[Show abstract][Hide abstract] ABSTRACT: Background Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD. Methods We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics. Results Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m2, 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6–3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests. Conclusions Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline.
[Show abstract][Hide abstract] ABSTRACT: Neurologic outcomes in CKD patients are pervasive; most common are cognitive impairment, stroke, and peripheral neuropathies. Despite a strong graded association between measures of renal function and cognitive function, cognitive impairment in CKD patients is largely undiagnosed. Annual and predialysis cognitive screening is critical to avoid adverse outcomes of missed diagnoses of cognitive impairment: medication noncompliance and inability to make informed decisions regarding initiating dialysis. Cerebrovascular disease, neurodegenerative disease, and inflammation contribute to a CKD model of accelerated vascular cognitive impairment. Risk of stroke increases significantly in CKD and ESRD patients, up to 7-fold during the month of dialysis initiation. Aggressive treatment with erythropoiesis-stimulating agents increases stroke risk appreciably. For stroke prevention in atrial fibrillation, warfarin and dose-adjusted newer anticoagulants appear effective in stage 3 CKD patients but are unproven or contraindicated in CKD stage 4 or higher. Management of uremic polyneuropathy, mononeuropathies, and uremic pruritus is described in this chapter.
[Show abstract][Hide abstract] ABSTRACT: Background:
There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB.
hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined.
Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older and more likely to be male and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57).
hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).
No preview · Article · Oct 2015 · Clinical Chemistry
[Show abstract][Hide abstract] ABSTRACT: aEuro broken vertical bar Schneider's findings may provide support for the hypothesis that increasing dialysis frequency and/or clearance could lead to long-term improvements in cognitive functions.aEuro broken vertical bar.
Preview · Article · Jun 2015 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
There is limited information on the risk of progression of chronic kidney disease (CKD) among individuals with CVD (cardiovascular disease). We studied the association between prevalent CVD and the risk of progression of CKD among persons enrolled in a long-term observational study.
A prospective cohort study of 3,939 women and men with CKD enrolled in the chronic renal insufficiency cohort (CRIC) study between June 2003 and June 2008. Prevalent cardiovascular disease (myocardial infarction/revascularization, heart failure, stroke, and peripheral vascular disease) was determined by self-report at baseline. The primary outcome was a composite of either end-stage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline.
One-third (1,316 of 3,939, 33.4%) of the study participants reported a history of any cardiovascular disease, and 9.6% (n = 382) a history of heart failure at baseline. After a median follow up of 6.63 years, 1,028 patients experienced the primary outcome. The composite of any CVD at baseline was not independently associated with the primary outcome (Hazard Ratio 1.04 95% CI (0.91, 1.19)). However, a history of heart failure was independently associated with a 29% higher risk of the primary outcome (Hazard Ratio 1.29 95% CI (1.06, 1.57)). The relationship between heart failure and risk of CKD progression was consistent in subgroups defined by age, race, gender, baseline eGFR, and diabetes. Neither the composite measure of any CVD or heart failure was associated with the rate of decline in eGFR.
Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease.
No preview · Article · Nov 2014 · American Journal of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Background:
Leukocytosis is a powerful predictor of incident chronic kidney disease (CKD) and related outcomes. However, the association between periodontitis measures and increased leukocytosis in the context of CKD has not been well described. We sought to identify which individual measures of periodontal disease may best associate with reduced estimated glomerular filtration rate (eGFR) and albuminuria, and to test if these measures were associated with increased leukocytosis in subjects with established CKD.
We estimated, among 13,270 participants in the National Health and Nutrition Examination Survey III study, the associations between case-based definition of periodontitis, clinical attachment loss (CAL) and pocket depth (PD) as individual measures of periodontal disease, with renal function measures and leukocytosis.
In adjusted multivariate analyses, case-based definition of severe periodontitis was associated with albuminuria (β = 0.003, p = 0.01) but not with eGFR. However, CAL and PD were all individually associated with both albuminuria (β = 0.08, p < 0.001 and β = 0.06, p < 0.001, respectively) and eGFR (β = -0.05, p < 0.001 and β = -0.03, p < 0.001, respectively). We found significant associations between elevated CAL and PD with leukocytosis. Lastly, we found a marked association between the joint presence of CKD and elevated CAL or PD with leukocytosis (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4-7.5 and OR 3.2, 95% CI 1.1-9.7, respectively).
Individual measures of periodontal disease are associated with renal function and heightened leukocytosis in CKD subjects. The significantly added inflammatory burden noted in CKD subjects with periodontal disease argue for targeting periodontitis treatment as part of our multifaceted approach to CKD patients.
