Urinary Albumin-to-creatinine Ratio Research Articles

Abstract 4132062: Early changes in albuminuria and their interaction with eplerenone treatment in patients hospitalized for acute heart failure: findings from the EARLIER trial

Background: Patients hospitalized for acute heart failure (AHF) have high degrees of congestion, which may be associated with albuminuria. Mineralocorticoid receptor antagonists (MRAs) have natriuretic effects, possibly diminishing the degree of albuminuria. However, early changes in albuminuria, their prognostic value and interaction with MRA therapy remain unclear in AHF. Methods: The EARLIER trial included patients with AHF who were randomized to receive eplerenone or placebo over 6 months. Urine albumin-to-creatinine ratio (UACR) at admission and week 1 were measured, and Cox proportional hazards models were used for analyses. Results: Among 296 patients (mean age, 67±13years; 72% male), median B-type natriuretic peptide was 386 (190-660) pg/ml, and mean left ventricular ejection fraction was 30±8%. Patients with an UACR of ≥30 mg/g at admission had more severe congestion and poorer exercise capacity compared to those without (all-P<0.01). From admission to week 1, UACR levels significantly decreased (P<0.01), without significant differences between treatment groups (P>0.10). UACR levels at both admission (adjusted-HR [95% CI]=1.23 [1.03-1.47]) and week 1 (adjusted-HR [95% CI]=1.23 [1.01-1.50]) were associated with the risk of cardiovascular death and hospitalization. Additionally, eplerenone vs. placebo reduced the risk of a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF, and/or out-of-hospital diuretic intensification (HR [95% CI]= 0.53 [0.29-0.97]), irrespective of the severity of albuminuria (P-for-interaction>0.10). Conclusion: In patients with AHF, the degree of albuminuria at both admission and week 1 was associated with post-discharge prognosis. Although eplerenone did not reduce albuminuria levels, the benefit from eplerenone was consistent regardless of the albuminuria severity.

Assessing the diagnostic utility of urinary albumin-to-creatinine ratio as a potential biomarker for diabetic peripheral neuropathy in type 2 diabetes mellitus patients

Background and aimsDiabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed.ResultsCompared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%.ConclusionElevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients.

Mineralocorticoid receptor antagonist combined with a SGLT2 inhibitor versus SGLT2 inhibitor alone in chronic kidney disease: a meta-analysis of randomized trials.

Sodium glucose co-transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs) reduce the progression of kidney disease. Whether the combination of these agents provides additional benefits compared to SGLT2i alone is worth exploring using data from randomized trials designed for this purpose. To assess the randomized treatment effect of MRAs combined with SGLT2i vs SGLT2i alone on markers of kidney and cardiovascular health. Random-effects meta-analysis of randomized trials testing the combination of MRAs with SGLT2i vs SGLT2i alone on albuminuria, blood pressure, estimated glomerular filtration rate (eGFR) and serum potassium among patients with chronic kidney disease (CKD). Four randomized trials were included with a total of 272 patients with CKD: eGFR varying between 30 and 60 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) between 90 and 500 mg/g, with >60% having type 2 diabetes. Treatment with MRAs plus SGLT2i vs SGLT2i alone reduced UACR by -33.6% (-42.6 to -24.7%), P <0.001, I2 =0%. MRAs plus SGLT2i vs SGLT2i alone reduced systolic blood pressure by -6.1 mmHg (-8.9 to -3.3) mmHg, eGFR by -3.4 mmHg (-5.2 to -1.6) mmHg, and increased serum potassium by +0.23 mmol/L (0.15 to 0.34) mmol/L; P <0.001 for all, without significant heterogeneity between trials (I2 <25%). In this meta-analysis, MRAs plus SGLT2i provided greater reductions in albuminuria and blood pressure compared to SGLT2i alone. Larger randomized trials with longer follow-up should test whether MRA/SGLT2i combination therapies improve cardiovascular and renal outcomes compared to SGLT2i alone.

Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk

Background: Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR). Methods: Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed. Results: Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter. Conclusions: This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.

Association of urinary volatile organic compounds and chronic kidney disease in patients with diabetes: real-world evidence from the NHANES.

