Fragilidade na doença renal crônica: prevalência e fatores associados

Abstract

Frailty is characterized by a decline in physiological reserves and is manifested by losses of body weight, muscle mass, strength, and energy. It is common in the elderly, and more prevalent among patients with chronic kidney disease (CKD), even in those at younger ages. The aim of this study was to assess the prevalence of frailty in patients with CKD not yet on dialysis and the possible factors common to both syndromes, for example, endothelial dysfunction, inflammatory markers, metabolic acidosis, anemia, and low level of vitamin D. We also aimed to develop a less subjective method of assessment of frailty and compare its performance with another used in patients with CKD, regarding to negative outcomes after one year of follow-up. In this study, we evaluated cross-sectionally 61 adult patients of both sexes with CKD stages 3 to 5 not yet in dialysis. The diagnosis of CKD was based on the criteria proposed by the National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF KDOQITM). The glomerular filtration rate (GFR) was estimated from serum creatinine using the MDRD formula. The diagnosis of frailty was based as proposed by Johansen et al. (2007), measuring slowness/weakness (SF-36), poor endurance/ exhaustion (SF-36), physical inactivity, and unintentional weight loss. A total of 5 points was possible, with 2 points for weakness and slowness and 1 point for each of the other criteria. Patients scoring ≥3 were defined as frail. Our instrument differed from Johansen’s since we use handgrip for assessment of weakness and 6 minutes walking test to assess physical inactivity. The patients were divided in not frail (NF) and frail (F). Besides the lab tests, the other variables assessed were C reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-), endothelial function (assessed by brachial artery flow-mediated vasodilatation), bone density (DXA), vitamin D (HPLC). The mean age of the 61 patients included in this study was 60,5±11,5 years old, 41 % were female, and 43,9% were white. There was no statistical difference between the main causes of CKD in frail and not frail patients: hypertension (26.9% vs. 31.4%), diabetes mellitus (11.4% vs. 18.0%), and glomerulonephritis (20.0% vs. 14.8%). The median (interquartil interval) serum creatinine was 2,3 (1,7-3,5) mg/dL, the GFR was 23 (16-39) mL/min/1.73 m2. The frailty syndrome was diagnosed in 42.6% of the patients. Although the frail patients were older (p= 0.0009), 30.8% were younger than 60 years. The frailty patients were more likely to be women (p= 0.02), had higher fat mass (p= 0.05), more osteoporosis (p= 0.01), higher PTH (p= 0.02), lower transferrin saturation ratio (p= 0.02) and more endothelial dysfunction (p= 0.05). The construct of frailty correlated positively with age (r= 0,25, p= 0.05), fat mass (r= 0.25, p= 0.04) and PTH (r= 0.30, p= 0.01), and negatively with endothelial dysfunction (r= -0.367, p= 0.004). In the regression analysis, female sex (OR: 11,3; IC 95% 2,3 - 55,6), age >60 years (OR: 4,0; IC 95% 1,0 – 16,2), obesity (OR: 6,6; IC 95% 1,1 – 36,7), and endothelial dysfunction (OR: 3,8; IC 95% 1,0 – 14,8) correlated with the frail phenotype. There was a 67% agreement of both criteria in identifying frail patients. However, when comparing both instruments of assessment of frailty, ours correlated better with negative outcomes. Frailty is frequent and early in CKD patients not yet in dialysis, and associates with negative outcomes. Bone mineral disorders, endothelial dysfunction seems to be potential mechanisms underlying the CKD and frailty.