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Low-Plasma Insulin-Like Growth Factor-1 Associates With Increased Mortality in Chronic Kidney Disease Patients With Reduced Muscle Strength

  • Zhimin Chen
    Affiliations
    Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China

    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Erik Nilsson
    Affiliations
    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Bengt Lindholm
    Affiliations
    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Olof Heimbürger
    Affiliations
    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Peter Barany
    Affiliations
    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Peter Stenvinkel
    Affiliations
    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Abdul Rashid Qureshi
    Affiliations
    Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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  • Jianghua Chen
    Correspondence
    Address correspondence to Jianghua Chen, MD, Pro, Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, No 79, Qingchun Road, Hangzhou, China.
    Affiliations
    Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
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      Objectives

      Chronic kidney disease (CKD) leads to metabolic and nutritional abnormalities including resistance to insulin-like growth factor-1 (IGF-1) action, and reduced muscle mass and strength. Low IGF-1 as well as low hand-grip muscle strength (HGS) are independent predictors of increased mortality in CKD patients.

      Methods

      In 685 patients (CKD Stage 3-5, median age 58 years; 62% men), baseline measurements of IGF-1, HGS, subjective global assessment (SGA), lean body mass index (LBMI), and metabolic and inflammatory biomarkers potentially linked to IGF-1 were analyzed in relation to mortality during 5 years of follow-up. We compared survival in 4 groups with high or low (cut-offs defined by receiver operating characteristic curve analysis) levels of IGF-1 and HGS.

      Results

      Patients with low IGF-1 were older; had lower BMI, HGS, and LBMI, were more likely to have diabetes, cardiovascular disease (CVD), and malnutrition (SGA >1); and had high-sensitivity C-reactive protein levels. During 5 years of follow-up, 208 patients died. The mortality rate was highest among patients with Low IGF-1 + Low HGS. In competing-risk regression analysis, Low IGF-1 + Low HGS was independently associated with 2.8 times higher all-cause mortality risk than Low IGF-1 + High HGS, after adjusting for Framingham’s CVD risk score, presence of CVD, SGA, dialysis status, high-sensitivity C-reactive protein, albumin, LBMI, and sample time in freezer.

      Conclusion

      Low IGF-1 was associated with increased all-cause mortality in patients who also had low HGS but not in those with high HGS, suggesting that the association of IGF-1 with survival in CKD patients depends on nutritional status.

