Urinary Albumin-to-creatinine Ratio Research Articles

Prevalence and Predictors of Peripheral Vascular Disease Amongst Predialysis Hypertensive Chronic Kidney Disease Patients in Southern Nigeria.

Peripheral vascular disease (PVD) is an atherosclerotic disease associated with increased morbidity and mortality among chronic kidney disease (CKD) patients. However, despite the substantial burden of PVD in CKD, local data are lacking. To determine the prevalence and predictors of PVD in predialysis CKD patients. The study was cross-sectional. One hundred fifty hypertensive CKD patients and age- and sex-matched hypertensive non-CKD subjects were consecutively enrolled at the renal unit of Delta State University Teaching Hospital (DELSUTH), Oghara. Structured questionnaires were used to obtain information on participants' demographic data and health status. PVD was defined by an ankle-brachial index of < 0.9 or > 1.4 in either lower extremity. eGFR was calculated from serum creatinine using the MDRD equation. The mean ages of the study and control groups were 48±14 and 51±15years, respectively. The sex ratio was 3:2 in favour of males for both the study and control groups. The majority of the study group was in CKD stage 4 (44%). The prevalence of PVD was higher among the CKD group compared with controls (24.0% vs. 14.7%).Of the CKD patients with PVD, 11.1% were symptomatic. Predictors of PVD in the study group were eGFR (B=0.010, 95%CI: 0.007-0.013), diastolic BP (B=-0.005, 95%CI: -0.007- -0.002), MAP (B=-0.018, 95%CI: -0.027- -0.008), urinary ACR (B=-0.0036, 95%CI: -0.040- -0.024) and smoking history (p<0.001, OR=14.71). PVD is common and largely asymptomatic in CKD patients. The predictors of PVD in this study were eGFR, diastolic BP, mean arterial pressure (MAP), urinary albumin to creatinine ratio (ACR), and smoking. A proactive assessment of PVD and early intervention in CKD patients is needed.

An Investigation on the Efficacy of Glucagon-Like Peptide 1 Receptor Agonists Drugs in Reducing Urine Albumin-to-Creatinine Ratio in Patients With Type 2 Diabetes: A Potential Treatment for Diabetic Nephropathy.

As diabetes mellitus becomes increasingly prevalent globally, so does diabetic nephropathy, a complication leading to one of the world's leading causes of end-stage renal disease (ESRD). Current research has linked an increase in the urine albumin-to-creatinine ratio (UACR), a marker for kidney damage, to a greater risk of adverse renal outcomes and ESRD in patients with diabetes. Of the diabetes medications studied and implemented in clinical settings, glucagon-like peptide-1 receptor agonist (GLP1-RA) drugs have been shown to not only help control HbA1c in diabetes but have also demonstrated numerous cardiovascular, hepatic, and renal benefits. The objective of our study was to assess the efficacy of GLP1-RA drugs in reducing UACR in patients with type 2 diabetes mellitus (T2 DM) to determine if GLP1-RAs could be used to provide renoprotection in diabetic nephropathy in addition to their glucose-lowering effects. Upon a comprehensive review of the literature, we conducted a statistical analysis to determine the efficacy of GLP1-RA monotherapy and combination therapy in reducing UACR in comparison to placebo and insulin glargine. Of the studies analyzed, GLP1-RAs exhibited a statistically significant effect in reducing UACR in comparison to a placebo but not in comparison to insulin glargine. GLP1-RA combination therapy (GLP1-RA used with either insulin glargine, metformin, or dapagliflozin) did not exhibit statistically significant UACR reductions in comparison with insulin glargine. However, GLP1-RA combination therapy showed a trend suggestive of being more effective than insulin glargine in reducing UACR, but due to the limited literature studying this treatment method, further studies in a more focused group of patients with diabetic nephropathy may produce stronger and more definitive results. GLP1-RA monotherapy or combination therapy has been determined to be an effective method for reducing UACR and decreasing the incidence of adverse renal outcomes associated with diabetic kidney disease. GLP1-RA therapy could serve as an alternative treatment in diabetic nephropathy to insulin glargine, which carries a higher risk of hypoglycemia and unintentional weight gain while potentially being less cost-effective.

