Albumin-to-creatinine Ratio Research Articles

PREVALENCE, Characteristics, and Awareness of Chronic Kidney Disease in Croatia: The EH-UH 2 Study

Background. National surveys have reported variable prevalence of chronic kidney disease (CKD), due to differences in the characteristics of the population, study design, equations used for the estimated glomerular filtration rate (eGFR), and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics, and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence of CKD and cardio–kidney–metabolic risk factors in Croatia, which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of the albumin-to-creatinine ratio (ACR) and eGFR (CKD-EPI equation). Comorbidities and anthropometric and social factors related to the prevalence of CKD were analyzed, and the CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥G3A A2, and CKD defined only as an eGFR <60 mL/min/1.73 m2 were estimated at 17.1%, 9.8%, and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p < 0.001). The weighted prevalence of an ACR >30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD was 9.5%. Persons unaware of CKD were older with lower income, less education, more frequent diabetes, hypertension (less frequently controlled), and milder renal impairment. Conclusions. In Croatia, the estimated prevalence of CKD is high, being presented more frequently in men than in women. CKD patients have an unfavorable CV risk profile. The awareness of CKD is very low, reflecting poor health literacy in the general population but also in health-care workers.

Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis.

Globally, the prevalence of chronic kidney disease (CKD) is increasing among young people living with HIV (YPLHIV), with inconsistent estimates. Aggregated data on the prevalence of CKD are needed in sub-Saharan Africa (SSA) to inform strategies for early diagnosis and management. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of CKD among YPLHIV in SSA. We searched Medline/PubMed, EMBASE, African Index Medicus, and African Journals Online for articles reporting the prevalence of CKD among YPLHIV in SSA using predefined search strategies up to 15th January 2024. The reference lists of identified articles were checked for additional eligible studies. The eligibility criteria were studies among YPLHIV aged 10-24 years reporting CKD prevalence defined by either glomerular filtration rate (GFR), albumin-to-creatinine ratio (ACR) or proteinuria. We used a narrative synthesis to report differences between the included studies. The DerSimonian-Laird random effects model was used to pool the CKD prevalence, and heterogeneity was assessed using the Cochrane Q-test and I-squared values. We assessed the risk of bias in each article using the Joanna Briggs Institute checklist and publication bias in a funnel plot and Egger's test. Of 802 retrieved articles, 15 fulfilled the eligibility criteria and were included in the meta-analysis. Of these, 12 (80%) were cross-sectional studies that used estimated GFR to diagnose CKD. Only one study followed the standard definition of CKD. The pooled CKD prevalence from 15 studies was 12% (95% CI 6.0-19.5%), ranging from 0.8% to 53.1% according to the definition used, with a high degree of heterogeneity (I2 = 97.7%, p<0.001). The included studies were of moderate quality, with no evidence of publication bias. Sensitivity analysis showed that the findings were robust to the methodological and analytic approach. CKD prevalence among YPLHIV is moderately high and highly heterogeneous across SSA. The standard definition of CKD should be used to enable estimation of CKD prevalence in different studies and settings. HIV programs enrolling YPLHIV should routinely screen for CKD to ensure early diagnosis and management. PROSPERO registration number: CRD42022347588.

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.

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

Antihypertensive treatment of masked hypertension guided by ambulatory blood pressure monitoring: a double-blind, placebo-controlled trial

