Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation

Aims

Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF.

Methods and results

In this pre-defined secondary analysis of EMPEROR-Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66–0.93] vs. 0.78 [0.64–0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57–0.94] vs. 0.72 [0.54–0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m²/year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF.

Conclusions

In patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.     

Impact of baseline kidney function on the effects of sodium-glucose co-transporter-2 inhibitors on kidney and heart failure outcomes: A systematic review and meta-analysis of randomized controlled trials

Aim

To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function.

Methods

We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality.

Results

Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is’ renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m² or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m² (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m² (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m² or higher (HR 0.87, 95% CI: 0.56-1.34).

Conclusions

SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.     

Burden and Outcomes of Heart Failure Hospitalizations in Adults With Chronic Kidney Disease

BackgroundData on rates of heart failure (HF) hospitalizations, recurrent hospitalizations, and outcomes related to HF hospitalizations in chronic kidney disease (CKD) are limited.ObjectivesThis study examined rates of HF hospitalizations and re-hospitalizations within a large CKD population and evaluated the burden of HF hospitalizations with the risk of subsequent CKD progression and death.MethodsThe prospective CRIC (Chronic Renal Insufficiency Cohort) study measured the estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) at baseline. The crude rates and rate ratios of HF hospitalizations and 30-day HF re-hospitalizations were calculated using Poisson regression models. Cox regression was used to assess the association of the frequency of HF hospitalizations within the first 2 years of follow-up with risk of subsequent CKD progression and death.ResultsAmong 3,791 participants, the crude rate of HF admissions was 5.8 per 100 person-years (with higher rates of HF with preserved ejection fraction vs. HF with reduced ejection fraction). The adjusted rate of HF was higher with a lower eGFR (vs. eGFR >45 ml/min/1.73 m²); the rate ratios were 1.7 and 2.2 for eGFR 30 to 44 and <30 ml/min/1.73 m² (vs. >45 ml/min/1.73 m²), respectively. Similarly, the adjusted rates of HF hospitalization were significantly higher in those with higher urine ACR (vs. urine ACR <30 mg/g); the rate ratios were 1.9 and 2.6 for urine ACR 30 to 299 and ≥300 mg/g, respectively. Overall, 20.6% of participants had a subsequent HF re-admission within 30 days. HF hospitalization within 2 years of study entry was associated with greater adjusted risks for CKD progression (1 hospitalization: hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.40 to 2.67; 2+ hospitalizations: HR: 2.14; 95% CI: 1.30 to 3.54) and all-cause death (1 hospitalization: HR: 2.20; 95% CI: 1.71 to 2.84; 2+ hospitalizations: HR: 3.06; 95% CI: 2.23 to 4.18).ConclusionsWithin a large U.S. CKD population, the rates of HF hospitalizations and re-hospitalization were high, with even higher rates across categories of lower eGFR and higher urine ACR. Patients with CKD hospitalized with HF had greater risks of CKD progression and death. HF prevention and treatment should be a public health priority to improve CKD outcomes.     

Development rate of chronic kidney disease in hepatitis C virus patients with advanced fibrosis after interferon therapy

