Lower Levels Of Kidney Function Research Articles

The Association of Ejection Fraction With Hospital-Associated Cardiac Arrest and Heart Failure Hospitalization Differs According to Baseline Estimated GFR

Chronic kidney disease (CKD) and left ventricular (LV) dysfunction are risk factors for cardiovascular events. We explore whether the association of LV ejection fraction (LVEF) with cardiac arrest, heart failure hospitalization, and all-cause mortality differs across stages of kidney impairment. We performed an observational cohort study of 19,032 patients from 2004 to 2014 with estimated glomerular filtration rate (eGFR)≤90 ml/min per 1.73 m2 and without end-stage kidney disease (ESKD). Cox regression models, incorporating an interaction term for eGFR and LVEF, were fit and adjusted for relevant covariates. Mean age of the patients was 67 ± 14 years, and 51% were male. The mean eGFR was 64 ± 19 ml/min per 1.73 m2 and LVEF was 54 ± 13%. Over a median follow-up of 3.0 (0.7-6.0) years there were 504 cardiac arrests, 4181 heart failure hospitalizations, and 6989 deaths. The association of LVEF with cardiac arrest and heart failure hospitalization differed according to continuous eGFR (P-interaction<0.01 for both outcomes). The association of LVEF with cardiac arrest in the lowest quartile was attenuated (adjusted hazard ration [aHR] per 5% higher LVEF 0.92; 95% confidence interval [CI] 0.88-0.96) compared to the highest eGFR quartile (aHR per 5% higher LVEF 0.85; 95% CI 0.78-0.91). The association of LVEF with heart failure hospitalization was similarly attenuated in the lowest eGFR quartile. There was no effect modification of LVEF by continuous eGFR for all-cause mortality (P-interaction 0.26). Among non-ESKD patients with eGFR≤90 ml/min per 1.73 m2, the association of LVEF with cardiac arrest and heart failure hospitalization is attenuated at lower levels of kidney function. Further research is required to elucidate what factors beyond LVEF drive these observations.

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.

Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease.

Anaemia occurs in chronic kidney disease (CKD) and is more prevalent with lower levels of kidney function. Anaemia in CKD is associated with death related to cardiovascular (CV) disease and infection. Established treatments include erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions. Oral hypoxia-inducible factors (HIF) stabilisers are now available to manage anaemia in people with CKD. We aimed to assess the benefits and potential harms of HIF stabilisers for the management of anaemia in people with CKD. We searched the Cochrane Kidney and Transplant Register of Studies up to 22 November 2021 through contact with the Information Specialist using search terms relevant to our review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Randomised and quasi-randomised studies evaluating hypoxia-inducible factors stabilisers compared to placebo, standard care, ESAs or iron supplementation in people with CKD were included. Five authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects pair-wise meta-analysis and expressed as a relative risk (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Evidence certainty was assessed using GRADE. We included 51 studies randomising 30,994 adults. These studies compared HIF stabilisers to either placebo or an ESA. Compared to placebo, HIF stabiliser therapy had uncertain effects on CV death (10 studies, 1114 participants): RR 3.68, 95% CI 0.19 to 70.21; very low certainty evidence), and nonfatal myocardial infarction (MI) (3 studies, 822 participants): RR 1.29, 95% CI 0.31 to 5.36; I² = 0%; very low certainty evidence), probably decreases the proportion of patients requiring blood transfusion (8 studies, 4329 participants): RR 0.51, 95% CI 0.44 to 0.60; I² = 0%; moderate certainty evidence), and increases the proportion of patients reaching the target haemoglobin (Hb) (10 studies, 5102 participants): RR 8.36, 95% CI 6.42 to 10.89; I² = 37%; moderate certainty evidence). Compared to ESAs, HIF stabiliser therapy may make little or no difference to CV death (17 studies, 10,340 participants): RR 1.05, 95% CI 0.88 to 1.26; I² = 0%; low certainty evidence), nonfatal MI (7 studies, 7765 participants): RR 0.91, 95% CI 0.76 to 1.10; I² = 0%; low certainty evidence), and nonfatal stroke (5 studies, 7285 participants): RR 1.06, 95% CI 0.71 to 1.56; I² = 8%; low certainty evidence), and had uncertain effects on fatigue (2 studies, 3471 participants): RR 0.80, 95% CI 0.56 to 1.16; I² = 0%; very low certainty evidence). HIF stabiliser therapy probably decreased the proportion of patients requiring blood transfusion (11 studies, 10,786 participants): RR 0.87, 95% CI 0.76 to 1.00; I² = 25%; moderate certainty evidence), but may make little or no difference on the proportion of patients reaching the target Hb (14 studies, 4601 participants): RR 1.00, 95% CI 0.93 to 1.07; I² = 70%; low certainty evidence), compared to ESA. The effect of HIF stabilisers on hospitalisation for heart failure, peripheral arterial events, loss of unassisted dialysis vascular access patency, access intervention, cancer, infection, pulmonary hypertension and diabetic nephropathy was uncertain. None of the included studies reported life participation. Adverse events were rarely and inconsistently reported. HIF stabiliser management of anaemia had uncertain effects on CV death, fatigue, death (any cause), CV outcomes, and kidney failure compared to placebo or ESAs. Compared to placebo or ESAs, HIF stabiliser management of anaemia probably decreased the proportion of patients requiring blood transfusions, and probably increased the proportion of patients reaching the target Hb when compared to placebo.

