Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants.
Setting and Participants
Participants were aged 21–74 years with CKD using age-based glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois from 2005–2008 while CRIC included Hispanics and non-Hispanics recruited at seven clinical centers from 2003–2007.
Blood pressure, angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use, CKD-associated complications
Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols
Among H-CRIC/ CRIC participants, 497 were Hispanic, 1650 non-Hispanic Black, and 1638 non-Hispanic White. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (p<0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic Blacks (51%) and Whites (40%) (p<0.01). Blood pressure > 130/80 mmHg was more common in Hispanics (62%) compared with Blacks (57%) and Whites (35%) (p<0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (p<0.05), even after stratifying by entry eGFR. Hispanics had the lowest receipt of ACE inhibitor/ARB among high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure > 130/80 mmHg. Mean eGFR (ml/min/m2) was lower in Hispanics (39.6) than in Blacks (43.7) and Whites (46.2), while median proteinuria was higher in Hispanics (0.72 g/d) than in Blacks (0.24 g/d) and Whites (0.12 g/d) (p<0.01).
Generalizability; observed associations limited by residual bias and confounding
Hispanics with CKD in CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts.
chronic kidney disease; Hispanics; epidemiology
Patients with chronic kidney disease (CKD) experience co-morbid illneses including cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between retinopathy and self reported CVD in a subgroup of the participants of the Chronic Renal Insufficiency Cohort (CRIC) study. In this observational, ancillary investigation, 2605 CRIC participants were invited to participate in this study, and non-mydriatic fundus photographs in both eyes were obtained in 1936 subjects. Photographs were reviewed in a masked fashion at a central photograph reading center. Presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter caliber were assessed using standard protocols by trained graders masked to information about study participants. History of self-reported cardiovascular disease was obtained using a medical history questionnaire. Kidney function measurements, traditional and non-traditional risk factors for CVD were obtained from the CRIC study. Greater severity of retinopathy was associated with higher prevalence of any cardiovascular disease and this association persisted after adjustment for traditional risk factors for CVD. Presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relationship between CVD prevalence and mean venular caliber. In conclusion, presence of retinopathy was associated with CVD, suggesting that retinovascular pathology may be indicative of macrovascular disease even after adjustment for renal dysfunction and traditional CVD risk factors. This would make assessment of retinal morphology a valuable tool in chronic kidney disease studies of CVD outcomes.
Retinopathy; chronic kidney disease; cardiovascular disease
Despite the significant morbidity and mortality attributable to cardiovascular disease (CVD), risk stratification remains an important challenge in the chronic kidney disease(CKD) population. We examined the discriminative ability of non-invasive measures of atherosclerosis, including carotid intima-media thickness(cIMT), carotid plaque, coronary artery calcification(CAC) and ascending and descending thoracic aorta calcification(TCAC), and Framingham Risk Score (FRS) to predict self-reported prevalent CVD.
Methods and Results
Participants were enrolled in the cIMT ancillary study of the Chronic Renal Insufficiency Cohort(CRIC) Study and also had all of the above measures within an 18 month period. CVD was present in 21% of study participants. C-statistics were used to ascertain the discriminatory power of each measure of atherosclerosis. The study population (n=220) was 64% male; 51% black and 45% white. The proportion of individuals with estimated glomerular filtration rate ≥60, 45–59, 30–44, and <30ml/min/1.73m2 was 21%, 41%, 28%, and 11%, respectively. In multivariable analyses adjusting for demographic factors, we failed to find a difference between CAC, carotid plaque, and cIMT as predictors of self-reported prevalent CVD (c-statistic 0.70, 95% confidence interval [CI]: 0.62–0.78; c-statistic 0.68, 95% CI: 0.60–0.75, and c-statistic 0.64, CI: 0.56–0.72, respectively). CAC was statistically better than FRS. FRS was the weakest discriminator of self-reported prevalent CVD (c-statistic 0.58).
There was a significant burden of atherosclerosis among individuals with CKD, ascertained by several different imaging modalities. We were unable to find a difference in the ability of CAC, carotid plaque, and cIMT to predict self-reported prevalent CVD.
carotid intima media thickness; coronary artery calcification; kidney; plaque
Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.
Settings and Participants
Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008.
