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

BMC Nephrology

Marcus Gomes Bastos¹  Natália Maria da Silva Fernandes³  Nadia Rezende Barbosa Raposo³  Fernando Antonio Basile Colugnati³  Júlio César Moraes Lovisi³  Henrique Novais Mansur² 

[1] Federal University of Juiz de Fora, José Lourenço Kelmer Street, 1300, Juiz de Fora, Minas Gerais, Brazil;Academic Centre of Vitoria, Federal University of Pernambuco, Vitória de Santo Antão, Pernambuco, Brazil;IMEPEN Foundation, Federal University of Juiz de Fora, Juiz de Fora, Brazil

关键词: Mortality;    Frailty;    Endothelium;    Chronic kidney disease;   

Others  :  1228361
DOI  :  10.1186/s12882-015-0150-1

 received in 2014-04-05, accepted in 2015-09-11,  发布年份 2015

【 摘 要 】

Background

Frailty 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.

Methods

In 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.

Results

The 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).

Conclusions

Although 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.

【 授权许可】

   
2015 Mansur et al.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Rockwood K, Song X, Macknight C, Bergman H, Hogan DB, McDowell I et al.. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005; 173(5):489-495.
• [2]Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J et al.. Collaborative Research Group for the Cardiovascular Health Study: Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2006; 56A(3):M146-M156.
• [3]Kosch M, Levers A, Barenbrock M, Matzkies F, Schaefer RM, Kisters K et al.. Accute effects of haemodialysis on endothelial function and large artery elasticity. Nephrol Dial Transplant. 2001; 16(8):1663-1668.
• [4]Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP et al.. The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis. 2004; 43(5):861-867.
• [5]Johansen LK, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol. 2007; 18(11):2960-2967.
• [6]Wilhelm-Leen ER, Hall YN, Tamura MK, Chertow GM. Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey. Am J Med. 2009; 122(7):664-671.
• [7]Roshanravan B, Khatri M, Robinson-Cohen C, Levin G, Patel KV, de Boer IH et al.. A prospective study of frailty in nephrology-referred patients with CKD. Am J Kidney Dis. 2012; 60(6):912-921.
• [8]Mansur HN, Damasceno VO, Bastos MG. Prevalence of frailty in patients with chronic kidney disease not yet and on dialysis. Braz J Nephrol. 2012; 34(2):153-160.
• [9]K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002; 39 Suppl 2:S1-S246.
• [10]Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130(6):461-70.
• [11]Brucki SM, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH. Suggestions for utilization of the mini-mental state examination in Brazil. Arq Neuropsiquiatr. 2003; 61(3B):777-781.
• [12]Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL et al.. Frailty: emergence and consequences in women aged 65 and older in the Women’s Health Initiative Observational Study. J Am Geriatr Soc. 2005; 53:1321-1330.
• [13]Evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001; 285(19):2486-97.
• [14]Melhus H, Snellman G, Gedeborg R, Byberg L, Berglund L, Mallmin H et al.. Plasma 25-hydroxyvitamin D levels and fracture risk in a community-based group of elderly men in Sweden. J Clin Endocrinol Metab. 2010; 95(6):2637-2645.
• [15]Barreto PS. One operational definition by population: the need for local evaluation of frailty. J Physiol Anthropol. 2011; 30(6):259-262.
• [16]Santos-Eggimann B, Cuénoud P, Spagnoli J, Junod J. Prevalence of frailty in middle-aged and older community-dwelling Europeans living in 10 countries. Gerontol A Biol Sci Med Sci. 2009; 64(6):675-681.
• [17]Alvarado BE, Zunzunnegui V, Beland F, Bamvita J. Life course social and health conditions linked to frailty in Latin American older men and women. J Gerontol. 2008; 63A(12):1399-1406.