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

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

The association between retinal microvasculature derived from optical coherence tomography angiography and systemic factors in type 2 diabetics.

To investigate the correlation between the retinal microvasculature using optical coherence tomography angiography (OCTA) and systemic factors in type 2 diabetes mellitus (T2DM) patients. This cross-sectional study obtained OCTA data from patients with T2DM administered at hospital and referred to ophthalmic services. Patient data about demographics, comorbid conditions, and blood biomarkers were extracted from electronic medical records. Data from OCTA scans obtained by CIRRUS HD-OCT Model 5,000 were obtained. Vessel density (VD) and perfusion density (PD) within the superficial capillary plexus, and foveal avascular zone (FAZ) area were automatically segmented. These parameters were tested for their correlations with systemic factors by univariate and multivariable linear regression analyses. A total of 144 T2DM patients (236 eyes) were available for analysis, with mean age of 53.6 (SD = 10.34) and 56.9% were male. Chronic kidney disease, cardiovascular disease, increased serum creatinine (Scr), red blood cell count (RBC), platelets (PLT), apolipoprotein B (APOB), and decreased urine albumin to creatinine ratio (UACR) were significantly associated with lower VD and PD (all p < 0.013). UACR and triglyceride (TRIG) were significantly correlated with FAZ area (all p < 0.017). In multivariate analyses, PLT, eGFR, and APOB were independent risk factors for retinal rarefaction, and UACR was a significant predictor of FAZ area. We found several systemic risk factors, such as PLT, renal function and lipid profiles were associated with PD, VD, and FAZ area among Chinese T2DM patients.

Wide-ranging performance of different eGFR equations in stage determination of Chronic Kidney Disease patients from endemic areas for CKD in Sri Lanka

Background: Chronic kidney disease of unknown etiology (CKDu) is a public health issue at epidemic proportions in North Central, Uwa and other provinces of Sri Lanka. The initial diagnosis and stage determination of the disease are based on estimated glomerular filtration rate (eGFR), and urine albumin to creatinine ratio (UACR) particularly at community level screening. In this context, harmony and performance of pertaining equations were verified. Methods: Three hundred and ninety-nine (399) volunteer CKD patients were recruited from select CKDu high prevalence areas (Padaviya, Girandurukotte, and Mahiyanganaya). Performance of kidney dysfunction determinants; serum creatinine (SCr), and serum Cystatin C (CysC), as well as markers; UACR, and eGFR variants; SCr based MDRD, SCr based EPI, serum CysC based EPI and SCr and CysC based EPI were scrutinized in terms of kidney disease improving global outcomes (KDIGO) heat-map guidelines. Results: Notable deviation was observed between SCr-based and CysC-based equations at early development of the disease (stage G1) suggesting that the latter may tend to under estimate disease development initially. UACR successfully confirmed diagnosis from eGFR equations including G1 proteinuric subjects (G1). Conclusions: Comparative study of marker performances should improve eGFR based identification of initial CKDu cases in Sri Lanka.

Extracellular E-selectin levels and its association with insulin resistance: Putative role of E-selectin as a biomarker of oxidative stress linked vascular manifestations in diabetic nephropathy

Introduction and aim: E-selectin, a cell adhesion molecule depicting nexus with oxidative stress in hyperglycemia has been documented in several other clinical conditions. The present study centers around the putative role of E-selectin as a biomarker of diabetic nephropathy linked to oxidative stress.&#x0D; &#x0D; Materials and Methods: 150 type 2 diabetics in the age group of 35 - 50 years were classified into three groups, comprising 50 each, based on albuminuria. Fifty healthy age and gender matched individuals constituted the control. Extracellular E-selectin and Insulin were quantitated appropriately. Measurement of HbA1c and microalbumin were also enabled. Routine biochemistry analyses were undertaken, based on established automated procedures. The study was initiated only following approval accorded by the Institutional Ethics Committee.&#x0D; &#x0D; Results: E-selectin levels in serum were significantly associated with Urine Albumin-to-Creatinine Ratio (UACR) and Insulin resistance in the light of estimated Glomerular Filtration Rate.&#x0D; &#x0D; Conclusion: E-selectin levels could thus act as a putative biomarker of diabetic nephropathy linked to oxidative stress, as observed in insulin resistant type 2 diabetes.