      Keywords

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      References

        • Fouque D.
        • Kalantar-Zadeh K.
        • Kopple J.
        • et al.
        A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease.
        Kidney Int. 2008; 73: 391-398
        • Dai L.
        • Mukai H.
        • Lindholm B.
        • et al.
        Clinical global assessment of nutritional status as predictor of mortality in chronic kidney disease patients.
        PLoS One. 2017; 12: e0186659
        • Qureshi A.R.
        • Alvestrand A.
        • Danielsson A.
        • et al.
        Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.
        Kidney Int. 1998; 53: 773-782
        • Stenvinkel P.
        • Heimburger O.
        • Paultre F.
        • et al.
        Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.
        Kidney Int. 1999; 55: 1899-1911
        • Stenvinkel P.
        • Barany P.
        • Chung S.H.
        • Lindholm B.
        • Heimbürger O.
        A comparative analysis of nutritional parameters as predictors of outcome in male and female ESRD patients.
        Nephrol Dial Transpl. 2002; 17: 1266-1274
        • Isoyama N.
        • Qureshi A.R.
        • Avesani C.M.
        • et al.
        Comparative associations of muscle mass and muscle strength with mortality in dialysis patients.
        Clin J Am Soc Nephrol. 2014; 9: 1720-1728
        • Sayer A.A.
        • Robinson S.M.
        • Patel H.P.
        • Shavlakadze T.
        • Cooper C.
        • Grounds M.D.
        New horizons in the pathogenesis, diagnosis and management of sarcopenia.
        Age Ageing. 2013; 42: 145-150
        • Heimburger O.
        • Qureshi A.R.
        • Blaner W.S.
        • Berglund L.
        • Stenvinkel P.
        Hand-grip muscle strength, lean body mass, and plasma proteins as markers of nutritional status in patients with chronic renal failure close to start of dialysis therapy.
        Am J Kidney Dis. 2000; 36: 1213-1225
        • Jones C.H.
        • Newstead C.G.
        • Will E.J.
        • Smye S.W.
        • Davison A.M.
        Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure.
        Nephrol Dial Transpl. 1997; 12: 1406-1413
        • Moreau-Gaudry X.
        • Guebre-Egziabher F.
        • Jean G.
        • et al.
        Serum creatinine improves body mass index survival prediction in hemodialysis patients: a 1-year prospective cohort analysis from the ARNOS study.
        J Ren Nutr. 2011; 21: 369-375
        • Thissen J.P.
        • Ketelslegers J.M.
        • Underwood L.E.
        Nutritional regulation of the insulin-like growth factors.
        Endocr Rev. 1994; 15: 80-101
        • Mak R.H.
        • Cheung W.W.
        • Roberts C.T.
        The growth hormone-insulin-like growth factor-I axis in chronic kidney disease.
        Growth Horm IGF Res. 2008; 18: 17-25
        • Feldt-Rasmussen B.
        • El Nahas M.
        Potential role of growth factors with particular focus on growth hormone and insulin-like growth factor-1 in the management of chronic kidney disease.
        Semin Nephrol. 2009; 29: 50-58
        • Juul A.
        • Scheike T.
        • Davidsen M.
        • Gyllenborg J.
        • Jorgensen T.
        Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study.
        Circulation. 2002; 106: 939-944
        • Vasan R.S.
        • Sullivan L.M.
        • D'Agostino R.B.
        • et al.
        Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study.
        Ann Intern Med. 2003; 139: 642-648
        • Burgers A.M.
        • Biermasz N.R.
        • Schoones J.W.
        • et al.
        Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality.
        J Clin Endocrinol Metab. 2011; 96: 2912-2920
        • Qureshi A.R.
        • Alvestrand A.
        • Divino-Filho J.C.
        • et al.
        Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients.
        J Am Soc Nephrol. 2002; 13: S28-S36
        • Fernández-Reyes M.J.
        • Alvarez-Ude F.
        • Sánchez R.
        • et al.
        Inflammation and malnutrition as predictors of mortality in patients on hemodialysis.
        J Nephrol. 2002; 15: 136-143
        • Jia T.
        • Gama Axelsson T.
        • Heimbürger O.
        • et al.
        IGF-1 and survival in ESRD.
        Clin J Am Soc Nephrol. 2014; 9: 120-127
        • Nilsson E.
        • Carrero J.J.
        • Heimbürger O.
        • Hellberg O.
        • Lindholm B.
        • Stenvinkel P.
        A cohort study of insulin-like growth factor 1 and mortality in haemodialysis patients.
        Clin Kidney J. 2016; 9: 148-152
        • Laughlin G.A.
        • Barrett-Connor E.
        • Criqui M.H.
        • Kritz-Silverstein D.
        The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study.
        J Clin Endocrinol Metab. 2004; 89: 114-120
        • Baune B.T.
        • Rothermundt M.
        • Ladwig K.H.
        • Meisinger C.
        • Berger K.
        Systemic inflammation (Interleukin 6) predicts all-cause mortality in men: results from a 9-year follow-up of the MEMO Study.
        Age (Dordr). 2011; 33: 209-217
        • Abdulle A.M.
        • Gillett M.P.
        • Abouchacra S.
        • et al.
        Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients.
        Mol Cell Biochem. 2007; 302: 195-201
        • Beberashvili I.
        • Sinuani I.
        • Azar A.
        • et al.
        IL-6 levels, nutritional status, and mortality in prevalent hemodialysis patients.
        Clin J Am Soc Nephrol. 2011; 6: 2253-2263
        • Pecoits-Filho R.
        • Barany P.
        • Lindholm B.
        • Heimburger O.
        • Stenvinkel P.
        Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment.
        Nephrol Dial Transpl. 2002; 17: 1684-1688
        • Musarò A.
        • McCullagh K.
        • Paul A.
        • et al.
        Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.
        Nat Genet. 2001; 27: 195-200
        • Cappola A.R.
        • Bandeen-Roche K.
        • Wand G.S.
        • Volpato S.
        • Fried L.P.
