Higher Urinary Albumin-creatinine Ratio Research Articles

Association between Kidney Stones and CKD: A Bidirectional Mendelian Randomization Study.

Kidney stones and CKD are common disorders with a substantial interaction. Although observational studies have suggested a potential for enhanced CKD risk after prior kidney stones, the exact relationship remains ambiguous. Shared comorbidities between two diseases were identified using unbiased screening. Genome-wide association study summary statistics were obtained from the UK Biobank (UKBB), FinnGen, and CKDGen, followed by genetic association analyses across various traits. Bidirectional Mendelian randomization (MR) analyses were performed to define causal links, complemented by multivariable MR that included the shared comorbidities including hypertension, diabetes, and obesity. Observational analyses were undertaken using cohorts from the Mayo Clinic and a UKBB subset. Despite identifying a total of 123 conditions as shared comorbidities, there was no significant genetic correlation between kidney stones and CKD. Unadjusted MR analysis revealed no significant association between kidney stones and CKD risk (UKBB [exposure]/FinnGen [outcome]: OR=0.97, 95% CI: 0.88∼1.06; FinnGen/UKBB: OR=1.17, 95% CI:0.98∼1.39). Kidney stones did significantly associate with a higher urinary albumin-creatinine ratio (UACR) (β=0.014, 95% CI: 0.002∼0.025), but this association disappeared in the multivariable MR model (β=0.009, 95% CI: -0.003∼0.020). Furthermore, in a cross-sectional analysis limited to the UKBB cohort, a robust regression model did not detect an independent association between kidney stones and UACR (β=0.16, 95% CI: -0.04∼0.35) or eGFR (β=0.10, 95% CI: -0.07∼0.28). Conversely, CKD associated with a diminished risk of kidney stones in multivariable MR models (UKBB/FinnGen: OR=0.77, 95% CI: 0.69∼0.87; FinnGen/UKBB: OR=0.73, 95% CI: 0.66∼0.81). Furthermore, in the Mayo Clinic cohort with available urinary biochemistries, lower eGFR was associated with lower urinary calcium excretion and urinary calcium oxalate/phosphate supersaturation. In this study, kidney stones were not independently associated with CKD. Conversely, CKD was associated with a lower risk of calcium kidney stones likely via changes in key urinary traits, including lower calcium excretion.

#2293 Cardiac autonomic neuropathy: an independent risk factor for renal decline in diabetic kidney disease

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the UK and worldwide. Due to its unpredictability and incurable nature, novel risk factors associated with incidence and progression of DKD need to be identified. One such factor is cardiac autonomic neuropathy (CAN). Many studies over last 30 years had demonstrated a significant relationship between CAN and incidence and progression of DKD using estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) as end points. However, no prospective studies have looked into relationship between CAN diagnosed by gold standard cardiac autonomic reflex tests (CARTs) and DKD with different prognostic risks as per KDIGO classification. The aim of the study is to examine this relationship further. Method Data from 91 participants (type 1 and type 2 DM) with eGFR >30 ml/min/1.73 m2 who underwent assessment for CAN using CARTs as per O'Brien's and Ewing's criteria during baseline visits performed between 2007 and 2010 were collected. Additional participants (n = 113) were also recruited in 2021 as part of iBEAt study which is an EU-funded, multi-centre renal imaging study to identify novel biomarkers for DKD. Data analysis for 204 participants in total was performed for this study. CAN was defined as 2 or more abnormal CARTs out of 5 (Table 1). The level of prognostic risk was calculated based on eGFR (G1-G5) and UACR (A1-A3), following KDIGO risk table from 2012 CKD guidelines. eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation and UACR was assessed by early morning urine sample. Participants were categorised as follow: low risk, moderate risk and high risk. Due to limited numbers of participants with G3 in eGFR, we have combined ‘high risk’ and ‘very high risk’ into one group. CAN was divided into 2 groups—with and without CAN. Differences in proportions were examined using chi-square test. The association between baseline CAN and risk of renal decline was assessed using multinominal logistic regression adjusted for baseline age, HbA1c, ACEi/ARBs use, retinopathy status, total cholesterol and triglyceride. If significant differences were found, individual groups were compared by Bonferroni post hoc test. All analyses were performed in SPSS (version 29.0) and correlations were considered significant if p < 0.05. Results We analysed data of 204 participants (130 T1DM, 74 T2DM), 44.6% (n = 91) of them were women, mean (SD) age at baseline visit was 51 (15.7) years, eGFR 82.6 (13) ml/min/1.73 m2, UACR 5.2 (21.8) mg/mmol, duration of diabetes at baseline 19.7 (12.3) years and 36.8% had hypertension. Baseline eGFR and UACR were available for 198 and 193 participants respectively. Of these, 42.9% (85/198) had G1, 47.5 (94/198) had G2 and 9.6 (19/198) had G3. For UACR, 80.8% (156/193) had A1, 15.5% (30/193) had A2 and 3.6% (7/193) had A3. 53.4% (103/204) of participants had CAN and 46.6% (101/204) had no CAN. A higher proportion of participants was in low prognostic risk category 77.8% (154/198), followed by 13.1% (26/198) with moderate risk and 9.8% (18/198) with high risk for CKD progression. The risk of DKD progression was significantly associated with presence of CAN in multinominal logistic regression analysis (p = 0.020). The presence of CAN was closely related to low risk (95% CI: 1.44 to 22.04, p = 0.013) and moderately increased risk (95% CI: 1.03 to 24.7, p = 0.04). The participants with moderate and high risk had lower eGFR (p < 0.001) and higher UACR with increased risk (p < 0.001) (Table 2). This finding was independent of baseline age, HbA1C, retinopathy, ACEI/ARB use, type of diabetes, cholesterol and triglyceride levels at baseline as measured by logistic regression. Conclusion To our knowledge, this is one of the first studies to examine the relationship between presence of CAN in three stages of prognostic risk in DKD. We demonstrated that presence of CAN was an independent risk factor for decline in renal function in DKD. Further large prospective studies are required to confirm the findings of this study and examine the underlying mechanisms how CAN leads to greater risk of DKD.

