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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.

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.

Background: Cardiovascular mortality is high in hemodialysis (HD) patients. Early arterial pressure wave reflections, reflecting arterial stiffness and the endogenous nitric oxide synthesis inhibitor asymmetric dimethylarginine (ADMA) levels predict mortality in HD patients. Therefore, we aimed to study changes in ADMA levels and central arterial pressure waveform during HD. Methods: Thirty-two chronic HD patients were studied before and after a HD session. In a subset of 22 patients without arrhythmias, pulse wave analysis was performed on radial artery (SphygmoCor). Augmentation index (AIx), defined as difference between the second and first systolic peak divided by central pulse pressure, was used as a measure of arterial stiffness. ADMA was measured in plasma with the ELISA technique. Homocysteine was measured in plasma using the EIA technique. Results: HD reduced both AIx (19%; p = 0.003) and ADMA levels (17%; p < 0.001). The magnitudes of changes in AIx and ADMA during HD were correlated (r = 0.44; p = 0.045). Mean arterial pressure change was not significant. HD reduced homocysteine levels, but homocysteine was not related to ADMA or AIx. Conclusion: The reduction in ADMA level seen after HD was associated with improvement in the central arterial pressure waveform, suggesting involvement of nitric oxide in the regulation of arterial stiffness in HD patients.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in cardiovascular disease (CVD). Apart from traditional risk factors, chronic inflammation, oxidative stress, malnutrition and endothelial dysfunction are important in CVD development in renal patients. Our aim was to investigate the relationship between high sensitivity C-reactive protein (CRP), endothelium dependent vasodilation (EDV) and oxidative stress markers in patients with CKD K/DOQI stage 3-5.

METHODS: Measurements of CRP, conjugated dienes (CD), lipid hydroperoxide (LOOH), oxidized low density lipoprotein,glutathione and albumin were performed in 44 consecutive patients with CKD stage 3-5. EDV was measured by methacholine infusion in the brachial artery and venous occlusion plethysmography.

RESULTS: Patients with high CRP had significantly lower glomerular filtration rates and albumin, but increased LOOH and CD. In multiple regression analysis, only LOOH and CD remained significant. Patients with poor EDV had increased urea and lower glutathione (GSH). In multiple regression analysis, GSH and urea were independently related to EDV. No correlation was found between CRP and endothelial function.

CONCLUSION: CRP was related to lipid peroxidation, while endothelial function was related to intracellular oxidative stress in patients with CKD. CRP and EDV were unrelated to each other. Therefore, CRP and endothelial function could provide complementary prognostic information regarding future cardiovascular disorders in renal patients.