        Association of IGF-I levels with muscle strength and mobility in older women.
        J Clin Endocrinol Metab. 2001; 86: 4139-4146
        • Yakar S.
        • Rosen C.J.
        • Beamer W.G.
        • et al.
        Circulating levels of IGF-1 directly regulate bone growth and density.
        J Clin Invest. 2002; 110: 771-781
        • Zapf J.
        • Froesch E.R.
        Insulin-like growth factors/somatomedins: structure, secretion, biological actions and physiological role.
        Horm Res. 1986; 24: 121-130
        • Carrero J.J.
        • Chmielewski M.
        • Axelsson J.
        • et al.
        Muscle atrophy, inflammation and clinical outcome in incident and prevalent dialysis patients.
        Clin Nutr. 2008; 27: 557-564
        • Livingstone C.
        Insulin-like growth factor-I (IGF-I) and clinical nutrition.
        Clin Sci (Lond). 2013; 125: 265-280
        • Ghanavatian S.
        • Diep L.M.
        • Barany P.
        • et al.
        Subclinical atherosclerosis, endothelial function, and serum inflammatory markers in chronic kidney disease stages 3 to 4.
        Angiology. 2014; 65: 443-449
        • Machowska A.
        • Sun J.
        • Qureshi A.R.
        • et al.
        Plasma Pentosidine and its association with mortality in patients with chronic kidney disease.
        PLoS One. 2016; 11: e0163826
        • Xu H.
        • Cabezas-Rodriguez I.
        • Qureshi A.R.
        • et al.
        Increased levels of Modified advanced Oxidation protein Products are associated with Central and peripheral blood pressure in peritoneal dialysis patients.
        Perit Dial Int. 2015; 35: 460-470
        • Isoyama N.
        • Machowska A.
        • Qureshi A.R.
        • et al.
        Elevated circulating S100A12 associates with vascular disease and Worse clinical outcome in peritoneal dialysis patients.
        Perit Dial Int. 2016; 36: 269-276
        • Snaedal S.
        • Heimburger O.
        • Qureshi A.R.
        • et al.
        Comorbidity and acute clinical events as determinants of C-reactive protein variation in hemodialysis patients: implications for patient survival.
        Am J Kidney Dis. 2009; 53: 1024-1033
        • Durnin J.V.
        • Womersley J.
        Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years.
        Br J Nutr. 1974; 32: 77-97
        • Siri W.E.
        Body composition from fluid spaces and density: analysis of methods. 1961.
        Nutrition. 1993; 9 (discussion 480, 492): 480-491
        • Kyle U.G.
        • Schutz Y.
        • Dupertuis Y.M.
        • Pichard C.
        Body composition interpretation. Contributions of the fat-free mass index and the body fat mass index.
        Nutrition. 2003; 19: 597-604
        • Qureshi A.R.
        • Olauson H.
        • Witasp A.
        • et al.
        Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification.
        Kidney Int. 2015; 88: 1356-1364
        • D'Agostino R.B.
        • Vasan R.S.
        • Pencina M.J.
        • et al.
        General cardiovascular risk profile for use in primary care: the Framingham Heart Study.
        Circulation. 2008; 117: 743-753
        • Latouche A.
        • Allignol A.
        • Beyersmann J.
        • Labopin M.
        • Fine J.P.
        A competing risks analysis should report results on all cause-specific hazards and cumulative incidence functions.
        J Clin Epidemiol. 2013; 66: 648-653
        • Velloso C.P.
        Regulation of muscle mass by growth hormone and IGF-I.
        Br J Pharmacol. 2008; 154: 557-568
        • Kostka T.
        • Arsac L.M.
        • Patricot M.C.
        • Berthouze S.E.
        • Lacour J.R.
        • Bonnefoy M.
        Leg extensor power and dehydroepiandrosterone sulfate, insulin-like growth factor-I and testosterone in healthy active elderly people.
        Eur J Appl Physiol. 2000; 82: 83-90
        • Papadakis M.A.
        • Grady D.
        • Tierney M.J.
        • Black D.
        • Wells L.
        • Grunfeld C.
        Insulin-like growth factor 1 and functional status in healthy older men.
        J Am Geriatr Soc. 1995; 43: 1350-1355
        • Janssen J.A.
        • Stolk R.P.
        • Pols H.A.
        • Grobbee D.E.
        • Lamberts S.W.
        Serum free and total insulin-like growth factor-I, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 Levels in healthy elderly individuals. Relation to self-reported quality of health and disability.
        Gerontology. 1998; 44: 277-280
        • Perice L.
        • Barzilai N.
        • Verghese J.
        • et al.
        Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function.
        Aging (Albany NY). 2016; 8: 2414-2424
        • Boonen S.
        • Lysens R.
        • Verbeke G.
        • et al.
        Relationship between age-associated endocrine deficiencies and muscle function in elderly women: a cross-sectional study.
        Age Ageing. 1998; 27: 449-454
        • Carrero J.J.
        • Johansen K.L.
        • Lindholm B.
        • Stenvinkel P.
        • Cuppari L.
        • Avesani C.M.
        Screening for muscle wasting and dysfunction in patients with chronic kidney disease.
        Kidney Int. 2016; 90: 53-66
        • Noori N.
        • Kovesdy C.P.
        • Bross R.
        • et al.
        Novel equations to estimate lean body mass in maintenance hemodialysis patients.
        Am J Kidney Dis. 2011; 57: 130-139
        • Jassal S.K.
        • Wassel C.L.
        • Laughlin G.A.
        • Barrett-Connor E.
        • Rifkin D.E.
        • Ix J.H.
        Urine creatinine-based estimates of fat-free mass in community-dwelling older persons: the Rancho Bernardo study.
        J Ren Nutr. 2015; 25: 97-102
      1. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. Canada-USA (CANUSA) Peritoneal Dialysis Study Group.
        J Am Soc Nephrol. 1996; 7: 198-207
        • Boger R.H.
        • Frystyk J.
        • Ledet T.
        • Moller N.
        • Flyvbjerg A.
        • Orskov H.
        Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease.
        Circulation. 2003; 107 (author reply e193): e193