Abstract Background Masked hypertension, office normotension combined with out-of-office hypertension, is associated with target organ damage (TOD), but whether antihypertensive treatment guided by out-of-office blood pressure (BP) would reduce TOD is unproven. Purpose To assess TOD change on antihypertensive treatment guided by ambulatory BP monitoring. Methods We conducted a double-blind, placebo-controlled randomized trial at 15 Chinese hospitals. Enrolment started on February 14, 2017 and follow-up ended on October 31, 2021. Patients of either sex, aged 30-70 years, not on antihypertensive drugs were eligible, if at two screening visits 1-week apart office BP was &amp;lt;140/&amp;lt;90 mm Hg and the 24 hour, daytime or nighttime ambulatory BP was ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg, respectively. Patients had ≥1 sign of TOD: ECG left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Active antihypertensive treatment consisted of allisartan starting at 80 mg/day to be increased to 160 mg/day at month 2 and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint included normalization of baPWV, ACR or LVH or ≥20% reduction in baPWV or ACR. Results Of 320 patients (43.1% women; mean age 54 years), 153 were randomized to active antihypertensive treatment and 167 to placebo. At baseline, office BP averaged 130/81 mm Hg and the 24 hour BP 136/84 mm Hg. The prevalence of elevated baPWV, ACR and LVH was 97.5%, 12.5%, and 7.8%. The 24-hour systolic/diastolic decreased by 9.0/5.6 mm Hg (95% CI: 7.5-10.5/4.8-6.5 mm Hg) on active treatment and by 1.4/1.0 mm Hg (-0.1-2.8/0.2-1.8 mm Hg) on placebo. Regression of TOD, the primary outcome, occurred more frequently in patients randomized to active treatment than in those assigned to placebo with 1 year rate of 45.8% (95% CI: 37.9-53.7%) and 25.8% (19.1-32.4%), respectively (P&amp;lt;.001 for between-group differences in BP and TOD). Per-protocol and subgroup analyses were confirmatory. Conclusions Masked hypertensive patients require antihypertensive treatment guided by out-of-office BP monitoring before subclinical TOD progresses to major cardiovascular complications.

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.

Sirt6 ameliorates high glucose-induced podocyte cytoskeleton remodeling via the PI3K/AKT signaling pathway

Background Podocyte injury plays an important role in the occurrence and progression of diabetic kidney disease (DKD), which leads to albuminuria. Cytoskeletal remodeling is an early manifestation of podocyte injury in DKD. However, the underlying mechanism of cytoskeletal remodeling has not been clarified. Histone deacetylase sirtuin6 (Sirt6) has been found to play a key role in DKD progression, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway directly regulates the cytoskeletal structure of podocytes. Whereas, the relationship between Sirt6, the PI3K/AKT pathway and DKD progression remains unclear. Methods Renal injury of db/db mice was observed by PAS staining and transmission electron microscope. Expression of Sirt6 in the glomeruli of db/db mice was detected by immunofluorescence. UBCS039, a Sirt6 activator, was used to explore the renal effects of Sirt6 activation on diabetic mouse kidneys. We also downregulating Sirt6 expression in podocytes using the Sirt6 inhibitor, OSS_128167, and induced upregulation of Sirt6 using a recombinant plasmid, after which the effects of Sirt6 on high glucose (HG)-induced podocyte damage were assessed in vitro. Podocyte cytoskeletal structures were observed by phalloidin staining. The podocyte apoptotic rate was assessed by flow cytometry, and PI3K/AKT signaling activation was measured by Western blotting. Results Db/db mice exhibited renal damage including elevated urine albumin-to-creatinine ratio (ACR), increased mesangial matrix, fused podocyte foot processes, and thickened glomerular basement membrane. The expression of Sirt6 and PI3K/AKT pathway components was decreased in db/db mice. UBCS039 increased the expressions of Sirt6 and PI3K/AKT pathway components and ameliorated renal damage in db/db mice. We also observed consistent Sirt6 expression was in HG-induced podocytes in vitro. Activation of the PI3K/AKT pathway via a Sirt6 recombinant plasmid ameliorated podocyte cytoskeletal remodeling and apoptosis in HG-treated immortalized human podocytes in vitro, whereas Sirt6 inhibition by OSS_128167 accelerated HG-induced podocyte damage in vitro. Conclusions Sirt6 protects podocytes against HG-induced cytoskeletal remodeling and apoptosis through activation of the PI3K/AKT signaling pathway. These findings provide evidence supporting the potential efficacy of Sirt6 activation as a promising therapeutic strategy for addressing podocyte injury in DKD.

Targeting RAC1 might be a potential therapeutic strategy for diabetic kidney disease: a Mendelian randomization study.