Changes in urinary albumin as a surrogate for kidney disease progression in people with type 2 diabetes.

It remains unclear whether urinary albumin changes can predict subsequent kidney disease progression in people with diabetes. This retrospective cohort study included 4570 Japanese adults with type 2 diabetes (T2D). The exposure was changes in urinary albumin-to-creatinine ratio (UACR) over 3years, categorized into three categories: ≤ -30%, minor change, or ≥ 30%. During the exposure period, eGFR decline was also examined and categorized into two categories: < 30% or ≥ 30% decline. The primary outcome was the composite of eGFR halving or initiation of kidney replacement therapy (KRT). The secondary outcome was the initiation of KRT. In the spline model, the hazard ratio for the primary outcome increased linearly on the log2 scale of UACR changes. When classified into six groups based on the categories of UACR changes and eGFR decline, people with a ≤ -30% UACR change and < 30% eGFR decline had a 38% lower incidence of the outcome compared to those with a minor UACR change and < 30% eGFR decline. Meanwhile, the risk in those with a ≤ -30% UACR change and ≥ 30% eGFR decline was 2.89 times. People with a ≥ 30% UACR change had the higher risk, regardless of whether a ≥ 30% eGFR decline occurred. Similar results were obtained in the secondary outcome. UACR changes can be a useful surrogate for kidney disease progression in people with T2D. However, when setting a decrease in UACR as the surrogate, it may be necessary to simultaneously evaluate kidney function decline.

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials.

These post hoc analyses of the Semaglutide Treatment Effect in People with obesity (STEP) 1-3 trials (NCT03548935, NCT03552757, and NCT03611582) explored the effects of semaglutide (up to 2.4 mg) on kidney function. STEP 1-3 included adults with overweight/obesity; STEP 2 patients also had type 2 diabetes. Participants received once-weekly subcutaneous semaglutide 1.0 mg (STEP 2 only), 2.4 mg, or placebo for 68 weeks, plus lifestyle intervention (STEP 1 and 2) or intensive behavioral therapy (STEP 3). Changes in urine albumin-to-creatinine ratio (UACR) and UACR status from baseline to week 68 were assessed for STEP 2. Changes in estimated glomerular filtration rate (eGFR) were assessed from pooled STEP 1-3 data. In STEP 2, 1,205 (99.6% total cohort) patients had UACR data; geometric mean baseline UACR was 13.7, 12.5, and 13.2 mg/g with semaglutide 1.0 mg, 2.4 mg, and placebo, respectively. At week 68, UACR changes were -14.8% and -20.6% with semaglutide 1.0 mg and 2.4 mg, respectively, and +18.3% with placebo (between-group differences [95% CI] vs. placebo: -28.0% [-37.3, -17.3], P < 0.0001 for semaglutide 1.0 mg; -32.9% [-41.6, -23.0], P = 0.003 for semaglutide 2.4 mg). UACR status improved in greater proportions of patients with semaglutide 1.0 mg and 2.4 mg versus placebo (P = 0.0004 and P = 0.0014, respectively). In the pooled STEP 1-3 analyses, 3,379 participants had eGFR data; there was no difference between semaglutide 2.4 mg and placebo in eGFR trajectories at week 68. Semaglutide improved UACR in adults with overweight/obesity and type 2 diabetes. In participants with normal kidney function, semaglutide did not have an effect on eGFR decline.