Depressive symptoms measured by Beck Depression Inventory (BDI)
Demographic and clinical factors
Elevated depressive symptoms (BDI >= 11) and antidepressant medication use
Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each).
Absence of clinical diagnosis of depression and use of non-pharmacologic treatments
Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. African Americans, Hispanics, and individuals with more advanced CKD had higher odds of elevated depressive symptoms and lower odds of antidepressant medication use.
Starting with the early stages, patients with chronic kidney disease (CKD) experience higher burden of cardiovascular disease (CVD). Moreover, CVD complications are the major cause of mortality in CKD patients as compared with complications from chronic kidney failure. While traditional CVD risk factors, including diabetes, hypertension, hyperlipidemia, obesity, physical inactivity, may be more prevalent among CKD patients, these factors seem to underestimate the accelerated cardiovascular disease in the CKD population. Search for additional biomarkers that could explain the enhanced CVD risk in CKD patients has gained increasing importance. Although it is unlikely that any single nontraditional risk factor would fully account for the increased CVD risk in individuals with CKD, oxidative stress appears to play a central role in the development and progression of CVD and its complications. We will review the data that support the contribution of oxidative stress in the pathogenesis of CVD in patients with chronic kidney failure.
Patients with chronic kidney disease (CKD) have an increased risk of developing peripheral arterial disease (PAD). We examined the cross-sectional association between novel risk factors and prevalent PAD among patients with CKD. A total of 3,758 patients with an estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m2 who participated in the chronic renal insufficiency cohort (CRIC) study were included in the current analysis. PAD was defined as an ankle-brachial index <0.9 or a history of arm or leg revascularization. After adjustment for age, sex, race, cigarette smoking, physical activity, history of hypertension and diabetes, pulse pressure, high-density lipoprotein cholesterol, eGFR, and CRIC clinical sites, several novel risk factors were significantly associated with PAD. For example, odds ratios (95% confidence intervals) for a one standard deviation higher level of risk factors were 1.18 (1.08–1.29) for log-transformed high sensitivity-C reactive protein, 1.18 (1.08–1.29) for white blood cell count, 1.15 (1.05–1.25) for fibrinogen, 1.13 (1.03–1.24) for uric acid, 1.14 (1.02–1.26) for hemoglobin A1c, 1.11 (1.00–1.23) for log-transformed homeostasis model assessment-insulin resistance, and 1.35 (1.18–1.55) for cystatin C. In conclusion, these data indicate that inflammation, prothrombotic state, oxidative stress, insulin resistance, and cystatin C were associated with an increased prevalence of PAD in patients with CKD. Further studies are warranted to examine the causal effect of these risk factors on PAD in CKD patients.
peripheral arterial disease; novel risk factors; chronic kidney disease
Lack of chronic kidney disease (CKD) awareness is common. Recent data suggest that the presence of concurrent diabetes may heighten CKD awareness, but current data have not supported the hypothesis that healthcare delivery or insurance status improves awareness in the diabetic population. Diabetes is associated with high cardiovascular disease (CVD) morbidity, especially in patients with CKD. We hypothesized that a highly prevalent co-morbid condition such as CVD in patients with diabetes would predict CKD awareness.
We utilized data from the National Kidney Foundation-Kidney Early Evaluation Program (KEEPTM), a large screening program designed to identify high-risk individuals for CKD and promote awareness.
Among 77,077 participants, CKD was identified in 20,200 and diabetes in 23,082. Prevalence of CVD was higher in participants with than without diabetes (39.5 vs. 22.0%) and in stage 3–5 compared to stage 1–2 CKD (43.3 vs. 34.4%). Patients with diabetes and CVD had a higher level of awareness than those without diabetes (8.2 vs. 2.2%). Among patients with diabetes and CVD, the presence of congestive heart failure was a better predictor of awareness [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.40–2.43] than endpoints such as myocardial infarction or stroke [OR 1.35 (95% CI 1.04–1.73) and OR 1.34 (95% CI 1.04–1.72), respectively].
While prevalence of CKD awareness remained low, our data suggest that in patients with diabetes the presence of CVD was associated with increased awareness in a targeted screening program for CKD awareness.
