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  - 
TY  - JOUR
A1  - Groop, Per-Henrik
A1  - Cooper, Mark E.
A1  - Perkovic, Vlado
A1  - Sharma, Kumar
A1  - Schernthaner, Guntram
A1  - Haneda, Masakazu
A1  - Hocher, Berthold
A1  - Gordat, Maud
A1  - Cescutti, Jessica
A1  - Woerle, Hans-Juergen
A1  - von Eynatten, Maximilian
T1  - Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D trial
JF  - Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease
N2  - Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5mg or placebo in addition to their stable glucose-lowering background therapy for 24weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24weeks with =0.05. MARLINA-T2D is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease.
KW  - Dipeptidyl peptidase-4 inhibition
KW  - linagliptin
KW  - type 2 diabetes
KW  - chronic kidney disease
KW  - glycaemic control
KW  - albuminuria
Y1  - 2015
U6  - https://doi.org/10.1177/1479164115579002
SN  - 1479-1641
SN  - 1752-8984
VL  - 12
IS  - 6
SP  - 455
EP  - 462
PB  - Sage Publ.
CY  - London
ER  -