Aim: The aim of this retrospective cohort study is to assess the development incidence and predictive factors for chronic kidney disease (CKD) after the termination of interferon therapy in hepatitis C virus (HCV) positive Japanese patients with liver cirrhosis. Methods: A total of 650 HCV positive, liver cirrhotic patients who were treated with interferon and showed an estimated glomerular filtration rate (eGFR) of ≥60 mL/min per 1.73 m² after the termination of interferon therapy were enrolled. CKD was defined as an eGFR of <60 mL/min per 1.73 m². End‐stage‐CKD was defined as an eGFR of <15 mL/min/1.73 m². The primary goal is the new development of CKD and end‐stage‐CKD. Results: Eighty‐five patients developed CKD, and six patients progressed to end‐stage‐CKD. The development rate of CKD was 5.2% at the 5th year, 14.5% at the 10th year and 30.6% at the 15th year. Multivariate Cox proportional hazards analysis showed that CKD occurred when patients had age increments of 10 years (hazard ratio: 2.32; 95% confidence interval [CI] 1.61–3.35; P < 0.001), eGFR decrements of 10 mL/min per 1.73 m² (hazard ratio: 1.66; 95% CI 1.27–2.16; P < 0.001), hypertension (hazard ratio: 2.00; 95% CI 1.13–3.53; P = 0.017), diabetes (hazard ratio: 1.79; 95% CI 1.02–3.14; P = 0.042), and non‐clearance of HCV (hazard ratio: 2.67; 95% CI 1.34–5.32; P = 0.005). The development rate of end‐stage‐CKD was 0.4% at the 5th year, 1.6% at the 10th year and 2.8% at the 15th year. Conclusions: The annual incidence for CKD among cirrhotic patients with HCV was determined to be about 1.0–1.5%. In addition, the annual incidence for end‐stage‐CKD is one order of magnitude lower than that of CKD.     

Metabolic syndrome and risk of progression of chronic kidney disease: a single-center cohort study in Japan

Metabolic syndrome (MetS) is a risk factor for the development of diabetes and cardiovascular disease, and recently was linked to incident chronic kidney disease (CKD). The purpose of this study is to examine whether MetS is associated with CKD progression in Japanese at a single center. Outcome variables were a decrease in estimated glomerular filtration rate (eGFR) of 50 % or 25 ml/min/1.73 m², end-stage renal disease (ESRD), death, or a composite outcome of all three. There were 213 subjects in the analysis, 40.4 % of whom met the criteria for MetS. The group of subjects with MetS had higher urinary albumin-to-creatinine (UACR) levels. Survival curves stratified by MetS status showed early separation of the curves and a significantly higher survival rate in the group without MetS (P = 0.0086). Comparisons with normoalbuminuria and microalbuminuria showed that macroalbuminuria was equally associated with predicted composite outcome (GFR, ESRD, or death) both in the presence and absence of MetS. Multivariate analyses for all covariates showed that eGFR (hazard ratio (HR) 8.286, 95 % confidence interval (CI) 2.360–28.044, P = 0.0012) and the UACR (HR 2.338, 95 % CI 1.442–3.861, P = 0.0005) at baseline were independently associated with the composite outcomes. The results show that MetS was associated with albuminuria in a cohort of Japanese CKD patients, and both MetS and albuminuria were independently associated with CKD progression.     

Clinical outcomes in patients with type 2 diabetes mellitus-related kidney disease: A Jordanian population cohort study

BackgroundDiabetic kidney disease (DKD) increases the risk of cardiovascular (CV) complications, kidney disease progression, and mortality. We aimed to determine the incidence and risk of these outcomes according to DKD phenotype among the Jordanian population.MethodsA total of 1172 type 2 diabetes mellitus patients with estimated glomerular filtration rates (eGFRs) of >30 ml/min/1.73 m² were followed-up from 2019 to 2022. At baseline, patients were classified according to the presence of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 ml/min/1.73 m²) into four phenotypes: non-DKD (reference category), albuminuric DKD without decreased eGFR, non-albuminuric DKD with decreased eGFR, and albuminuric DKD with decreased eGFR.ResultsMean follow-up was 2.9 ± 0.4 years. Overall, 147 patients (12.5 %) experienced CV events, while 61 (5.2 %) demonstrated kidney disease progression (eGFR: <30 ml/min/1.73 m²). The mortality rate was 4.0 %. Multivariable-adjusted risk for CV events and mortality was greatest for the albuminuric DKD with decreased eGFR group (hazard ratio [HR]: 1.45, 95 % confidence interval [CI]: 1.02–2.33 and HR: 6.36, 95 % CI: 2.98–13.59, respectively), with the risk increasing when adjusted for prior CV history (HR: 1.47, 95 % CI: 1.06–3.42 and HR: 6.70, 95 % CI: 2.70–16.60, respectively). Risk of a ≥40 % decline in eGFR was greatest for the albuminuric DKD with decreased eGFR group (HR: 3.45, 95 % CI: 1.74–6.85), followed by the albuminuric DKD without decreased eGFR group (HR: 1.6, 95 % CI: 1.06–2.75).ConclusionThus, patients with albuminuric DKD and decreased eGFR were at greater risk for poor CV, renal, and mortality outcomes compared to other phenotypes.     

