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  - 
TY  - JOUR
A1  - Gallo, Linda A.
A1  - Ward, Micheal S.
A1  - Fotheringham, Amelia K.
A1  - Zhuang, Aowen
A1  - Borg, Danielle J.
A1  - Flemming, Nicole B.
A1  - Harvie, Ben M.
A1  - Kinneally, Toni L.
A1  - Yeh, Shang-Ming
A1  - McCarthy, Domenica A.
A1  - Koepsell, Hermann
A1  - Vallon, Volker
A1  - Pollock, Carol
A1  - Panchapakesan, Usha
A1  - Forbes, Josephine M.
T1  - Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice
JF  - Scientific Reports
N2  - Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.
KW  - SGLT2 inhibitor
KW  - empagliflozin
KW  - glucose lowering agent
KW  - kidney disease
KW  - type 2 diabetes
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167678
VL  - 6
IS  - 26428
ER  -