TY  - JOUR
A1  - Ocak, Gurbey
A1  - Drechsler, Christiane
A1  - Vossen, Carla Y.
A1  - Vos, Hans L.
A1  - Rosendaal, Frits R.
A1  - Reitsma, Pieter H.
A1  - Hoffmann, Michael M.
A1  - März, Winfried
A1  - Ouwehand, Willem H.
A1  - Krediet, Raymond T.
A1  - Boeschoten, Elisabeth W.
A1  - Dekker, Frido W.
A1  - Wanner, Christoph
A1  - Verduijn, Marion
T1  - Single Nucleotide Variants in the Protein C Pathway and Mortality in Dialysis Patients
JF  - PLOS ONE
N2  - Background: The protein C pathway plays an important role in the maintenance of endothelial barrier function and in the inflammatory and coagulant processes that are characteristic of patients on dialysis. We investigated whether common single nucleotide variants (SNV) in genes encoding protein C pathway components were associated with all-cause 5 years mortality risk in dialysis patients. 
Methods: Single nucleotides variants in the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were genotyped in 1070 dialysis patients from the NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort) and in 1243 dialysis patients from the German 4D cohort. 
Results: Factor V Leiden was associated with a 1.5-fold (95% CI 1.1-1.9) increased 5-year all-cause mortality risk and carriers of the AG/GG genotypes of the PROC rs1799809 had a 1.2-fold (95% CI 1.0-1.4) increased 5-year all-cause mortality risk. The other SNVs in THBD, PROC, and PROCR were not associated with 5-years mortality. 
Conclusion: Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients.
KW  - human brian endothelium
KW  - factor-V-Leiden
KW  - venous thrombosis
KW  - activated receptor-1
KW  - vascular access
KW  - severe sepsis
KW  - gene polymorphism
KW  - organ dysfunktion
KW  - ischemic stroke
KW  - renal disease
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116265
SN  - 1932-6203
VL  - 9
IS  - 5
ER  - 
TY  - JOUR
A1  - Drechsler, Christiane
A1  - Ritz, Eberhard
A1  - Tomaschitz, Andreas
A1  - Pilz, Stefan
A1  - Schönfeld, Stephan
A1  - Blouin, Katja
A1  - Bidlingmaier, Martin
A1  - Hammer, Fabian
A1  - Krane, Vera
A1  - März, Winfried
A1  - Allolio, Bruno
A1  - Fassnacht, Martin
A1  - Wanner, Christoph
T1  - Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients
JF  - European Heart Journal
N2  - Background: Sudden cardiac death is common and accounts largely for the excess mortality of patients on maintenance dialysis. It is unknown whether aldosterone and cortisol increase the incidence of sudden cardiac death in dialysis patients.

Methods and results: We analysed data from 1255 diabetic haemodialysis patients participating in the German Diabetes and Dialysis Study (4D Study). Categories of aldosterone and cortisol were determined at baseline and patients were followed for a median of 4 years. By Cox regression analyses, hazard ratios (HRs) were determined for the effect of aldosterone, cortisol, and their combination on sudden death and other adjudicated cardiovascular outcomes. The mean age of the patients was 66 ± 8 years (54% male). Median aldosterone was <15 pg/mL (detection limit) and cortisol 16.8 µg/dL. Patients with aldosterone levels >200 pg/mL had a significantly higher risk of sudden death (HR: 1.69; 95% CI: 1.06–2.69) compared with those with an aldosterone <15 pg/mL. The combined presence of high aldosterone (>200 pg/mL) and high cortisol (>21.1 µg/dL) levels increased the risk of sudden death in striking contrast to patients with low aldosterone (<15 pg/mL) and low cortisol (<13.2 µg/dL) levels (HR: 2.86, 95% CI: 1.32–6.21). Furthermore, all-cause mortality was significantly increased in the patients with high levels of both hormones (HR: 1.62, 95% CI: 1.01–2.62).

Conclusions: The joint presence of high aldosterone and high cortisol levels is strongly associated with sudden cardiac death as well as all-cause mortality in haemodialysed type 2 diabetic patients. Whether a blockade of the mineralocorticoid receptor decreases the risk of sudden death in these patients must be examined in future trials.
KW  - mortality
KW  - kidney disease
KW  - cardiovascular events
KW  - sudden cardiac death
KW  - cortisol
KW  - aldosterone
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132562
VL  - 34
ER  -