Progression of Renal Impairment and Chronic Kidney Disease in Chronic Heart Failure: An Analysis From GISSI-HF

Background

Data on the natural change in renal function in patients with chronic heart failure (HF) are limited.

Hypertension and hyperglycemia and the combination thereof enhances the incidence of chronic kidney disease (CKD) in middle-aged and older males

Aim: Chronic kidney disease (CKD) may be an etiologic cause of aging, hypertension, diabetes mellitus (DM), and metabolic syndrome. However, the influence of these cardiovascular risk factors and their combination on the development of CKD remains controversial. This retrospective study evaluated the influence of cardiovascular risk factors and their combination on the incidence of CKD during a 6-year follow-up period in middle-aged and older males. Methods: The subjects were 303 males without a history of cardiovascular disease, stroke, renal dysfunction, or dialysis treatment. A biochemical analysis, blood pressure (BP) analysis, and anthropometry measurements were performed every year, and the classification of CKD was also assessed based on the estimated glomerular filtration rate (<60 ml/min/1.73 m²) and/or presence of proteinuria. Results: After 6 years, the incidence of CKD was noted in 32 subjects. According to a multivariable analysis, hypertension (hazard ratio [HR]: 3.95, 95% confidence of interval [CI]: 1.64–9.49, p = 0.002) and hyperglycemia (HR: 3.27, 95% CI: 1.42–7.56, p = 0.006) were significantly associated with the incidence of CKD. According to a Cox proportional hazards model, the HR for the incidence of CKD was significantly higher in the combination of high-normal BP/hypertension and impaired fasting glucose/DM group than in the combination of normotensive and normal glucose tolerance group (HR: 7.16, 95% CI: 2.43–17.25, p = 0.001). Conclusions: These results suggest that the hypertension and hyperglycemia and their combination may be associated with the incidence of CKD.     

Dipyridamole treatment is associated with improved renal outcome and patient survival in advanced chronic kidney disease

Dipyridamole has been shown to decrease proteinuria and improve renal function progression especially in early chronic kidney disease (CKD) patients with glomerulonephropathy. A combination therapy of dipyridamole with aspirin could prevent second strokes in the general population. Whether these effects of dipyridamole are also true in advanced CKD patients and whether dipyridamole could improve renal outcomes or patient survival is unknown. We retrospectively analyzed an observational cohort of 3074 participants with CKD stage 3–5 from southern Taiwan, of whom 871 (28.3%) had received dipyridamole treatment ≥50 mg/d for ≥3 months and more than half of the observation period. The mean age was 63.6 ± 13.4 years and the mean estimated glomerular filtration rate (eGFR) was 25.5 mL/min/1.73 m². After inverse probability of treatment weighted adjustment by propensity score, there were no differences between the dipyridamole-treated and untreated groups. Dipyridamole treatment was associated with decreased odds for rapid eGFR decline [odds ratio, 0.755; 95% confidence interval (CI), 0.595–0.958; p = 0.007] and progression of urine protein-to-creatinine ratio (odds ratio, 0.655; 95% CI, 0.517–0.832; p = 0.002). In survival analysis, the dipyridamole-treated group was also associated with a decreased risk for end-stage renal disease (hazard ratio, 0.847; 95% CI, 0.733–0.980; p = 0.011) and all-cause mortality (hazard ratio, 0.765; 95% CI, 0.606–0.971; p = 0.001) but not for cardiovascular events. Our findings demonstrate that dipyridamole treatment is significantly associated with better renal outcomes and patient survival in patients with CKD stage 3–5. Further investigations are warranted to confirm these independent positive effects.     

