Urinary Albumin-to-creatinine Ratio Levels Research Articles

Synergistic reduction in albuminuria in type 2 diabetic mice by esaxerenone (CS-3150), a novel nonsteroidal selective mineralocorticoid receptor blocker, combined with an angiotensin II receptor blocker

Esaxerenone is a novel selective mineralocorticoid receptor (MR) blocker that was recently approved in Japan to treat hypertension. In phase II and III studies, esaxerenone plus a renin–angiotensin system inhibitor markedly reduced the urinary albumin-to-creatinine ratio (UACR) in hypertensive patients with diabetic nephropathy. To evaluate a direct renoprotective effect by MR blockade independent of an antihypertensive effect in the context of diabetic nephropathy, esaxerenone (3 mg/kg), olmesartan (an angiotensin II receptor blocker; 1 mg/kg), or both were orally administered to KK-Ay mice, a type 2 diabetes model, once daily for 56 days. Urinary albumin (Ualb), UACR, and markers, such as podocalyxin, monocyte chemoattractant protein-1 (MCP-1), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were measured, along with systolic blood pressure (SBP), fasting blood glucose, and serum K+ levels. Prior to the initiation of drug administration, KK-Ay mice showed higher blood glucose, insulin, Ualb excretion, and UACR levels than C57BL/6 J mice, a nondiabetic control, indicating the development of diabetic renal injury. Combined treatment with esaxerenone and olmesartan significantly reduced the change in UACR from baseline compared with the change associated with vehicle at week 8 (−1.750 vs. 0.339 g/gCre; P < 0.002) and significantly inhibited the change in Ualb from baseline compared with the change associated with vehicle at week 8 (P < 0.002). The combination treatment also reduced urinary excretion of podocalyxin and MCP-1, but did not influence 8-OHdG excretion, SBP, blood glucose, or serum K+ levels. Overall, esaxerenone plus olmesartan treatment ameliorated diabetic nephropathy in KK-Ay mice without affecting SBP, suggesting that the renoprotective effects of esaxerenone could be exerted independently of its antihypertensive effect.

Plasma Metabolomics Identifies Markers of Impaired Renal Function: A Meta-analysis of 3089 Persons with Type 2 Diabetes.

There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease. To investigate associations between plasma metabolites and kidney function in people with type 2 diabetes (T2D). 3089 samples from individuals with T2D, collected between 1999 and 2015, from 5 independent Dutch cohort studies were included. Up to 7 years follow-up was available in 1100 individuals from 2 of the cohorts. Plasma metabolites (n = 149) were measured by nuclear magnetic resonance spectroscopy. Associations between metabolites and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and eGFR slopes were investigated in each study followed by random effect meta-analysis. Adjustments included traditional cardiovascular risk factors and correction for multiple testing. In total, 125 metabolites were significantly associated (PFDR = 1.5×10-32 - 0.046; β = -11.98-2.17) with eGFR. Inverse associations with eGFR were demonstrated for branched-chain and aromatic amino acids (AAAs), glycoprotein acetyls, triglycerides (TGs), lipids in very low-density lipoproteins (VLDL) subclasses, and fatty acids (PFDR < 0.03). We observed positive associations with cholesterol and phospholipids in high-density lipoproteins (HDL) and apolipoprotein A1 (PFDR < 0.05). Albeit some metabolites were associated with UACR levels (P < 0.05), significance was lost after correction for multiple testing. Tyrosine and HDL-related metabolites were positively associated with eGFR slopes before adjustment for multiple testing (PTyr = 0.003; PHDLrelated < 0.05), but not after. This study identified metabolites associated with impaired kidney function in T2D, implying involvement of lipid and amino acid metabolism in the pathogenesis. Whether these processes precede or are consequences of renal impairment needs further investigation.

Thyroid Parameters and Kidney Disorder in Type 2 Diabetes: Results from the METAL Study.