Chronic kidney disease (CKD) is common in patients with diabetes mellitus (DM). Volatile organic compounds (VOCs) are widespread pollutants that may impact DM development. This study aims to explore the association between urinary VOC metabolites and CKD in patients with DM. Adult National Health and Nutrition Examination Survey (NHANES) 2011 to 2018 participants with DM were included in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Multivariable regression models were used to analyze the associations between urinary VOC metabolites and CKD. A total of 1,295 participants with DM and a mean age of 59 years were included. After adjustment for demographic and clinical characteristics, elevated levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) (tertile 2: adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI): 1.15-2.85, p = 0.012), N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) (tertile 2: aOR = 1.84, 95% CI: 1.10-3.08, p = 0.021), DHBMA (tertile 3: aOR = 1.93, 95% CI: 1.12-3.35, p = 0.020), and phenylglyoxylic acid (PGA) (tertile 3: aOR = 1.71, 95% CI: 1.11-2.63, p = 0.017) were significantly associated with increased likelihood of CKD. Specific urinary VOC metabolite levels are positively associated with an increased risk of CKD in patients with DM. These findings suggest that monitoring urinary VOC metabolites could be important for the prevention and management of CKD in this population. Future longitudinal studies should focus on establishing causality and elucidating the underlying mechanisms of these associations.

Relationship between extracellular water to total body water ratio and severe diabetic retinopathy in type 2 diabetes.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes, and identifying the risk factors for severe DR is important. We aimed to investigate the relationship between severe DR and the extracellular water to total body water ratio (ET ratio). Retrospective cross-sectional study. Department of Endocrinology, Metabolism, and Diabetes at Kyushu University Hospital. A total of 205 adults with type 2 diabetes (T2D) were included. The patients were divided into two groups: non-proliferative DR (non-PDR; n = 161, 126 with no DR and 35 with simple DR) and proliferative DR (PDR; n = 44, 18 with pre-proliferative DR and 26 with PDR). The ET ratio was measured using bioelectrical impedance analysis. The ET ratio was significantly higher in the PDR group than in the non-PDR group (0.390 vs. 0.398; P < .0001). Multivariate logistic regression analysis showed that the ET ratio was significantly associated with PDR, independent of known risk factors for DR progression. In the subgroup analysis by age, multivariate logistic regression analysis revealed a significant association between the ET ratio and PDR, independent of known risk factors for DR progression in patients younger than 60 years. However, in patients 60 years and older, only the urinary albumin to creatinine ratio (UACR) showed a significant association with PDR in a model using the UACR and the ET ratio. In patients with T2D younger than 60 years, the ET ratio may be a useful indicator for identifying severe DR.

The trans-differentiation promotion of parietal epithelial cells by magnesium isoglycyrrhizinate to improve podocyte injury induced by high fructose consumption