• [18]Bautmans I, Gorus E, Njemini R, Mets T. Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation. BMC Geriatrics. 2007;7:5.
• [19]Leng S, Chaves P, Koenig K, Walston J. Serum interkeukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002; 50(7):1268-1271.
• [20]Chang SS, Weiss CO, Xue Q-I, Fried LP. Association between inflammatory- related disease burden and frailty: results from the Women’s Health and Aging Studies (WHAS) I and II. Arch Gerontol Geriatr. 2012; 54(1):9-15.
• [21]Fried LP, Xue Q-I, Cappola AR, Ferrucci L, Chaves P, Varadhan R et al.. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci. 2009; 64(10):1049-1057.
• [22]Sanders JL, Boudreau RM, Fried LP, Walston JD, Harris TB, Newman AB. Measurement of organ structure and function enhances understanding of the physiological basis of frailty: the Cardiovascular Health Study. J Am Geriatr Soc. 2011; 59(9):1581-1588.
• [23]Hubbard RE, Lang A, Lewellyn DJ, Rockwood K. Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci. 2010; 65(4):377-381.
• [24]Shardell M, Hicks GE, Miller RR, Kritchevsky S, Andersen D, Bandinelli S et al.. Association of low vitamin D levels with the frailty syndrome in men and women. J Gerontol A Biol Sci Med Sci. 2009; 64(1):69-75.
• [25]Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA et al.. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab. 2010; 95(12):5266-5273.
• [26]Ensrud KE, Blackwell TL, Caulley JA, Cummings SR, Barrett-Connor E, Dam TL et al.. Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc. 2010; 59(1):101-106.
• [27]Cuppari L, Carvalho AB, Draibe AS. Vitamin D status of chronic kidney disease patients living in a Sunny Country. J Ren Nutr. 2008; 18(5):408-414.
• [28]Diniz HF, Romão MF, Elias RM, Romão Júnior JE. Vitamin D deficiency and insufficiency in patients with chronic kidney disease. J Bras Nefrol. 2012; 34(1):58-63.
• [29]Grassi G, Quarti-Trevano F, Seravalle G, Arenare F, Volpe M, Furiani S et al.. Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension. 2011; 57(4):846-851.
• [30]Martens CR, Edwards DG. Peripheral vascular dysfunction in chronic kidney disease. Cardiol Res Pract. 2011;201:257–67.
• [31]Nakayama T, Sato W, Kosuqi T, Zhang L, Campbell-Thompson M, Yoshimura A et al.. Endothelial injury due to eNOS deficiency accelerates the progression of chronic renal disease in the mouse. Am J Physiol Renal Physiol. 2009; 296(2):F317-327.
• [32]Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2008; 19(2):213-216.
• [33]Chen JLT, Lerner D, Ruthazer R, Castaneda-Sceppa C, Levey AS. Association of physical activity with mortality in chronic kidney disease. J Nephrol. 2008; 21(2):243-252.
• [34]Rockwood K, Song X, Mitnitski A. Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey. CMAJ. 2011; 183(8):E487-E494.
• [35]Shi J, Song X, Yu P, Tang Z, Mitnitski A, Fang X et al.. Analysis of frailty and survival from late middle age in the Beijing Longitudinal Study of Aging. BMC Geriatrics. 2011; 11:17. BioMed Central Full Text
• [36]Fallah N, Mitnitski A, Searle SD, Gahbauer EA, Gill TM, Rockwood K. Transitions in frailty status in older adults in relation to mobility: a multistate modeling approach employing a deficit count. J Am Geriatr Soc. 2011; 59(3):524-529.
• [37]Masel MC, Ostir GV, Ottenbache KJ. Frailty, mortality, and health related quality of life in older Mexican Americans. J Am Geriatr Soc. 2010; 58(11):2149-2153.
• [38]García-González J-J, García-Peña C, Franco-Marina F. A frailty index to predict the mortality risk in a population of senior Mexican adults. BMC Geriatr. 2009; 9:47. BioMed Central Full Text
• [39]Bao Y, Dalrymple L, Chertow GM, Kaysen GA, Johansen KL. Frailty, dialysis initiation, and mortality in end-stage renal disease. Arch Intern Med. 2012; 172(14):1071-1077.