Evaluation of Racial, Ethnic, and Socioeconomic Disparities in Initiation of Kidney Failure Treatment During the First 4 Months of the COVID-19 Pandemic

Persons with kidney failure require treatment (ie, dialysis or transplantation) for survival. The burden of the COVID-19 pandemic and pandemic-related disruptions in care have disproportionately affected racial and ethnic minority and socially disadvantaged populations, raising the importance of understanding disparities in treatment initiation for kidney failure during the pandemic. To examine changes in the number and demographic characteristics of patients initiating treatment for incident kidney failure following the COVID-19 pandemic by race and ethnicity, county-level COVID-19 mortality rate, and neighborhood-level social disadvantage. This cross-sectional time-trend study used data from US patients who developed kidney failure between January 1, 2018, and June 30, 2020. Data were analyzed between January and July 2021. COVID-19 pandemic. Number of patients initiating treatment for incident kidney failure and mean estimated glomerular filtration rate (eGFR) at treatment initiation. The study population included 127 149 patients with incident kidney failure between January 1, 2018, and June 30, 2020 (mean [SD] age, 62.8 [15.3] years; 53 021 [41.7%] female, 32 932 [25.9%] non-Hispanic Black, and 19 835 [15.6%] Hispanic/Latino patients). Compared with the pre-COVID-19 period, in the first 4 months of the pandemic (ie, March 1 through June 30, 2020), there were significant decreases in the proportion of patients with incident kidney failure receiving preemptive transplantation (1805 [2.1%] pre-COVID-19 vs 551 [1.4%] during COVID-19; P < .001) and initiating hemodialysis treatment with an arteriovenous fistula (2430 [15.8%] pre-COVID-19 vs 914 [13.4%] during COVID-19; P < .001). The mean (SD) eGFR at initiation declined from 9.6 (5.0) mL/min/1.73 m2 to 9.5 (4.9) mL/min/1.73 m2 during the pandemic (P < .001). In stratified analyses by race/ethnicity, these declines were exclusively observed among non-Hispanic Black patients (mean [SD] eGFR: 8.4 [4.6] mL/min/1.73 m2 pre-COVID-19 vs 8.1 [4.5] mL/min/1.73 m2 during COVID-19; P < .001). There were significant declines in eGFR at initiation for patients residing in counties in the highest quintile of COVID-19 mortality rates (9.5 [5.0] mL/min/1.73 m2 pre-COVID-19 vs 9.2 [5.0] mL/min/1.73 m2 during COVID-19; P < .001), but not for patients residing in other counties. The number of patients initiating treatment for incident kidney failure was approximately 30% lower than projected in April 2020. In this cross-sectional study of US adults, the COVID-19 pandemic was associated with a substantially lower number of patients initiating treatment for incident kidney failure and treatment initiation at lower levels of kidney function during the first 4 months, particularly for Black patients and people living in counties with high COVID-19 mortality rates.