Estimated Glomerular Filtration Rate Variability in Patients With Heart Failure and Chronic Kidney Disease

BackgroundGreater variability in the estimated glomerular filtration rate (eGFR) is associated with higher mortality in patients with chronic kidney disease (CKD). Heart failure (HF) is common in CKD and may increase variability through changes in hemodynamic and volume regulation. We sought to determine if patients with vs without HF have higher kidney function variability in CKD, and to define the association with mortality.Methods and ResultsPatients undergoing coronary angiography from 2003 to 2013 with an eGFR of less than 60 mL/min/1.73 m² were evaluated from the Duke Databank for Cardiovascular Disease. Variability in the eGFR, measured as the coefficient of variation (CV) of residuals from the regression of eGFR vs time, was calculated spanning 3 months to 2 years after catheterization. Mortality was assessed 2 to 7 years after catheterization. Patients were grouped into 3 HF phenotypes: HF with reduced ejection fraction, HF with preserved ejection, and no HF. Regression was used to evaluate associations between HF phenotypes and variability in the eGFR and between variability in the eGFR and mortality rate with stratification by HF phenotype. Among 3767 participants, the median eGFR at baseline was 45 mL/min/1.73 m² (interquartile range 33-53 mL/min/1.73 m²), and longitudinal measures of eGFR over 21 months had within-patient residual variability (CV) of 14% (9%–20%). In adjusted analyses, variability in the eGFR was greater in those with HF with preserved ejection (n = 695, CV difference 0.98%, 95% confidence interval 0.14%–1.81%) or HF with reduced ejection fraction (n = 800, CV difference 2.51%, 95% confidence interval 1.66%–3.37%) relative to no HF (n = 2272). In 3068 participants eligible for mortality analysis, the presence of HF and greater variability in the eGFR were each associated independently with higher mortality, but there was no evidence of interaction between variability in the eGFR and any HF phenotype (all P for interaction ≥.49).ConclusionsVariability in the eGFR is greater in patients with HF and associated with mortality. Prediction algorithms and classification schemes should consider not only static, but also dynamic eGFR variability in HF and CKD prognostication.     

Glomerular Filtration Rate and Initiation of Dialysis

The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis at higher glomerular filtration rate (GFR) has increased over the past decade. Recent data suggest that it may be associated with increased mortality. The goal of this analysis was to compare survival outcomes in patients with early and late start dialysis. We performed a retrospective analysis of hemodialysis (HD) incident patients from 1 January 2010 to 30 September 2014. Patients were classified into two groups by estimated GFR at dialysis initiation (eGFR ≥10: early start and <10 mL/min per 1.73m²: late start). Logistic regression was used to evaluate factors associated with early and late dialysis start, and Kaplan–Meier graphs and Cox regression models in survival analysis. In this total incident population (N = 235), 42 patients had an early dialysis start. Compared with the group with an eGFR of <10 mL/min per 1.73 m² at dialysis start, a Cox model showed an incremental increase in mortality associated with earlier dialysis start (P = 0.027). Independent factors (P < 0.05) associated with mortality in the multivariable Cox model in early dialysis start were: hypertension (HR 9.32, CI: 1.34–17.87), diabetes (HR 1.8, CI: 0.4–13.2) and albumin <3.5 g/dL (HR 1.5, CI: 0.8–6.2). Older patients (HR 0.084, CI: 0.008–0.863) with low phosphorus levels (HR 0.02, CI: 0.0–0.527) also had statistically significant results, although they showed a reduced risk of mortality. Early dialysis initiation was associated with an increased mortality risk, arguing against aggressive early dialysis initiation based primarily on eGFR alone.     