Objective Diabetic kidney disease is one of the most common microvascular complications of diabetes mellitus. We aimed to analyze the association of thyroid parameters with kidney disorders, especially in euthyroid participants. Methods The data were obtained from a cross-sectional study, the METAL study. Thyroid parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxin (T4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), of 4136 participants with type 2 diabetes were measured. Two structure parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD) and thyroid secretory capacity (SPINA-GT), and two pituitary thyrotropic function indices, including Jostel's TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Kidney disorders were described according to the presence of reduced estimated glomerular filtration rate (eGFR) and/or higher urinary albumin to creatinine ratio (UACR). Results The prevalence of kidney disorders increased with decreasing FT3 or T3 and increasing FT4 or T4 quartile levels (all P < 0.05). After full adjustment, linear regression showed that UACR levels were negatively associated with FT3 and T3 (P < 0.001). In addition, eGFR was positively associated with FT3 and T3 and was negatively associated with TSH and FT4 levels and TgAb positivity (all P < 0.05). By using binary logistic regression, higher TSH and FT4 and lower FT3 and T3 were associated with kidney disorders (all P < 0.05). Similar results were seen in sensitivity analyses, which were performed in 3035 euthyroid diabetic participants; however, TSH was no longer related to them. The area under the receiver operating characteristic curve (AUROC) of lower FT3 for existing kidney disorder was greater than that for any other thyroid hormones (all P < 0.001). The cutoff value of FT3 for reduced eGFR was 4.39 pmol/L. Regarding thyroid homeostasis parameters, SPINA-GD was negatively associated with three statuses of kidney disorders, and TSHI and TTSI were positively associated with reduced eGFR (all P < 0.05). Conclusions Among patients with type 2 diabetes, elevated TSH and FT4 (or T4), lower FT3 (or T3), TgAb positivity, lower SPINA-GD, and higher TSHI and TTSI were associated with kidney disorders. The lower FT3, even within the normal range (<4.38 pmol/L), may be the factor most related to reduced eGFR compared with other thyroid hormones in diabetic patients.

URINE ALBUMIN-TO-CREATININE RATIO AND ESTIMATED GLOMERULAR FILTRATION RATE IN MATCHED GROUPS OF TYPE 2 DIABETES MELLITUS PATIENTS RECEIVING METFORMIN AND METFORMIN-SULFONYLUREA

Objective: Renal disease complications in type 2 diabetes mellitus patients are characterized by progressive urinary albumin excretion and decreasedglomerular filtration. The drugs most commonly prescribed as antidiabetic therapy in Indonesia are metformin and sulfonylurea. It is still unclearwhether the effect of metformin-sulfonylurea on kidney is different from that of metformin monotherapy.Methods: We compared the effectiveness of metformin monotherapy and metformin-sulfonylurea combination to the urine albumin-to-creatinineratio (UACR) and estimated glomerular filtration rate (eGFR) as renal function parameters. Study subjects were patients on either of these drugregimens for at least 1 year. We collected 88 samples from type 2 diabetes mellitus patients (37 patients on metformin and 51 on metforminsulfonylurea).The patients fasted for 8 h before urine and blood collection for UACR and eGFR analysis. We measured the eGFR using the chronickidney disease epidemiology collaboration (CKD-EPI) equation, serum creatinine, and urine creatinine by colorimetric enzymatic assay, and urinealbumin by immunoturbidimetry.Results: The eGFR level in the metformin and metformin-sulfonylurea groups was within the normal range, but lower in the metformin group(79.59±2.81) than in the metformin-sulfonylurea group (87.82±2.82) (p=0.018). In addition, hyperfiltration cases were more frequent in metforminsulfonylureagroup (p=0.029). The UACR in patients taking metformin-sulfonylurea (177.95±60.92) was higher than that in the metformin group(49.58±14.19) but the difference between them was not significant (p=0.099).Conclusion: Metformin monotherapy was associated with a lower frequency of hyperfiltration and lower UACR level compared to metforminsulfonylureacombination.