Full-text · Article · Nov 2014 · Nephron Clinical Practice
[Show abstract][Hide abstract] ABSTRACT: Purpose of review:
This review presents the role of combination therapy of renin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease.
Three large randomized controlled trials comparing combination therapy of renin-angiotensin-aldosterone system blockade to monotherapy in individuals with increased cardiovascular risk, chronic kidney disease, or diabetic nephropathy have been reported. These trials - ONTARGET, ALTITUDE, and VA NEPHRON-D - demonstrated an excess risk of adverse effects [especially acute kidney injury (AKI) and hyperkalemia] with combination therapy, without significant benefit in reducing cardiovascular and renal morbidity.
Current evidence supports avoiding dual renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Subsequent studies of dual renin-angiotensin-aldosterone system blockade should examine adverse event risks and renal progression endpoints.
No preview · Article · Jul 2014 · Current Opinion in Nephrology and Hypertension
[Show abstract][Hide abstract] ABSTRACT: Background:
Renal hemodynamic measurements are complicated to perform in patients with cirrhosis, yet they provide the best measure of risk to predict hepatorenal syndrome (HRS). Currently, there are no established biomarkers of altered renal hemodynamics in cirrhosis validated by measured renal hemodynamics.
In this pilot study, simultaneous measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), renal resistive indices and biomarkers were performed to evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients without ascites, 5 with diuretic-sensitive and 2 diuretic-refractory ascites).
Patients with diuretic-refractory ascites had the lowest mean GFR (36.5 ml/min/1.73 m(2)) and RPF (133.6 ml/min/1.73 m(2)) when compared to those without ascites (GFR 82.9 ml/min/1.73 m(2), RPF 229.9 ml/min/1.73 m(2)) and with diuretic-sensitive ascites (GFR 82.3 ml/min/1.73 m(2), RPF 344.1 ml/min/1.73 m(2)). A higher mean filtration fraction (FF) (GFR/RPF 0.36) was noted among those without ascites compared to those with ascites. Higher FF in patients without ascites is most likely secondary to the vasoconstriction in the efferent glomerular arterioles (normal FF ~0.20). In general, renal resistive indices were inversely related to FF. While patients with ascites had lower FF and higher right kidney main and arcuate artery resistive indices, those without ascites had higher FF and lower right kidney main and arcuate artery resistive indices. While cystatin C and β2-microglobulin performed better compared to Cr in estimating RPF, β-trace protein, β2-microglobulin, and SDMA, and (SDMA+ADMA) performed better in estimating right kidney arcuate artery resistive index.
The results of this pilot study showed that identification of non-invasive biomarkers of reduced RPF and increased renal resistive indices can identify cirrhotics at risk for HRS at a stage more amenable to therapeutic intervention and reduce mortality from kidney failure in cirrhosis.
No preview · Article · Jun 2014 · American Journal of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Conventional creatinine-based glomerular filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by nonradiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the "bias," "precision," and "accuracy" of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG), and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores (differences between mGFR and estimated GFR [eGFR] or between mGFR and CrCl, or between mGFR and CG equation for each subject) (RMSE = 23.56) was significantly better than that of CrCl (37.69, P = 0.001), CG (RMSE = 36.12, P = 0.002), and GFR-estimating equations based on cystatin C only. Its accuracy as quantified by percentage of eGFRs that differed by greater than 30% with respect to mGFR was significantly better compared to CrCl (P = 0.024), CG (P = 0.0001), 4-variable MDRD (P = 0.027), and CKD-EPI creatinine 2009 (P = 0.012) equations. However, for 23.61% of the subjects, GFR estimated by CKD-EPI creatinine-cystatin C equation differed from the mGFR by more than 30%.
The diagnostic performance of CKD-EPI creatinine-cystatin C equation (2012) in patients with cirrhosis was superior to conventional equations in clinical practice for estimating GFR. However, its diagnostic performance was substantially worse than reported in subjects without cirrhosis.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To determine the 99th percentile upper reference limit for the highly sensitive cardiac troponin T assay (hs-cTnT) in three large independent cohorts.
The presently recommended 14 ng/L cutpoint for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization.
Data were included from three well characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease and kidney disease (subcohort 1) and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex and race.
The 99th percentile values for the hs-cTnT assay in DHS, ARIC and CHS were 18, 22 and 36 ng/L respectively (subcohort 1) and 14, 21 and 28 ng/L respectively (subcohort 2). These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men aged 65-74 with no cardiovascular disease in our study had cTnT values above the current myocardial infarction threshold.
Use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay.
Preview · Article · Apr 2014 · Journal of the American College of Cardiology