Cardiovascular disease; Chronic kidney disease; Diabetes mellitus; KEEP
Coronary artery calcification (CAC) is associated with increased mortality risk in the general population. Although individuals with chronic kidney disease (CKD) are at markedly increased mortality risk, the incidence, prevalence, and prognosis of CAC in CKD is not well-understood.
Cross-sectional observational study.
Setting and Participants
Analysis of 1,908 participants who underwent coronary calcium scanning as part of the multi-ethnic CRIC (Chronic Renal Insufficiency Cohort) Study.
Estimated glomerular filtration rate (eGFR) computed using the Modification of Diet in Renal Disease (MDRD) Study equation, stratified by race, sex and diabetic status. eGFR was treated as a continous variable and a categorical variable compared to the reference range of >60 ml/min/1.73 m2
CAC detected using CT scans using either an Imatron C-300 electron beam computed tomography scanner or multi-detector CT scanner. CAC was computed using the Agatston score, as a categorical variable. Analyses were performed using ordinal logistic regression.
We found a strong and graded relationship between lower eGFR and increasing CAC. In unadjusted models, ORs increased from 1.68 (95% CI, 1.23–2.31) for eGFR from 50–59 to 2.82 (95% CI, 2.06–3.85) for eGFR of <30. Multivariable adjustment only partially attenuated the results (OR, 1.53; 95% CI, 1.07–2.20) for eGFR<30.
Use of eGFR rather than measured GFR.
We demonstrated a graded relationship between severity of CKD and CAC, independent of traditional risk factors. These findings supports recent guidelines that state that if vascular calcification is present, it should be considered as a complementary component to be included in the decision making required for individualizing treatment of CKD.
Metabolic syndrome (MetS) is a clinical syndrome that consists of visceral obesity, dyslipidemia, hypertension, and impaired insulin sensitivity. Although individual components of MetS have been implicated in the development of chronic kidney disease (CKD), few studies have examined the effect of combinations of the components of MetS on the development of CKD and cardiovascular disease (CVD). The prevalence of MetS is increasing worldwide in both developing and developed countries, and early detection and treatment of MetS would be a cost-effective strategy for preventing the development of CKD. Visceral obesity and insulin resistance are two important features of MetS that may be associated with renal damage. Lifestyle modifications, including caloric restriction and exercise, are necessary to treat MetS. Initial antihypertensive therapy should consist of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. An improved understanding of the mechanism responsible for the association between MetS and renal damage should be helpful in determining the treatment regimens directed at cardiovascular and renal protection.
Background. Renal disease is commonly described as a complication of metabolic syndrome (MetS) but some recent studies suggest that Chronic Kidney disease (CKD) may actually antecede MetS. Few studies have explored the predictive utility of co-clustering CKD with MetS for cardiovascular disease (CVD) mortality. Methods. Data from a nationally representative sample of United States adults (NHANES) was utilized. A sample of 13115 non-pregnant individuals aged ≥35 years, with available follow-up mortality assessment was selected. Multivariable Cox Proportional hazard regression analysis techniques explored the relationship between co-clustered CKD, MetS and CVD mortality. Bayesian analysis techniques tested the predictive accuracy for CVD Mortality of two models using co-clustered MetS and CKD and MetS alone. Results. Co-clustering early and late CKD respectively resulted in statistically significant higher hazard for CVD mortality (HR = 1.80, CI = 1.45–2.23, and HR = 3.23, CI = 2.56–3.70) when compared with individuals with no MetS and no CKD. A model with early CKD and MetS has a higher predictive accuracy (72.0% versus 67.6%), area under the ROC (0.74 versus 0.66), and Cohen's kappa (0.38 versus 0.21) than that with MetS alone. Conclusion. The study findings suggest that the co-clustering of early CKD with MetS increases the accuracy of risk prediction for CVD mortality.