BackgroundPodocytes have limited proliferative capacity, which leads to irreversible glomerular injury in diverse kidney diseases. Magnesium isoglycyrrhizinate (MgIG), a hepatoprotective agent in clinic, has been reported to improve glomerular podocyte injury. However, the underlying mechanism of MgIG in ameliorating podocyte injury remains unclear. PurposeGlomerular parietal epithelial cells (PECs) are recognized as podocyte progenitors and play a pivotal role in the recovery following glomerular injury. This work aims to investigate the protective mechanisms of MgIG in mitigating glomerular injury by promoting PEC trans-differentiation. Study DesignA rat model of progressive glomerular podocyte injury, and in vitro models using the primary podocytes and primary PECs, were established to further explore the pharmacological mechanism of MgIG. MethodsFour-week-old male Sprague-Dawley (SD) rats were fed a 10% fructose solution for 3, 6, 9 and 12 weeks to induce glomerular injury. The effect of MgIG on the progressive changes in podocytes and PECs, and the correlation between PEC density and podocyte loss, were analyzed. The mechanism of MgIG in triggering PEC trans-differentiation was investigated, by examining adenosine secretion in injured podocytes, as well as the expression of cluster of differentiation 44 (CD44), nephrin, adenosine receptor A2B (ARA2B) and glucocorticoid receptor (GR) in PECs were examined both in vivo and in vitro. ResultsRats fed a high fructose diet exhibited progressive changes in glomerular PECs, including increased cell density and a preference for trans-differentiation. A positive correlation was observed between PEC density and podocyte loss. Co-culture experiments demonstrated that extracellular adenosine accumulation in injured podocytes induced by high fructose exposure promoted PEC trans-differentiation via ARA2B. MgIG significantly improved podocyte injury and exhibited effects similar to dexamethasone on nephrin upregulation activation and CD44 inhibition. Moreover, the inhibitory effect of MgIG on PEC ARA2B activation was more effective than that of dexamethasone. The co-expression of paired box 2 (PAX2)+-Nephrin+ in glomeruli indicated that MgIG induced PEC trans-differentiation and podocyte regeneration in model rats. Accordingly, podocyte loss and increased urine albumin-to-creatinine ratio (UACR) were also alleviated. Moreover, MgIG, which acts as a GR agonist to activate GR, reversed the upregulation of CD44 and decreased ARA2B induced by tumor necrosis factor-α (TNF-α) in primary PECs. The siRNA interference experiment manifested that MgIG exhibited a more pronounced enhancement of GR upregulation, in contrast to ARA2B activation, to promote PEC trans-differentiation. ConclusionThis work reports for the first time that PECs respond to the accumulation of extracellular adenosine from injured podocytes via activating ARA2B and focuses on the role of adenosine and adenosine receptors in the trans-differentiation of PECs. Furthermore, this study provides the first evidence that MgIG may promote podocyte regeneration by enhancing PEC trans-differentiation through GR activation, providing a research basis for investigating the glucocorticoid-like activity of MgIG in ameliorating glomerular podocyte injury.

Systematic review and meta-analysis of biological variation data of urine albumin, albumin to creatinine ratio and other markers in urine

IntroductionSignificant variations in Biological Variation (BV) estimates have been reported for urine markers. This study aimed to systematically review and critically appraise BV studies for albumin, creatinine, albumin-to-creatinine ratio (ACR), and other urine markers to perform a meta-analysis of eligible studies. MethodsPublications were identified through a systematic search and evaluated using the Biological Variation Data Critical Appraisal Checklist (BIVAC). BIVAC-compliant studies (grades A-C; A being fully compliant) conducted in healthy individuals were included in the meta-analysis, providing within-subject (CVI) and between-subject (CVG) BV estimates with 95% confidence intervals for various sample collection types. ResultsOut of 37 studies evaluated, 16 were included (one grade A, three B, twelve C). No eligible publications were identified for meta-analysis of albumin and ACR. Limited data were available for first-morning urine specimens. A CVI between 15% and 30% was found for most measurands in 24-hour urine samples, while CVI estimates for random urine appeared higher. ConclusionPublished BV studies on urine markers utilized different sample collections and reporting units. Most were considered unfit for use or ineligible for meta-analysis. Given the critical role of urine albumin and ACR in chronic kidney disease risk assessment, there is a need for more BIVAC-compliant studies.

Association between normal range UACR and insulin resistance and prediabetes among US adults:

Abstract Background Recent studies have shown that urine albumin-to-creatinine ratio (UACR) within the normal range is associated with increased risk of hypertension, diabetes, cardiovascular death and all-cause death. However, the relationship between normal range UACR and the prevalence of insulin resistance (IR) and prediabetes has not been explored. Methods The study included 14,208 US adults with normal range UACR values and without diabetes from the National Health and Nutrition Survey (1999-2018). The outcome variables included IR and prediabetes, as defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis were conducted to examine the relationship of UACR with IR and prediabetes. Results The weighted multivariate linear regression analysis showed that a 1-standard deviation (SD) increment in ln (UACR) was positively associated with fasting plasma glucose (FPG) (β = 0.02, 95% CI: 0.01, 0.04), glycosylated hemoglobin (β = 0.01, 95% CI: 0.00, 0.02), fasting serum insulin (FSI) (β = 0.50, 95% CI: 0.31, 0.68), and homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.14, 95% CI: 0.09, 0.19). The weighted multivariate logistic regression analysis revealed that a 1-SD increment in ln (UACR) was significantly associated with an increased prevalence of prediabetes (OR = 1.10, 95% CI: 1.04-1.15), but not with IR (OR = 1.05, 95% CI: 0.99-1.12). With the lowest quartile of UACR as a reference, ORs (95% CIs) for IR in the second, third, and fourth quartiles were 1.10 (0.86, 1.15), 1.15 (0.98, 1.33), and 1.12 (0.95, 1.32), respectively, and ORs (95% CIs) for prediabetes were 1.35 (1.19, 1.52), 1.32 (1.14, 1.53), and 1.44 (1.24, 1.66), respectively. Subgroup analysis indicated that smoking had a significant impact on the association between UACR and prediabetes. The association between UACR and prediabetes was more significant in smokers than in non-smokers (P for interaction = 0.03). RCS regression analysis revealed a non-linear positive dose-response association between UACR and indicators of diabetes. Conclusion Elevated UACR, even within the normal range, was positively associated with indicators of diabetes and increased prevalence of prediabetes among US adults. Smoking had a significant impact on the association between UACR and prediabetes, with a more pronounced association observed among smokers.uacr with diabetes markersUacr with ir and prediabetes

Albuminuria is associated with progression of diastolic dysfunction in patients at risk for cardiovascular disease

Abstract Background The number of the patients with heart failure with preserved ejection fraction (HFpEF) is increasing as society ages, which indicates that the number of pre-HFpEF patients is increasing even more. To combat this sociomedical burden, it is critical to establish cost-effective and simple biomarkers to identify the high-risk population at early phase of the disease. Recent studies demonstrated the association between albuminuria and incident heart failure, but the prognostic impact of albuminuria on diastolic dysfunction, an early phenotype of HFpEF, has not been elucidated. Purpose To examine the impact of albuminuria on the diastolic function over time in the patients with cardiovascular risks. Methods One hundred and fifty-eight patients with at least one cardiovascular risk factor without history of heart failure were followed up for 5 years. Echocardiogram was conducted at baseline, year 3, and year 5. Diastolic dysfunction was defined as E/e’ &amp;gt;14. Albuminuria was defined as urine albumin-to-creatinine ratio (UACR) 30 ≧mg/gCre. The patients with ejection fraction &amp;lt;40% and those had diastolic dysfunction at baseline were excluded from the study. The relationship between albuminuria at baseline and diastolic function at year 3 and 5 were investigated. Results Among 158 subjects, 27 showed albuminuria at baseline and the prevalence of hypertension, dyslipidemia, and diabetes was not significantly different between patients with and without albuminuria. The baseline E/e’ tended to be higher in patients with albuminuria, although the difference was not statistically significant (Fig1: E/e’ = 10.0±2.4 vs. 9.4±2.2, p = 0.08) . However, the patients with albuminuria showed a steeper increase in E/e’ than those without albuminuria, and the significant difference was observed at year 3, that was even greater at year 5 (Fig1: E/e’ = 11.1±2.8 vs 10.0±2.6, p = 0.04 in year 3, E/e’ = 12.5±4.1 vs 10.3±2.9, p = 0.002 in year 5, respectively). Furthermore, log UACR at baseline showed significant correlation with E/e’ at year 5 (p = 0.02, r = 0.21) and normo-, micro-, and macroalbuminuria (UACR&amp;lt;30, 30-300, and &amp;gt;300mg/gCre, respectively) at baseline showed elevated E/e’ at year 5 in this order ( p = 0.01 for UACR&amp;lt;30 vs. 30-300mg/gCre, and p = 0.04 for UACR&amp;lt;30 vs. &amp;gt;300mg/gCre, reapectively ). The prevalence of incident diastolic dysfunction increased greater in patients with albuminuria throughout the follow-up period and the difference reached statistical significance at year 5 (Fig2: 18.5% vs. 9.2%, p = 0.28 for year 3, and 25.9% vs. 8.4%, p = 0.009 for year 5, respectively). Conclusion In the patients with cardiovascular risk factors, albuminuria was associated with development and progression of diastolic dysfunction over subsequent 5 years. Future prospective study is warranted to investigate the effectiveness of albuminuria-directed care to prevent development of HFpEF.