Post–Acute Kidney Injury Proteinuria and Subsequent Kidney Disease Progression

Among patients who had acute kidney injury (AKI) during hospitalization, there is a need to improve risk prediction such that those at highest risk for subsequent loss of kidney function are identified for appropriate follow-up. To evaluate the association of post-AKI proteinuria with increased risk of future loss of renal function. The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective cohort study including 4 clinical centers in North America included 1538 patients enrolled 3 months after hospital discharge between December 2009 and February 2015. Urine albumin-to-creatinine ratio (ACR) quantified 3 months after hospital discharge. Kidney disease progression defined as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease. Of the 1538 participants, 769 (50%) had AKI durring hospitalization. The baseline study visit took place at a mean (SD) 91 (23) days after discharge. The mean (SD) age was 65 (13) years; the median eGFR was 68 mL/min/1.73 m2; and the median urine ACR was 15 mg/g. Overall, 547 (37%) study participants were women and 195 (13%) were black. After a median follow-up of 4.7 years, 138 (9%) participants had kidney disease progression. Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (hazard ratio [HR], 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, 0.82). The performance of urine ACR was stronger in patients who had had AKI than in those who had not (C statistic, 0.70). A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics) including ACR provided better discrimination for predicting kidney disease progression after hospital discharge among those who had had AKI (C statistic, 0.85) vs those who had not (C statistic, 0.76). In the entire matched cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months after discharge, AKI (HR, 1.46; 95% CI, 0.51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, 0.50-4.72 for AKI stage 1 vs non-AKI; HR, 0.56; 95% CI, 0.07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, 0.33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression. Proteinuria level is a valuable risk-stratification tool in the post-AKI period. These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study.

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR < 30 mg/g, n = 136, NA), microalbuminuria (UACR at 30-300 mg/g, n = 132, MA), and clinical albuminuria (UACR > 300 mg/g, n = 122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects (P < 0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR (P < 0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

Relationship between Clinical Features of Diabetic Retinopathy and Systemic Factors in Patients with Newly Diagnosed Type II Diabetes Mellitus.

BackgroundWe investigated the relationship between clinical features of diabetic retinopathy (DR) and systemic factors in patients with newly diagnosed type II diabetes mellitus (T2DM).MethodsRetrospective review of newly diagnosed T2DM-patients who underwent complete ophthalmic examinations at the time of T2DM diagnosis were conducted. We reviewed DM related systemic factor data and investigated systemic factors related to the presence of DR at T2DM diagnosis. In DR patients, the relationship between DR severity and systemic factors was analyzed.ResultsOf 380 patients, forty (10.53%) patients had DR at the initial ophthalmologic examination. Glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), urine albumin to creatinine ratio (UACR), and urine microalbumin level were significantly higher in DR patients than in patients without DR. In the multivariate logistic regression analysis, high HbA1C was a significant risk factor for the presence of DR at new T2DM diagnosis (odds ratio, 2.372; P < 0.001). HbA1C, FPG, UACR, and urine microalbumin level showed significantly positive correlations with DR severity .ConclusionIn patients with newly diagnosed T2DM, 10.53% have DR at initial ophthalmologic examination and high HbA1C, FPG, UACR and urine microalbumin levels. These factors are significantly positively correlated with DR severity. Therefore, more careful fundus examination is needed for newly diagnosed T2DM patients with high HbA1C, FPG, UACR, and urine microalbumin levels.

Association of Longitudinal Trajectory of Albuminuria in Young Adulthood With Myocardial Structure and Function in Later Life