The prevalence of obesity and diabetes continues to rise in the United States and worldwide. These findings parallel the expansion of childhood obesity and diabetes. Obesity is a central component of the cardiorenal metabolic syndrome (CRS) which increases the risk for cardiovascular disease (CVD) and chronic kidney disease (CKD). The hallmark of obesity, CRS, and early type 2 diabetes is insulin resistance, a result of decreased insulin metabolic signaling due, in part, to enhanced serine phosphorylation and/or proteasome-mediated degradation of the insulin receptor substrate. Cardiovascular and renal insulin resistance significantly contributes to endothelial dysfunction, impaired cardiac diastolic and vascular relaxation, glomerular injury, and tubular dysfunction. In this context, multiple factors including oxidative stress, increased inflammation, and inappropriate activation of the renin-angiotensin-aldosterone and the sympathetic nervous system contribute to overweight- and obesity-induced systemic and tissue insulin resistance. One common link between obesity and the development of insulin resistance appears to be a low-grade inflammatory response resulting from dysfunctional innate and adaptive immunity. In this regard, there has been recent work on the role of dipeptidyl peptidase-4 (DPP-4) in modulating innate and adaptive immunity. The direct effects of DPP-4 on immune cells and the indirect effects through GLP-1-dependent and -independent pathways suggest effects of DPP-4 inhibition may have beneficial effects beyond glycemic control in improving CVD and renal outcomes. Accordingly, this review addresses new insights into the role of DPP-4 in immune modulation and the potential beneficial effects of DPP-4 inhibitors in insulin resistance and associated CVD and CKD prevention.
DPP-4; Cardiorenal syndrome; Obesity; Diabetes; Insulin resistance
Purpose of review
Patients with chronic kidney disease (CKD) have the highest risk for atherosclerotic cardiovascular disease (CVD). Current interventions have been insufficiently effective in lessening excess incidence and mortality from CVD in CKD patients versus other high-risk groups. This review focuses on traditional and CKD-related risks as well as key mechanisms of macrophage foam cell formation that underlie the excess CVD in the setting of CKD.
Hyperlipidemia, particularly increased low density lipoprotein (LDL) cholesterol, is the key factor in atherogenesis in the general population, but has not been found to be the overriding risk for greater CVD in CKD, especially as renal damage progresses. Although higher incidence of CVD in CKD is not due to higher serum lipids per se, CKD is associated with abnormal lipid metabolism that is proatherogenic. CKD-related risks, including inflammation and disturbances in mineral metabolism, have been implicated. In addition, perturbations of the macrophage, a cell that is central in atherogenesis, may be important.
The mechanisms underlying the heightened risk for CVD in CKD have been the focus of intense study and may relate to the combined effects of traditional and CKD-specific risks involving inflammation and lipid metabolism, especially perturbation of macrophage cholesterol homeostasis.
ABCA1; atherosclerosis; cholesterol; CKD; macrophage
Limited data are available on the risk ratios for fatal cardiovascular disease (CVD) outcome from gout and chronic kidney disease (CKD) in non-diabetic individuals.
Nationwide population-based retrospective prospective study with a 5-year follow-up to investigate the association between physician-diagnosed gout and CKD in non-diabetics aged 50 and above who had no pre-existing serious CVD and the subsequent risk of death from CVD. Hazard ratios (HR) of CVD mortality were adjusted for gender, age, smoking- and alcoholism-related diagnoses, hypertension, hyperlipidemia, atrial fibrillation and Charlson’s comorbidity index score.
A case cohort (n=164,463) having gout and a control cohort (n= 3,694,377) having no gout were formed. The prevalence of gout in this study was 4.26% whereas that of gout plus CKD was 8.17%. Male to female ratio among the individuals with gout was 3.2:1. The relative risk (RR) of subsequent cardiovascular mortality between the case and control cohort was 1.71 (95% confidence interval (CI), 1.66-1.75). The presence of CKD in nondiabetic subjects with no gout (control group) has a RR of CVD mortality at 3.05 (95% CI, 2.94-3.15). The presence of gout has protective effect on subjects with CKD with a RR of 1.84 (95% CI, 1.71-1.98). As compared with individuals with no gout, the adjusted HR (aHR) for CVD mortality among the individuals with gout was 1.10 (95% CI 1.07-1.13). In a Cox model, when compared with subjects having neither gout nor CKD, the aHR in subjects with no gout but with CKD is 1.76 (95% CI, 1.70-1.82); in subjects with gout but without CKD, 1.10 (1.07-1.13); interestingly, the aHR is attenuated in subjects with concomitant gout plus CKD which is 1.38 (1.29-1.48).
