). Between baseline and end of treatment, the effect of dapagliflozin compared with placebo on the decline of total eGFR slope in patients with type 2 diabetes was 1·18 mL/min per 1·73 m2 per year (0·79 to 1·56) and without type 2 diabetes was 0·46 mL/min per 1·73 m2 per year (-0·10 to 1·03; pinteraction=0·040). The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the effect of dapagliflozin on eGFR slope was also more pronounced in patients with higher baseline HbA1c and UACR. Dapagliflozin significantly slowed long-term eGFR decline in patients with chronic kidney disease compared with placebo. The mean difference in eGFR slope between patients treated with dapagliflozin versus placebo was greater in patients with type 2 diabetes, higher HbA1c, and higher UACR. AstraZeneca.

Urinary albumin creatinine ratio associated with postoperative delirium in elderly patients undergoing elective non-cardiac surgery: A prospective observational study.

IntroductionThe blood‐brain barrier (BBB) disruption contributes to postoperative delirium, but cost‐effective and non‐invasive assessment of its permeability is not practicable in the clinical settings. Urine albumin to creatinine ratio (UACR), reflecting systemic vascular endothelial dysfunction, may be a prognostic and predictive factor associated with postoperative delirium. The aim was to analyze the relationship between UACR and postoperative delirium in elderly patients undergoing elective non‐cardiac surgery.Materials and methodsThrough stratified random sampling, a cohort of 408 individuals aged 60 years and older scheduled for elective non‐cardiac surgery were included between February and August 2019 in the single‐center, prospective, observational study. The presence of delirium was assessed using the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM‐ICU) on the day of surgery, at 2 h after the surgery ending time and on the first 3 consecutive days with repeated twice‐daily, with at least 6‐h intervals between assessments. Urine samples were collected on one day before surgery, and 1st day and 3rd day after surgery. The primary outcome was the presence of postoperative delirium, and association of the level of UACR with postoperative delirium was evaluated with unadjusted/adjusted analyses and multivariable logistic regression.ResultsPostoperative delirium was observed in 26.75% (107 of 400) of patients within 3 days post‐surgery. UACR‐Pre (OR, 1.30; 95% CI, 1.14–1.49, p < 0.001), UACR‐POD1 (OR, 1.20; 95% CI, 1.13–1.27, p < 0.001), and UACR‐POD3 (OR, 1.14; 95% CI, 1.08–1.20, p < 0.001) between the delirium and non‐delirium groups show a significant difference, even after adjusting for age, education levels, and other factors.ConclusionAs the marker of endothelial dysfunction, the high perioperative UACR value may be linked to the postoperative delirium in elderly patients undergoing elective non‐cardiac surgery.

Blood lead, vitamin D status, and albuminuria in patients with type 2 diabetes.

Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%-15.5%) in diabetic patients with 25(OH)D<50nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI,-5.18% to 9.78%) in those with 25(OH)D≥50nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03-1.15) and 0.99 (95% CI, 0.86-1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D<50nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60mL/min/1.73m2). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.

Stronger Association of Albuminuria with the Risk of Vascular Complications than Estimated Glomerular Filtration Rate in Type 2 Diabetes

Introduction: Albuminuria is a risk factor for macro- and microvascular complications of type 2 diabetes (T2D).With an increasing trend of normoalbuminuria, however, of the 2 predictors – estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) – which one is a better predictor of vascular complications of T2D is not clear. Objective: This study aimed to compare the impacts of albuminuria and eGFR on patients with T2D associated with micro- and macrovascular complications. Methods: This retrospective study recruited 4,715 patients with T2D and grouped them based on the values of UACR (high UACR: ≥30 mg/g, low UACR: <30 mg/g) and eGFR (mL/[min × 1.73 m²]) (G1: eGFR ≥ 90; G2: eGFR = 60–89; G3–5: eGFR < 60) from April 2008 to November 2018. Logistic regression analysis was carried out for risk factors in patients with diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD), left ventricular remodeling, diastolic disorders, and carotid atherosclerotic plaque in 6 different groups: low UACR + G1 (control group), low UACR + G2, low UACR + G3–5, high UACR + G1, high UACR + G2, and high UACR + G3–5. Patients were grouped according to the change in the UACR value (UACR-decreased group: ≤−30%, UACR-stable group: −30 to 30%, and UACR-increased group ≥30%), eGFR value (eGFR-decreased group: >3%, and eGFR-stable group: ≤3%) and followed up. Results: Compared with the control group, patients with higher albuminuria and lower eGFR had higher adjusted odds ratio (OR) trends of complications, especially in the high UACR + G3–5 group. The OR of 2.010, 3.444, 1.633, 2.742, and 3.014 were obtained for DR, DPN, PAD, left ventricular remodeling, and diastolic disorders, respectively. No statistically significant difference was found in the risk of complications within each one of 2 phenotypes, regardless of the change in the eGFR. After grouping by eGFR, the regression analysis of the urinary protein level in each stage revealed that a majority of complications had a statistically significant difference, except for DR and PAD in the high UACR + G3–5 group. DR in the follow-up study had a higher risk in the UACR-stable/increased group than the UACR-decreased group (UACR stable: OR = 2.568; 95% confidence interval (CI): 1.128–5.849; p = 0.025; UACR increased: OR = 2.489; 95% CI: 1.140–5.433; p = 0.022). Conclusion: UACR is a more predictive risk factor for diabetic complications compared with a reduced eGFR.