Chronic kidney disease in patients with heart failure in German primary care practices: the InspeCKD study

Abstract Background Chronic kidney disease (CKD) is, alongside type 2 diabetes mellitus, the most common comorbidity in patients with heart failure (HF), with a prevalence of 40-50%. HF patients should therefore be screened, monitored, and treated according to international Kidney Disease Improving Global Outcomes (KDIGO) conclusions for early identification and intervention of CKD, with annual determination of eGFR to monitor kidney function and annual urine albumin-to-creatinine ratio (UACR) testing as appropriate. Early diagnosis is important as therapeutic options can be offered to slow the progression of CKD and reduce the risk of cardiovascular complications and mortality. Purpose Currently, there are only limited data available regarding screening, diagnosis and treatment of CKD for HF patients in German primary care physician (PCP) practices. Therefore, this analysis of the InspeCKD study was designed to examine the frequency of use of CKD-specific laboratory diagnostics in HF patients in routine PCP care. Methods In the current data analysis, fully anonymized patient data from German PCP practices were evaluated. In accordance with the screening recommendation of the KDIGO guideline, adult patients with diabetes, hypertension and/or cardiovascular disease, including HF, with at least one year of observation period were included in the analysis. Results The overall patient cohort comprised 448.837 patients from 1.244 German PCP practices. Of the 7.9% HF patients, 6.1% participated in a disease management program (DMP) for coronary heart disease. The average age of HF patients was 74 years. The prevalence of diagnosed CKD in HF patients during the observational period (mean: 1.7 years) was 26.8%. Within the subgroup of patients with HF, serum creatinine to estimate GFR was measured at least once in 48.5% of patients. Urine dipstick testing for albuminuria was performed in 7.4% of patients and UACR was measured at least once in 0.3% of patients. In patients with at least one documented measurement, eGFR and UACR were checked 2.2 and 0.9 times, respectively, per patient and year. Of the HF patients with laboratory-confirmed CKD according to KDIGO criteria, 81.8% were not diagnosed with CKD. Conclusion The analysis shows that, given the high prevalence of CKD in HF patients and the current KDIGO recommendations for early identification and intervention of CKD, a substantial proportion of HF patients in German PCP practices did not receive adequate laboratory diagnostics for early diagnosis of CKD. In addition, the majority of patients with laboratory-confirmed CKD were not diagnosed. Early detection of CKD and the use of evidence-based therapeutic options can significantly reduce the risk of CKD progression. In conclusion, there is an urgent need to raise awareness among PCPs about secondary and tertiary prevention of CKD in patients with HF and to include coordinated CKD screening recommendations in HF guidelines.

The effect of the combined treatment with dulaglutide and dapagliflozin in arterial elasticity, cardiac function, albuminuria and endothelial thickness in type 2 diabetes mellitus after 12 months

Abstract Background The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established. Purpose In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria. Methods A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR). Results Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p&amp;lt;0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p&amp;lt;0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p&amp;lt;0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively). Conclusions Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.

Associations of the TyG index with albuminuria and chronic kidney disease in patients with type 2 diabetes.

Diabetes-related kidney disease reduces patients' quality of life, increases the risk of death, and is associated with insulin resistance (IR). The triglyceride-glucose (TyG) index is a simple and inexpensive alternative to IR measurement. Furthermore, the relationship between albuminuria and chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we aimed to investigate the association of TyG index with albuminuria and CKD in patients with T2DM. Data from 01/2013-12/2017 period were obtained from the Population Health Data Archive's Diabetes Complications Data Set. A total of 1048 patients with T2DM were included in this study. CKD is defined as an estimated glomerular filtration rate < 60 ml/min-1.1.73 m-2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Albuminuria is defined as a UACR ≥ 30 mg/g. The TyG index is calculated by measuring the triglyceride and fasting blood glucose levels. Logistic regression models were used to analyze the association between albuminuria, CKD with T2DM and TyG index. We identified 1048 subjects, 63.03% of whom were men. The mean age was 46.21 years, and the mean body mass index was 26.742 kg/m2. CKD and albuminuria detection rates showed an increasing trend in the different TyG subgroups. (p = 0.008, p = 0.006). Using the Q1 group as a baseline, the risk of albuminuria and CKD was significantly greater in the group Q3 (OR = 1.514, 95% CI 1.121-2.047 P = 0.05), and the same result was obtained after adjusting for covariates (OR = 2.241, 95% CI 1.245-4.034, P = 0.007). Subgroup analyses revealed a significant increase in the incidence of albuminuria and CKD in the group Q3 compared to that in the Q1 group. The TyG index is positively associated with albuminuria and CKD in patients with T2DM and may be a marker for predicting the occurrence of early kidney injury in patients with T2DM. Clinicians should test this indicator early to detect lesions and improve patient prognosis.