Among non-diabetic individuals aged 50 years or above who had no preceding serious CVD, those with gout were 1.1 times more likely to die from CVD as were individuals without gout. The presence of gout appears to attenuate the risk of subsequent CV mortality in subjects with CKD. Further studies should focus on finding an explanation for the protective effect of gout on CV mortality in patients with CKD.
Incidence of cardiovascular disease (CVD) is remarkably high among patients with chronic kidney disease (CKD), even in the early microalbuminuric stages with normal glomerular filtration rates. Proximal tubule cells (PTCs) mediate metabolism and urinary excretion of vasculotoxic substances via apical and basolateral receptors and transporters. These cells also retrieve vasculoprotective substances from circulation or synthesize them for release into the circulation. PTCs are also involved in the uptake of sodium and phosphate, which are critical for hemodynamic regulation and maintaining the mineral balance, respectively. Dysregulation of PTC functions in CKD is likely to be associated with the development of CVD and is linked to the progression to end-stage renal disease. In particular, PTC dysfunction occurs early in diabetic nephropathy, a leading cause of CKD. It is therefore important to elucidate the mechanisms of PTC dysfunction to develop therapeutic strategies for treating cardiorenal syndrome in diabetes.
Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD prior to reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD.
To describe the baseline characteristics of renal transplant recipients (RTRs) enrolled in a clinical trial of homocyteine lowering with a standard multivitamin containing high doses of folic acid, vitamins B6 and B12 aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine (tHcy) concentrations, and the prevalence of diabetes and previous cardiovascular disease (CVD).
Cross sectional survey within a randomized controlled trial (RCT) cohort.
Setting and Participants
Participants were recruited from kidney transplant clinics in the U.S., Canada, and Brazil. Eligible participants had elevated levels of homocysteine (≥12.0 μmol/L in men and ≥11.0 μmol/L in women) and kidney function measured by Cockroft Gault estimated creatinine clearance of 30 mL/min or greater.
Among 4,110 randomized participants 38.9% had diabetes, and 19.5% had previous CVD. Mean (± standard deviation) tHcy concentrations were 17.1 ± 6.3 μmol/L, while the mean (± standard deviation) creatinine clearance was 66.4 ± 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate (eGFR) consistent with stage 2-3 CKD (i.e., eGFR 30-89 mL/min).
Analysis is based on cross-sectional data from a RCT, self-report of co-morbid illnesses, and level of kidney function was estimated.
A large population of stable RTRs who are at high risk for the development of CVD (both de novo and recurrent) has been recruited into FAVORIT and are likely to experience a sufficient number of events to address the primary hypothesis of the trial.
chronic kidney disease; renal transplantation; hyperhomocysteinemia; creatinine clearance; estimated GFR; arteriosclerosis; diabetes
Patients with chronic kidney disease (CKD) have a disproportionate risk of cardiovascular disease. This study was designed to assess the association between two noninvasive measures of cardiovascular risk, pulse wave analysis (PWA), and carotid intima-media thickness (IMT), in a cohort of CKD patients enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study.
Three hundred and sixty-seven subjects with CKD enrolled in the CRIC study at the University of Pennsylvania site (mean age 59.9 years, blood pressure 129/74 mm Hg, estimated glomerular filtration rate 48 ml/min/1.73 m2, IMT 0.8 mm) had both carotid IMT and PWA measurements. Carotid ultrasound was also used to determine the presence of plaque. PWA was used to determine augmentation index (AI), amplification ratio (AMPR), aortic pulse pressure (C_PP), and central aortic systolic pressure (C_SP).
IMT was significantly associated with all PWA-derived measures. However, on multivariable linear regression analysis, only AMPR (regression coefficient −0.072, P = 0.006), C_PP (regression coefficient 0.0025, P < 0.001), and C_SP (regression coefficient 0.0017, P < 0.001) remained significantly associated with IMT. The prevalence of carotid plaque in the cohort was 59%. Of the PWA-derived measures, only C_PP was significantly associated with the presence of carotid plaque (P < 0.001).
PWA-derived measures are associated with carotid IMT and plaque in the CKD. Of these measures, C_PP was most associated with carotid IMT and plaque.
