Association of frailty with endothelial dysfunction and its possible impact on negative outcomes in Brazilian predialysis patients with chronic kidney disease

Abstract

BackgroundFrailty is a state of physiological vulnerability common in the elderly. It is more predominant in patients with Chronic Kidney Disease in comparison to healthy subjects, which can also be diagnosed in non-elderly individuals and be associated with innumerous causes such as muscle strength, body composition and inflammation. The association between frailty and endothelial function, as well as the association between frailty and the combined outcome of mortality multiple cause and start of renal replace therapy were assessed.MethodsIn the initial analysis, sixty-one predialysis patients with Chronic Kidney Disease stages were evaluated and included in this study. Due to patient drop-out during follow-up, fifty-seven patients were subsequently re-evaluated 12 months later. The diagnosis of frailty was based on the Johansen et al. (J Am Soc Nephrol 18(11):2960-67, 2007) criteria. The groups were divided into Non-frail and Frail. Sociodemographic, inflammatory markers (IL-6, TNF-?, CRP-us), endothelial dysfunction (flow-mediated vasodilatation - FMD), body composition (DXA) and the 25-hidroxi-vitamin D parameters were analyzed.ResultsThe average age of the patients used in the study was 64.9 ± 10.3 years old. The predominance of frailty was 42.6 %, of which 46 % were non-elderly. After some adjustments, frailty was associated with gender (OR = 11.32; IC 95 % = 2.30 to 55.67), advanced age (OR = 4.07; IC 95 % = 1.02 to 16.20), obesity (OR = 6.63; IC 95 % = 0.82 to 11.44) and endothelial dysfunction (OR = 3.86; IC 95 % = 1.00 to 14.88). The ratio of the incidence of frail subjects to the variable outcome was 2.5 (CI 95 %, 1.04 to 6.50).ConclusionsAlthough an observational study does not allow one to determine the casual relation between frailty and endothelial dysfunction, we conclude that frailty was predominant in our sample of Brazilian patients with chronic kidney disease on predialysis, even in elderly individuals. This was linked to either worse endothelial function or mortality.

Is Frailty a Modifiable Risk Factor of Future Adverse Outcomes in Elderly Patients with Incident End-Stage Renal Disease?

“…Up until recently, the reason why frailty was associated with adverse clinical outcomes has been unclear. Subjects with frailty tended to have endothelial dysfunction ( 32 ) and inflammation ( 33 ). These subclinical pathophysiologic disturbances may explain the intimate association between frailty and various comorbidities, such as diabetes and cardiovascular diseases ( 10 11 23 24 27 28 30 ).…”

Chapter 4 Frailty and specific diseases

“…Of the 12 articles cited here, eight measured frailty using the CHS criteria. [59][60][61][62][63] Some of these studies found that frail CKD patients had significantly lower physical and mental component scores on the Short Form-36 Health Survey than non-frail CKD patients. CKD was associated with increased frailty or reduced physical function (OR 1.30-3.12).…”

“…Walker et al carried out a systematic review of cohort studies and observational studies that examined how frailty impacts CKD outcomes. [59][60][61] Two of the studies reported that frailty in CKD patients was associated with increased likelihood of mortality or dialysis therapy (OR 2.0-2.5). In patients with CKD, frailty was associated with a greater likelihood of dialysis and death (OR 2.00-5.88).…”

“…58 A number of studies examined the relationship of frailty with different stages of CKD, and they reported greater frailty prevalence with increasing stages (5.9-14.0% at stages 1 and 2, 10.7-56.0% at stages 3-5). [59][60][61][62][63] Some of these studies found that frail CKD patients had significantly lower physical and mental component scores on the Short Form-36 Health Survey than non-frail CKD patients. [59][60][61] Two of the studies reported that frailty in CKD patients was associated with increased likelihood of mortality or dialysis therapy (OR 2.0-2.5).…”

“…[59][60][61][62][63] Some of these studies found that frail CKD patients had significantly lower physical and mental component scores on the Short Form-36 Health Survey than non-frail CKD patients. [59][60][61] Two of the studies reported that frailty in CKD patients was associated with increased likelihood of mortality or dialysis therapy (OR 2.0-2.5). 62,63 Some studies have examined the relationship of frailty with estimated glomerular filtration rate (eGFR).…”