Safety and efficacy of initiation SGLT in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease on top of standard therapy with ARNI or ACE-i

Abstract Quadruple therapy remains underused in cases of heart failure with a reduced ejection fraction (HFrEF). Among eligible patients most of them take ACE-i/ARB and B-blockers, less MRAs and ARNI. There are many questions of adding new foundational drugs, especially in the case of coexisting of HFrEF and chronic kidney disease (CKD). The aim was to compare the safety and effectiveness of initiation SGLT in patients (P) with HFrEF and CKD on standard therapy with ARNI or ACE-I. Methods we identified 54 symptomatic P with HFrEF (EF≤40%) and CKD 3 (eGFR between 30 and 60 ml/min) on standard therapy (ACE-I or ARNI, B-blockers, MRAs). All P were divided into 2 groups: group 1- 26 P on ARNI, B-blockers, MRAs; group 2- 28 P on ACE-I, B-blockers, MRAs. All P started on dapagliflozin (D) with a dose of 10 mg daily. The potassium (K), creatinine levels, eGFR, clinic BP were estimated at baseline and at weeks 1, 2, 4, 6, 8, 12. At baseline and at weeks 4, 12 NT-proBNP, urine albumin-to-creatinine ratio (UCAR) were estimated and P underwent 24-hour BP measurements. Results At week 1 after initiation of D a mean eGFR deсreased not significant in both group. At week 2 in group 1 mean eGFR decreased by 1,9±1.1 ml/min/1.73m2, P&amp;lt;.05 and group 2-2,5±1.9 ml/min/1.73m2, P&amp;lt;.05. At week 4 in both groups mean eGFR deсreased significantly, but in group 2 the decline of eGFR was more pronounced (-2,4±2.6 ml/min/1.73m2 vs.-3,3±2.5 ml/min/1.73m2, P=.04), with not significant decreasing to 6, 8, 12 weeks. At week 1mean K changed not significantly after start of therapy in both groups. At week 4 in group 1mean K deсreased significantly from 4.97±0.6 to 4.63±0.57 mEq/l (P&amp;lt;.05), in group 2 K deсreased not significant. At week 4 in group 1 was a greater reduction NT-proBNP than in group 2 (-234±42 vs. -143±32 ng/L, P&amp;lt;.05). At week 12 in both groups a significant decrease NT-proBNP were observed, but in group 1 more pronounced (-865±89 ng/L and -573±78 ng/L, (P&amp;lt;.01; P&amp;lt;.05 respectively). UCAR was also reduced significantly in both groups, but in group 1 more pronounced (P&amp;lt;.01; P&amp;lt;.05 respectively). In group 1, there were more cases of symptomatic hypotension (10 vs. 8, P&amp;lt;.05) and greater decrease mean BP than in group 2 (P&amp;lt;.05), but it didn’t result in a withdrew. In return, maen doses diuretics were carefully decreased in both groups. At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.328, P&amp;lt;.05). By linear regression analysis the eGFR was associated with NT-proBNP change (P&amp;lt;.05). Conclusion In patients with HFrEF and CKD, adding SGLT to standard therapy with ARNI, B-blockers, MRAs were paralleled by marked improvements in the neurohumoral profile by significantly reduced NT-proBNP compared with ACE-I, B-blockers, MRAs. SGLT initiation caused an early drop in eGFR, but in group ARNI the decline of eGFR was less pronounced with greater reduction in the albuminuria and was accompanied by decreased potassium level.

