TY  - JOUR
A1  - Tsuprykov, Oleg
A1  - Ando, Ryotaro
A1  - Reichetzeder, Christoph
A1  - von Websky, Karoline
A1  - Antonenko, Viktoriia
A1  - Sharkovska, Yuliya
A1  - Chaykovska, Lyubov
A1  - Rahnenfuehrer, Jan
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Tammen, Harald
A1  - Alter, Markus L.
A1  - Klein, Thomas
A1  - Ueda, Seiji
A1  - Yamagishi, Sho-ichi
A1  - Okuda, Seiya
A1  - Hocher, Berthold
T1  - The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo. The urine albumin-to-creatinine ratio was significantly decreased by 66% with linagliptin and 92% with telmisartan versus placebo. Blood pressure was significantly lowered by telmisartan, but it was not affected by linagliptin. As shown by mass spectrometry, the number of altered peptide signals for linagliptin in plasma was 552 and 320 in the kidney. For telmisartan, there were 108 peptide changes in plasma and 363 in the kidney versus placebo. Linagliptin up-regulated peptides derived from collagen type I, apolipoprotein C1, and heterogeneous nuclear ribonucleoproteins A2/B1, a potential downstream target of atrial natriuretic peptide, whereas telmisartan up-regulated angiotensin II. A second study was conducted to confirm these findings in 5/6 nephrectomy wild-type and genetically deficient DPP-4 rats treated with linagliptin or placebo. Linagliptin therapy in wild-type rats was as effective as DPP-4 genetic deficiency in terms of albuminuria reduction. Thus, linagliptin showed comparable efficacy to telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. However, the underlying pathways seem to be different. Copyright (C) 2016, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
KW  - albuminuria
KW  - angiotensin receptor blockers
KW  - chronic kidney disease
KW  - DPP-4 inhibition
KW  - proteinuria
KW  - proteomic analysis
Y1  - 2016
U6  - https://doi.org/10.1016/j.kint.2016.01.016
SN  - 0085-2538
SN  - 1523-1755
VL  - 89
SP  - 1049
EP  - 1061
PB  - Nature Publ. Group
CY  - New York
ER  -