This study aimed to ascertain the causal association between Ras-related C3 botulinum toxin substrate 1 (RAC1) and the incidence and progression of diabetic kidney disease (DKD) through Mendelian randomization analysis. RAC1 expression, evaluated using expression quantitative trait loci data from the eQTLGen Consortium, was served as the exposure variable. Outcomes encompassed the risk of DKD, end-stage renal disease (ESRD), albuminuria assessed by the urinary albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) among individuals with diabetes. Causal associations were computed using the inverse variance weighted (IVW), weighted median, and MR-PRESSO models. Additionally, we conducted analyses for heterogeneity, horizontal pleiotropy, and sensitivity. This study revealed a causal association between the genetic activation of RAC1 and an elevated risk of DKD among individuals with diabetes [IVW, odds ratio (OR) = 1.28, 95% confidence intervals (CI) 1.08-1.51, P = 0.004]. Furthermore, increased expression of RAC1 was linked to a higher risk of ESRD (IVW, OR = 1.20, 95% CI 1.02-1.43, P = 0.032). Excessive RAC1 expression was causally associated with elevated ACR (IVW, β = 0.052, 95% CI 0.003-0.100, P = 0.036). However, the analysis regarding RAC1 and eGFR showed significant heterogeneity and pleiotropy, with no discernible causal relationship. These findings suggested a positive correlation between the genetic activation of RAC1 and the incidence of DKD, the risk of ESRD, and exacerbated albuminuria among individuals with diabetes. Targeting RAC1 might potentially serve as a therapeutic strategy for DKD.

A-201 The Impact of Implementing the CKD-EPI 2021 Equation for Calculation of Estimated Glomerular Filtration Rate (eGFR) and the Kidney Failure Risk Equation (KFRE) on a Large Community Laboratory Population

Abstract Background Community laboratories in Ontario, Canada have reported estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009 equation without race adjustment since 2020. In 2023, the Canadian Society of Nephrology recommended implementation of the CKD-EPI 2021 equation for eGFR, which does not incorporate a race-based modifier. Community laboratories will also report the 5-year Kidney Failure Risk Equation (KFRE), a risk prediction model to estimate the risk of renal failure in people with chronic kidney disease (CKD) Stages 3 to 5 (eGFR &amp;lt;60 mL/min/1.73m2), which is more accurate than judging by eGFR alone. This study assessed the impact of implementing the CKD-EPI 2021 equation for eGFR and the 5-year KFRE in a large community laboratory population. Methods Laboratory results for serum creatinine and urine albumin to creatinine ratio (ACR), patient sex and age were extracted from Dynacare’s laboratory information system for November 2023. The CKD-EPI 2009 without race adjustment and the CKD-EPI 2021 were calculated. Reclassification of CKD stage using the CKD-EPI 2021 equation was assessed. The 4-variable 5-year KFRE was calculated for patients in CKD Stage 3-5 (eGFR &amp;lt;60 mL/min/1.73m2) when all parameters including, patient age, sex, creatinine and ACR, were available. Results Data was extracted for 242,843 patients. The median age was 61 years old and 47% of the population was female. The calculated median eGFR was 83 and 87 mL/min/1.73m2 when the CKD-EPI 2009 with no race adjustment, and CKD-EPI 2021 equation, respectively, were applied. Linear regression analysis showed a correlation of 0.997 with a slope of 0.990 and y-intercept of 4.513. A total of 13.0% (n=31,679) of patients were reclassified into a less progressive CKD stage when the CKD-EPI 2021 was applied compared to the CKD-EPI 2009 without race adjustment. Notable, was the reclassification of 21.8% (n=6899) of those patients from Stage 3a to 2, i.e. patients no longer have CKD (eGFR &amp;gt;60 mL/min/1.73m2) based on the new calculation. 64.8% (n=20513) of patients were reclassified from Stage 2 to 1, 9.4% (n=2977) were reclassified from Stage 3b to 3a, 3.5% (n=1102) were classified from Stage 4 to 3b, and 0.6% (n=188) were reclassified from Stage 5 to 4. The 5-year KFRE was calculated when creatinine and ACR were included on the same order and the patient was classified as Stage 3 to 5 (n=12,737 patients with eGFR &amp;lt;60 mL/min/1.73m2). The 5-year KFRE showed increasing median risk, 1%, 4%, 27%, 95%, as CKD stage increased from 3a, 3b, 4 and 5, respectively. 1.1% (n=58) of patients in Stage 3a, 43.3% (n=1584) of patients in Stage 3b, 96.6% (n=1994) of patients in Stage 4, and 100% (n=401) of patients in Stage 5 met the KFRE threshold of ≥5% for referral to nephrology. Conclusions Implementation of the CKD-EPI 2021 resulted in reclassification to a less progressive CKD stage. Use of the KFRE as a clinical decision tool will increase patient referral to nephrology. This study provided insight into the impact of the implementation of the CKD-EPI 2021 and KFRE and highlights the underutilization of ACR in a community population.