Congestion as a crucial factor determining albuminuria in patients with cardiorenal disease.

Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. The median age was 74years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300mg/g and 64 (7.4%) had a UACR >300mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2=57.6%), systolic blood pressure (R2=21.1%), previous furosemide equivalent dose (FED; R2=7.5%), antigen carbohydrate 125 (CA125; R2=6.1%), diabetes mellitus (R2=5.6%) and oedema (R2=1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.

Dapagliflozin treatment of patients with chronic kidney disease without diabetes across different albuminuria levels (OPTIMISE-CKD).

We compared kidney and cardiorenal protection in patients without type 2 diabetes across urine albumin-creatinine ratio (UACR) levels after initiation on dapagliflozin for the treatment of chronic kidney disease (CKD). OPTIMISE-CKD is an observational study describing dapagliflozin treatment for CKD. Adult patients with CKD without type 2 diabetes were included in the primary analysis. Baseline UACR was grouped as normal/mildly elevated (0-29mg/g), low (30-200mg/g) and high (>200mg/g). Outcomes were estimated glomerular filtration rate (eGFR) trajectories/slopes, cardiorenal complications and all-cause mortality. In total, 1480 patients had low (n=796) and high (n=684) UACR. The two groups were similar at baseline, aged 75 and 74years, and 42% and 39% female, respectively. After dapagliflozin initiation, an acute eGFR dip of 3mL/min/1.73m2 was observed, followed by a flat development in both groups. The eGFR slope [95% confidence interval (CI)] for patients with low UACR was 0.79mL/min/1.73m2 per year (-0.59, 2.56), and similar to patients with high UACR [0.40mL/min/1.73m2 per year (-0.46, 1.38)]. Risks of cardiorenal complications and all-cause mortality were similar, with adjusted hazard ratios of 0.89 (95% CI 0.66, 1.19) and 1.10 (95% CI 0.63, 1.92), respectively. Analogous results were found in those with normal/mildly elevated UACR. Dapagliflozin in patients without type 2 diabetes for the treatment of CKD demonstrated similar kidney protection, cardiorenal and all-cause mortality risk across UACR levels. This suggests that the efficacy of dapagliflozin found in clinical trials expands to real-world patients with CKD, regardless of albuminuria levels.

