Cardiometabolic syndrome and chronic kidney disease: what is the link?

The term metabolic syndrome or cardiometabolic syndrome describes the clustering of several cardiovascular and renal risk factors, including type 2 diabetes mellitus, central obesity, hypertension, and dyslipidemia. Over the past 15 years, several studies have examined the association between the metabolic/cardiometabolic syndrome or its central component, insulin resistance, with the presence of elevated urine albumin excretion. Intrarenal changes associated with the cardiometabolic syndrome result in elevated glomerular filtration rate, impaired pressure natriuresis, endothelial dysfunction related to changes in nitric oxide and, hence, impaired renal autoregulation and enhanced chronic inflammation. The aforementioned changes that occur in the cardiometabolic syndrome all contribute to the development of renal injury. While this review focuses on the epidemiology and mechanisms associated with vascular/renal injury, it must be remembered that prevention and treatment of kidney disease require a multifactorial approach. Weight loss through diet and exercise can reverse many of these pathophysiologic adaptations. Pharmacologic intervention should be aimed at achieving guideline goals and include insulin sensitizers to aid in tight glycemic control, lipid control, blockade of the renin-angiotensin-aldosterone system for blood pressure reduction, and anti-inflammatory therapies.     

Dignity in older age: what do older people in the United Kingdom think?

BACKGROUND: Dignity is a complex concept and there is little empirical research to show how older people view dignity. This study, using qualitative methods, explored the concept of dignity from the older person's perspective. METHODS: 15 focus groups and two individual interviews were conducted in 12 different settings, with a total of 72 participants. Participants were purposively sampled to ensure a mix of socio-economic status, ethnicity, gender, age (65+) and level of fitness. Focus groups were audio-taped and transcribed. The method of constant comparison was used to analyse the data. RESULTS: There was strong evidence to suggest that dignity was salient to the concerns of older people. Dignity was seen as a multi-faceted concept: (i). dignity of identity (self-respect/esteem, integrity, trust); (ii). human rights (equality, choice); and (iii). autonomy (independence, control). Examples of dignity being jeopardised rather than being enhanced were given. A loss of self-esteem arose from being patronised, excluded from decision-making, and being treated as an 'object'. Lack of integrity in society meant that there was an inability to trust others and an increased vulnerability. Equality was an important issue but many felt that government policies did not support their rights. CONCLUSIONS: This work identifies the different ways dignity is conceptualised by older people. The evidence showed that person centred care for older people needs to be specifically related to communication, privacy, personal identity and feelings of vulnerability. It provides evidence for policy makers and professionals to tailor policies and practices to the needs of the older person.     

Kawasaki disease in siblings in close temporal proximity to each other—what are the implications?

Clinical Rheumatology - Kawasaki disease (KD) is the commonest medium vessel vasculitis in children. The etiology of KD remains an enigma despite extensive research. Infections are considered to be...     

Clinical assessment of dehydration in older people admitted to hospital: what are the strongest indicators?

Due to an absence of published primary data, this study explores dehydration prevalence and the change in physiological parameters frequently used to assess dehydration (fluid deficit) in older hospitalized people, as no standard measurement method exists. This observational longitudinal cohort study recruited 43 people aged 60 years or over, voluntarily admitted to a tertiary teaching hospital's Geriatric and Rehabilitation Unit (GARU). Over 40 clinical, hematological and urinary biochemical parameters employed by medical officers during dehydration assessment, identified through literature, interviews and focus group were investigated. Short-term weight changes, intra- and inter-rater repeatability of dehydration assessments were completed to assess validation and precision of the clinician's clinical dehydration assessment. Systolic blood pressure drop on standing, sternal skin turgor, tongue dryness and body mass index (BMI) were associated with hydration status; demonstrated clinically meaningful differences between groups. BMI negatively confounded the association between dehydration and systolic blood pressure drop on standing. Physical, rather than biochemical, parameters more often identified mild dehydration. The findings challenge common expectations of hematological and physiological measurement changes occurring in older people clinically assessed as dehydrated and emphasize the need to adjust for potential confounders during exploration of the associations of clinical parameters with dehydration status.     

Does ALLHAT change the management of hypertension in chronic kidney disease?

ALLHAT was designed to test the hypothesis that “newer” antihypertensive agents are superior to a thiazide diuretic for cardiovascular outcomes. Pre-specified secondary outcomes included the development of endstage renal disease (ESRD) (dialysis, renal transplantation, or death from renal cause) and estimated glomerular filtration rate (GFR). ALLHAT showed no differences in the overall rates of ESRD between those randomized to chlorthalidone, amlodipine, or lisinopril. It showed a slower rate of decline of GFR among those randomized to amlodipine in both diabetics and nondiabetics, and in the composite end point (ESRD or ≥ 50% decline in GFR) in nondiabetics. The results of ALLHAT are consistent with other studies that, for the patient population studied (presumably largely nonalbuminuric patients with and without diabetes), at systolic BP < 130 mm Hg, there is no difference for renal outcomes between a thiazide diuretic, dihydropyridine calcium channel blocker, and ACEI-initiated treatment for 5 to 6 years of follow-up. These results suggest that BP control per se remains the most important objective for this patient population.     

Chlamydial nucleic acids in synovium in osteoarthritis: what are the implications?