Background. SCreening for Occult REnal Disease (SCORED) is a novel screening guideline recently developed to identify individuals with a high likelihood of having prevalent chronic kidney disease (CKD). This simple scoring system, developed from general US representative samples and independently validated, was shown to outperform current clinical practice guidelines. Recently, CKD screening in individuals with cardiovascular disease (CVD) has been emphasized. We therefore evaluated the SCORED model in CVD patients in order to better understand the implications of CKD screening in this population.
Methods. Two clinical trials that enrolled patients with heart attack (N = 2481) or stroke (N = 3680) were combined to create our sample. The performance of the SCORED guideline was evaluated by standard diagnostic measures. Correlations among various risk scores and their predictive abilities for recurrent CVD were ascertained.
Results. For heart attack and stroke patients, respectively, the SCORED guideline yielded sensitivity of 94 and 97%, specificity of 27 and 11%, positive predictive value of 32 and 30%, negative predictive value of 93 and 89%, with AUC of 0.75 and 0.68. SCORED was strongly correlated with other risk scores and exhibited a similar performance in the prediction of recurrent CVD.
Conclusions. The higher risk of CKD in CVD patients with high SCORED values is demonstrated. This simple education and screening tool may help promote awareness of CKD in CVD patients, in addition to general populations, and assess the CKD risk and its relationship with recurrent CVD.
CKD; CVD; ENRICHD; VISP
The prevalence of diabetes, hypertension, and cardiovascular disease (CVD) and chronic kidney disease (CKD) is increasing in concert with obesity. Insulin resistance, metabolic dyslipidemia, central obesity, albuminuria and hypertension commonly cluster to comprise the cardiometabolic syndrome. Emerging evidence supports a shift in our understanding of the crucial role of elevated serum aldosterone in promoting insulin resistance and resistant hypertension. Aldosterone enhances tissue generation of oxygen free radicals and systemic inflammation. This increase in oxidative stress and inflammation, in turn, contributes to impaired insulin metabolic signaling, reduced endothelial-mediated vasorelaxation and associated cardiovascular and renal structural and functional abnormalities. In this context, recent investigation indicates that hyperaldosteronism, which is often associated with obesity, contributes to impaired pancreatic beta-cell function as well as diminished skeletal muscle insulin metabolic signaling. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated, in part, by aldosterone's non-genomic as well as genomic signaling through the mineralocorticoid receptor (MR). In the cardiometabolic syndrome there are increased circulating levels of glucocorticoids, which can also activate MR signaling in cardiovascular, adipose, skeletal muscle, neuronal, and liver tissue. Further, there is increasing evidence that fat tissue produces a lipid soluble factor that stimulates aldosterone production from the adrenal zona glomerulosa. Recently, have we learned that MR blockade improves pancreatic insulin release, insulin-mediated glucose utilization, endothelium-dependent vasorelaxation as well as reducing the progression of CVD and CKD. In summary, aldosterone excess exerts detrimental metabolic effects that contribute to the development of the CMS and resistant hypertension as well as CVD and CKD.
Aldosterone; Insulin Resistance; Hypertension; Cardiometabolic Syndrome
The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease (ESRD), with limited data on less advanced chronic kidney disease (CKD) stages.
A total of 3267 adult participants (50% non-Hispanic blacks, 46% females) with CKD from the Chronic Renal Insufficiency Cohort (CRIC) were included in this study. None of the study participants had been on dialysis. Those with self-identified race/ethnicity other than non-Hispanic black or white (N=323) or those without ECG data (N=22) were excluded. AF was ascertained by a 12-lead electrocardiogram (ECG) and self-report. Age- sex- race/ethnicity-specific prevalence rates of AF were estimated and compared between subgroups. Cross sectional associations and correlates with prevalent AF were examined using unadjusted and multivariable adjusted logistic regression analysis.
The mean estimated glomerular filtration rate (GFR) was 43.6 (±13.0) ml/min/1.73 m2. AF was present in 18% of the study population and in more than 25% of those 70 years or older. In multivariable adjusted models, 1-SD increase in age (11 years) [odds ratio (OR) and CI 95%: 1.27 (1.13, 1.43), P<0.0001], female sex [0.80 (0.65, 0.98), P=0.0303], smoking (former vs. never) [1.34 (1.08, 1.66), P= 0.0081], history of heart failure [3.28 (2.47, 4.36), P<0.001], and history of cardiovascular disease [1.94 (1.56, 2.43), P<0.0001] were significantly associated with AF. Race/ethnicity, hypertension, diabetes, body mass index, physical activity, education, high sensitivity C-reactive protein, total cholesterol, and alcohol intake were not significantly associated with AF. An estimated GFR <45 ml/min/1.73 m2 was associated with AF in an unadjusted model [1.35 (1.13–1.62)); P=0.0010)], but not after multivariable adjustment [1.12 (0.92– 1.35), P=0.2710].
