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Renal dysfunction is a strong and independent risk factor for mortality and cardiovascular complications in renal transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Njurmedicin, The ALERT Study Group.)
(The ALERT Study Group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Njurmedicin, The ALERT Study Group)ORCID iD: 0000-0001-6710-6422
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2005 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 5, no 8, 1986-1991 p.Article in journal (Refereed) Published
Abstract [en]

Renal transplant recipients (RTR) have shortened life expectancy, primarily due to premature cardiovascular disease (CVD). Traditional CVD risk factors are highly prevalent. In addition, several non-traditional risk factors may contribute to the high risk. The aim of the study was to evaluate the effects of renal dysfunction on mortality and cardiovascular complications in 1052 placebo-treated patients of the Assessment of LEscol in Renal Transplantation (ALERT) trial. Follow-up was 5-6 years and endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke. The effects of serum creatinine at baseline on these endpoints were evaluated. Elevated serum creatinine in RTR was a strong and independent risk factor for MACE, cardiac, non-cardiovascular, and all-cause mortality, but not for stroke or non-fatal MI alone. Serum creatinine was associated with increased mortality and MACE, independent of established CVD risk factors. Graft loss resulted in increased incidences of non-cardiovascular death, all-cause mortality, MACE and non-fatal MI. In conclusion, elevated serum creatinine is a strong risk factor for all-cause, non-cardiovascular and cardiac mortality, and MACE, independent of traditional risk factors, but not for stroke or non-fatal MI alone.

Place, publisher, year, edition, pages
2005. Vol. 5, no 8, 1986-1991 p.
Keyword [en]
Cardiovascular disease, mortality, renal transplant function, risk factor
National Category
Urology and Nephrology
Research subject
URN: urn:nbn:se:uu:diva-104310DOI: 10.1111/j.1600-6143.2005.00983.xISI: 000230291500028PubMedID: 15996249OAI: oai:DiVA.org:uu-104310DiVA: diva2:219641
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2015-02-11
In thesis
1. Renal Dysfunction and Cardiovascular Disease
Open this publication in new window or tab >>Renal Dysfunction and Cardiovascular Disease
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors.

We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors.

Renal transplant dysfunction as CVD and mortality risk factor was also studied. Renal transplant dysfunction was a risk factor for mortality and for combined CVD endpoint. The risk by renal transplant dysfunction was independent of traditional CVD risk factors as well as transplantation-specific risk factors. Only moderate increase in serum creatinine resulted in mortality and CVD risk comparable to diabetes, older age and higher low density lipoprotein levels.

In haemodialysis patients, the effects of a dialysis session on non-traditional CVD risk factors were studied. A HD session reduced asymmetric dimethylarginine (ADMA) and homocysteine levels, as well as augmentation index (AIx). The change in AIx was related to ADMA plasma level change.

In patients with stage 3-5 chronic kidney disease (CKD), endothelium dependent vasodilation (EDV) was studied together with markers of oxidative stress and C-reactive protein (CRP). CRP was related to lipid peroxidation, while EDV was related to intracellular antioxidative capacity measured by reduced glutathione levels.

These studies demonstrate that mild to moderate renal dysfunction is independently associated with increased CVD risk in apparently healthy people, as well as in renal transplant recipients. The mechanisms by which renal dysfunction increases CVD risk are yet to be elucidated. We suggest that arterial stiffness could be reduced in haemodialysis patients by increasing nitric oxide bioavailability. In stage 3-5 CKD patients, improving intracellular antioxidative capacity may result in endothelial function improvement.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 75 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 158
Internal medicine, renal dysfunktion, cardiovascular disease, risk factor, mortality, endothelial dysfunction, arterial stiffness, oxidative stress, inflammation, renal transplantation, haemodialysis, general population, Invärtesmedicin
urn:nbn:se:uu:diva-6941 (URN)91-554-6594-3 (ISBN)
Public defence
2006-09-15, Enghoffsalen, Akademiska Sjukhuset, ing 50, Uppsala, 09:15
Available from: 2006-06-01 Created: 2006-06-01 Last updated: 2013-06-13Bibliographically approved

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