Role of Emerging Urinary Biomarkers in Predicting Progressive Deterioration of Kidney Function in Congenital Anomalies of Kidney and Urinary Tract: Trefoil Family Factor 3, Alpha Soluble Klotho and Urinary Microalbuminuria

IntroductionChronic kidney disease is an irreversible fate of many CAKUT (Congenital Abnormalities of the Kidneys and Urinary Tract) patients. Biomarkers involved in the disease progression are raised early in the disease process and aid in identifying the individuals at risk of progressive renal function decline. AimsTo determine and compare the initial levels of urinary biomarkers in patients of CAKUT with asymptomatic controls and to correlate the same with progression of renal disease. ResultsThis study includes 66 children with CAKUT and 22 healthy controls. Initial levels of three urinary Biomarkers: Trefoil family factor 3 (TFF3), Alpha soluble Klotho and Albumin-to-creatinine ratio (ACR) was recorded. Kidney function was assessed initially and at the end of 1 y follow up. Progressive deterioration of renal disease was noted in 26 (fall in GFR by >10 ml/min/m2). Median levels of urinary TFF3, alpha soluble Klotho and ACR was higher in patients with CAKUT (263, 18, 56 mcg/gCr) as compared to controls (15, 5, 6 mcg/gCr) and was further higher in patients having a progressive kidney disease (586, 40, 182 mcg/gCr). The cut-off value of the TEF3 to diagnose progressive renal disease was 178 mcg/g Cr with sensitivity and specificity of 95 % and 96 %, respectively. Using a cut-off of 29 mg/g Cr for ACR, sensitivity and specificity were 97 and 96 %, respectively.Urinary soluble Klotho was a relatively poor urinary biomarker with sensitivity and specificity of only 70 and 78 %, respectively, at a cut-off value of 18 mcg/g Cr. ConclusionTFF3 and ACR are useful biomarkers which can be included in the biomarker panel to identify patients having a progressive renal disease and are at a risk of developing CKD.

The Role of Nitric Oxide, Lipocalin-2, and Proinflammatory Cytokines on Proteinuria and Insulin Resistance in Type 2 Diabetes Mellitus Subgroups.

Nitric oxide (NO) is a bioactive signaling molecule that mediates various physiological and biological processes. Type 2 diabetes mellitus (T2DM) can be categorized into several subgroups according to fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels. Few studies have closely examined the effect of NO and lipocalin-2 on albuminuria and insulin resistance in T2DM subgroups. This study investigated the role of NO, lipocalin-2, and proinflammatory cytokines on the development of proteinuria and insulin resistance in patients with T2DM subgroups. A total of 256 subjects, including 191 patients with T2DM and 65 non-diabetic healthy individuals, were evaluated. NO metabolites (NOx), lipocalin-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured. Patients with T2DM were classified into three subgroups: patients with FPG-defined diabetes (PG-DM), those with HbA1c-defined diabetes (HA-DM), and those who met the criteria for both FPG and HbA1c (PG/HA-DM). The albumin-to-creatinine ratio (ACR) and the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated. NOx, lipocalin-2, and TNF-α levels were significantly higher in patients with T2DM than in healthy individuals. Patients with PG/HA-DM had significantly higher NOx levels than those with PG-DM or HA-DM. Of the patients with high NOx levels, patients with lipocalin-2 elevation exhibited higher ACR and HOMA-IR than those without lipocalin-2 elevation. NOx was positively correlated with lipocalin-2, ACR, HOMA-IR, and TNF-α but not with HOMA-B and IL-6. The upper quartile of NOx levels led to a 1.2-fold increase in the risk of albuminuria (odds ratio: 1.215; 95% CI: 1.012-2.418; p < 0.001). NO plays a crucial role in proteinuria and insulin resistance by collaborating with lipocalin-2 and TNF-α, showing significantly higher levels in patients with PG/HA-DM than in those with PG-DM or HA-DM.