Niclosamide from an anthelmintic drug to a promising adjuvant therapy for diabetic kidney disease: randomized clinical trial

BackgroundDiabetic kidney disease (DKD) is a serious complication that begins with albuminuria and often leads to a rapid progressive decline in renal function. Niclosamide is a potent inhibitor of the Wnt/β-catenin pathway, which controls the expression of multiple genes of the renin–angiotensin–aldosterone system (RAAS), which in turn is influences the progression of DKD. This study was conducted to evaluate the effect of niclosamide as adjuvant therapy on DKD.MethodsOut of 127 patients screened for eligibility, 60 patients completed the study. After randomization, 30 patients in the niclosamide arm received ramipril plus niclosamide, and 30 patients in the control arm received ramipril only for 6 months. The primary outcomes were the changes in urinary albumin to creatinine ratio (UACR), serum creatinine, and estimated glomerular filtration rate (eGFR). The secondary outcomes were measurements of urinary matrix metalloproteinase-7 (MMP-7), 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), and podocalyxin (PCX). Comparisons between the two arms were done using student t-test. Correlation analysis was done using Pearson correlation.ResultsNiclosamide decreased UACR by 24% (95% CI − 30 to − 18.3%) while there was a rise in UACR in the control arm by 11% (95% CI 4 to 18.2%) after 6 months (P < 0.001). Moreover, a significant reduction in MMP-7 and PCX was noticed in the niclosamide arm. Regression analysis revealed a strong association between MMP-7, which is a noninvasive biomarker predicting the activity of the Wnt/β-catenin signaling, and UACR. A 1 mg/dL decline in MMP-7 level was associated with a 25 mg/g lowering in UACR (B = 24.95, P < 0.001).ConclusionThe addition of niclosamide to patients with diabetic kidney disease receiving an angiotensin-converting enzyme inhibitor significantly reduces albumin excretion. Further larger-scale trials are needed to confirm our results.Trial registration: The study was prospectively registered on clinicaltrial.gov on March 23, 2020, with identification code NCT04317430.

A Retrospective Cohort Study That Examined the Impact of Cannabis Consumption on Long-Term Kidney Outcomes.

Background: Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. Materials and Methods: Post hoc analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.S. centers during 2009-2015. Associations between self-reported cannabis consumption and the categorical and continuous outcomes were determined using multivariable Cox regression and linear mixed models, respectively. Results: Over a mean follow-up of 4.5±1.8 years, 94 participants without chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2) who consumed cannabis had similar rates of annual eGFR decline versus 889 nonconsumers (mean difference=-0.02 mL/min/1.73 m2/year, p=0.9) and incident CKD (≥25% reduction in eGFR compared with the 3-month post-hospitalization measured eGFR and achieving CKD stage 3 or higher) (adjusted hazard ratio [aHR]=1.2; 95% confidence interval [CI]=0.7-2.0). Nineteen participants with CKD (eGFR <60 mL/min/1.73 m2) who consumed cannabis had more rapid eGFR decline versus 597 nonconsumers (mean difference=-1.3 mL/min/1.73 m2/year; p=0.02) that was not independently associated with an increased risk of CKD progression (≥50% reduction in eGFR compared with the 3-month post-hospitalization eGFR, reaching CKD stage 5, or receiving kidney replacement therapy) (aHR=1.6; 95% CI=0.7-3.5). Cannabis consumption was not associated with the rate of change in urine albumin to creatinine ratio (UACR) over time among those with (p=0.7) or without CKD (p=0.4). Conclusions: Cannabis consumption did not adversely affect the kidney function of participants without CKD but was associated with a faster annual eGFR decline among participants with CKD. Cannabis consumption was not associated with changes in UACR over time, incident CKD, or progressive CKD regardless of baseline kidney function. Additional research is needed to investigate the kidney endocannabinoid system and the impact of cannabis use on kidney disease outcomes.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults

PurposeWe investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults.MethodsThis was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria.ResultsHR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, β = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, β = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, β = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014).ConclusionHR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Optimal threshold of urinary albumin-to-creatinine ratio (UACR) for predicting long-term cardiovascular and noncardiovascular mortality.