Nearly one in five participants in CRIC, a national study of CKD, had evidence for AF at study entry, a prevalence similar to that reported among patients with ESRD and 2–3 times of that reported in the general population. Risk factors for AF in this CKD population do not mirror those reported in the general population.
Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD) and mortality. The increase in CKD in recent decades has paralleled increases in obesity, diabetes, and the metabolic syndrome. Physical inactivity is a modifiable risk factor that may affect the development and course of CKD. It is well established that exercise training improves a number of metabolic factors, including blood pressure and insulin resistance, which would be expected to preserve renal function as well as lower CVD risk. Epidemiological studies have suggested that partaking in vigorous physical activity may protect against kidney disease. However, to date few studies have rigorously measured physical activity levels. Instead, investigators have relied on subjective measures of physical activity and patient recall. This is particularly problematic when attempting to capture low- and very-low-intensity physical activity and in quantifying sedentary behavior. Improvements in vascular endothelial function, insulin sensitivity, adipocytokine profiles, and oxidative stress likely mediate the benefits of physical activity on the kidney. While formal exercise recommendations have been published for diabetes and hypertension, guidelines regarding the optimal type, frequency, intensity and duration of physical activity for preventing CKD have yet to be formalized.
Cardiovascular disease; Chronic kidney disease; Diabetes; Exercise; Obesity; Physical activity; Renal function
A low rate of blood pressure control has been reported among patients with chronic kidney disease (CKD). These data were derived from population-based samples with a low rate of CKD awareness.
Setting & Participants
Data from the baseline visit of the Chronic Renal Insufficiency Cohort (CRIC) study (n=3612) were analyzed. Participants with an estimated glomerular filtration rate of 20 to 70 ml/min/1.73m2 were identified from physician offices and review of laboratory databases.
Prevalence and awareness of hypertension, treatment patterns, control rates and factors associated with hypertension control.
Following a standardized protocol, blood pressure was measured three times by trained staff and hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or self-reported antihypertensive medication use. Patients’ awareness and treatment of hypertension were defined using self-report and two levels of hypertension control were evaluated: systolic/diastolic blood pressure <140/90 mmHg and <130/80 mmHg.
The prevalence of hypertension was 85.7%, and 98.9% of CRIC participants were aware of this diagnosis, 98.3% were treated with medications while 67.1% and 46.1% had their hypertension controlled to <140/90 mmHg and <130/80 mmHg, respectively. Of CRIC participants with hypertension, 15%, 25%, 26% and 32% were taking one, two, three and four or more antihypertensive medications, respectively. After multivariable adjustment, older patients, blacks, those with higher urinary albumin excretion were less likely while participants taking ACE-inhibitors and angiotensin receptor blockers were more likely to have controlled their hypertension to <140/90 mmHg and <130/80 mmHg.
Data were derived from a single study visit.
Despite almost universal hypertension awareness and treatment in this cohort of patients with CKD, rates of hypertension control were sub-optimal.
Both metabolic syndrome (MetS) and chronic kidney disease (CKD) are major global health issues. Current clinical markers used to reflect renal injury include albuminuria and estimated glomerular filtration rate (eGFR). Given the same eGFR level, urine albumin might be a better risk marker to predict progression of CKD and future development of cardiovascular diseases (CVDs). Serum Cystatin C is emerging as a new biomarker for early detection of renal injury associated with MetS and cardiovascular risk. In addition to each component, MetS per se influences the incidence and prognosis of renal injury and the odds ratios increased with the increase in the number of metabolic abnormalities. Hyperinsulinemia, activation of rennin-angiotensin-aldosterone system, increase of oxidative stress, and inflammatory cytokines are proposed to be the plausible biological link between MetS and CKD. Weight control, stick control of blood pressure, glucose, and lipids disorders may lead to lessening renal injury and even the subsequent CVD.
Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. Cardiovascular disease (CVD) is a major cause of mortality in patients with mild-to-moderate CKD and end-stage renal disease. There is accumulating evidence that the increase in CVD burden is present in CKD patients prior to dialysis, due both to conventional risk factors and kidney-specific disease. Detection and initiation of treatment for CVD risk factors at early stages of CKD should be effective in reducing CVD events before as well as after the onset of kidney failure.
Materials and Methods:
The study sample consisted of a total of 112 subjects aged ≤12 years: 60 CKD patients and 52 healthy control individuals. All subjects were investigated for a group of CVD risk factors such as: Hypertension, diabetes, dyslipidemia, physical inactivity, body mass index (BMI), family history of CVD, hypoalbuminemia, albuminuria, anemia, Ca x P product, and inflammation in terms of C-reactive protein (CRP).
Patients (40 males and 20 females) were categorized into four CKD stages (2, 3, 4, and 5) where, Stage 4 had the highest frequency, followed by Stages 3, 5 and 2. Evaluation of the patients indicated that they were shorter, had lower weight and had higher systolic and diastolic blood pressure as compared with control subjects. Frequency of physical inactivity among patients was two-fold higher than controls (50% vs. 25%). The patients showed significantly higher levels of cholesterol (163.6±39.8 vs. 141.8±24.2 mg/dL, P<0.0001), triglycerides (145.5±67.1 vs. 82.9±39.8 mg/dL, P<0.0001), low-density lipoprotein (92.6±31.9 vs. 72.5±19 mg/dL, P<0.0001) and albumin/creatinine ratio (1792±3183 vs. 11.1±6.6 mg/g, P<0.0001). Moreover, the patients had lower levels of high-density lipoprotein (41.9±11.0 vs. 52.7±11.7 mg/dL, P<0.0001), hemoglobin (9.8±1.4 vs. 11.9±0.8 g/dL, P<0.0001) and albumin (4.6±0.6 vs. 4.8±0.2 g/dL, P=0.012). The CRP showed higher occurrence among patients (40% were positive for CRP). Calcium and phosphorus evaluation showed significantly lower calcium and higher phosphorus among patients. However, the difference in Ca X P product was not statistically significant.
The study indicates that many of the CVD risk factors are associated with the different stages of CKD in children patients prior to dialysis, and that some of these factors are exacerbated as CKD progresses.
Cardiovascular disease; cardiovascular risk factors; children; chronic kidney disease
Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney disease (CKD).
HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3–5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD).
A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker.
This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study.
autonomic nervous system; cardiovascular disease risk factors; cardiovascular outcomes; cohort study; end-stage renal disease
Chronic kidney disease (CKD) is associated with an increased risk for incident cardiovascular disease (CVD), but the role of statin for the primary prevention of acute cardiovascular events in CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied.
Post-hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study.
Setting and Participants
Multicenter, randomized, double-blind, placebo-controlled trial of 5608 men and 997 women without CVD randomized to lovastatin or placebo.
Placebo or lovastatin 20 mg daily
Outcomes and Measurements
First major acute cardiovascular event in participants with mild CKD and kidney function loss among persons with or without CKD. Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation.
At baseline, the mean estimated glomerular filtration rate among CKD participants (n=304) was 53.3 ± 6.0 mL/min/1.73m2. After an average follow-up of 5.3 ± 0.8 years, the incidence of a fatal and non-fatal cardiovascular disease event was lower in CKD participants receiving lovastatin than in those on placebo (adjusted relative risk (RR): 0.31, 95% CI 0.13–0.72; p=0.01). Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD. Lovastatin did not reduce the annualized mean decline in estimated glomerular filtration rate (−1.3 ± 0.07 vs. −1.4 ± 0.07 mL/min/1.73m2/year, respectively, p=0.1), the frequency of ≥ 25% decrease in kidney function [adjusted RR: 1.10, 95% CI 0.96 to 1.28, p=0.2] or incident CKD (adjusted RR 1.04, 95% CI 0.86 to 1.27, p=0.6).
Unable to determine cause and duration of kidney disease and information regarding proteinuria was not available.
Lovastatin is effective for the primary prevention of CVD in CKD, but is not effective in decreasing kidney function loss in persons with no CVD.