Ayurvedic management for hypertension with micro albuminuria: a case report

Hypertension is a non-communicable disease in which the pressure of blood pushing against the arterial walls becomes high. In chronic stage it leads to severe systemic diseases, which affects heart, kidney, lung etc. The main causative factors are unhealthy food and lifestyle, stress, smoking, Alcohol, obesity and hereditary. Microalbuminuria in Hypertension is an early sign of kidney damage and is considered as a predictor for the end stage of renal disease and cardiovascular disease. So, it is of great importance to manage microalbuminuria or high urine albumin creatinine ratio and progression of kidney disease in hypertensive patient. In Ayurveda references no proper description of hypertension is available. By viewing the pathogenesis and physiology, it is formed by the involvement of Tridoshas, Srotorodha, and Dhatudushti. The present case is a 60-year male patient was diagnosed uncontrolled hypertension with microalbuminuria, admitted for 1month, presented with complaints such as frothy urine, over tiredness, uncontrolled anger and increased blood pressure during evening time, not controlled by hypertensive modern medicines. His urine albumin-creatinine ratio was 106.98 mg/dl of creatinine, microalbumin in urine 138 mg/dl and uric acid was 11.5 mg/dl. He was advised the internal Ayurveda medicines, diet restriction and yogic breathing exercise. Within one month of treatment the urine albumin creatinine ratio and uric acid was reduced and became normal. His blood pressure also became controlled and recovered all symptoms. Ayurvedic treatment module appears to be safe and efficacious with early recovery and better outcomes in this case.

Prevalence and Associated Factors of Atherosclerotic Plaque and Stenosis in Renal Arteries: A Community-Based Study.

The epidemiology of renal artery atherosclerosis in community populations is poorly documented. This study aimed to determine the prevalence of renal artery plaque (RAP) and atherosclerotic renal artery stenosis (ARAS), and the association of plaque and stenosis with vascular risk factors and kidney disease markers among community-dwelling adults. We conducted a cross-sectional analysis of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study. RAP and ARAS were evaluated by thoracoabdominal computed tomography angiography. A total of 3045 adults aged 50-75years were included. The prevalence of RAP and ARAS was 28.7% and 4.8%, respectively. The prevalence of RAP and ARAS was 41.3% and 7.7% in individuals aged ≥60years, 42.9% and 8.7% in hypertensives, and 45.4% and 8.5% in individuals with chronic kidney disease. Older age, hypertension, higher total cholesterol level, and lower high-density lipoprotein cholesterol level were independently associated with RAP and ARAS. A higher urinary albumin-creatinine ratio was independently associated with RAP, whereas a reduced estimated glomerular filtration rate was independently associated with ARAS. In conclusion, there was a non-negligible prevalence of RAP and ARAS among the older, community population in China.

Prevalence of stunting and determinants of growth failure in children with Type 1 diabetes

Objectives: India is home to the highest number of prevalent cases of Type-1 diabetes (T1D) in children. There is scarcity of data on the growth failure of children with diabetes, especially those having complications and comorbidities, thus, we conducted this study with the objective to determine the prevalence and predictors of stunting in children with T1D. Methods: This cross-sectional study included 350 children and adolescents aged 1–18 years with T1D. Demographic data, anthropometry, diet, sexual maturity rating, and biochemical measurements were performed using standard protocols. Short stature was defined as height for age Z-score <−2. p<0.05 was considered statistically significant. Results: We report a 15.7% prevalence of stunting in our cohort of children with T1D. Stunted children had higher cholesterol, lower hemoglobin, lower mid-parental height Z-scores, and higher urinary albumin creatinine ratio. Binary logistic regression revealed that pre-existing comorbidities, compromised renal function, longer disease duration, and short mid-parental height were significant predictors of stunting. Conclusion: A little under one-sixth of children with T1D had short stature. Monitoring growth in these patients, especially in subjects with short parents, prolonged duration of diabetes, existing comorbidities, and deteriorating renal function are critical.

Frailty and chronic kidney disease: associations and implications.

Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

Depression and incident cardiovascular disease among patients with chronic kidney disease

BackgroundDepression is associated with an increased risk of cardiovascular disease (CVD) and is prevalent among patients with chronic kidney disease (CKD). We aimed to identify the association of depression with incident CVD. MethodsWe studied patients with CKD stages 2–4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) and excluded participants with preexisting CVD. The Cox proportional hazard model was used to examine the association between baseline depression [Beck's Depression Inventory (BDI) score ≥11] and incidence of CVD (cerebrovascular accident, myocardial infarction, heart failure, or peripheral artery disease). Models were adjusted for age, sex, race, estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR), systolic and diastolic blood pressure, and 10-year estimated CVD risk. ResultsAmong 2585 CRIC study participants, 640 (25%) patients had depression at study baseline. Compared to patients without depression, patients with depression were more likely to be women (56% vs. 46%), non-White (68% vs. 53%), with household income <$20,000 (53% vs. 26%), without a high school degree (31% vs. 15%), uninsured (13% vs. 7%), with lower eGFR (42 vs. 46 ml/min/1.73 m (Palmer et al., 2013 Jul)22), and with higher UACR (90 vs. 33 mg/g). In multivariate analyses, depression was associated with a 29% increased risk of developing CVD (adjusted hazard ratio 1.29, 95% confidence interval 1.03–1.62, p = 0.03). BDI (as a continuous variable) was associated with CVD (adjusted hazard ratio 1.017, 95% confidence interval 1.004–1.030, p = 0.012). ConclusionsAmong patients with CKD stages 2–4 enrolled in CRIC without preexisting CVD, depression was associated with a 29% increased risk of incident CVD.

Association between urinary C-megalin levels and progressive kidney dysfunction: a cohort study based on the diabetes distress and care registry at Tenri (DDCRT 24).

The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes. We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30mL/min/1.73 m2. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline. Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent. High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs.

#4666 ASSOCIATION BETWEEN URINARY ALBUMIN CREATININE RATIO AND CARDIOVASCULAR DISEASE

Abstract Background and Aims The association between microalbuminuria and cardiovascular disease (CVD) is accumulating in various patient populations. However, when stratified by sex, the relationship between microalbuminuria and CVD remains unclear. Method We obtained data from the 2011–2014 and 2019–2020 Korea National Health and Nutrition Examination Survey (KNHANES). Microalbuminuria was measured based on spot urine albumin-creatinine ratio (UACR). The Framingham risk score (FRS) model was implemented to evaluate the CVD risk. Linear and logistic regression models were used to identify the associations of microalbuminuria status with cardiometabolic predictors and CVD status determined by the FRS score. Results Among 19,340 representative Korean participants, the (UACR) in Korean women and men with history of CVD was higher than in those without history of CVD. Among patients without history of CVD, multivariate regression analysis showed that a high UACR was related to older age, lower high-density lipoprotein cholesterol level, higher total cholesterol level, higher systolic blood pressure, higher prevalence of current smoking, higher prevalence of diabetes, and higher anti-hypertensive medication use in both women and men. The UACR showed a positive linear correlation with the Framingham risk score in both women and men. Conclusion The presence of microalbuminuria was significantly associated with the cardiometabolic risk factors and the increased risk of CVD evaluated by FRS model in both women and men in a nationally representative sample of Korea.

Association between urinary albumin creatinine ratio and cardiovascular disease.

The association between microalbuminuria and cardiovascular disease (CVD) is accumulating in various patient populations. However, when stratified by sex, the relationship between microalbuminuria and CVD remains unclear. We obtained data from the 2011-2014 and 2019-2020 Korea National Health and Nutrition Examination Survey (KNHANES). Microalbuminuria was measured based on spot urine albumin-creatinine ratio (UACR). The Framingham risk score (FRS) model was implemented to evaluate the CVD risk. Linear and logistic regression models were used to identify the associations of microalbuminuria status with cardiometabolic predictors and CVD status determined by the FRS score. Among 19,340 representative Korean participants, the (UACR) in Korean women and men with history of CVD was higher than in those without history of CVD. Among patients without history of CVD, multivariate regression analysis showed that a high UACR was related to older age, lower high-density lipoprotein cholesterol level, higher total cholesterol level, higher systolic blood pressure, higher prevalence of current smoking, higher prevalence of diabetes, and higher anti-hypertensive medication use in both women and men. The UACR showed a positive linear correlation with the Framingham risk score in both women and men. The presence of microalbuminuria was significantly associated with the cardiometabolic risk factors and the increased risk of CVD evaluated by FRS model in both women and men in a nationally representative sample of Korea.

Association of the gut microbiome with kidney function and damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

ABSTRACT Background The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking. Methods In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n = 2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n = 700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n = 3,635). Results Higher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6 y. Conclusions Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.