Kidney function and dementia risk in community-dwelling older adults: the Shanghai Aging Study

BackgroundAssociation between kidney dysfunction and dementia has been studied in western cohorts, but with inconsistent conclusions which may be due to the different measurements of kidney function. We aim to verify the hypothesis that lower levels of kidney function would be associated with increased risk of incident dementia in Chinese elderly.MethodsOne thousand four hundred twelve dementia-free participants aged 60 years or older from the Shanghai Aging Study were enrolled and followed up for 5.3 years on average. Glomerular filtration rate (GFR) was calculated by using combined creatinine–cystatin C CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Diagnoses of incident dementia and Alzheimer’s disease (AD) were established using DSM-IV and NINCDS-ADRDA criteria based on medical, neurological, and neuropsychological examinations to each participant. Cox proportional regression was used to analyze the association of baseline GFRcrcys levels with incident dementia/AD, adjusting age, gender, education years, APOE-ε4, diabetes, hypertension, baseline Mini-Mental State Examination score, and proteinuria.ResultsA total of 113 (8%) and 84 (7%) participants developed dementia and AD. Comparing to participants with high GFRcrcys (≥ 80 ml/min/1.73 m2), participants with low (< 67 ml/min/1.73 m2) and moderate GFRcrcys (67 ≤ GFR < 80 ml/min/1.73 m2) had increased risk of incident dementia with hazard ratios (HRs) of 1.87 (95% CI 1.02–3.44) and 2.19 (95% CI 1.21–3.95) after adjustment for confounders, respectively. Low (HR = 2.27 [95%CI 1.10–4.68]) and moderate (HR = 2.14 [95% CI 1.04–4.40]) GFRcrcys at baseline was also independently associated with incident AD after adjustments when comparing to high GFRcrcys. The significant association between GFRcrcys and dementia risk was observed in female but not in male participants.ConclusionsGFRcrcys may be considered as a marker of an individual’s vulnerability to the increased risk of cognitive decline.

Sedentary Time and White Matter Hyperintensity Volume in Older Adults.

Cerebrovascular disease in the form of white matter hyperintensities (WMH) increases with age and is associated separately with sedentary time and reduced kidney function. A better understanding of the relationships among these variables would help clarify whether sedentary time should be considered more closely in older adults at particular levels of kidney function to reduce the risk of WMH. We analyzed information from 94 healthy community-dwelling older adults to determine the association of sedentary time and WMH in nondemented, nondepressed older adults, and whether level of kidney function was an effect modifier of the relationship between sedentary time and WMH. Sedentary behavior was measured using the Sedentary Behavior Questionnaire. White matter hyperintensity was assessed using whole-brain 3T magnetic resonance imaging T1- and T2-weighted images. Kidney function was calculated by the epi-chronic kidney disease formula for estimated glomerular filtration rate (eGFR). Exposures or predictors were sedentary time, age, sex, education in years, Framingham stroke risk 10-yr prediction score, and eGFR. The analytical approach was multiple linear regression. Adjusting for age, sex, education in years, Framingham stroke risk 10-yr prediction score, greater sedentary time was associated with greater WMH but this effect was dependent on level of eGFR (sedentary time-eGFR interaction b = -0.0005, P = 0.022). At eGFR values of 69, 81, and 93 mL·min per 1.73 m (the 25th, 50th, and 75th percentiles), sedentary time b coefficients were b = 0.021 (95% confidence interval [CI], 0.011-0.031), b = 0.015 (95% CI, 0.008-0.022), and b = 0.009 (95% CI, 0.003-0.016). The effect weakened linearly as eGFR increased, with no significant association at eGFR ≥97 mL·min per 1.73 m. Findings suggest that sedentary time is associated with WMH in persons with an eGFR ≤96 mL·min per 1.73 m and that this association is stronger with lower levels of kidney function.

The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study.

