To evaluate the longitudinal relationship between moderate chronic kidney disease (CKD), decline in kidney function, and microalbuminuria with subsequent cognitive decline and incident dementia.
This ...study is based on a population-based cohort of 7,839 subjects over 65 years with 7 years of follow-up. Glomerular filtration rate was estimated (eGFR) using the CKD-EPI equation. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) and dementia was actively screened and diagnosed.
At baseline, 12% of the participants had an eGFR <60 mL/min/1.73 m(2). A total of 564 incident dementia cases were diagnosed during the follow-up. Low baseline eGFR values were not associated with an increased risk of incident dementia or cognitive decline over the 7-year follow-up, except a borderline significant association with dementia with vascular component. However, eGFR decline over the first 4-year period was associated with higher risk of dementia with vascular component (relative risk = 5.35 1.76-16.3 in those with eGFR decline >4 mL/min/1.73 m(2)/y compared with those <4) and with higher cognitive decline on the MMSE (-0.12 points, p < 0.01 in those with eGFR >4 mL/min/1.73 m(2)/y compared with those <4) in the 3 subsequent years. Proteinuria tended to be associated with an increased risk of subsequent dementia with vascular component.
Despite a large sample and a long follow-up, we found no increased risk of cognitive decline or dementia associated with low eGFR level. However, faster eGFR decline was associated with global cognitive decline and incident dementia with vascular component, suggesting that this association may be mediated by vascular mechanisms.
The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need ...for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term ‘protein–energy wasting’ for loss of body protein mass and fuel reserves. ‘Kidney disease wasting’ refers to the occurrence of protein–energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein–energy wasting that occurs infrequently in kidney disease. Protein–energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein–energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein–energy wasting but do not define protein–energy wasting. Clinical staging and potential treatment strategies for protein–energy wasting are to be developed in the future.
Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to ...readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.
Aims
Drug prescription is difficult to manage in patients with chronic kidney disease (CKD). We assessed the prevalence and determinants of inappropriate drug prescriptions (whether contraindications ...or inappropriately high doses) with regard to kidney function in patients with CKD under nephrology care. We also assessed the impact of the equation used to estimate GFR on the prevalence estimates.
Methods
The CKD‐REIN cohort includes 3033 outpatients with CKD (eGFR between 15 and 60 ml min−1 1.73 m−2). We examined the daily doses of pharmacological agents prescribed at study entry. Inappropriate prescription was defined as the reported prescription of either a contraindicated drug or an indicated drug at an inappropriately high dose level with regard to the patient's GFR, as estimated with the CKD‐EPI equation, the de‐indexed CKD‐EPI equation, or the Cockcroft–Gault (CG) equation. Multivariate logistic regression was used to assess the determinants of inappropriate prescription risk.
Results
At baseline, patients' median interquartile range number of drugs prescribed per patient was 8 5–10. Half of the patients had been prescribed at least one inappropriate drug. Anti‐gout, cardiovascular agents and antidiabetic agents accounted for most of the inappropriate prescriptions. The percentage of inappropriate prescriptions varied from one GFR equation to another: 52% when using the CKD‐EPI equation, 47% when using the de‐indexed CKD‐EPI equation and 41% with the CG equation. A multiple logistic regression analysis showed significantly higher odds ratios 95% confidence interval for inappropriate prescriptions in male patients (1.28 1.07; 1.53), patients with diabetes (1.34 1.06; 1.70), those with a high BMI (1.58 1.25; 1.99), and those with a low GFR (10.2 6.02; 17.3). The risk of having at least one inappropriate prescription increased with the number of drugs per patient (P for trend < 0.0001) and therefore the odds ratio was 5.88 4.17; 8.28 for those who received at least 11 prescribed medications compared to those who received fewer than 5.
Conclusion
Our results emphasize the complexity of drug management for CKD patients, for whom inappropriate prescription appears to be common.
Context:
Recent data indicate that the secreted glycoprotein sclerostin may be involved in vascular calcification (VC).
Objective:
The objective of the study was to establish whether serum sclerostin ...levels are associated with VC in patients with rheumatoid arthritis (RA).
Design:
This was a cross-sectional study.
Setting:
The study was conducted with ambulatory care.
Patients:
We compared 75 RA patients with 75 age- and gender-matched control participants.
Intervention:
Coronary artery calcification (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography.
Main Outcome Measure:
Serum sclerostin levels (determined with an ELISA) were assessed. A statistical analysis was performed to identify the determinants of serum sclerostin and VC.