Single spot albumin to creatinine ratio as an independent predictor of 12 years follow-up mortality in acute coronary syndromes without ST-segment elevation

Abstract Background To the best of our knowledge there is no evidence of the association between microalbuminuria, measured as single spot urine albumin to creatinine ratio (ACR), with very long-term mortality in patients with non-ST segment Elevation Acute Coronary Syndromes. Aim To evaluate the association between admission ACR and very long-term all-cause mortality in an unselected cohort of non-ST-segment elevation acute coronary syndromes patients. Methods A prospective cohort study was conducted, including patients with non-ST-segment elevation acute coronary syndromes admitted in the Intensive Care Unit. The ACR was determined in spontaneous urine samples during the first 24 hours after admission and analyzed by immunoturbidimetry. The primary endpoint was all-cause mortality during the follow-up. Actuarial survival curves were compared by log rank test and a logistical Cox regression analysis was performed to identify variables independently associated with mortality in the follow-up. Statistics were calculated using the IBM Statistics program SPSS version 26. Results 600 patients were analyzed. The overall average ACR value was 7 mg/gr (95% CI 4-26). 76% had normoalbuminuria (ACR 0-30 mg/gr), 22% had microalbuminuria (ACR 30-300 mg/gr), and 1.5% had macroalbuminuria (ACR &amp;gt; 300 mg/gr). The median and interquartile range of follow-up was 12 years (95% IC 11-14). The average ACR among those who met the primary endpoint was 59.15 mg/gr (95% CI 52-66) and among the survivors, 27.66 mg/gr (95 % CI 63-77), p &amp;gt; 0,003. ACR terciles were defined by 33th and 66th percentiles: tercile 1: patients with ACR of 0 to 4 mg/gr, tercile 2: ACR from 4 to 17 mg/g and tercile 3 values greater than 17mg/gr. Strong associations were observed between ACR with age, hypertension, stroke and history of COPD, previous use of angiotensin II converter/blocking enzyme inhibitors, systolic blood pressure at admission, ST segment deviation, left ventricle ejection fraction and elevation of serum Troponin T and CPK MB. All cause-mortality during the follow-up was 14% (CI 95% 11-17). Elevation of ACR was significantly associated with long term mortality risk: log rank test chi square: 133.936, p = 0.0001. By multivariate Cox regression analysis adjusted by age, gender, diabetes, hypertension, serum creatinine, troponin T elevation, ST segment deviation, previous AMI, prior use of aspirin, statins and percutaneous coronary intervention after hospitalization, the ACR was independently associated with a 12-year follow-up mortality: OR 13 (95% IC 5-35; p &amp;lt; 0.0001). Conclusion Single spot urine ACR at admission is a strong predictor of 12-year follow-up mortality in an unselected cohort of patients with non-ST-segment elevation acute coronary syndromes.Baselines characteristics of cohortsMultivariable COX regression analysis

Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial.

Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min-1 1.73 m-2 and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g-1) and body mass index ≥27 kg m-2. Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g-1 (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min-1 1.73 m-2; and mean body mass index was 36.2 (s.d. 5.6) kg m-2. Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 .

Impact of metabolic abnormalities on the association between normal-range urinary albumin-to-creatinine ratio and cardiovascular mortality: evidence from the NHANES 1999–2018

BackgroundThe urinary albumin to creatinine ratio (UACR) is associated with adverse cardiovascular outcomes, even when within the normal range. However, the potential modification of this effect by metabolic abnormalities remains unclear. This study explored whether metabolic abnormalities modify the association between normal-range UACR and cardiovascular mortality.MethodsThis cohort study included 27,298 U.S. adults from the National Health and Nutrition Examination Survey 1999–2018, with mortality follow-up through December 31, 2019. Normal UACR (< 30 mg/g) was considered. Metabolic abnormalities were categorized into three groups based on the number of metabolic abnormality components: metabolic health (0 components), pre-metabolic syndrome (Pre-MetS, 1–2 components), and metabolic syndrome (MetS, 3–5 components). Multivariable Cox proportional hazards regression was used to estimate the association between normal UACR and cardiovascular mortality, stratified by metabolic abnormality groups.ResultsOver a median follow-up of 9.67 years, 764 cardiovascular deaths occurred. In the fully adjusted model, higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, but not in metabolically healthy individuals. When UACR was divided into tertiles, the highest tertile was associated with a 60% and 79% higher risk of cardiovascular mortality in the Pre-MetS and MetS groups, respectively, compared with the lowest tertile (Pre-MetS: HR, 1.60 [95% CI: 1.19–2.15]; MetS: HR, 1.79 [95% CI: 1.34–2.41]).ConclusionA higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, underscoring the need for early renal risk management in this population.

