Increased arterial inflammation in individuals with stage 3 chronic kidney disease

  • Richard A. P. Takx
  • Megan H. MacNabb
  • Hamed Emami
  • Amr Abdelbaky
  • Parmanand Singh
  • Zachary R. Lavender
  • Marcelo di Carli
  • Viviany Taqueti
  • Courtney Foster
  • Jessica Mann
  • Robert A. Comley
  • Chek Ing Kiu Weber
  • Ahmed Tawakol
Original Article



While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using 18F-FDG PET/CT in patients with CKD and in matched controls.


This restrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed.


Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 ± 0.49 vs. 2.16 ± 0.43; p = 0.002). Arterial SUV correlated inversely with eGFR (r = −0.299, p = 0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC).


Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of cardiovascular events.


Atherosclerosis Chronic kidney disease FDG PET/CT Inflammation 


Compliance with ethical standards


F. Hoffmann-La Roche Ltd., Switzerland

Conflicts of interest

Jessica Mann, Robert A. Comley and Chek Ing Kiu Weber were employed by, and owned stock F. Hoffmann-La Roche Ltd., Basel, Switzerland, at the time of the study.

All other authors have no relationships relevant to the contents of this article to disclose.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Infomed consent

For this type of study, formal consent is not required.


  1. 1.
    Hoerger TJ, Simpson SA, Yarnoff BO, Pavkov ME, Rios Burrows N, Saydah SH, et al. The future burden of CKD in the United States: a simulation model for the CDC CKD initiative. Am J Kidney Dis. 2015;65:403–11. doi: 10.1053/j.ajkd.2014.09.023.PubMedCrossRefGoogle Scholar
  2. 2.
    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305. doi: 10.1056/NEJMoa041031.PubMedCrossRefGoogle Scholar
  3. 3.
    Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85–97. doi: 10.1161/CIRCULATIONAHA.106.678342.PubMedCrossRefGoogle Scholar
  4. 4.
    Shlipak MG, Fried LF, Cushman M, Manolio TA, Peterson D, Stehman-Breen C, et al. Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA. 2005;293:1737–45. doi: 10.1001/jama.293.14.1737.PubMedCrossRefGoogle Scholar
  5. 5.
    Kiu Weber CI, Duchateau-Nguyen G, Solier C, Schell-Steven A, Hermosilla R, Nogoceke E, et al. Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease stages 3 and 4. Clin Kidney J. 2014;7:167–73. doi: 10.1093/ckj/sfu017.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Rennen HJ, Boerman OC, Oyen WJ, Corstens FH. Imaging infection/inflammation in the new millennium. Eur J Nucl Med. 2001;28:241–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–24. doi: 10.1016/j.jacc.2006.05.076.PubMedCrossRefGoogle Scholar
  8. 8.
    Rudd JH, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002;105:2708–11.PubMedCrossRefGoogle Scholar
  9. 9.
    Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, et al. Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med. 2008;49:871–8. doi: 10.2967/jnumed.107.050294.PubMedCrossRefGoogle Scholar
  10. 10.
    Figueroa AL, Abdelbaky A, Truong QA, Corsini E, MacNabb MH, Lavender ZR, et al. Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. JACC Cardiovasc Imaging. 2013;6:1250–9. doi: 10.1016/j.jcmg.2013.08.006.PubMedCrossRefGoogle Scholar
  11. 11.
    Rudd JH, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, et al. (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007;50:892–6. doi: 10.1016/j.jacc.2007.05.024.PubMedCrossRefGoogle Scholar
  12. 12.
    Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol. 2006;48:1825–31. doi: 10.1016/j.jacc.2006.03.069.PubMedCrossRefGoogle Scholar
  13. 13.
    Wu YW, Kao HL, Huang CL, Chen MF, Lin LY, Wang YC, et al. The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers. Eur J Nucl Med Mol Imaging. 2012;39:399–407. doi: 10.1007/s00259-011-1994-7.PubMedCrossRefGoogle Scholar
  14. 14.
    Rogers IS, Nasir K, Figueroa AL, Cury RC, Hoffmann U, Vermylen DA, et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc Imaging. 2010;3:388–97. doi: 10.1016/j.jcmg.2010.01.004.PubMedCrossRefGoogle Scholar
  15. 15.
    Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med. 2009;50:1611–20. doi: 10.2967/jnumed.109.065151.PubMedCrossRefGoogle Scholar
  16. 16.
    Paulmier B, Duet M, Khayat R, Pierquet-Ghazzar N, Laissy JP, Maunoury C, et al. Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events. J Nucl Cardiol. 2008;15:209–17. doi: 10.1016/j.nuclcard.2007.10.009.PubMedCrossRefGoogle Scholar
  17. 17.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro 3rd AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol. 2013;62:909–17. doi: 10.1016/j.jacc.2013.04.066.PubMedCrossRefGoogle Scholar
  19. 19.
    Blomberg BA, Thomassen A, de Jong PA, Simonsen J, Lam M, Nielsen A, et al. Impact of personal characteristics and technical factors on quantification of sodium 18F-fluoride uptake in human arteries: prospective evaluation of healthy subjects. J Nucl Med. 2015;56:1534–40. doi: 10.2967/jnumed.115.159798.PubMedCrossRefGoogle Scholar
  20. 20.
    Kirsch J, Buitrago I, Mohammed TL, Gao T, Asher CR, Novaro GM. Detection of coronary calcium during standard chest computed tomography correlates with multi-detector computed tomography coronary artery calcium score. Int J Cardiovasc Imaging. 2012;28:1249–56. doi: 10.1007/s10554-011-9928-9.PubMedCrossRefGoogle Scholar
  21. 21.
    Einstein AJ, Johnson LL, Bokhari S, Son J, Thompson RC, Bateman TM, et al. Agreement of visual estimation of coronary artery calcium from low-dose CT attenuation correction scans in hybrid PET/CT and SPECT/CT with standard Agatston score. J Am Coll Cardiol. 2010;56:1914–21. doi: 10.1016/j.jacc.2010.05.057.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol. 2002;39:695–701.PubMedCrossRefGoogle Scholar
  23. 23.
    McCullough PA, Sandberg KR, Dumler F, Yanez JE. Determinants of coronary vascular calcification in patients with chronic kidney disease and end-stage renal disease: a systematic review. J Nephrol. 2004;17:205–15.PubMedGoogle Scholar
  24. 24.
    Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2008;19:213–6. doi: 10.1681/ASN.2007080854.PubMedCrossRefGoogle Scholar
  25. 25.
    Haydar AA, Hujairi NM, Covic AA, Pereira D, Rubens M, Goldsmith DJ. Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography. Nephrol Dial Transplant. 2004;19:2307–12. doi: 10.1093/ndt/gfh120.PubMedCrossRefGoogle Scholar
  26. 26.
    Hoh CK. Clinical use of FDG PET. Nucl Med Biol. 2007;34:737–42. doi: 10.1016/j.nucmedbio.2007.07.001.PubMedCrossRefGoogle Scholar
  27. 27.
    Gallagher BM, Fowler JS, Gutterson NI, MacGregor RR, Wan CN, Wolf AP. Metabolic trapping as a principle of radiopharmaceutical design: some factors resposible for the biodistribution of [18F] 2-deoxy-2-fluoro-D-glucose. J Nucl Med: Off Publ Soc Nucl Med. 1978;19:1154–61.Google Scholar
  28. 28.
    Gerich JE, Meyer C, Woerle HJ, Stumvoll M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care. 2001;24:382–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Laffon E, Cazeau AL, Monet A, de Clermont H, Fernandez P, Marthan R, et al. The effect of renal failure on 18F-FDG uptake: a theoretic assessment. J Nucl Med Technol. 2008;36:200–2. doi: 10.2967/jnmt.107.049627.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Richard A. P. Takx
    • 1
    • 3
  • Megan H. MacNabb
    • 1
  • Hamed Emami
    • 1
  • Amr Abdelbaky
    • 1
  • Parmanand Singh
    • 1
    • 7
  • Zachary R. Lavender
    • 1
  • Marcelo di Carli
    • 4
  • Viviany Taqueti
    • 4
  • Courtney Foster
    • 4
  • Jessica Mann
    • 5
  • Robert A. Comley
    • 5
  • Chek Ing Kiu Weber
    • 5
  • Ahmed Tawakol
    • 1
    • 2
    • 6
  1. 1.Cardiac MR PET CT ProgramMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Cardiology DivisionMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Department of RadiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  4. 4.Division of Radiology, Department of MedicineBrigham & Women’s Hospital and Harvard Medical SchoolBostonUSA
  5. 5.F. Hoffmann-La Roche Ltd.BaselSwitzerland
  6. 6.Massachusetts General HospitalBostonUSA
  7. 7.Division of CardiologyNew York Presbyterian Hospital, Weill Cornell Medical CollegeNew YorkUSA

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