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Renal transplant dysfunction - importance quantified in comparison with traditional risk factors for cardiovascular disease and mortality
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.ORCID iD: 0000-0001-6710-6422
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2006 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 21, no 8, 2282-2289 p.Article in journal (Refereed) Published
Abstract [en]

Background. Renal transplant recipients (RTR) mainly die of premature cardiovascular disease. Traditional cardiovascular disease risk factors are prevalent in RTR. Additionally, non-traditional risk factors seem to contribute to the high risk. The impact of renal dysfunction was compared with traditional risk factors for cardiovascular morbidity and mortality in 1052 placebo-treated patients of the ALERT trial.

Methods. All patients were on cyclosporine-based immunosuppressive therapy, follow-up was 5-6 years and captured endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke.

Results. A calculated 84 mu mol/l increase in serum creatinine was needed to double the risk for cardiac death, an increase of 104 mu mol/l to double the risk for non-cardiovascular death and an increase of 92 mu mol/l to double the risk for all-cause mortality. MACE risk was doubled if serum creatinine was elevated by 141 mu mol/l, age was increased by 23 years, or LDL-cholesterol by 2 mmol/l. Diabetes increased the incidences of cardiac death, all-cause mortality, MACE, stroke and non-fatal MI. A serum creatinine increase of similar to 130 mu mol/l, or similar to 20 years increase in age was calculated as similar in risk for cardiac death, all-cause mortality and MACE, and comparable to risk of diabetes in RTR.

Conclusion. An increase in serum creatinine of 80-100 mu mol/l doubles the risk for cardiac death, non-cardiovascular death and all-cause mortality in RTR. An increase of 130 mu mol/l in serum creatinine or similar to 20 years increase in age is comparable to risk of diabetes.

Place, publisher, year, edition, pages
2006. Vol. 21, no 8, 2282-2289 p.
Keyword [en]
cardiovascular disease, creatinine, mortality, renal transplantation, risk factors, transplant function
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-94634DOI: 10.1093/ndt/gfl095ISI: 000239906500037PubMedID: 16574686OAI: oai:DiVA.org:uu-94634DiVA: diva2:168546
Available from: 2006-06-01 Created: 2006-06-01 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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