Clinical Validation of a Mobile-Based ACR (Urine Albumin-to-Creatinine Ratio) Test Kit: Comparative Analysis with Benchtop Devices

Background: Albuminuria, a marker for diabetes complications and kidney disease, is typically tested in hospitals, limiting patient monitoring. The mobile-based ACR (urine albumin-to-creatinine ratio) test, QSCheck-UISACR, was developed for easy detection of albuminuria. This study aimed to validate its clinical efficacy compared to a conventional benchtop device (Cybow R-50S) for early kidney disease diagnosis. Methods: Conducted in three hospitals with 303 kidney disease patients, urine samples were tested using both the mobile ACR kit and the benchtop device. Parameters measured included microalbumin, creatinine, and their ratio (albumin-to-creatinine ratio). Exact Agreement and Within One Block Agreement were calculated to compare methods.Results: Data collected from three university hospitals were aggregated and analyzed, showing that the microalbumin Exact Agreement was 73.3%, with a Within One Block Agreement of 96.0%. For creatinine, the Exact Agreement was 75.6%, and the Within One Block Agreement was 95.7%. Based on these two test results, the albumin-to-creatinine ratio analysis demonstrated an Exact Agreement of 78.5% and a Within One Block Agreement of 98.0%. These findings highlight the robust performance of the tests across the evaluated biomarkers.Conclusions: The mobile-based ACR test kit demonstrated high accuracy and comparability to the benchtop device, suggesting its potential as a reliable tool for early kidney disease screening in primary care settings, enhancing patient accessibility and reducing healthcare costs.

Frailty assessment and outcomes in primary care for patients with diabetes during Ramadan: implications for risk evaluation and care plans.

Frailty is a critical concern for older adults, impacting their susceptibility to adverse events and overall quality of life. This study aimed to determine the frailty status of patients 60 years or older in Abu Dhabi Ambulatory Healthcare Services (AHS) and assess its relation to the stress exerted by Ramadan fasting and the occurrence of any adverse outcomes. In this prospective observational study, participants were included if the attending physicians used the IDF-DAR risk stratification assessment tool. A tele-interview was conducted to complete the FRAIL score within 6 weeks before Ramadan 1,444 (CE 2022). The outcome was assessed through another tele-interview and an electronic medical record review after Ramadan. According to the FRAIL assessment tool, among the 204 patients aged 60 years or older included in the study, 109 (53.4%) were classified as either frail or pre-frail. In total, 20 (9.8%) patients were frail, that is, 1 out of 10, and 89 (43.6%) were pre-frail. The remaining 95 (46.6%) patients were robust. Using logistic regression to assess the occurrence of adverse outcomes after Ramadan fasting, a higher frailty score was identified as the third independent risk factor [B = 0.4, OR = 1.5 (1-2.02-1.86), and p = 0.039] for experiencing an adverse event. The identified factors associated with frailty were age, increased albumin-to-creatinine ratio (ACR), chronic kidney diseases (CKDs), and ischemic heart diseases (beta = 0.27, p = 0.003; beta = 0.24, p = 0.004; beta = 0.2, p = 0.039; and beta = 0.18, p = 0.041, respectively). One-third of the frail patients had an event, while the incidence in pre-frail patients was 11.2%, and among the robust patients, the incidence was 6.3%. Physicians' global assessment of frailty did not align well with the structured FRAIL scoring. Only five (25%) out of the 20 patients identified as frail by the FRAIL assessment tool were also judged as frail or having cognitive function impairment by the physicians' global assessment tool. Frailty is prevalent among elderly patients with diabetes. Disparity exists between subjective and objective frailty assessments, emphasizing the need for standardized evaluation methods. Using the FRAIL tool is recommended for patients aged 60 or older with diabetes in Abu Dhabi.