Albuminuria, as measured by single urine albumin-to-creatinine ratio (UACR) levels, is associated with cardiac remodeling and adverse clinical outcomes. The longitudinal patterns of change in UACR through young adulthood and their associations with myocardial structure and function later in life remain unclear. To describe the trajectory of albuminuria as measured by UACR across a 20-year span and evaluate the association of albuminuria trajectory with echocardiographic indices of structure and function in middle age. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of black and white participants aged 18 to 30 years at baseline (March 1985 to June 1986) were evaluated over 30 years. Participants underwent evaluations at 4 urban US sites. Data were collected from March 1985 to May 2016, and data were analyzed from September 2018 to April 2019. Trajectories of UACR from the year 10 examination to the year 30 examination as determined by latent class modeling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 30 examination. Of the 2647 included participants, 1441 (54.4%) were white, 1206 (45.6%) were black, and the mean (SD) age was 35.2 (3.6) years. A total of 5 trajectory groups of UACR were identified, including 1718 participants (64.9%) in the low-stable group, 682 (25.8%) in the moderate-stable group, 116 (4.4%) in the high-stable group, 88 (3.3%) in the moderate-increasing group, and 43 (1.6%) in the high-increasing group. Apart from the high-increasing cohort, the remaining 4 groups had median baseline UACR levels less than 30 mg/g. Male sex, current smoking, diabetes, and elevated blood pressure were more common in the moderate-increasing and high-increasing UACR groups. After adjustment for clinical variables and baseline UACR levels, there were significant differences in left ventricular (LV) mass by trajectory group (mean [SE] LV mass: high-increasing, 98.4 [3.4] g/m2; moderate-increasing, 91.7 [2.2] g/m2; high-stable, 86.0 [2.1] g/m2; moderate-stable, 82.3 [0.8] g/m2; low-stable, 78.6 [0.5] g/m2; P < .001). Significant differences by trajectory group were also noted in LV longitudinal strain, e' tissue velocities, and estimated LV filling pressures, even after adjustment for clinical variables and baseline UACR level. The association of trajectory group with indices of myocardial structure and function remained significant after adjustment for clinical variables and cumulative UACR from the year 10 to year 25 examinations. There are distinct patterns of change in albuminuria among young adults over a 20-year span, and these trajectory groups cannot be identified by baseline UACR level alone. Dynamic changes in albuminuria are independently associated with adverse alterations to cardiac structure, LV systolic function, and LV diastolic function.

Serum testosterone acts as a prognostic indicator in polycystic ovary syndrome-associated kidney injury.

Polycystic ovary syndrome (PCOS) is closely related with the onset and development of metabolic abnormalities. However, the correlation between PCOS and kidney injury has not been clarified, and the underlying mechanism remains unknown. Herein, we performed a prospective survey in 55 PCOS and 69 healthy participants. Furthermore, the correlation analyses between serum testosterone and renal functional manifestations of patients and healthy subjects, including urinary albumin to creatinine ratio (UACR), urinary κ‐light chains (KapU), urinary λ‐light chains (LamU), urinary α1‐microglobulin (α1‐MU), and urinary β2‐microglobulin (β2‐MU), were analyzed. Compared with that in normal subjects, the levels of serum testosterone and UACR were significantly higher in PCOS patients. Serum testosterone is significantly correlated with the disease severity of PCOS. Although urinary excretions of KapU, LamU, α1‐MU, and β2‐MU did not increase in PCOS patients, they had a significantly positive correlation with the extent of serum testosterone in PCOS patients. IN vitro, primary cultured human ovary granulosa cells (GCs) were isolated from the follicular fluid (FF) extracting from PCOS patients and controls. FF, especially which extracted from PCOS patients with a high expression of serum testosterone, significantly induced cell apoptosis and inflammation in human GCs. To examine the communication between PCOS and kidney injury, a human proximal tubular epithelial cell line (HKC‐8) was cultured and administered FF. Interestingly, FF from PCOS patients with a higher level of serum testosterone induced fibrotic lesions in HKC‐8 cells. These data suggest serum testosterone plays a critical role in PCOS and PCOS‐associated kidney injury. Serum testosterone may serve as a promising indicator for kidney fibrotic injury outcomes in PCOS patients.

Ideal Cardiovascular Health is Inversely Associated with Subclinical Atherosclerosis: A Prospective Analysis

ObjectiveIdeal cardiovascular health (CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ≥ 40 years. MethodsThis study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and urinary albumin-to-creatinine ratio (UACR). ResultsBoth the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline (all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline (both P values for trend < 0.05) but a borderline significant association with baPWV (P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques (odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT (OR = 0.60; 95% CI 0.42-0.84), and increased baPWV (OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression (both P values for interaction < 0.05). ConclusionThe numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.

