NDT Advance Access originally published online on April 9, 2008
Nephrology Dialysis Transplantation 2008 23(9):2957-2964; doi:10.1093/ndt/gfn167
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Excess mortality due to interaction between protein-energy wasting, inflammation and cardiovascular disease in chronic dialysis patients
1 Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands 2 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden 3 Hans Mak Institute, Naarden 4 Department of Nephrology, Academic Medical Centre, Amsterdam, The Netherlands
Correspondence and offprint requests to: Renée de Mutsert, Leiden University Medical Centre, Clinical Epidemiology, C9-P, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel: +31-71-526-6534; Fax: +31-71-526-6994; E-mail: r.de_mutsert{at}lumc.nl
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Abstract |
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Background. Protein-energy wasting (PEW), inflammation and cardiovascular diseases (CVD) clearly contribute to the high mortality in chronic dialysis. Our aim was to examine the presence of additive interaction between these three risk factors in their association with long-term mortality in dialysis patients.
Methods. Patients from a prospective multi-centre cohort study among ESRD patients starting with their first dialysis treatment [the Netherlands Co-operative Study on the Adequacy of Dialysis-2 (NECOSAD-II)] with complete data on these risk factors were included (n = 815, age: 59 ± 15 years, 60% men, 65% HD). Hazard ratios (HR) were calculated for all-cause mortality in 7 years of follow-up. The presence of interaction between the three risk factors was examined, based on additivity of effects.
Results. Of all patients, 10% only suffered from PEW (1–5 on the 7-point subjective global assessment), 11% from inflammation (CRP 
10 mg/L), 14% from CVD and 22% had any combination of two components. Only 6% of the patients had all three risk factors. Patients with either PEW (HR: 1.6, 95% CI: 1.3–2.0), inflammation (1.6, 1.3–2.0) or CVD (1.7, 1.4–2.1) had an increased mortality risk. In patients with all three risk factors, the crude mortality rate of 45/100 person-years was 16 deaths/100 person-years higher than expected from the addition of the solo effects of PEW, inflammation and CVD. The relative excess risk due to interaction was 2.9 (95% CI: 0.3–5.4), implying additive interaction. After adjustment for age, sex, treatment modality, primary kidney diseases, diabetes and malignancy the HR for patients with all three risk factors was 4.8 (95% CI: 3.2–7.2).
Conclusions. The concurrent presence of PEW, inflammation and CVD increased the mortality risk strikingly more than expected, implying that PEW interacts with inflammation and CVD in dialysis patients.
Keywords: cardiovascular disease; chronic dialysis; inflammation; mortality risk; protein–energy wasting
* AJ Apperloo, JA Bijlsma, M Boekhout, WH Boer, PJM van der Boog, HR Büller, M van Buren, FTh de Charro, CJ Doorenbos, MA van den Dorpel, A van Es, WJ Fagel, GW Feith, CWH de Fijter, LAM Frenken, JACA van Geelen, PGG Gerlag, JPMC Gorgels, W Grave, RM Huisman, KJ Jager, K Jie, WAH Koning-Mulder, MI Koolen, Hovinga TK Kremer, ATJ Lavrijssen, AJ Luik, J van der Meulen, KJ Parlevliet, MHM Raasveld, FM van der Sande, MJM Schonck, MMJ Schuurmans, CEH Siegert, CA Stegeman, P Stevens, JGP Thijssen, RM Valentijn, GH Vastenburg, CA Verburgh, HH Vincent, PF Vos.
Received for publication: 11. 1.08
Accepted in revised form: 4. 3.08
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