DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy

Kidney and Blood Pressure Research

Volumn 36, Issue 1, 2012, Pages 119-130

  Alter, Markus L ^a,b   Ott, Ina M ^b,c   Von Websky, Karoline ^b,c   Tsuprykov, Oleg ^b,c   Sharkovska, Yuliya ^b   Krause Relle, Katharina ^b,c   Raila, Jens ^c   Henze, Andrea ^c   Klein, Thomas ^d   Hocher, Berthold ^b,c,e  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^c UNIVERSITY OF POTSDAM   (Germany)

^d BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^e Institut für Ernährungswissenschaft   (Germany)

Author keywords

Diabetic nephropathy; DPP 4 inhibitor; Linagliptin; Renin angiotensin system

Indexed keywords

LINAGLIPTIN; MALONALDEHYDE; OSTEOPONTIN; TELMISARTAN;

ALBUMINURIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DISEASE COURSE; GLOMERULOSCLEROSIS; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; SYSTOLIC BLOOD PRESSURE;

ANGIOTENSIN RECEPTOR ANTAGONISTS; ANIMALS; BENZIMIDAZOLES; BENZOATES; BLOOD PRESSURE; DIABETES MELLITUS, EXPERIMENTAL; DIABETIC NEPHROPATHIES; DIPEPTIDYL PEPTIDASE 4; DISEASE MODELS, ANIMAL; DRUG THERAPY, COMBINATION; ENZYME INHIBITORS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NITRIC OXIDE SYNTHASE TYPE III; OXIDATIVE STRESS; PURINES; QUINAZOLINES; STREPTOZOCIN; TREATMENT OUTCOME;

EID: 84869238002     PISSN: 14204096     EISSN: 14230143     Source Type: Journal    
DOI: 10.1159/000341487     Document Type: Article

References (57)