Relationship between phthalate exposure and kidney function in Taiwanese adults as determined through covariate-adjusted standardization and cumulative risk assessment

Few studies have investigated the associations between phthalate exposure and kidney function indicators in adults by simultaneously performing covariate-adjusted creatinine standardization, cumulative risk assessment, and mixture analysis. Thus, we applied these methods simultaneously to investigate the aforementioned associations in an adult population. This cross-sectional study analyzed data (N = 839) from a community-based arm of the Taiwan Biobank. The levels of 10 urinary phthalate metabolites were measured and calculated as the sum of the molar concentrations of the dibutyl phthalate metabolite (ΣDBPm) and di(2-ethylhexyl) phthalate (DEHP) metabolite (ΣDEHPm). The hazard index (HI) and daily intake (DI) were estimated by measuring the urinary levels of the phthalate metabolite. Kidney function biomarkers were assessed by measuring the following: blood urea nitrogen (BUN), uric acid, the albumin-to-creatinine ratio (ACR), and the estimated glomerular filtration rate (eGFR). Generalized linear models were implemented to examine the associations between exposure to individual phthalates, HI scores, and kidney function biomarkers. We also employed Bayesian kernel machine regression (BKMR) to analyze the relationships between exposure to various combinations of phthalates and kidney function. ΣDEHPm levels were significantly and positively associated with BUN and ACR levels, and ΣDBPm levels were positively associated with ACR levels. In addition, eGFR was negatively associated with ΣDBPm and ΣDEHPm levels. In the BKMR model, a mixture of 10 phthalate metabolites was significantly associated with BUN, uric acid, ACR, and eGFR results. Higher DIDEHP and higher DIDnBP values were significantly associated with lower eGFRs and higher ACRs, respectively. Higher DIDiBP and DIDEP values were significantly associated with higher uric acid levels. A higher HI was significantly associated with lower eGFRs and higher ACRs. Our results suggest that exposure to environmental phthalates is associated with impaired kidney function in Taiwanese adults.

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

Elevated serum albumin-to-creatinine ratio as a protective factor on clinical outcomes among critically ill patients with sepsis: a retrospective study.

The aim of this study was to examine the prognostic significance of serum albumin-to-creatinine ratio (ACR) in critically ill patients with sepsis. This retrospective study analyzed sepsis cases admitted to the Affiliated Hospital of Jiangsu University between January 2015 and November 2023. The patients were divided into four groups based on their ACR upon admission to the intensive care unit (ICU). Laboratory data were collected at the time of ICU admission, and the primary outcome measure was in-hospital all-cause mortality. Kaplan-Meier survival curves were generated to illustrate the differences in 30-/60-day mortality among the various groups. Multivariate Cox regression models and restricted cubic splines (RCS) were utilized to explore the association between ACR and all-cause mortality in sepsis patients. Subgroup analyses were conducted to examine the impact of other covariates on the relationship between ACR and all-cause mortality. A total of 1,123 eligible patients were included in the study, with a median ACR of 0.169. The in-hospital mortality rate was 33.7%, the ICU mortality rate was 31.9%, and the 30-day mortality rate was 28.1%. Kaplan-Meier survival analysis demonstrated that patients with higher ACR had a significantly lower risk of 30-/60-day mortality (log-rank p < 0.001). Multivariable Cox proportional hazards analyses revealed that ACR was an independent predictor of in-hospital death (HR: 0.454, 95% CI 0.271-0.761, p = 0.003), ICU death (HR: 0.498, 95% CI 0.293-0.847, p = 0.010), and 30-day death (HR: 0.399, 95% CI 0.218-0.730, p = 0.003). For each 1-unit increase in ACR, there was a 1.203-fold decrease in the risk of death during the hospital stay. The RCS curve illustrated a non-linear negative correlation between ACR and in-hospital mortality (p for non-linear =0.018), ICU mortality (p for non-linear =0.005), and 30-day mortality (p for non-linear =0.006). Sensitivity analysis indicated consistent effect sizes and directions in different subgroups, confirming the stability of the results. Low ACR levels were identified as independent risk factors associated with increased in-hospital, ICU, and 30-day mortality in sepsis patients. ACR can serve as a significant predictor of the clinical outcome of sepsis.

Serum Albumin-to-Creatinine Ratio Predicts One-Year Mortality in Elderly Patients with Non-ST-Elevation Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Prospective Cohort Analysis.