Traditional cutoff values of urinary albumin-to-creatinine ratio (UACR) for predicting mortality have recently been challenged. In this study, we investigated the optimal threshold of UACR for predicting long-term cardiovascular and non-cardiovascular mortality in the general population. Data for 25,302 adults were extracted from the National Health and Nutrition Examination Survey (2005-2014). Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of UACR for cardiovascular and non-cardiovascular mortality. A Cox regression model was established to examine the association between UACR and cardiovascular and non-cardiovascular mortality. X-tile was used to estimate the optimal cutoff of UACR. The UACR had acceptable predictive value for both cardiovascular (AUC (95% CI) for 1-year, 3-year and 5-year mortality, respectively: 0.769 (0.711-0.828), 0.764 (0.722-0.805) and 0.763 (0.730-0.795)) and non-cardiovascular (AUC (95% CI) for 1-year, 3-year and 5-year mortality, respectively: 0.772 (0.681-0.764), 0.708 (0.686-0.731) and 0.708 (0.690-0.725)) mortality. The optimal cutoff values were 16 and 30mg/g for predicting long-term cardiovascular and non-cardiovascular mortality, respectively. Both cutoffs of UACR had acceptable specificity (0.785-0.891) in predicting long-term mortality, while the new proposed cutoff (16mg/g) had higher sensitivity. The adjusted hazard ratios of cardiovascular and non-cardiovascular mortality for the high-risk group were 2.50 (95% CI 1.96-3.18, P < 0.001) and 1.92 (95% CI 1.70-2.17, P < 0.001), respectively. Compared to the traditional cutoff value (30mg/g), a UACR cutoff of 16mg/g may be more sensitive for identifying patients at high risk for cardiovascular mortality in the general population.

Correlation between urine vitamin D-binding protein and early-stage renal damage in Type 2 diabetes.

The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage. A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR. Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage. The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.

Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population.

Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanic/Latino people, a population with high risk for metabolic disease. We used data from 3736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin-to-creatinine ratio (UACR). Metabolites were quantified in fasting serum through nontargeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites, in covariate-adjusted models that accounted for the study design. In total, 132 metabolites were available for replication in the Hypertension Genetic Epidemiology Network study ( n =300), and 29 metabolites were available for replication in the Malmö Offspring Study ( n =999). Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-glutamine and D-glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism. Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanic/Latino population. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_02_08_CJN09070822.mp3.

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

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

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

Association Between CKD and Major Hemorrhage in Older Persons: Data From the Aspirin in Reducing Events in the Elderly Randomized Trial

Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking. We used data from a double-blind randomized controlled trial of aspirin in persons aged≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR)< 60 ml/min per 1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR)≥ 3 mg/mmol (26.6 mg/g). We compared bleeding rates in those with and without CKD, undertook multivariable analyses, and explored effect modification with aspirin. Of 19,114 participants, 17,976 (94.0%) had CKD status recorded, of whom 4952 (27.5%) had CKD. Participants with CKD had an increased rate of major bleeding events compared with those without CKD (10.4/1000 vs. 6.3/1000 person-years [py], respectively) and increased bleeding risk (risk ratio [RR] 1.60; 95% confidence interval [CI]: 1.40, 1.90 for eGFR< 60 ml/min per 1.73 m2) and RR (2.10; 95% CI: 1.70, 2.50) for albuminuria. In adjusted analyses, CKD was associated with a 35% increased risk of bleeding (hazard ratio [HR] 1.37; 95% CI: 1.15, 1.62; P< 0.001). Other risk factors were older age, hypertension, smoking, and aspirin use. There was no differential effect of aspirin on bleeding by CKD status (test of interaction P= 0.65). CKD is independently associated with an increased risk of major hemorrhage in older adults. Increased awareness of modifiable risk factors such as discontinuation of unnecessary aspirin, blood pressure control, and smoking cessation in this group is warranted.