Nut Consumption and Renal Function Among Women at High Risk (FS10-05-19)

ObjectivesWomen with gestational diabetes (GDM) are at increased risk for renal complications later in life. Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations of nut intake and renal function among women with prior GDM. MethodsWe studied 330 women from the Danish National Birth Cohort (1996–2002) with a GDM pregnancy who participated in a clinical exam 9 to 16 years after the index pregnancy as part of the Diabetes & Women’s Health Study (2012–2014) and were free of major chronic diseases at follow-up. Habitual past year intake of nine types of nuts was ascertained at follow-up using a food frequency questionnaire. Total nut intake was classified as none (<1 serving/mo), monthly (2–3 servings/mo), weekly (1–6 servings/wk), and daily (>1 serving/d). Estimated glomerular filtration rate (eGFR) via CKD-EPI equation and urine albumin-to-creatinine ratio (UACR) were calculated based on serum creatinine (mg/dL) and urine albumin (mg/L), and creatinine (mg/dL) measurements respectively. We estimated % differences with 95% confidence intervals (CI) in these outcomes by nut intake adjusted for current body mass index, age, physical activity, energy intake, and dietary variables. We explored possible non-linear relations using restricted cubic splines. ResultsA significant non-linear U-shaped association was detected between total nut consumption and UACR (P = 0.001) with lowest UACR levels among women with weekly consumption. Compared to women with weekly intake (n = 222), adjusted UACR levels were 86% [95% CI: 15%, 200%] and 23% [−1%, 54%] higher among women with no or monthly nut intake, respectively, while UACR levels were 118% [22%, 286%] higher among women with daily intake. Compared to weekly consumers, adjusted eGFR levels were 9% [0%, 19%] higher among daily consumers. ConclusionsModerate nut consumption may be beneficial to kidney health among women with prior GDM. Funding SourcesIntramural Research Program of the NICHD, March of Dimes Birth Defects Foundation, Innovation Fund Denmark, Health Foundation, Heart Foundation, EU, Danish Diabetes Academy supported by Novo Nordisk Foundation, and NIH Building Interdisciplinary Research Careers in Women’s Health Program.

Association between serum 25-hydroxyvitamin D and diabetic kidney disease in Chinese patients with type 2 diabetes.

ObjectiveThe objective was to assess the association between 25-hydroxyvitamin D (25OHD) level and diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes.MethodsData pertaining to 351 in-patients with type 2 diabetes were collected. Subjects were classified into three groups based on the level of urinary albumin-to-creatinine ratio (UACR). UACR < 30 mg/g was defined as normoalbuminuria, while UACR levels of 30–300 mg/g and ≥ 300 mg/g were defined as microalbuminuria and macroalbuminuria, respectively. Serum 25OHD and other clinical characteristics among various UACR groups were compared. The relationship between albuminuiria and 25OHD was analyzed.ResultsThe prevalence of 25OHD insufficiency in the microalbuminuria group was significantly higher than that in the normoalbuminuria group (25.1% vs. 19.6%; P < 0.05); patients with macroalbuminuria had the highest prevalence of 25OHD deficiency (37.8%; P < 0.01 versus normoalbuminuria). Logistic regression analyses demonstrated that low 25OHD levels were associated with DKD [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.16–1.97). The association was more robust after adjusting for sex, hypertension, increased systolic blood pressure, glycemic status, and hyperuricemia (OR = 1.62, 95% CI 1.19–2.20).ConclusionsThe prevalence of vitamin D insufficiency/deficiency in patients with albuminuria was overtly higher than that in patients without albuminuria among Chinese adults with type 2 diabetes. Vitamin D insufficiency/deficiency was independently associated with DKD in type 2 diabetes.