1. Tomson C, Udayaraj U, Gilg J, Ansell D: Comorbidities in UK patients at the start of renal replacement therapy. Nephrol Dial Transplant 2007;22:vii58-68.
2. Mann JFE, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsärinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TL, Teo KK, Yusuf S: Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008;372:547-553.
3. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559.
4. Higashi Y, Sasaki S, Nakagawa K, Ueda T, Yoshimizu A, Kurisu S, Matsuura H, Kajiyama G, Oshima T: A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study. J Am Coll Cardiol 2000;35:284-291.
5. Jandeleit-Dahm KAM, Tikellis C, Reid CM, Johnston CI, Cooper ME: Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens 2005;23:463-473.
6. Burnier M: Angiotensin II type 1 receptor blockers. Circulation 2001;103:904-912.
7. Kosugi T, Heinig M, Nakayama T, Matsuo S, Nakagawa T: eNOS knockout mice with advanced diabetic nephropathy have less benefit from renin-angiotensin blockade than from aldosterone receptor antagonists. Am J Pathol 2010;176:619-629.
8. Makino H, Haneda M, Babazono T, Moriya T, Ito S, Iwamoto Y, Kawamori R, Takeuchi M, Katayama S: Prevention of transition from incipient to overt nephropathy with telmisartan in patients with type 2 diabetes. Diabetes care 2007;30:1577-1578.
9. Schmieder RE, Delles C, Mimran A, Fauvel JP, Ruilope LM: Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes. Diabetes care 2007;30:1351-1356.
10. Hocher B, Sharkovska Y, Mark M, Klein T, Pfab T: The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats. Int J Cardiol DOI: 10.1016/j. ijcard.2011.12.007.
11. Chaykovska L, von Websky K, Rahnenführer J, Alter ML, Heiden S, Fuchs H, Runge F, Klein T, Hocher B: Effects of DPP-4 inhibitors on the heart in a rat model of uremic cardiomyopathy. PlosO one 2011;6:e27861.
12. Hocher B, Reichetzeder C, Alter M. Renal and Cardiac Effects of DPP4 Inhibitors. Kidney Blood Press Res 2012;36:65-84.
13. Vickers SP, Cheetham SC, Birmingham GD, Rowley HL, Headland KR, Dickinson K, Grempler R, Hocher B, Mark M, Klein T. Effects of the DPP-4 Inhibitor, Linagliptin, in Diet-Induced Obese Rats: A Comparison in Naive and Exenatide-Treated Animals. Clin. Lab 2012;58:787-799.
14. Nauck MA: Glucagon-like peptide 1 (GLP-1) in the treatment of diabetes. Horm Metab Res DOI:10.1055/s-2004-826175.
15. Ahrén B, Simonsson E, Larsson H, Landin-Olsson M, Torgeirsson H, Jansson P-A, Sandqvist M, Båvenholm P, Efendic S, Eriksson JW, Dickinson S, Holmes D: Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes care 2002;25:869-875.
16. Bergman AJ, Stevens C, Zhou YY, Yi B, Laethem M, Smet M, Snyder K, Hilliard D, Tanaka W, Zeng W, Tanen M, Wang AQ, Chen L, Winchell G, Davies M, Ramael S, Wagner JA, Herman GA: Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther 2006;28:55-72.
17. Deacon C, Holst JJ: Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs 2010;19:133-140.
18. Graefe-Mody EU, Padula S, Ring A, Withopf B, Dugi KA: Evaluation of the potential for steady-state pharmacokinetic and pharmacodynamic interactions between the DPP-4 inhibitor linagliptin and metformin in healthy subjects. Curr Med Res Opin 2009;25:1963-1972.
19. Hüttner S, Graefe-Mody EU, Withopf B, Ring A, Dugi KA: Safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of BI 1356, an inhibitor of dipeptidyl peptidase 4, in healthy male volunteers. J Clin Pharmacol 2008;48:1171-1178.
20. Heise T, Graefe-Mody EU, Hüttner S, Ring A, Trommeshauser D, Dugi K: Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab 2009;11:786-794.
21. Brosius F, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB, Harris RC, Kakoki M, Kretzler M, Leiter EH, Levi M, McIndoe RA, Sharma K, Smithies O, Susztak K, Takahashi N, Takahashi T: Mouse models of diabetic nephropathy. J Am Soc Nephrol 2009;20:2503-2512.
22. Kanetsuna Y, Takahashi K, Nagata M, Gannon MA, Breyer MD, Harris RC, Takahashi T: Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice. Am J Pathol 2007;170:1473-1484.
23. Nakagawa T, Sato W, Glushakova O, Heinig M, Clarke T, Campbell-Thompson M, Yuzawa Y, Atkinson MA, Johnson RJ, Croker B: Diabetic endothelial nitric oxide synthase knockout mice develop advanced diabetic nephropathy. J Am Soc Nephrol 2007;18:539-550.
24. Sharkovska Y, Kalk P, von Websky K, Relle K, Pfab T, Alter M, Fischer Y, Hocher B. Renoprotective Effects of Combined Endothelin-Converting Enzyme/Neutral Endopeptidase Inhibitor SLV338 in Acute and Chronic Experimental Renal Damage. Clin Lab 2011;57:507-515.
25. Zatz R, Dunn B, Meyer TW, Anderson S, Rennke H, Brenner B: Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 1986;77:1925-1930.
26. Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, Motoyama T, Saito Y, Ogawa Y, Miyamoto Y, Nakao K: T-786-C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999;99:2864-2870.
27. Tsukada T, Yokoyama K, Arai T, Takemoto F, Hara S, Yamada A, Kawaguchi Y, Hosoya T, Igari J: Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Biophys Res Commun 1998;245:190-193.
28. Veldman BA, Spiering W, Doevendans PA, Vervoort G, Kroon AA, Leeuw PW, Smits P: The Glu298Asp polymorphism of the NOS 3 gene as a determinant of the baseline production of nitric oxide. J Hypertens 2002;20:2023-2027.
29. Zanchi A, Moczulski DK, Hanna LS, Wantman M, Warram JH, Krolewski AS: Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism. Kidney Int 2000;57:405-413.