Results:
AAC and CAC were more prevalent and more severe in patients with RA than in controls. Higher levels of AAC (P = .02) and a higher lumbar bone mineral density (BMD; P = .03) were identified as independent determinants of higher serum sclerostin levels in RA patients, whereas male gender (P = .03), higher lumbar BMD (P < .0001), and low estimated glomerular rate (P < .001) were identified as determinants in controls. In RA patients, a multivariate logistic regression analysis indicated that older age P < .01, with an odds ratio (OR) per year 1.10 and male gender (P = .02, OR 6.79) were independent determinants of CAC and that older age (P < .001, OR 1.16) were independent determinants of AAC. In controls, the independent determinants were older age (P < .01, OR 1.19), hypertension (P < .01, OR 7.31), and lumbar BMD (P = .03, OR per 30 mg/cm2 increment of 1.14) for CAC and older age (P = .01, OR 1.11) for AAC.
Conclusions:
Serum sclerostin levels were significantly and independently associated with AAC in RA patients.
To make an evidence-based evaluation of the relationship between kidney failure and cardiovascular risk, we reviewed the literature obtained from a PubMed search using pre-defined keywords related to ...both conditions and covering 18 years (1986 until end 2003). Eighty-five publications, covering 552 258 subjects, are summarized. All but three studies support a link between kidney dysfunction and cardiovascular risk. More importantly, the association is observed very early during the evolution of renal failure: an accelerated cardiovascular risk appears at varying glomerular filtration rate (GFR) cut-off values, which were ≥60 ml/min in at least 20 studies. Many studies lacked a clear definition of cardiovascular disease and/or used a single determination of serum creatinine or GFR as an index of kidney function, which is not necessarily corresponding to well-defined chronic kidney disease. In six studies, however, chronic kidney dysfunction and cardiovascular disease were well defined and the results of these confirm the impact of kidney dysfunction. It is concluded that there is an undeniable link between kidney dysfunction and cardiovascular risk and that the presence of even subtle kidney dysfunction should be considered as one of the conditions necessitating intensive prevention of this cardiovascular risk.
Summary
The hormone fibroblast growth factor 23 (FGF23) is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. In a cohort of 142 patients with ...CKD stages 2–5D, plasma FGF23 was independently associated with aortic calcification but not with pulse wave velocity or bone mineral density.
Introduction
FGF23 is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. Previous studies related to FGF23 and vascular and bone outcomes have been restricted to dialysis patients. The aim of the present study was to establish whether or not plasma FGF23 is associated with aortic and coronary calcification, arterial stiffness, and bone mineral density in patients with early as well as late stages of CKD.
Methods
In a cohort of 142 patients with CKD stages 2–5D, we made routine biochemistry and intact FGF23 determinations, and assessed aortic and coronary calcification, bone mineral density (BMD), and arterial stiffness by multislice spiral computed tomography and automated pulse wave velocity (PWV).
Results
Plasma intact FGF23 levels were elevated in CKD patients; the elevation preceded that of serum phosphate in early-stage CKD. Patients with elevated FGF23 levels had higher aortic and coronary calcification scores than patients with lower FGF23 levels. Multivariate linear regression analysis indicated that only age (
p
< 0.001) and FGF23 (
p
= 0.008) were independently associated with aortic calcification score. Plasma FGF23 was neither associated with PWV nor with BMD.
Conclusion
Our data suggest that plasma FGF23 is an independent biomarker of vascular calcification in patients with various CKD stages including early stages. The association between vascular calcification and FGF23 levels appears to be independent of BMD. It remains to be seen whether this association is independent of bone turnover and bone mass.
Abstract
The exclusion of chronic kidney disease (CKD) patients from clinical trials—particularly cardiovascular trials—remains a long-standing, unsolved problem, which prevents the optimization of ...clinical care in these patients. The situation recalls the insufficient recruitment of women in cardiovascular trials until the 1980s, a problem that was only resolved following regulatory interventions. Regulatory agencies are in a unique position to promote recruitment of CKD patients in clinical trials. The main stakeholders, namely patients’ associations and scientific societies, should make major lobbying efforts to persuade these agencies that the issue is an absolute public health priority.
Individuals with rheumatoid arthritis (RA) are at increased risk for morbidity and mortality from cardiovascular disease. Excess cardiovascular mortality in RA patients cannot be fully explained by ...conventional cardiovascular risk factors. The purpose of this review is to discuss recent progress concerning the prevalence and pathophysiological aspects of vascular calcification in RA. RA patients have early-onset diffuse calcification involving multiple vascular beds compared to age and sex-matched controls. Pathogenesis of vascular calcification in RA patients is not fully understood, but specific mediators such as proinflammatory cytokines and not global inflammation could be involved. The possible link between osteoporosis and vascular calcification in RA will not be discussed. Finally, potential targets to reduce vascular calcification in RA will be discussed.
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