Albuminuria and Microalbuminuria as Predictors of Cognitive Performance in a General Population: An 11-Year Follow-Up Study

Microalbuminuria, defined as urine albumin-to-creatinine ratio (UACR)>3.0 mg/mmol and ≤ 30 mg/mmol, is an early marker of endothelial damage of the renal glomeruli. Recent research suggests an association among microalbuminuria, albuminuria (UACR > 3.0 mg/mmol), and cognitive impairment. Previous studies on microalbuminuria, albuminuria, and cognition in the middle-aged have not provided repeated cognitive testing at different time-points. We hypothesized that albuminuria (micro- plus macroalbuminuria) and microalbuminuria would predict cognitive decline independently of previously reported risk factors for cognitive decline, including cardiovascular risk factors. In addition, we hypothesized that UACR levels even below the cut-off for microalbuminuria might be associated with cognitive functioning. These hypotheses were tested in the Finnish nationwide, population-based Health 2000 Survey (n = 5,921, mean age 52.6, 55.0% women), and its follow-up, Health 2011 (n = 3,687, mean age at baseline 49.3, 55.6% women). Linear regression analysis was used to determine the associations between measures of albuminuria and cognitive performance. Cognitive functions were assessed with verbal fluency, word-list learning, word-list delayed recall (at baseline and at follow-up), and with simple and visual choice reaction time tests (at baseline only). Here, we show that micro- plus macroalbuminuria associated with poorer word-list learning and a slower reaction time at baseline, with poorer word-list learning at follow-up, and with a steeper decline in word-list learning during 11 years after multivariate adjustments. Also, higher continuous UACR consistently associated with poorer verbal fluency at levels below microalbuminuria. These results suggest that UACR might have value in evaluating the risk for cognitive decline.

Albuminuria and Microalbuminuria asPredictors of Cognitive Performance inaGeneral Population: An 11-Year Follow-Up Study.

Microalbuminuria, defined as urine albumin-to-creatinine ratio (UACR)>3.0 mg/mmol and ≤ 30 mg/mmol, is an early marker of endothelial damage of the renal glomeruli. Recent research suggests an association among microalbuminuria, albuminuria (UACR > 3.0 mg/mmol), and cognitive impairment. Previous studies on microalbuminuria, albuminuria, and cognition in the middle-aged have not provided repeated cognitive testing at different time-points. We hypothesized that albuminuria (micro- plus macroalbuminuria) and microalbuminuria would predict cognitive decline independently of previously reported risk factors for cognitive decline, including cardiovascular risk factors. In addition, we hypothesized that UACR levels even below the cut-off for microalbuminuria might be associated with cognitive functioning. These hypotheses were tested in the Finnish nationwide, population-based Health 2000 Survey (n = 5,921, mean age 52.6, 55.0% women), and its follow-up, Health 2011 (n = 3,687, mean age at baseline 49.3, 55.6% women). Linear regression analysis was used to determine the associations between measures of albuminuria and cognitive performance. Cognitive functions were assessed with verbal fluency, word-list learning, word-list delayed recall (at baseline and at follow-up), and with simple and visual choice reaction time tests (at baseline only). Here, we show that micro- plus macroalbuminuria associated with poorer word-list learning and a slower reaction time at baseline, with poorer word-list learning at follow-up, and with a steeper decline in word-list learning during 11 years after multivariate adjustments. Also, higher continuous UACR consistently associated with poorer verbal fluency at levels below microalbuminuria. These results suggest that UACR might have value in evaluating the risk for cognitive decline.

Albuminuria and Endothelial Dysfunction in Patients with Non-Diabetic Chronic Kidney Disease.