Exercise reduces the risk of chronic kidney disease in individuals with nonalcoholic fatty liver disease: A nationwide cohort study

AimsRecent studies of individuals with nonalcoholic fatty liver disease (NAFLD) have indicated benefits of exercise in improving outcomes. We investigated whether exercise reduces the risk of chronic kidney disease (CKD) in individuals with NAFLD.MethodsA total of 7275 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) cohort, and 40,418 participants with NAFLD from the National Health Insurance Service (NHIS) cohort were included for the cross-sectional and longitudinal analyses, respectively. For the cross-sectional analysis, the primary outcome was prevalent CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m². For the longitudinal analysis, the primary outcome was incident CKD, defined as the occurrence of eGFR <60 mL/min/1.73m² or proteinuria (≥ trace) on two consecutive measurements during follow-up.ResultsIn the KNHANES cohort, prevalent CKD was observed in 229 (6.1%), 48 (2.6%), and 36 (2.1%) participants in the 0, 1-2, and ≥ 3 exercise sessions/week groups, respectively. The likelihood of prevalent CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted OR 0.49; 95% CI, 0.33-0.71; P < 0.001). During a median follow-up of 5.0 years in the NHIS cohort, incident CKD occurred in 1,047 (9.7/1,000 person-years), 188 (7.3/1,000 person-years), and 478 (7.4/1,000 person-years) participants in the 0, 1-2, and ≥ 3 sessions/week groups, respectively. The risk of incident CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted HR 0.85; 95% CI, 0.76-0.95; P = 0.004).ConclusionsExercise was significantly associated with a reduced risk of both prevalent and incident CKD in individuals with NAFLD.     

Kidney Dysfunction and the Risk of Developing Aortic Stenosis

Background

Chronic kidney disease (CKD) and aortic stenosis (AS) share many risk factors.

Uric acid, hypertension, and chronic kidney disease among Alaska Eskimos: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study

J Clin Hypertens (Greenwich).****;**:**–**. ©2011 Wiley Periodicals, Inc. It is unknown what role uric acid (UA) may play in the increasing rates of cardiovascular disease (CVD) among Alaska Eskimos. UA is associated with both hypertension (HTN) and chronic kidney disease (CKD). The authors analyzed 1078 Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) participants. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine measures using the Modification of Diet in Renal Disease equation. CKD was defined by an eGFR of <60 mL/min/1.73 m². The authors adjusted for age, sex, education, diabetes, hypertension (or eGFR), obesity, lipids, and smoking status; 7% (n=75) had prevalent CKD. eGFR decreased with increasing tertiles of serum UA (P<.001). UA was independently associated with prevalent CKD (adjusted odds ratio [OR] and 95% confidence interval [CI] of 2.04 (1.62–2.56), respectively). Twenty‐one percent (n=230) had prevalent HTN and UA was independently associated with prevalent HTN (adjusted OR, 1.2; 95% CI, 1.1–1.5). UA is independently associated with prevalent CKD and HTN in this population.     

No survival benefit from early‐start dialysis in a population‐based,inception cohort study of Swedish patients with chronic kidney disease

Abstract. Evans M., Tettamanti G., Nyrén O., Bellocco R., Fored C.M., Elinder C.‐G. (Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden; University of Milano‐Bicocca, Milan, Italy; Karolinska Institutet, Stockholm, Sweden) No survival benefit from early‐start dialysis in a population‐based, inception cohort study of Swedish patients with chronic kidney disease. J Intern Med 2010; 269 : 289–298. Objective. To investigate how the timing of dialysis initiation is associated with mortality. Design. Population‐based, prospective, observational cohort study. Setting. Clinical laboratories (n = 69) provided information on all patients in Sweden whose serum creatinine level for the first time and exceeded 3.4 mg dL^?1 (men) or 2.8 mg dL^?1 (women) between 20 May 1996 and 31 May 1998. Subjects. All patients (n = 901), aged 18–74 years, in whom the cause of serum creatinine elevation was chronic kidney disease, were included in the study; participants were interviewed and followed for 5–7 years. Main outcome measures. Information on date of death was obtained from a national Swedish population register. Early‐start dialysis [estimated glomerular filtration rate from serum creatinine (eGFR) ≥7.5 mL min^?1 per 1.73 m²] was compared to late start of dialysis (eGFR <7.5 mL min^?1 per 1.73 m²), and no dialysis. Relative risk [hazard ratio (HR)] of death was modelled with time‐dependent multivariate Cox proportional hazards regression. Results. Mean eGFR was 16.1 mL min^?1 per 1.73 m² at inclusion and 7.6 mL min^?1 per 1.73 m² at the start of dialysis. Among the 385 patients who started dialysis late, 36% died during follow‐up compared to 52% of 323 who started early. The adjusted HR for death was 0.84 [95% confidence interval (CI) 0.64, 1.10] among late versus early starters. The mortality among nondialysed patients increased significantly at eGFR below 7.5 mL min^?1 per 1.73 m² (HR 4.65; 95% CI 2.28, 9.49; compared to eGFR 7.5–10 mL min^?1 per 1.73 m²). After the start of dialysis, the mortality rate further increased. Compared to nondialysed patients with eGFR ≤15 mL min^?1 per 1.73 m², adjusted HR was 2.65 (95% CI 1.80, 3.89) for patients receiving dialysis. Conclusion. We found no survival benefit from early initiation of dialysis.     