30. Ezzidi I, Mtiraoui N, Mohamed MBH, Mahjoub T, Kacem M, Almawi W: Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and -786TC gene variants with diabetic nephropathy. J Diabetes Complicat 2008;22:331-338.
31. Brosius FC: New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy. Rev Endocr Metab Disord 2008;9:245-254.
32. Futrakul N, Butthep P, Vongthavarawat V, Futrakul P, Sirisalipoch S, Chaivatanarat T, Suwanwalaikorn S: Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy. Clin Hemorheol Microcirc 2006;34:373-381.
33. Ritz E, Schmieder RE, Pollock CA: Renal protection in diabetes: lessons from ONTARGET. Cardiovasc Diabetol 2010;9:60.
34. Ladeia AM, Ladeia-Frota C, Pinho L, Stefanelli E, Adan L: Endothelial dysfunction is correlated with microalbuminuria in children with short-duration type 1 diabetes. Diabetes care 2005;28:2048-2050.
35. de Zeeuw D, Remuzzi G, Parving H-H, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM: Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 2004;65:2309-2320.
36. Iseki K, Ikemiya Y, Iseki C, Takishita S: Proteinuria and the risk of developing end-stage renal disease. Kidney Int 2003;63:1468-1474.
37. Arnlöv J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, Benjamin EJ, D'Agostino RB, Vasan RS: Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation 2005;112:969-975.
38. Hillege HL, Fidler V, Diercks GFH, van Gilst WH, Zeeuw D, van Veldhuisen DJ, Gans ROB, Janssen WMT, Grobbee DE, Jong PE: Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002;106:1777-1782.
39. Nagakura T, Yasuda N, Yamazaki K, Ikuta H, Tanaka I: Enteroinsular axis of db/db mice and efficacy of dipeptidyl peptidase IV inhibition. Metab Clin Exp 2003;52:81-86.
40. Thomas L, Tadayyon M, Mark M: Chronic treatment with the dipeptidyl peptidase-4 inhibitor BI 1356 [(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3- methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione] increases basal glucagon-like peptide-1 and improves glycemic control in diabetic rodent models. J Pharmacol Exp Ther 2009;328:556-563.
41. Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE, Shulman NB, Stamler J: Blood pressure and end-stage renal disease in men. N Engl J Med 1996;334:13-18.
42. Senkel S, Lucas B, Klein-Hitpass L, Ryffel GU: Identification of target genes of the transcription factor HNF1beta and HNF1alpha in a human embryonic kidney cell line. Biochim Biophys Acta 2005;1731:179-190.
43. Mizobuchi M, Towler D, Slatopolsky E: Vascular calcification: the killer of patients with chronic kidney disease. J Am Soc Nephrol 2009;20:1453-1464.
44. Yan X, Sano M, Lu L, Wang W, Zhang Q, Zhang R, Wang L, Chen Q, Fukuda K, Shen W: Plasma concentrations of osteopontin, but not thrombin-cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 2010;9:70.
45. Grieve DJ, Cassidy RS, Green BD: Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control? Br J Pharmacol 2009;157:1340-1351.
46. Del Rio D, Stewart AJ, Pellegrini N: A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005;15:316-328.
47. Siems W, Quast S, Carluccio F, Wiswedel I, Hirsch D, Augustin W, Hampi H, Riehle M, Sommerburg O: Oxidative stress in chronic renal failure as a cardiovascular risk factor. Clin Nephrol 2002;58:S12-S19.
48. Suzuki D, Miyata T, Saotome N, Horie K, Inagi R, Yasuda Y, Uchida K, Izuhara Y, Yagame M, Sakai H, Kurokawa K: Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol 2009;10:822-832.
49. Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS: Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. Kidney Int 2002;61:186-194.
50. Horie K, Miyata T, Maeda K, Miyata S, Sugiyama S, Sakai H, van Ypersole Strihou C, Monnier VM, Witztum JL, Kurokawa K: Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. J Clin Invest 1997;100:2995-3004.
51. Hendarto H, Inoguchi T, Maeda Y, Ikeda N, Zheng J, Takei R, Yokomizo H, Hirata E, Sonoda N, Takayanagi R: GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases. Metabolism 2012;61:1422-1434.
52. Schuff A, Steven S, Schell R, Schuhmacher S, Oelze M, Knorr M, Hausding M, Daub S, Münzel T, Klein T, Daiber A: Comparison of the Direct and Indirect Antioxidant Effects of DPP-4 Inhibitors: The Anti-Inflammatory and Vasodilatory Potential of Linagliptin. American Diabetes Association Scientific Sessions 2011 (ADA) 2011;71:981-PP.
53. Hocher B, Ziebig R, Altermann C, Krause R, Asmus G, Richter CM, Slowinski T, Sinha P, Neumayer HH: Different impact of biomarkers as mortality predictors among diabetic and nondiabetic patients undergoing hemodialysis. J Am Soc Nephrol 2003;14:2329-2337.
54. Chaykovska L, Tsuprrykov O, Hocher B: Biomarkers for the Prediction of Mortality and Morbidity in Patients with Renal Replacement Therapy. Clin Lab 2011;57:455-467.
55. Alter ML, Kretschmer A, von Websky K, Tsuprykov O, Reichetzeder C, Simon A, Stasch JP, Hocher B: Early Urinary and Plasma Biomarkers for Experimental Diabetic Nephropathy. Clin Lab 2012;58:659-671.
56. Mitrovic V, Seferovic P, Dodic, D, Krotin M, Neskovic A, Dickstein K, Devoogd H, Böcker C, Ziegler D, Godes M, Najow R, Essers H, Verboom C, Hocher B: Cardio-Renal Effects of the A1 Adenosine Receptor Antagonist SLV320 in Patients with Heart Failure. Circulation: Heart Failure 2009;2:523-531.
57. Hocher B: Adenosine A1 Receptor Antagonists in Clinical Research and Development. Kidney Int 2010;78:438-445.