BackgroundAlbuminuria has been associated with cardiovascular events, but whether such an association can be explained by endothelial dysfunction is not fully understood. In this study, we examined the relationship between the urine albumin-to-creatinine ratio (UACR) and biomarkers of endothelial function in patients with chronic kidney disease (CKD).Material/MethodsThe cross-sectional associations of renal dysfunction and UACR with procoagulant and inflammatory factors were evaluated for 151 consecutive CKD (stage 3–5) patients. Subjects were grouped by UACR (≤300 mg/g or >300 mg/g) and estimated glomerular filtration rate (eGFR) (30≤ eGFR <60, 15≤ eGFR <30, or eGFR <15 ml/min per 1.73 m2).ResultsA higher UACR level was associated with an increase in von Willebrand factor antigen (vWF: Ag) levels, vWF activity, factor VIII, interleukin-2, and log (interleukin-6), even after adjustment for risk factors. Linear regression analysis indicated that for every 88.5 mg/g increase in UACR, the vWF activity and factor VIII were elevated by 8.3% and 6.3%, respectively. The factorial design ANOVA data showed no statistically significant interaction between UACR and CKD stage with procoagulant and inflammatory factors.ConclusionsOur study shows an eGFR-independent association of higher UACR with elevations in markers of endothelial dysfunction and inflammatory factors in CKD patients.

Anagliptin ameliorates albuminuria and urinary liver-type fatty acid-binding protein excretion in patients with type 2 diabetes with nephropathy in a glucose-lowering-independent manner

ObjectiveThe objective of this study is to elucidate the effect of anagliptin on glucose/lipid metabolism and renoprotection in patients with type 2 diabetic nephropathy.MethodsTwenty-five patients with type 2 diabetic nephropathy...

Changes in urine albumin to creatinine ratio with the initiation of hydroxyurea therapy among children and adolescents with sickle cell disease.

Renal damage is a progressive complication of sickle cell disease (SCD) that begins in childhood and may progress to renal failure and early mortality in 12% of adults with hemoglobin SS (HbSS) SCD. Early sickle nephropathy is characterized by hyperfiltration and microalbuminuria; therefore, urine albumin to creatinine ratio (ACR) is an effective screening tool for its detection. This study investigated the effect of hydroxyurea (HU) therapy on urine ACR levels among children with SCD. A retrospective review was conducted to identify all patients with HbSS or HbSβ0 thalassemia of age 7-18 years who began HU therapy in 2011-2013; a control group of patients not on HU were matched by age and baseline hemoglobin. All urine ACR measurements ≤24 months prior to and ≥24 months after HU initiation were recorded. There were 63 eligible patients on HU and 13 (25%) with albuminuria prior to HU initiation. Among those with baseline albuminuria, the median ACR was 96 mg/g prior to HU, 39 mg/g at 1 year (P=0.02), and 25 mg/g at 2 years (P=0.03). Albuminuria normalized in 37.5% (6/16) after 1 year and 61% (8/13) after 2 years of HU therapy. Among those without albuminuria prior to HU, 13% (6/47) developed albuminuria during HU therapy. Sixteen percent (13/80) of control patients had albuminuria in the beginning of study period, which normalized in 15% (two of 13) of patients at 1-year follow up. Introduction of HU is associated with significant decreases in urine ACR in children with SCD and albuminuria.

Association of estimated glomerular filtration rate and urine albumin-to-creatinine ratio with incidence of cardiovascular diseases and mortality in chinese patients with type 2 diabetes mellitus \u2013 a population-based retrospective cohort study

BackgroundEstimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) are renal markers associated with risks of cardiovascular diseases (CVD) and all-cause mortality in diabetic patients. This study aims to quantify such risks in Chinese diabetic patients based on eGFR and UACR.MethodsThis was a territory-wide retrospective cohort study on primary care diabetic patients with documented eGFR and UACR but without baseline CVD in 2008/2009. They were followed up till 2013 on CVD events and mortality. Associations between eGFR/UACR and incidence of CVD/mortality were evaluated by multivariable Cox proportional models adjusted with socio-demographic and clinical characteristics.ResultsThe data of 66,311 patients who had valid baseline eGFR and UACR values were analysed. The risks of CVD events and mortality increased exponentially with the decrease in eGFR, with a hazard ratio (HR) increasing from 1.63 to 4.55 for CVD, and from 1.70 to 9.49 for mortality, associated with Stage 3 to 5 CKD, compared to Stage 1 CKD. UACR showed a positive linear association with CVD events and mortality. Microalbuminuria was associated with a HR of 1.58 and 2.08 for CVD and mortality in male (1.48 and 1.79 for female), respectively, compared to no microalbuminuria. Male patients with UACR 1–1.4 mg/mmol and eGFR ≥90 ml/min/1.73 m2 (60–89 ml/min/1.73 m2) had a HR of 1.25 (1.43) for CVD. Female patients with UACR 2.5–3.4 mg/ml and eGFR ≥90 ml/min/1.73 m2 (60–89 ml/min/1.73 m2) had a HR of 1.45 (1.65) for CVD.ConclusionsRisks of CVD events and mortality increased exponentially with eGFR drop, while UACR showed positive predictive linear relationships, and the risks started even in high-normal albuminuria. UACR-based HR was further modified according to eGFR level, with risk progressed with CKD stage. Combining eGFR and UACR level was more accurate in predicting risk of CVD/mortality. The findings call for more aggressive screening and intervention of microalbuminuria in diabetic patients.