Renal Function-Dependent Associations of Statins with Outcomes of Ischemic Stroke

Aim: Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function.Methods: We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke.Results: Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3–5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m². Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60–89 mL/min/1.73 m². Statin therapy in patients with an eGFR of 60–89 mL/min/1.73 m² may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57).Conclusions: In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.     

Association of Frailty based on self-reported physical function with directly measured kidney function and mortality

Background

Use of serum creatinine to estimate GFR may lead to underestimation of the association between self-reported frailty and kidney function. Our objectives were to evaluate the association of measured GFR (mGFR) with self-reported frailty among patients with CKD and to determine whether self-reported frailty was associated with death after adjusting for mGFR.

Methods

Participants in the Modification of Diet in Renal Disease study (1989–1993) had GFR measured using iothalamate clearance (mGFR), and GFR was estimated based on the CKD-EPI creatinine (eGFRcr) and cystatin C (eGFRcys) equations. We defined self-reported frailty as three or more of: exhaustion, poor physical function, low physical activity, and low body weight. Death was ascertained through 2007 using the National Death Index and the United States Renal Data System.

Results

Eight hundred twelve MDRD participants (97 %) had complete data on self-reported frailty (16 % prevalence, N?=?130) and mGFR (mean (SD) 33.1?±?11.7 ml/min/1.73 m²). Higher GFR was associated with lower odds of self-reported frailty based on mGFR, (OR 0.71, 95 % CI 0.60–0.86 per 10 ml/min/1.73 m²), eGFRcr (OR 0.80, 95 % CI 0.67–0.94 per 10 ml/min/1.73 m²), and eGFRcys (OR 0.75, 95 % CI 0.62–0.90 per 10 ml/min/1.73 m²). Median follow-up was 17 (IQR 11–18) years, with 371 deaths. Self-reported frailty was associated with a higher risk of death (HR 1.71, 95 % CI 1.26–2.30), which was attenuated to a similar degree when mGFR (HR 1.48, 95 % CI 1.08–2.00), eGFRcr (HR 1.57, 95 % CI 1.15–2.10), or eGFRcys (HR 1.51, 95 % CI 1.10–2.10) was included as an indicator of kidney function.

Conclusions

We found an inverse association between kidney function and self-reported frailty that was similar for mGFR, eGFR and eGFRcys. In this relatively healthy cohort of clinical trial participants with CKD, using serum creatinine to estimate GFR did not substantially alter the association of GFR with self-reported frailty or of self-reported frailty with death.