Abstract P671: Association Between Renal Function and Silent Cerebrovascular Disease in Japanese Men

Background and Aim: To determine whether a mild decrease in renal function is an indicator of early detection of silent cerebrovascular disease, we conducted a cross-sectional study in 735 community-dwelling Japanese men. Methods: The prevalence of silent cerebrovascular disease was defined as intracranial artery stenosis (ICAS), lacunar infarctions (LIs), cerebral microbleeds (CMBs), periventricular hyperintensities (PVHs: grade ≥2), and deep and subcortical white matter hyperintensities (DSWMHs: grade ≥3), using brain magnetic resonance imaging independently evaluated by two specialists. In addition, a total cerebral small vessel disease (TCSVD) score was used, summing LIs, CMBs, PVHs, and DSWMHs. We calculated the estimated glomerular filtration rate calculated with creatinine or cystatin C (eGFRcr or eGFRcys) using the CKD-EPI formula for Japanese and the equations by the Japanese Society of Nephrology, respectively. The urinary albumin/creatinine ratio (UACR) was dichotomized at 30 mg/gCre, and the low group was further divided into tertiles. eGFRcr and eGFRcys were also dichotomized at 60 ml/min/1.73 m 2 , and the high group was further divided into tertiles. The odds ratios (ORs) and 95% confidence intervals (95%CIs) for the prevalence of silent cerebrovascular disease by renal function were calculated using binary or ordinal multivariable adjusted logistic regression models. Results: The prevalence of ICAS, LIs, CMBs, and white matter lesions (WMLs: the prevalence of PVHs or DSWMHs) was 30% (220/735), 21% (155/735), 14% (102/735), and 32% (237/735), respectively. The multivariable adjusted ORs (95%CI) of the prevalence of CMBs and TCSVD score were higher in the high UACR (&gt;30mg/gCre) group (3.83 (1.90-7.73) and 1.75 (1.12-2.74), respectively) than in the low UACR (≤4.7 mg/gCre) group; the linear trend was significant (p &lt;0.001 and p=0.025, respectively). The multivariable adjusted ORs (95%CI) of TCSVD score was higher in the decreased (&lt;60 ml/min/1.73 m 2 ) eGFRcr or eGFRcys group (1.70 (0.998-2.91) and 1.85 (1.10-3.10), respectively) than in the high eGFRcr group (≥75.9 ml/min/1.73 m 2 ) or the high eGFRcys group (≥83.3 ml/min/1.73 m 2 ); the linear trend was shown (p=0.036 and p=0.072, respectively). The multivariable adjusted ORs (95%CI) of the prevalence of WML was higher in the decreased (&lt;60 ml/min/1.73 m 2 ) and mildly decreased (60-69.9 ml/min/1.73 m 2 ) eGFRcr groups (2.41 (1.31-4.43) and 1.78 (1.05-3.02), respectively) than in the high eGFRcr group (≥75.9 ml/min/1.73 m 2 ); the linear trend was significant (p&lt;0.001). eGFRcys and the prevalence of WML also showed similar associations. Conclusion: Decreased renal function was associated with the presence of silent cerebrovascular disease. Our results suggest that even a mild decline in renal function may be an indicator of early detection of silent cerebrovascular disease.

Abstract 24: Association of the Gut Microbiome With Kidney Function and Damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Background: The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities such as cardiovascular disease, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking. Methods: In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n=2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features, adjusting for covariates, and also stratified by diabetes status. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n=700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n=3,635) ( Figure 1a ). Results: Higher eGFR was significantly associated with overall gut microbiome composition, greater abundance of species from Prevotella , Faecalibacterium , Roseburia , and Eubacterium , and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide) ( Figure 1b ). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in the UAC ratio ( Figure 1c ). Conclusions: Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.

Relations of postural change in blood pressure with hypertension-mediated organ damage in middle-aged adults of the Framingham heart study: A cross-sectional study.

