TY  - JOUR
A1  - Dschietzig, Thomas Bernd
A1  - Krause-Relle, Katharina
A1  - Hennequin, Maud
A1  - von Websky, Karoline
A1  - Rahnenfuhrer, Jan
A1  - Ruppert, Jana
A1  - Groena, Hans Juergen
A1  - Armbruster, Franz Paul
A1  - Bathgate, Ross A. D.
A1  - Aschenbach, Joerg R.
A1  - Forssmann, Wolf-Georg
A1  - Hocher, Berthold
T1  - Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.
KW  - Diabetic nephropathy
KW  - Diabetic cardiomyopathy
KW  - Fibrosis
KW  - Inflammation
KW  - Relaxin
Y1  - 2015
U6  - https://doi.org/10.1159/000368484
SN  - 1420-4096
SN  - 1423-0143
VL  - 40
IS  - 1
SP  - 77
EP  - 88
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Ong, Albert C. M.
A1  - von Websky, Karoline
A1  - Hocher, Berthold
T1  - Endothelin and Tubulointerstitial Renal Disease
JF  - Seminars in nephrology
N2  - All components of the endothelin (ET) system are present in renal tubular cells. In this review, we summarize current knowledge about ET and the most common tubular diseases: acute kidney injury (AKI) and polycystic kidney disease. AKI originally was called acute tubular necrosis, pointing to the most prominent morphologic findings. Similarly, cysts in polycystic kidney disease, and especially in autosomal-dominant polycystic kidney disease, are of tubular origin. Preclinical studies have indicated that the ET system and particularly ETA receptors are involved in the pathogenesis of ischemia-reperfusion injury, although these findings have not been translated to clinical studies. The ET system also has been implicated in radiocontrast-dye-induced AKI, however, ET-receptor blockade in a large human study was not successful. The ET system is activated in sepsis models of AKI; the effectiveness of ET blocking agents in preclinical studies is variable depending on the model and the ET-receptor antagonist used. Numerous studies have shown that the ET system plays an important role in the complex pathophysiology associated with cyst formation and disease progression in polycystic kidney disease. However, results from selective targeting of ET-receptor subtypes in animal models of polycystic kidney disease have proved disappointing and do not support clinical trials. These studies have shown that a critical balance between ETA and ETB receptor action is necessary to maintain structure and function in the cystic kidney. In summary, ETs have been implicated in the pathogenesis of several renal tubulointerstitial diseases, however, experimental animal findings have not yet led to use of ET blockers in human beings. (C) 2015 Elsevier Inc. All rights reserved.
KW  - Endothelin
KW  - acute kidney injury
KW  - polycystic kidney disease
KW  - ADPKD
KW  - ET-1
KW  - ETA
KW  - ETB
Y1  - 2015
U6  - https://doi.org/10.1016/j.semnephrol.2015.03.004
SN  - 0270-9295
SN  - 1558-4488
VL  - 35
IS  - 2
SP  - 197
EP  - 207
PB  - Elsevier
CY  - Philadelphia
ER  - 
TY  - CHAP
A1  - Reichetzeder, Christoph
A1  - von Websky, Karoline
A1  - Tsuprykov, Oleg
A1  - Antonenko, V.
A1  - Samarin, Azin Mohagheghi
A1  - Hocher, Berthold
T1  - Effects of DPP-4 inhibition on glomerular and tubular function in a rat model of ischaemia-reperfusion injury
T2  - Diabetologia : journal of the European Association for the Study of Diabetes (EASD)
Y1  - 2015
SN  - 0012-186X
SN  - 1432-0428
VL  - 58
SP  - S34
EP  - S35
PB  - Springer
CY  - New York
ER  -