OBJECTIVE: To study whether there is evidence of bacterial DNA in some osteoarthritic (OA) joint tissues, and the clinical implications of finding bacterial DNA in this relatively noninflammatory disease. METHODS: Polymerase chain reaction (PCR) was used to detect DNA of Chlamydia trachomatis, Chlamydia pneumoniae, and other bacteria using panbacterial primers in synovial membranes and other articular tissues of 32 consecutive patients undergoing surgery for hip and knee OA. Patients were interviewed and examined postoperatively. Operative reports were reviewed and followup examinations were accomplished on all patients. RESULTS: Nine of 32 patients with OA (28.1%) had evidence for bacterial DNA in joint tissues with at least one set of primers for Chlamydia: 7 for C. trachomatis (21.9%), 2 for C. pneumoniae (6.2%). Five of 32 (15.6%) patients had postoperative complications; 3 of these were in patients who showed amplified DNA of C. trachomatis in joints and one in a patient in whom we detected Escherichia coli. CONCLUSION: C. trachomatis and C. pneumoniae nucleic acids can be present in joints in some cases of apparently classical OA. Whether chlamydial or other difficult to culture bacterial presence is associated with complications is suggested, but remains to be determined. Simple presence of C. trachomatis by PCR does not define a clinical syndrome or disease course.     

Obesity in chronic kidney disease: good or bad?

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in chronic kidney disease (CKD) patients. As traditional risk factors cannot alone explain the high prevalence and incidence of CVD in this high-risk population, the complex of insulin resistance, oxidative stress, and endothelial dysfunction has increasingly been studied as important non-traditional risk factors. Recent studies show that the adipose tissue is a complex organ with functions far beyond the mere storage of energy. Indeed, it has recently been shown that fat tissue secretes a number of adipokines - including leptin, adiponectin and retinol-binding protein, as well as cytokines such as resistin, visfatin, tumor necrosis factor and interleukin-6. Adipokine serum levels are furthermore markedly elevated in CKD, likely due to a decreased renal excretion. Evidence suggests that these pluripotent signaling molecules may have multiple effects modulating insulin signaling, endothelial health and putatively CVD. As fat tissue is also a storage depot for energy, much needed in the catabolic milieu of uremia, further research is still needed to elucidate the likely complex interactions between these signaling networks, vascular health and outcome in this high-risk population.     

Genome-wide association studies of chronic kidney disease: what have we learned?

The past 3 years have witnessed a dramatic expansion in our knowledge of the genetic determinants of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). However, heritability estimates of eGFR indicate that we have only identified a small proportion of the total heritable contribution to the phenotypic variation. The majority of associations reported from genome-wide association studies identify genomic regions of interest and further work will be required to identify the causal variants responsible for a specific phenotype. Progress in this area is likely to stem from the identification of novel risk genotypes, which will offer insight into the pathogenesis of disease and potential novel therapeutic targets. Follow-up studies stimulated by findings from genome-wide association studies of kidney disease are already yielding promising results, such as the identification of an association between urinary uromodulin levels and incident CKD. Although this work is at an early stage, prospects for progress in our understanding of CKD and its treatment look more promising now than at any point in the past.     

Obesity--the risk factor of cardiovascular disease in patients with chronic kidney disease?

In general population obesity is regarded as a predisposing factor for chronic disease such as type 2 diabetes and cardiovascular disease. Obesity increases the risk of kidney disease and adversely affects the progress of kidney disease among patients with diagnosed kidney disease. The main reason of mortality in chronic kidney disease patients is cardiovascular disease, however, the real meaning of obesity as a risk factor of cardiovascular diseases is still uncertain. While in a general population obesity causes higher cardiovascular mortality, many studies reflect inverse association in chronic kidney disease patients. Obesity is associated with better survival, contrary to general population obesity appears to be a protective factor of cardiovascular disease. The name of this phenomenon is "reverse epidemiology" or "obesity paradox", in dialysis patients known as a "risk-factor-paradox". Some studies do not confirm this paradox association in patients with chronic kidney disease.     

Is inflammation the link between atherosclerosis and vascular calcification in chronic kidney disease?

Atherosclerosis and vascular calcification often co-exist in chronic kidney disease (CKD) patients. Although the former has been recently recognized as an active inflammatory process, atherosclerosis-related calcification of the intima is still viewed as a passive epiphenomenon. Recent experimental data showed that ossification of the internal vascular wall might also be an active inflammatory process interrelated to atherosclerosis. Factors like RANKL (receptor activator of nuclear factor kappaB ligand), RANK and osteoprotegerin modulate vascular calcification and at the same time are involved in the process of atherosclerosis. Moreover, basic calcium phosphate crystals could interact with and activate monocytes-macrophages that produce proinflammatory cytokines capable of initiating - via endothelial activation and leukocyte adhesion - the atherosclerotic process. Thus, vascular calcification might be an active player and not simply an epiphenomenon in atherosclerosis. Should the above-mentioned data be confirmed in future studies, calcification of the internal vascular wall and atherosclerosis might be viewed and treated as tightly interconnected and linked by inflammation processes in CKD patients.     

Anaemia, diabetes and chronic kidney disease: where are we now?

Anaemia is a common finding in people with diabetes and chronic kidney disease and failure of the kidney to produce erythro-poietin in response to a falling haemoglobin concentration is a key component, correlating with the degree of albuminuria, renal dysfunction and iron deficiency. Anaemia in diabetes is associated with a number of adverse outcomes, including increased risk of all cause and cardiovascular mortality. Whether or not anaemia is a marker or mediator of adverse outcome still remains to be completely resolved. Treatment of anaemia in diabetes has quality of life benefits and reduces transfusion requirements. Correction of anaemia to normal haemoglobin concentrations is associated with significant adverse cardiovascular outcomes and is not recommended, escalating doses of erythropoiesis-stimulating agents should be avoided. The treatment of anaemia in people with diabetes and chronic kidney disease should begin with optimisation of iron stores. An aspirational haemoglobin concentration range of 10-12 g/dl with anaemia management, balances proven benefits of anaemia treatment with potential cardiovascular risk.