Dysregulation of compensatory mechanisms to regulate blood pressure (BP) upon postural change is a phenotype of BP variability and an emerging risk factor for cardiovascular outcomes. We assessed postural change in BP (starting 2 min after standing from a supine position), carotid-femoral pulse wave velocity (cfPWV), and markers of hypertension-mediated organ damage (HMOD) in the heart, kidney, and brain in Framingham Third Generation, Omni-2, and New Offspring Spouse Cohort participants. We related vascular measures (postural change in BP measures and cfPWV) with HMOD in 3,495 participants (mean age 47 years, 53% women) using multivariable logistic and linear regression models. In multivariable-adjusted models, we did not observe significant associations of vascular measures with presence of left ventricular hypertrophy, albuminuria, covert brain infarcts, or white matter hyperintensities (Bonferroni-adjusted P-values > 0.05/20 > 0.0025). In multivariable models, greater cfPWV (est. β = 0.11 ± 0.03; P < 0.001), but not postural change in BP measures (Bonferroni-adjusted P-values > 0.05/20 > 0.0025), was associated with higher white matter free water using brain magnetic resonance imaging. In multivariable models, greater postural change in pulse pressure was associated with higher urinary albumin-creatinine ratio (est. β = 0.07 ± 0.02; P < 0.001). No other postural change in BP measure was associated with urinary albumin-creatinine ratio (Bonferroni-adjusted P-values > 0.05/20 > 0.0025). In sex-specific analyses, higher cfPWV was associated with higher urinary albumin-creatinine ratio in men (est. β: 0.11 ± 0.04; P = 0.002) but not in women (est. β: 0.03 ± 0.03; P = 0.44). We also observed marginal to strong effect modification by above vs. at/below median postural change in BP for the association of cfPWV with urinary albumin-creatinine ratio (Bonferroni-adjusted interaction P < 0.001-0.01). Vascular measures were not related to left ventricular mass index or fractional anisotropy (Bonferroni-adjusted P-values > 0.05/20 > 0.0025). Baroreflex dysfunction is associated with greater subclinical kidney damage. Additionally, relations of higher aortic stiffness with greater kidney damage may be modified by associated baroreflex dysregulation.

Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria

BackgroundPeople with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. ObjectivesThe aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. MethodsCanagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m2) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. ResultsA total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m2, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). ConclusionsRisk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791)

Effects of dapagliflozin on cardiovascular and kidney events by baseline eGFR and UACR in patients with type 2 diabetes mellitus: a patient-level pooled analysis of DECLARE-TIMI 58 and DAPA-CKD trials

Abstract Background The sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death (CVD) and the risk of kidney events in patients type 2 diabetes mellitus (T2DM) and high cardiovascular risk or chronic kidney disease in the DECLARE-TIMI 58 and DAPA-CKD trials. These events are more common at lower levels of kidney function. Combining data from the two trials creates an opportunity to examine the effect of dapagliflozin across the spectrum of baseline kidney function. Purpose To determine the effects of dapagliflozin on HHF/CVD and kidney endpoints across a broad range of kidney function in the combined dataset. Methods We conducted a post hoc analysis of pooled patient-level data from DECLARE and DAPA-CKD. The effects of dapagliflozin compared with placebo on HHF/CVD and kidney endpoints (defined as sustained eGFR decrease ≥40%, end-stage kidney disease, or renal death) were assessed in the combined cohorts and in subgroups of baseline eGFR (&amp;lt;45, 45-&amp;lt;60, 60-&amp;lt;90, ≥90 mL/min/1.73 m2) and urinary albumin:creatinine ratio (UACR) (&amp;lt;30, 30-&amp;lt;300, 300-&amp;lt;1000, ≥1000 mg/g). Results A total of 19,748 patients with T2DM were included. Median (IQR) follow up time was 4.1 (3.7–4.4) years. Median eGFR was 85 (65–95) mL/min/1.73 m2 and UACR 18.2 (7–135) mg/g. Overall, dapagliflozin reduced the risk of HHF/CVD by 18% (HR 0.82, 95% CI 0.73–0.92, p&amp;lt;0.001) and kidney endpoints by 40% (HR 0.60, 95% CI 0.52–0.69, p&amp;lt;0.001). Overall rates of HHF/CVD and kidney endpoints were higher with lower eGFR (p&amp;lt;0.001) and with higher UACR (p&amp;lt;0.001). There were consistent relative risk reductions in HHF/CVD and kidney events with dapagliflozin across eGFR (p-interaction 0.25 and 0.32, respectively, Figure 1) and UACR (p-interaction 0.29 and 0.83, respectively, Figure 2) subgroups. The absolute rate difference (ARD) with dapagliflozin for CVD/HHF ranged from 0.1 events per 1000 patient years in patients in normal categories of eGFR and UACR to 1.0–1.7 events in patients in the most abnormal categories. Likewise, the ARD for kidney events ranged from 0.2 events per 1000 patient years in the normal eGFR and UACR groups to 2.5–4.3 events in patients in the most abnormal categories. Conclusion In this pooled analysis of pts with T2DM, there was higher risk of HHF/CVD and kidney events with lower eGFR and higher UACR. Dapagliflozin consistently reduced these events regardless of baseline eGFR and UACR, with large absolute risk reductions in patients with lower eGFR and higher UACR. Funding Acknowledgement Type of funding sources: None.

