Skip to main content
Top
Published in: BMC Nephrology 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Henrique Novais Mansur, Júlio César Moraes Lovisi, Fernando Antonio Basile Colugnati, Nadia Rezende Barbosa Raposo, Natália Maria da Silva Fernandes, Marcus Gomes Bastos

Published in: BMC Nephrology | Issue 1/2015

Login to get access

Abstract

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.
Literature
1.
go back to reference 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):489–95.CrossRefPubMedPubMedCentral 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):489–95.CrossRefPubMedPubMedCentral
2.
go back to reference 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):M146–56. 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):M146–56.
3.
go back to reference 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):1663–68.CrossRefPubMed 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):1663–68.CrossRefPubMed
4.
go back to reference 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):861–7.CrossRefPubMed 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):861–7.CrossRefPubMed
5.
go back to reference Johansen LK, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol. 2007;18(11):2960–7.CrossRefPubMed Johansen LK, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol. 2007;18(11):2960–7.CrossRefPubMed
6.
go back to reference 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):664–71.CrossRefPubMedPubMedCentral 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):664–71.CrossRefPubMedPubMedCentral
7.
go back to reference 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):912–21.CrossRefPubMedPubMedCentral 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):912–21.CrossRefPubMedPubMedCentral
8.
go back to reference 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):153–60. 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):153–60.
9.
go back to reference National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39 Suppl 2:S1–S246. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39 Suppl 2:S1–S246.
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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):777–81.CrossRefPubMed 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):777–81.CrossRefPubMed
12.
go back to reference 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;53:1321–30.CrossRefPubMed 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;53:1321–30.CrossRefPubMed
13.
go back to reference The Third Report of the National Cholesterol Education Program (NECP). Expert Panel on Detection. Evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97.CrossRef The Third Report of the National Cholesterol Education Program (NECP). Expert Panel on Detection. Evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97.CrossRef
14.
go back to reference 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):2637–45.CrossRefPubMed 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):2637–45.CrossRefPubMed
15.
go back to reference Barreto PS. One operational definition by population: the need for local evaluation of frailty. J Physiol Anthropol. 2011;30(6):259–62.CrossRef Barreto PS. One operational definition by population: the need for local evaluation of frailty. J Physiol Anthropol. 2011;30(6):259–62.CrossRef
16.
go back to reference 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):675–81.CrossRef 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):675–81.CrossRef
17.
go back to reference 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):1399–406.CrossRef 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):1399–406.CrossRef
18.
go back to reference 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. 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.
go back to reference 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):1268–71.CrossRefPubMed 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):1268–71.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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):1049–57.CrossRefPubMed 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):1049–57.CrossRefPubMed
22.
go back to reference 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):1581–8.CrossRefPubMedPubMedCentral 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):1581–8.CrossRefPubMedPubMedCentral
23.
go back to reference 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):377–81.CrossRefPubMed 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):377–81.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
25.
go back to reference 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):5266–73.CrossRefPubMedPubMedCentral 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):5266–73.CrossRefPubMedPubMedCentral
26.
go back to reference 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):101–6.CrossRefPubMedPubMedCentral 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):101–6.CrossRefPubMedPubMedCentral
27.
go back to reference 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):408–14.CrossRefPubMed 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):408–14.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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):846–51.CrossRefPubMed 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):846–51.CrossRefPubMed
30.
go back to reference Martens CR, Edwards DG. Peripheral vascular dysfunction in chronic kidney disease. Cardiol Res Pract. 2011;201:257–67. Martens CR, Edwards DG. Peripheral vascular dysfunction in chronic kidney disease. Cardiol Res Pract. 2011;201:257–67.
31.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
32.
go back to reference Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2008;19(2):213–6.CrossRefPubMed Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2008;19(2):213–6.CrossRefPubMed
33.
go back to reference 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):243–52.PubMed 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):243–52.PubMed
34.
go back to reference 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):E487–94.CrossRefPubMedPubMedCentral 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):E487–94.CrossRefPubMedPubMedCentral
35.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
36.
go back to reference 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):524–9.CrossRefPubMedPubMedCentral 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):524–9.CrossRefPubMedPubMedCentral
37.
go back to reference 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):2149–53.CrossRefPubMedPubMedCentral 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):2149–53.CrossRefPubMedPubMedCentral
38.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
39.
go back to reference 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):1071–7.CrossRefPubMedPubMedCentral 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):1071–7.CrossRefPubMedPubMedCentral
Metadata
Title
Association of frailty with endothelial dysfunction and its possible impact on negative outcomes in Brazilian predialysis patients with chronic kidney disease
Authors
Henrique Novais Mansur
Júlio César Moraes Lovisi
Fernando Antonio Basile Colugnati
Nadia Rezende Barbosa Raposo
Natália Maria da Silva Fernandes
Marcus Gomes Bastos
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2015
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-015-0150-1

Other articles of this Issue 1/2015

BMC Nephrology 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.