     

Impaired frontal executive function and predialytic chronic kidney disease

OBJECTIVES: To investigate the nature of frontal dysfunction associated with chronic kidney disease (CKD) in people without stroke or depressive disorders. DESIGN: Cross‐sectional. SETTING: Community based. PARTICIPANTS: Five hundred twenty‐nine community‐dwelling participants. MEASUREMENTS: Participants with CKD were classified into one of three diagnostic groups based on their estimated glomerular filtration rate (eGFR): normal (≥60.0 mL/min per 1.73 m²), mild CKD (45.0–59.9 mL/min per 1.73 m²), or moderate to severe CKD (<45.0 mL/min per 1.73 m²). Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery, lexical fluency, digit span test, and the 64‐card Wisconsin Card Sorting Test. RESULTS: Perseverative responses and perseverative errors were significantly more prevalent in the group with moderate to severe CKD than in those without CKD and those with mild CKD. The mean number of perseverative responses was 28.6±16.9 in participants with moderate to severe CKD, 19.0±11.4 in those with mild CKD, and 17.1±10.6 in those without CKD (P<.001, ANCOVA). The mean number of perseverative errors was 23.1±12.3 in participants with moderate to severe CKD, 16.2±8.3 in those with mild CKD, and 14.8±7.8 in those without CKD (P<.001, analysis of covariance). The odds ratios in the fully adjusted model for the presence of moderate to severe CKD for perseverative responses and perseverative errors were 4.82 (95% confidence interval (CI)=2.14–10.85, P<.001) and 5.01 (95% CI=2.22–11.28, P<.001), respectively. CONCLUSION: Frontal dysfunction, particularly perseverative errors and responses, was associated with moderate to severe CKD in the population studied.     

Prognostic implications of chronic kidney disease and anemia after percutaneous coronary intervention in acute myocardial infarction patients

Anemia is a common complication of chronic kidney disease (CKD), and a few studies suggest that both CKD and anemia have a marked impact on the prognosis of patients with cardiovascular disease. We retrospectively analyzed the prevalence of CKD and anemia in 312 patients with acute myocardial infarction (AMI). The patients were divided into four groups according to the presence of CKD and anemia. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73 m², and anemia was defined according to the World Health Organization definition. Of 312 AMI patients, 166 (53.2%) had CKD and 87 (27.8%) had anemia. A powerful relationship was observed between both CKD and anemia and major adverse cardiac and cerebrovascular events (MACCE) or death by any cause. After adjustment for comorbidities, the hazard ratio (HR) for MACCE was significantly higher in the anemia-only group (HR 5.42, 95% confidence interval (CI) 1.38–21.27, P = 0.015), the CKD-only group (HR 6.4, 95% CI 2.09–19.58, P = 0.001), and the CKD and anemia group (HR 11.61, 95% CI 3.65–36.89, P < 0.001). With respect to death by any cause, the HR was significantly higher in the CKD-only group (HR 2.68, 95% CI 1.02–7.02, P = 0.045) and the CKD and anemia group (HR 4.40, 95% CI 1.56–12.43, P = 0.005). One-half of the patients with AMI had CKD as well. Furthermore, when anemia coexisted with CKD, these conditions had a multiplicative amplification effect on the risk of MACCE and death by any cause in patients with AMI.     

Noninvasive central pulse pressure is an independent determinant of renal function

The purpose of this study was to investigate the prognostic properties of different BP measurements for renal function decrement and early chronic kidney disease (CKD) in community‐dwelling populations with normal renal function at baseline. A total of 1426 participants were included and followed for a median of 4.8 years (interquartile range, 4.5‐5.2), and central hemodynamic profile and estimated glomerular filtration rate (eGFR) were evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of greater than 3 mL/min per 1.73 m² per year; the other was the new incidence of CKD. At the end of follow‐up, mean eGFR decreased from 93.39 ± 13.46 mL/min per 1.73 m² to 85.72 ± 14.81 mL/min per 1.73 m², and the incidence of rapid eGFR decline and CKD were 20.7% and 5.6%, respectively. In multivariate linear regression analysis, central pulse pressure (PP), age, fasting blood glucose, and concentration of homocysteine were independent determinants of the change in renal function. Not only in the prediction of rapid eGFR decline but also in the incident of CKD, baseline central PP was the only BP component that consistently independently associated with both outcomes after adjustment for various confounders. When compared with subjects in the lowest quartile of central PP, those in the highest quartile demonstrated a significantly increased risk of CKD (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.08‐2.96; P = .006). The study showed that central PP emerged as an independent predictor of the decline in renal function.