BACKGROUND Recently, the albumin-to-creatinine ratio (ACR) has been suggested as a valuable biomarker for adverse events in acute myocardial infarction. However, the prognostic value of ACR in very elderly patients (≥80 years) with non-ST-elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) remains unclear. MATERIAL AND METHODS A total of 354 very elderly patients with NSTE-ACS who underwent PCI were included in this study and followed up for 1 year. Patients were divided into 3 groups according to ACR tertiles. Logistic regression analysis proportional hazard model was used to determine the prognostic value of ACR. RESULTS Sixty-two patients (17.5%) with 114 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during 1-year follow-up. Patients with lower ACR tended to be older and had a lower serum albumin level and higher uric acid and creatinine levels (P<0.05). Moreover, patients with lower ACR levels had elevated all-cause mortality and MACCEs. Kaplan-Meier analysis suggested that patients with a lower ACR had a significantly lower survival rate free of all-cause mortality and MACCEs. Multivariable logistic regression analysis demonstrated that ACR was an independent predictor of all-cause mortality in these patients. ROC analysis showed that when ACR was ≤42.8, sensitivity and specificity were 75.2% and 80.2%, respectively, and the area under the ROC curve was 0.802 (95% CI: 0.745-0.859; P<0.001). CONCLUSIONS A lower ACR was associated with a higher incidence of all-cause mortality in very elderly patients with NSTE-ACS after PCI. The ACR is a promising indicator for risk stratification and prognostic assessment in these individuals.

Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function

ObjectivesWe aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2.DesignObservational...

Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease.

Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin-to-creatinine ratio (ACR) 30mg/g is a cut-off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR>60mL/min/1.73m2 are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher-risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non-invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs. Hypertensive patients were classified in control group (C) with ACR<10mg/g, and high-normal group (HN) with ACR 10-30mg/g. Isolated uEVs were characterized by western blotting and electron microscopy and the protein cargo was analyzed by untargeted proteomics (LC-MS/MS) in a first discovery cohort. Protein confirmation was performed in a different cohort by ExoView. Immunohistochemistry of human kidney biopsies was also performed to evaluate the potential of uEVs to reflect renal damage. HN albuminuria does not affect the uEVs concentration, size, or tetraspanin profile. Among >6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long-chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD. Alterations in the EV-mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD.

A Population Pharmacokinetic Model of Tocilizumab in Kidney Transplant Patients Treated for Chronic Active Antibody-Mediated Rejection: Comparison of Plasma Exposure Between Intravenous and Subcutaneous Administration Schemes.

Tocilizumab prevents the clinical worsening of chronic active antibody-mediated rejection (CAAMR) in kidney transplant recipients. Following a global shortage of the intravenous pharmaceutical form in 2022, patients were switched from monthly intravenous administration of 8 mg/kg to weekly subcutaneous injection of 162 mg, raising the question of bioequivalence between these schemes of administration. We aimed to compare the areas under the curve (AUC) of tocilizumab in virtual simulations of populations treated with the two administration schemes and to identify the covariates that could contribute to pharmacokinetic variability of tocilizumab in kidney transplant patients with CAAMR who received tocilizumab as salvage treatment. This retrospective monocentric study included 43 kidney transplant patients (202 tocilizumab concentrations) with CAAMR treated with intravenous or subcutaneous tocilizumab between December 2020 and January 2023. We developed a population pharmacokinetic model using nonlinear mixed effects modeling and identified the covariates that could contribute to tocilizumab AUC variability. Monte Carlo simulations were then performed to assess the subcutaneous and intravenous tocilizumab AUC for 0-28 days (M1), 56-84 days (M3), 140-168 days (M6), and 308-336 days (M12). Bioequivalence was defined by SC/IV AUC geometric mean ratios (GMRs) between 0.80 and 1.25. A two-compartment model with parallel linear and nonlinear elimination best described the concentration-time data. Significant covariates for tocilizumab clearance were body weight, urinary albumin-to-creatinine ratio (ACR), and inflammation status [C-reactive protein (CRP) ≥5 mg/L]. The GMR values and their 90% confidence intervals at M3, M6, and M12 were within the 0.8-1.25 margin for equivalence. Conversely, the 90% prediction intervals of the GMR were much wider than the 90% confidence intervals and did not fall within 0.8 and 1.25. From month 3 of treatment, the subcutaneous and intravenous tocilizumab administration schemes provided average bioequivalent pharmacokinetic exposure at the population level but not at the individual level. Body weight, inflammation, ACR, and administration scheme should be considered to personalize the dose of tocilizumab for patients with CAAMR. Further studies are required to determine the target of tocilizumab exposure in kidney transplant patients with CAAMR.