Healthcare resource utilisation and related costs of patients with CKD from the UK: a report from the DISCOVER CKD retrospective cohort.

Chronic kidney disease (CKD) is widely reported to decrease quality of life, increase morbidity and mortality and cause increased healthcare resource utilisation (HCRU) as the disease progresses. However, there is a relative paucity of accurate and recent estimates of HCRU in this patient population. Our aim was to address this evidence gap by reporting HCRU and related costs in patients with CKD from the UK primary and secondary care settings. HCRU and cost estimates of CKD were derived for UK patients included in the DISCOVER CKD cohort study using clinical records from the Clinical Practice Research Datalink linked to external databases. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using the urinary albumin:creatinine ratio (UACR) and estimated glomerular filtration rate. Hospitalisation rates more than tripled between low (A1) and high (A3) UACR categories and the mean annual per-patient costs ranged from £4966 (A1) to £9196 (A3) and from £4997 (G2) to £7595 (G5), demonstrating that a large healthcare burden can be attributed to a relatively small number of patients with later stage CKD, including those with kidney failure and/or albuminuria. HCRU and costs associated with CKD impose a substantial burden on the healthcare system, particularly in the more advanced stages of CKD. New interventions that can delay the progression of CKD to kidney failure may not only prolong the patient's life, but would also provide significant resource and cost savings to healthcare providers.

Oxidative stress contributes to reductions in microvascular endothelial- and nitric oxide-dependent dilation in women with a history of gestational diabetes.

Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease (CVD) and ∼7 times as likely to develop type 2 diabetes as their age-matched counterparts. However, the mechanism(s) mediating these associations remain unclear. We hypothesized that endothelium- and (nitric oxide) NO-dependent dilation would be attenuated through oxidant stress mechanisms in the microvasculature of women with a history of GDM compared with control women with a history of uncomplicated pregnancy (HC). Ten HC (35 ± 4 yr) and 10 GDM (34 ± 4 yr) underwent a standard local heating protocol (42°C; 0.1°C·s-1). Two intradermal microdialysis fibers were placed in the ventral forearm for local delivery of lactated Ringer's (control) or 5 mM l-ascorbate. After full expression of the local heating response, 15 mM NG-nitro-l-arginine methyl ester (NO synthase inhibition) was perfused. Red cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC = flux/MAP) was standardized to maximum (% CVCmax; 28 mM SNP + 43°C). Urine albumin:creatinine ratio (ACR) was measured. GDM had attenuated endothelium-dependent (GDM: 67 ± 7 vs. HC: 90 ± 4% CVCmax; P < 0.001) and NO-dependent (GDM: 54 ± 7 vs. HC: 71 ± 3% CVCmax; P = 0.001) dilation at the control site and tended to have higher urine ACR (P = 0.06). Both endothelium-dependent (R2 = 0.53, P = 0.02) and NO-dependent (R2 = 0.56, P = 0.01) dilation were related to urine ACR in GDM. l-ascorbate perfusion improved endothelium-dependent (82 ± 5% CVCmax; P = 0.03 vs. control) and NO-dependent (68 ± 5% CVCmax; P = 0.02 vs. control) dilation in GDM but had no effect in HC (P > 0.05). Otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and this dysfunction is mediated, in part, by oxidative stress.NEW & NOTEWORTHY Women who have gestational diabetes during pregnancy are at greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. However, the mechanisms mediating this increased risk are unclear. Herein, we demonstrate that microvascular dysfunction, mediated by increase in oxidative stress, persists after pregnancy in women who had gestational diabetes, despite the remission of glucose tolerance.