Nigella sativa tea mitigates type-2 diabetes and edema: a case report

Diabetes is a major deadly disease. In 2019 alone, it caused an estimated 1.5 million deaths world-wide. Cases of diabetes are rising rapidly in low- and middle-income countries. Natural remedies that can lower the glucose level would be very useful, particularly to people living in low- and middle-income countries. A 2-year case study was carried out, therefore, to determine if Nigella sativa tea can lower the glucose level in a 72-year-old man with type-2 diabetes, stage 3–4 chronic kidney disease, and congestive heart failure. Changes in body weight, lipids, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) were also studied. N. sativa tea was prepared with N. sativa, barley, and wheat seeds. The 72-year-old drank approximately 50 ml of N. sativa tea daily, in the morning. Results showed that after drinking N. sativa tea daily, hypoglycemia started to occur and occurred more frequently as time went by and that the glycated hemoglobin, HbA1c, was decreasing. Subsequently, the dosages of insulin glargine and insulin aspart were reduced by 33% and 50%, respectively. Results also showed that weight loss led to the 72-year-old cutting back his intake of the diuretic furosemide by at least 50%. His triglycerides level was also lower and there were no changes in his total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. His eGFR was stable but his UACR was worsening. N. sativa tea is easy to prepare, costs very little, and could be a natural remedy for mitigating diabetes and edema. Many more studies on N. sativa are warranted.

Effect of frailty, physical performance, and chronic kidney disease on mortality in older patients with diabetes : a retrospective longitudinal cohort study

BackgroundDeclined renal function is associated with physical function impairment and frailty in a graded fashion. This study aimed to examine the relationship between renal function, frailty and physical performance with mortality in older patients with diabetes, while also determining their combined effects on patient outcome.MethodsA retrospective longitudinal study was conducted in elderly patients with diabetes. Kidney disease staging was based on clinical practice guidelines of the International Society of Nephrology, and chronic kiney disease (CKD) was defined as urinary albumin to creatinine ratio (UACR) > 30 mg/g, persistent reduction in estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m2 or both. The modified Rockwood frailty index (RFI) was composed of cumulative health deficits, and physical function was determined by handgrip strength (HGS). Additionally, a timed up and go (TUG) test was assessed at baseline. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the association between CKD, frailty, physical function and mortality.ResultsFor the 921 enrolled patients, their mean age was 82.0 ± 6.7 years. After a median 2.92 (interquartile range [IQR] 1.06–4.43) year follow-up, the survival rate was 67.6% and 85.5% in patients with and without CKD, respectively. The mortality hazard ratio (crude HR) with CKD was 5.92 for those with an RFI higher than 0.313 (95% CI 3.44–10.18), 2.50 for a TUG time longer than 21 s (95% CI 1.22–5.13), and 2.67 for an HGS lower than 10.57 kg in females or 20.4 kg in males (95% CI 1.12–6.37). After multivariate adjustment, the mortality hazard ratio for an RFI ≥ 0.313 was 5.34 (95% CI 2.23–12.80) in CKD patients, but not in patients without CKD. In subgroup analysis, patients experiencing CKD and frailty, or physical function impairment, had the lowest survival proportion followed by only frailty/declined physical function, only CKD, without CKD, and non-frailty/non-physical impairment.ConclusionCKD, frailty and physical function impairment were all associated with an increased mortality risk in older patients with diabetes, while the combined effects of these 3 factors were seen on patient outcome.

Association of a low ankle brachial index with progression to end-stage kidney disease in patients with advanced-stage diabetic kidney disease

Introductions The effect of a low ankle-brachial index (ABI) in patients with advanced-stage diabetic kidney disease is not fully understood. This study investigates the prevalence of a low ABI in patients with advanced-stage diabetic kidney disease, which was defined as a urinary albumin-to-creatinine ratio (UACR) ≥300 mg/g and an estimated glomerular filtration rate (eGFR) between 15–60 mL/min/1.73 m2. Furthermore, the association between a low ABI and end-stage kidney disease (ESKD) was determined. Methods This single-center, retrospective, cohort study included 529 patients with advanced-stage diabetic kidney disease who were stratified into groups according to the ABI: high (>1.3), normal (0.9–1.3), and low (<0.9). The Kaplan-Meier method and Cox proportional analysis were used to examine the association between the ABI and ESKD. Results A total of 42.5% of patients with a low ABI progressed to ESKD. A low ABI was associated with a greater risk of ESKD (hazard ratio (HR): 1.073). After adjusting for traditional chronic kidney disease risk factors, a low ABI remained associated with a greater risk of ESKD (HR: 1.758; 95% confidence interval: 1.243–2.487; p = 0.001). Conclusions These results indicate that patients with a low ABI should be monitored carefully. Furthermore, preventive therapy should be considered to improve the long-term kidney survival of patients with residual kidney function.