Increased Cardiometabolic Risk in Men with Hypoprolactinemia: A Pilot Study

Low prolactin levels in men predispose them to mood disturbances, sexual dysfunction, and diabetes. The purpose of the current study was to assess cardiometabolic risk in males with hypoprolactinemia. This prospective study included three age-matched groups of young and middle-aged men: individuals with cabergoline-induced hypoprolactinemia (n = 15), cabergoline-treated subjects with prolactin levels within the reference range (n = 20), and untreated men with normal prolactin levels (n = 31). In men with hypoprolactinemia, the cabergoline dose was reduced in order to normalize prolactin concentration. Anthropometric parameters, blood pressure, QRISK3 score; plasma concentrations of prolactin, glucose, insulin, lipids, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and testosterone; whole-blood levels of glycated hemoglobin (HbA1C); urinary albumin-to-creatinine ratio (UACR); and carotid intima–media thickness were assessed at baseline and six months later. Men with hypoprolactinemia were characterized by higher body mass index, fat content, waist circumference, systolic blood pressure, fasting and 2 h post-load glucose, HbA1C, HOMA1-IR, uric acid, hsCRP, fibrinogen, homocysteine, and UACR; by lower HDL cholesterol and testosterone; by greater intima–media thickness; and by a higher QRISK3 score than their peers with normal prolactin levels. There were no statistically significant differences in the measured parameters between both groups of men with normal prolactin levels. Normalization of prolactin concentration was accompanied by normalization of biochemical variables, systolic blood pressure, and QRISK3 score. Although cabergoline dose reduction did not cause statistically significant changes in the remaining anthropometric parameters and intima–media thickness, six months later, they did not differ from those observed in the remaining study groups. Our findings suggest that iatrogenic hypoprolactinemia is associated with increased cardiometabolic risk, which is reversible and resolves after the normalization of prolactin levels.

Study on PINK1 Expression and Its Clinical Value in Diabetic Nephropathy.

To explore PTEN-induced putative kinase 1 (PINK1) expression and its clinical value in diabetic nephropathy. Ninety patients with diabetic nephropathy were recruited and divided into metformin hydrochloride monotherapy group, telmisartan monotherapy group and combination therapy (metformin and telmisartan) group. Renal function indices and PINK1 expression, inflammatory factors, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels were detected. The correlation between PINK1 and inflammatory factors, renal function indicators including estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and serum creatinine (SCr)] were analyzed by Pearson correlation. Following treatments, the combination therapy group exhibited increased PINK1 expression levels and decreased ROS levels compared to the groups receiving metformin hydrochloride or telmisartan monotherapy. The combination therapy group showed significant improvements in renal function indices and inflammatory markers. Additionally, the MMP ratio in the combination therapy group was higher compared to the two monotherapy groups. Furthermore, PINK1 was negatively correlated with UACR, SCr, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), while positively correlated with eGFR and interleukin-2 (IL-2). PINK1 exhibits low expression levels in patients with diabetic nephropathy and its expression is strongly associated with the inhibition of disease progression, thereby offering significant clinical diagnostic value. Additionally, it may serve as a potential biological marker for clinical diagnosis and treatment of diabetic nephropathy.

Integrated temporal transcriptional and epigenetic single-cell analysis reveals the intrarenal immune characteristics in an early-stage model of IgA nephropathy during its acute injury.

Kidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription. We aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI). A murine model was utilized to mimic 3 immunological states -"immune stability (IS), immune activation (IA) and immune remission (IR)" in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). The analyses revealed 7 major cell types and 24 clusters based on 72304 single-cell transcriptomes, allowing for the identification and characterization of various immune cell types within each cluster. Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress. This study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.