ABSTRACT Diabetes is a common cause of chronic kidney disease (CKD), but in aggregate, non-diabetic diseases account for a higher proportion of cases of CKD than diabetes in many parts of the world. Inhibition of the renin–angiotensin system reduces the risk of kidney disease progression and treatments that lower blood pressure (BP) or low-density lipoprotein cholesterol reduce cardiovascular (CV) risk in this population. Nevertheless, despite such interventions, considerable risks for kidney and CV complications remain. Recently, large placebo-controlled outcome trials have shown that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce the risk of CV disease (including CV death and hospitalization for heart failure) in people with type 2 diabetes who are at high risk of atherosclerotic disease, and these effects were largely independent of improvements in hyperglycaemia, BP and body weight. In the kidney, increased sodium delivery to the macula densa mediated by SGLT-2 inhibition has the potential to reduce intraglomerular pressure, which may explain why SGLT-2 inhibitors reduce albuminuria and appear to slow kidney function decline in people with diabetes. Importantly, in the trials completed to date, these benefits appeared to be maintained at lower levels of kidney function, despite attenuation of glycosuric effects, and did not appear to be dependent on ambient hyperglycaemia. There is therefore a rationale for studying the cardio-renal effects of SGLT-2 inhibition in people at risk of CV disease and hyperfiltration (i.e. those with substantially reduced nephron mass and/or albuminuria), irrespective of whether they have diabetes.

Relationship between chronic kidney disease with diabetes or hypertension and frailty in community-dwelling Japanese older adults.

The aim of the present study was to evaluate the relationship between kidney function with concomitant diabetes or hypertension and frailty in community-dwelling Japanese older adults. The participants were 9606 residents (community-dwelling Japanese older adults) who completed baseline assessments. The estimated glomerular filtration rate (mL/min/1.73 m2 ) was determined according to the serum creatinine level, and participants were classified into four mutually exclusive categories: ≥60.0 (normal range), 45.0-59.9, 30.0-44.9 and <30.0 mL/min/1.73 m2 . Frailty status was defined using five criteria as described by Fried: slow gait speed, muscle weakness, low physical activity, exhaustion and unintentional weight loss. Participants who met three, four or five criteria satisfied the definition of having frailty. Multivariate logistic regression was used to examine the relationships between estimated glomerular filtration rate and frailty. After multivariate adjustment, participants with lower kidney function (estimated glomerular filtration rate <30.0 mL/min/1.73 m2 ) were more frail (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.01-3.59). In addition, individuals with a history of diabetes (OR 2.76, 95% CI 1.21-8.24) or hypertension (OR 2.53, 95% CI 1.45-5.12) showed a significantly increased risk of frailty in the lower kidney function group, regardless of multivariate controls. Furthermore, the analyses showed an even greater increase in the risk of frailty in patients with a history of both diabetes and hypertension (OR 3.67, 95% CI 1.13-14.1) CONCLUSIONS: A lower level of kidney function was associated with a higher risk of frailty in community-dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 1527-1533.

Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKD.

Pulmonary hypertension (PH) is associated with poor outcomes in the dialysis and general populations, but its effect in CKD is unclear. We evaluated the prevalence and predictors of PH measures and their associations with long-term clinical outcomes in patients with nondialysis-dependent CKD. Chronic Renal Insufficiency Cohort (CRIC) Study participants who had Doppler echocardiography performed were considered for inclusion. PH was defined as the presence of estimated pulmonary artery systolic pressure (PASP) >35 mmHg and/or tricuspid regurgitant velocity (TRV) >2.5 m/s. Associations between PH, PASP, and TRV and cardiovascular events, renal events, and all-cause mortality were examined using Cox proportional hazards models. Of 2959 eligible participants, 21% (n=625) had PH, with higher rates among those with lower levels of kidney function. In the multivariate model, older age, anemia, lower left ventricular ejection fraction, and presence of left ventricular hypertrophy were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with higher risk for death (hazard ratio, 1.38; 95% confidence interval, 1.10 to 1.72) and cardiovascular events (hazard ratio, 1.23; 95% confidence interval, 1.00 to 1.52) but not renal events. Similarly, TRV and PASP were associated with death and cardiovascular events but not renal events. In this study of patients with CKD and preserved left ventricular systolic function, we report a high prevalence of PH. PH and higher TRV and PASP (echocardiographic measures of PH) are associated with adverse outcomes in CKD. Future studies may explain the mechanisms that underlie these findings.