Association of Albuminuria and Estimated Glomerular Filtration Rate with Functional Performance Measures in Older Adults with Chronic Kidney Disease

Background: Chronic kidney disease (CKD) is increasingly common and disproportionately affects older adults. The contribution of kidney disease to the functional impairment noted in the elderly CKD population is unclear. Methods: This is a cross-sectional analysis of a hypertensive cohort of people aged ≥75 years from the Systolic Blood Pressure Intervention Trial. We evaluated estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) as predictors of 3 measures of functional status: EuroQol-5 Dimensional (EQ-5D) score, Falls Efficacy Scale (FES) score, and gait speed. Linear regression models were used to evaluate the associations between our independent variables and outcome measures. Results: Our analysis included 2,620 participants, mean age of 79.9 (4.0) years. Unadjusted models showed that lower eGFR level and higher UACR level were associated with lower EQ-5D (p < 0.001 for both) and slower gait speed (p < 0.001 for both) and worse scores on FES (p = 0.032 and p = 0.039). In the fully adjusted models, higher levels of UACR remained significantly associated with lower EQ-5D scores and slower gait speed (p = 0.011 and p = 0.002, respectively). In contrast, level of eGFR was not associated with any functional outcome measures when accounting for covariates. Conclusions: In individuals aged ≥75 years, albuminuria and eGFR were associated with impairments in physical performance and self-reported functional status; however, only the association with albuminuria remained after adjusting for relevant demographics and comorbidities. Evaluation of albuminuria may provide an additional tool for identifying older individuals at risk for functional impairment.

Urinary albumin-to-creatinine ratio is associated with white matter lesions severity in first-ever stroke patients

BackgroundThe presence of white matter lesions (WML) is an indicator of small vessel disease; however, the underlying pathological mechanisms are still unclear. We aimed to investigate the association of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) with WML severity in first-ever stroke patients. MethodsWe retrospectively enrolled 284 consecutive patients (177 male; median age 72years) admitted to our stroke center between May 2010 and January 2012. eGFR and UACR measurements were performed on admission. WML severity was assessed using the Fazekas classification. Severe WML was defined as a Fazekas grade of 2 or higher. The impact of eGFR and UACR on severe WML was evaluated using multiple logistic regression analysis. ResultsAge (P<0.0001), sex (P=0.0094), eGFR (P=0.0173), UACR (P=0.0001), hypertension (P=0.0436), and brain natriuretic peptide (P=0.0354) were significantly associated with severe WML. On multivariable logistic regression analysis, high UACR (≥39.6mg/g creatinine, P=0.039), but not low eGFR (≤74ml/min/1.73m2, P=0.3672), was independently associated with severe WML. Comparisons between the UACR levels showed that severe WML was more frequent in the UACR ≥300mg/g creatinine group than in the UACR <30.0mg/g creatinine group after multivariate adjustment (OR, 2.25; 95% CI, 1.04–5.00; P=0.039). However, there was no significant association between eGFR and severe WML. ConclusionsOur data suggest that high UACR, but not eGFR, is independently associated with severe WML.