Sarcopenia Juan Jesús Carrero Dept Medical Epidemiology and Biosta9s9cs Karolinska Ins9tutet, Sweden.
1 Revisi&ng the concept of sarcopenia in geriatric diseases
Nephrol Dial Transplant. 2017 Jul 1;32(7):1127-1136. 2013 ERA- EDTA report
Worse quality of life, difficult management, mortality Nephrol Dial Transplant. 2017 Jul 1;32(7):1127-1136.
Loss of Muscle mass in CKD Uremia per se Dialysis Lifestyle factors Associated comorbidi5es Stenvinkel, Carrero et al. Nephrol Dial Transplant. 2016 Jul;31(7):1070-7.
CKD also affects muscle func7on, strength, mobility and exercise capacity Muscle mass Muscle strength Two complementary aspects of musculoeskeletal health Affected by different risk factors With different clinical implications Benefited from different treatment strategies
330 incident dialysis pa9ents with DEXA appendicular mass and handgrip strength Compared with reference popula9ons Age was the main determinant of muscle mass Muscle strength was instead explained by inflamma9on, PEW and comorbidi9es Low strength Normal strength Low muscle mass Normal muscle mass Total 20% 15% 36% 24% 41% 64% Total 44% 66% 100% Physical inac9vity was associated with muscle strength, but not muscle mass Clin J Am Soc Nephrol. 2014 Oct 7;9(10):1720-8.
Disassocia7on of muscle mass and strength; successful vs unsuccessful (pathological) aging Muscle func7on is affected by: Muscle mass Use/disuse Muscle fiber composi7on Inflamma7on, disease Neurological aspects
108 elderly HD and 122 elderly controls. Mid- thigh muscle area (magne9c resonance) and 6- min walking distance HD pa7ents had worse muscle func7on than controls, even a_er controlling for muscle mass, age and comorbidi9es. This muscle mass/ strength dissasocia9on may be more pronounced in CKD J Ren Nutr. 2015 Jul;25(4):371-5.
We need to beker understand these two aspects (mass and strength/performance) of muscle health Reduced fiber cross sec9onal area Reduced mitochondrial quality Reduced capillary density Skeletal muscle quality abnormali9es in ESRD Intramuscular fat infiltra&on Changes in the fiber type Carrero JJ, et al. J Ren Nutr. 2013;23:77-90.
Intramuscular adipocyte infiltra7on and age- related sarcopenia Regardless of muscle mass and fat, aging associated with an important loss of muscle strength coupled with intramuscular adipose 9ssue infiltra9on. 1700 men and women analyzed 5 years appart Muscle Mass Muscle strength Muscle Mass Muscle strength Subcut fat Intramusc fat Subcut fat Intramusc fat Am J Clin Nutr. 2009 Dec;90(6):1579-85.
Intramuscular fat infiltra7on in CKD AJKD 2003 As es9mated by MRI, the amount of adipose 9ssue infiltrated in thigh muscle was greater for CKD pa9ents than for age- sex- matched controls CT IMAGE 3 RD LUMBAR VERTEBRA Intramuscular fat infiltra7on shown in green of a control (1) and a HD (2) age- sex- matched elderly Courtesy of Carla Avesani and Nilian Carla Souza
Sarcopenia in geria7c diseases Low muscle strength Low muscle mass Low muscle performance Successful versus unsuccessful aging
2 Diagnosis of sarcopenia in CKD. The problem of mul&ple defini&ons
Sarcopenia, lack of consensus on its defini7on Common aspects : Muscle func7on: handgrip strength or gait speed (velocidad de la marcha). Muscle mass: appendicular skeletal mass index (extremi9es)
OK, but how do we define low? Common aspects: Some9mes based on <2 SD below reference popula9ons Some9mes based on specific cutoffs derived from single studies (Swiss cohort and Rancho Bernardo study)
A\er standardizing for age, sex and ethnicity, norma7ve HGS We differed may between more countries different geographically than we close thought to each other or with similar economic development 140.000 individuals from 17 countries of varying incomes and sociocultural sejngs. Lancet 2015; 386: 266-273
3-63% 102 elderly HD pa7ents J Nutr Health Aging. 2014 Jul;18(7):710-7. 2-31% 25-75% We are currently unable to clinically diagnose sarcopenia in CKD 325 PD pa7ents Nutr Clin Pract. 2017 Aug;32(4):539-544.
3 Clinical consequences of sarcopenia in CKD.
Separately, both low muscle mass and strength are strong outcome predictors Nephrology (Carlton). 2017 Feb;22(2):118-124.