Comparative Effectiveness of Statin Therapy in Chronic Kidney Disease and Acute Myocardial Infarction: A Retrospective Cohort Study

BackgroundWhether there is a kidney function threshold to statin effectiveness in patients with acute myocardial infarction is poorly understood. Our study sought to help fill this gap in clinical knowledge. MethodsWe undertook a new-user cohort study of the effectiveness of statin therapy by level of estimated glomerular filtration rate (eGFR) in adults who were hospitalized for myocardial infarction between 2000 and 2008. Data came from the Cardiovascular Research Network. The primary clinical outcomes were 1-year all-cause mortality and cardiovascular hospitalizations, with adverse outcomes of myopathy and development of diabetes mellitus. We calculated incidence rates, the number needed to treat, and used Cox proportional hazards regression with propensity score matching and adjustment to control for confounding, with testing for variation of effect by level of kidney function. ResultsCompared with statin non-initiators (n = 5583), statin initiators (n = 5597) had a lower propensity score-adjusted risk for death (hazard ratio 0.79; 95% confidence interval [CI], 0.71-0.88) and cardiovascular hospitalizations (hazard ratio 0.90; 95% CI, 0.82-1.00). We found little evidence of variation in effect by level of eGFR (P = .86 for death; P = .77 for cardiovascular hospitalization). Adverse outcomes were similar for statin initiators and statin non-initiators. The number needed to treat to prevent 1 additional death over 1 year of follow-up ranged from 15 (95% CI, 11-28) for eGFR <30 mL/min/1.73 m2 requiring statin treatment over 2 years to prevent 1 additional death, to 67 (95% CI, 49-118) for patients with eGFR >90 mL/min/1.73 m2. ConclusionsOur findings suggest that there is potential for important public health gains by increasing the routine use of statin therapy for patients with lower levels of kidney function.

The Association Between Kidney Function and Cognitive Decline in Community-Dwelling, Elderly Japanese People

ObjectivesThe aim of this study was to evaluate the relationship between chronic kidney disease (CKD) and cognitive decline in community-dwelling older adults without dementia. DesignCross-sectional. SettingObu Study of Health Promotion for the Elderly in Japan. ParticipantsThe participants were 4686 residents (community-dwelling older adults without dementia) who completed baseline assessments. MeasurementsThe estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) was determined according to the creatinine level, and participants were classified into three mutually exclusive categories: normal (≥60.0 mL/min/1.73 m2), mild CKD (45.0–59.9 mL/min/1.73 m2), or moderate to severe CKD (<45.0 mL/min/1.73 m2). Cognitive function was assessed using the National Center for Geriatrics and Gerontology-Functional Assessment Tool. Multivariate logistic regression was used to examine the relationships between eGFR and cognitive decline. ResultsAfter multivariate adjustment, participants with lower eGFR had lower cognitive function scores on most domains (P < .05). In particular, participants with advanced CKD (eGFR <45 mL/min/1.73 m2) were more likely to have significant cognitive decline on the Trail Making Test part A (odds ratio = 2.347, 95% confidence interval = 1.525–3.614) and the Symbol Digit Substitution Task (odds ratio = 2.308, 95% confidence interval = 1.486–3.585) than those with normal and mild CKD. ConclusionsA lower level of kidney function was associated with lower cognitive performance in attention and processing speed. These results suggest that eGFR might be an effective method to screen for cognitive decline in community-dwelling older adults.

Cognitive impairment in chronic kidney disease: keep vascular disease in mind

Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) and is associated with lower quality of life, more difficulty adhering to medications, and worse survival. Prior data suggest a relationship between vascular disease and cognitive impairment in individuals with CKD, although overall risk factors remain poorly understood. Critically, clinicians should be aware of the high rates of cognitive impairment that occur in all stages of CKD, which, although sometimes subtle, may impact comprehension and decision making in these individuals and may herald future, more debilitating impairment.

Kidney Function and Prevalent and Incident Frailty

Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty. In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

Chronic kidney disease is associated with adverse outcomes among elderly patients taking clopidogrel after hospitalization for acute coronary syndrome

BackgroundChronic kidney disease (CKD) is associated with worse outcomes among patients with acute coronary syndrome (ACS). Less is known about the impact of CKD on longitudinal outcomes among clopidogrel treated patients following ACS.MethodsUsing a retrospective cohort design, we identified patients hospitalized with ACS between 10/1/2005 and 1/10/10 at Department of Veterans Affairs (VA) facilities and who were discharged on clopidogrel. Using outpatient serum creatinine values, estimated glomerular filtration rate [eGFR (1.73 ml/min/m2)] was calculated using the CKD-EPI equation. The association between eGFR and mortality, hospitalization for acute myocardial infarction (AMI), and major bleeding were examined using Cox proportional hazards models.ResultsAmong 7413 patients hospitalized with ACS and discharged taking clopidogrel, 34.5% had eGFR 30–60 and 11.6% had eGFR < 30. During 1-year follow-up after hospital discharge, 10% of the cohort died, 18% were hospitalized for AMI, and 4% had a major bleeding event. Compared to those with eGFR > =60, individuals with eGFR 30–60 (HR 1.45; 95% CI: 1.18-1.76) and < 30 (HR 2.48; 95% CI: 1.97-3.13) had a significantly higher risk of death. A progressive increased risk of AMI hospitalization was associated with declining eGFR: HR 1.20; 95% CI: 1.04-1.37 for eGFR 30–60 and HR 1.47; 95% CI: 1.22-1.78 for eGFR < 30. eGFR < 30 was independently associated with over a 2-fold increased risk in major bleeding (HR 2.09; 95% CI: 1.40-3.12) compared with eGFR > = 60.ConclusionLower levels of kidney function were associated with higher rates of death, AMI hospitalization, and major bleeding among patients taking clopidogrel after hospitalization for ACS.

Chronic kidney disease and life expectancy

Life expectancy is commonly used as an indicator of health and reflects disease burden in the population. The life expectancy for patients with lower levels of kidney function has not been reported. The abridged life table method was applied to calculate the life expectancies of men and women from age 30 to 85 years, by levels of kidney function as defined by estimated glomerular filtration rate (eGFR): ≥ 60, 45-59, 30-44 and 15-29 mL/min/1.73 m(2). Men and women aged 40 years had a life expectancy of 30.5 and 34.6 years at eGFR ≥ 60 mL/min/1.73 m(2), 24.5 and 28.7 years at eGFR 45-59 mL/min/1.73 m(2), 14.5 and 16.5 years at eGFR 30-44 mL/min/1.73 m(2) and 10.4 and 9.1 years at eGFR 15-29 mL/min/1.73 m(2), respectively. Life expectancy was longer for women compared with men at all ages and eGFR categories, other than for eGFR 15-29 mL/min/1.73 m(2) where there was no difference in life expectancy by gender. A lower level of kidney function is associated with a reduction in life expectancy for both men and women.

Risk factors for progression of chronic kidney disease

The present review provides an overview of the identified risk factors for chronic kidney disease (CKD) progression emphasizing the pediatric population. Over the past 10 years, there have been significant changes to our understanding and study of preterminal kidney failure. Recent refinements in the measurement of glomerular filtration rate and glomerular filtration rate estimating equations are important tools for identification and association of risk factors for CKD progression in children. In pediatric CKD, lower level of kidney function at presentation, higher levels of proteinuria, and hypertension are known markers for a more rapid decline in glomerular filtration rate. Anemia and other reported risk factors from the pregenomic era require further study and validation. Genome-wide association studies have identified genetic loci that have provided novel genetic risk factors for CKD progression. With cohort studies of children with CKD becoming mature, they have started to yield important refinements to the assessment of CKD progression. Although many of the traditional risk factors for renal progression will certainly be assessed, such cohorts will be important for evaluating novel risk factors identified by genome-wide studies.