What about together (sarcopenia)? Malnutri9on, inflamma9on, depression and cogni9ve dysfunc9on Malnutri9on and higher mortality risk Ren Fail. 2016 Apr;38(3):364-71. Loss of Appendicular muscle mass in haemodialysis pa9ents is associated with increased self- reported depression, anxiety and lower general health scores. Alston H, Burns A, Davenport A. Depression, anxiety and lower general health scores Nephrology (Carlton). 2017 May 25. doi: 10.1111/nep.13075. [Epub ahead of print]
Sarcopenia leads to Frailty Sarcopenia Progressive and generalized loss of skeletal muscle mass and strength Frailty Mul9dimen9onal loss of reserves: muscle, energy, physical independence, social ability, cogni9on and health
Low muscle mass versus low strength; different clinical implica7ons? 330 incident dialysis pa9ents with DEXA appendicular mass and handgrip strength Regardless of muscle stores, muscle strength was associated with mortality Isoyama et al. Clin J Am Soc Nephrol. 2014 Oct 7;9(10):1720-8.
Whole- body muscle mass using pre- dialysis bioimpedance spectroscopy measurements, gait speed and grip strength in 645 prevalent hemodialysis pa9ents Measures of muscle func9onality were beler predictors of mortality than measures of muscle mass. Muscle func9onality measures were associated with mortality independently of muscle size. The associa9on between muscle size and mortality was dependent of muscle func7onality Kidney Int. 2017 Jul;92(1):238-247.
4 Treatment of sarcopenia. In Geriatrics, interven9ons should focus on increasing muscle strength and improving physical func5on rather than simply increasing lean mass. J Am Geriatr Soc 57:1411 1419, 2009.
EXERCISE; BUT WHICH EXERCISE? Aerobic and resistance exercise improve muscle in different ways Variable Aerobic exercise Resistance exercise Fat mass Muscle mass Muscle strength Res9ng heart rate Physical endurance Basal metabolism Braith RW, et al. Circula&on. 2006;113:2642-2650. 26
Resistance training improves muscle performance and exercise tolerance/capacity in elderly HD pa7ents Exercise tolerance (peak/maximum oxygen consump9on) Changes in walking ability (6- min walking distance) Kidney Int Rep. 2017 Jun 21;2(6):1096-1110.
HD pa9ents (n = 21) underwent a 16- week control period, followed by 16 weeks of resistance training 3 9mes weekly Increased myonuclear content of type II muscle fibers Muscle Nerve. 2015 Nov;52(5):736-45.
Supervised exercise programs in PD? Center- barriers Funding, lack of 9me and of appropriate personnel Nephron Clin Pract. 2014;128(1-2):67-72. PD- barriers Concerns for presence of dialysate in the peritoneal cavity Precau9ons regarding PD catheter loss Increased risk of hernias Increased risk of infec9on at the catheter site (swimming) Greenwood. Perit Dial Int. 2017 Nov-Dec;37(6):595-597.
6 male PD pa9ents Strenuous exercise (weight li_ing, jogging, cycling) done with full abdomen results in excessive intra- abdominal pressure. Less- intense exercises such as cycling produced less IA pressure than jogging. Nephron. 1986;44(2):129-35.
13 PD pa9ents undertaking an aerobic exercise program for 12- weeks Significant improvements in peak aerobic capacity (VO 2max ) and quality of life No informa9on on muscle mass or func9on Am J Kidney Dis. 1998 Dec;32(6):1011-8.
Physical inac7vity Simply walking can be good 24 CKD stage 4 pa9ents randomized to usual daily ac9vi9es or regular walking exercise (30 min/d, 5 9mes/week) for 6- months Regular walking exerted an7- inflammatory effects through: Reduc7on in the ra7o IL- 6/IL- 10 Downregula7on of T- lymphocyte and monocyte ac7va7on J Am Soc Nephrol. 2014 Sep;25(9):2121-30
HD pa9ents randomized to a simple, personalized walking exercise program at home for 6 months. Exercise improved Physical performance (but not muscle mass) Exercise capacity Quality of life Cogni9ve func9on scores Those who completed the 6- month interven9on experienced lower hospitaliza9on and mortality rates J Am Soc Nephrol. 2017 Apr;28(4):1259-1268.
Sarcopenia Sarcopenia is a geriatric syndrome that refers to abnormali9es in muscle mass AND func9on. No consensus for opera9onal sarcopenia criteria hinders clinical applica9on. Therapeu7c op7ons are not well defined. Targe9ng muscle strength and quality may be more relevant than targe9ng muscle mass. This may involve resistance training programmes. Some considera9ons and precau9ons may be needed when designing supervised exercise programmes in PD, but increased walking can be a good start Adequately designed exercise interven9ons are needed in PD. juan.jesus.carrero@ki.se