Chronic Kidney Disease and Cognitive Function in Older Adults: Findings from the Chronic Renal Insufficiency Cohort Cognitive Study

To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors. Cross-sectional. Chronic Renal Insufficiency Cohort Study. Eight hundred twenty-five adults aged 55 and older with CKD. Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean). Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59). In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

Hospital Performance and Differences by Kidney Function in the Use of Recommended Therapies After Non–ST-Elevation Acute Coronary Syndromes

Chronic kidney disease (CKD) is associated with an increased risk of cardiac events and death; however, underuse of guideline-recommended therapies is widespread. The extent to which hospital performance affects the care of patients with CKD and non-ST-segment elevation acute coronary syndromes (NSTE ACSs) is unknown. Observational cohort. 81,374 patients with NSTE ACSs treated at 327 US hospitals. Hospital performance, measured by quartiles of composite adherence to American Heart Association class I guidelines for therapy acutely (aspirin, beta-blockers, clopidogrel, heparin, and glycoprotein IIb/IIIa inhibitors) and at discharge (aspirin, clopidogrel, angiotensin-converting enzyme inhibitors, and lipid-lowering agents) in eligible patients. Use of each American Heart Association class I acute and discharge therapy stratified by continuous estimated glomerular filtration rate (eGFR). Multivariable models were adjusted for demographics, clinical factors, and hospital features. Better-performing hospitals had lower prescribing rates for most therapies (5 of 9) with lower levels of kidney function, whereas lower-performing hospitals were more likely to have similar prescribing rates across the eGFR spectrum, suggesting that prescribing patterns at these hospitals were insensitive to differences in eGFR. Observational design, selection bias of study cohort. Patients with lower levels of kidney function admitted with NSTE ACSs are less likely to receive evidence-based therapies. Treatment disparities related to CKD are most evident at top-performing hospitals.

Kidney Function and Cognitive Impairment in US Adults: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity. Cross-sectional. 23,405 participants (mean age, 64.9 +/- 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample. Estimated glomerular filtration rate (eGFR). Cognitive impairment. Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m(2). Kidney function was analyzed in 10-mL/min/1.73 m(2) increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment. CKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m(2) decrease in eGFR less than 60 mL/min/1.73 m(2) was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m(2) or greater. Longitudinal measures of cognitive function were not available. In US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD.

NSF: WHAT WE KNOW AND WHAT WE NEED TO KNOW: Patient Characteristics and Risk Factors for Nephrogenic Systemic Fibrosis Following Gadolinium Exposure

AbstractNephrogenic systemic fibrosis (NSF) is a systemic illness, which only affects patients with kidney failure. NSF risk increases with progressively lower levels of kidney function. It is characterized by red skin areas or plaques that develop over several weeks to painful thickened skin with a “woody” texture, resembling “peau d’orange.” It may ultimately cause flexion contractures of joints. Skin biopsy reveals thickened collagen bundles, mucin deposition, proliferation of fibroblasts and elastic fibers, without inflammation. Originally described as nephrogenic fibrosing dermopathy (NFD), because of its primarily cutaneous manifestation, it was renamed NSF because of the involvement of various organs like the lungs, myocardium, or striated muscles. The pathogenesis of the disease is not known yet, but recently we suggested a strong association between development of NSF and exposure to gadolinium‐based contrast (GBC) agents, thereafter confirmed by other authors. As a consequence of our recent observations, medical authorities imposed restrictions that exclude patients with advanced levels of renal insufficiency from potentially important magnetic resonance imaging studies with gadolinium. Unfortunately, the only alternatives in many situations (examination of brain, lungs, vasculature) are imaging modalities using iodinated radiocontrast agents. Thus, clinicians are faced with weighing the potential risk of NSF from GBC exposure against the risk of acute kidney injury‐associated with radiocontrast media. In this dilemma, clinicians must identify patients at high‐risk to develop NSF. Known risk factors critical for the development of NSF after exposure to GBC agents (certain chelates and higher doses) are end‐stage renal disease requiring dialysis, especially those with little or no residual renal function, and advanced kidney disease not on dialysis. Other potential risk factors include metabolic acidosis, iron overload/intravenous iron, divalent ion disturbances, endothelial/vascular injury, and high erythropoietin doses. Further studies are required.