64
Views
3
CrossRef citations to date
0
Altmetric
Review

The role of renin inhibition in treating the hypertensive patient with diabetes: a summary of preclinical and clinical evidence

Pages 251-263 | Published online: 10 Jan 2014

References

  • Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. US Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA, USA (2011).
  • Alderman MH, Cohen H, Madhavan S. Diabetes and cardiovascular events in hypertensive patients. Hypertension33(5), 1130–1134 (1999).
  • Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract.87(1), 4–14 (2010).
  • Kearney PM, Whelton M, Reynolds K et al. Global burden of hypertension: analysis of worldwide data. Lancet365(9455), 217–223 (2005).
  • Wong ND, Lopez VA, L’Italien G et al. Inadequate control of hypertension in US adults with cardiovascular disease comorbidities in 2003–2004. Arch. Intern. Med.167(22), 2431–2436 (2007).
  • Eguchi K, Pickering TG, Kario K. Why is blood pressure so hard to control in patients with Type 2 diabetes? J. Cardiometab. Syndr.2(2), 114–118 (2007).
  • Chobanian AV, Bakris GL, Black HR et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension42(6), 1206–1252 (2003).
  • American Diabetes Association. Standards of medical care in diabetes – 2011. Diabetes Care34(Suppl. 1), S11–S61 (2011).
  • Mancia G, Laurent S, Agabiti-Rosei E et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J. Hypertens.27, 2121–2158 (2009).
  • Basile J. New therapeutic options in patients prone to hypertension: a focus on direct renin inhibition and aldosterone blockade. Am. J. Med. Sci.337(6), 438–444 (2009).
  • Lewis EJ, Hunsicker LG, Clarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to Type 2 diabetes. N. Engl. J. Med.345(12), 851–860 (2001).
  • Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with Type 2 diabetes and nephropathy. N. Engl. J. Med.345(12), 861–869 (2001).
  • Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N. Engl. J. Med.345(23), 1667–1675 (2001).
  • Yusuf S, Sleight P, Pogue J et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N. Engl. J. Med.342(3), 145–153 (2000).
  • Appel LJ, Wright JT Jr, Greene T et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N. Engl. J. Med.363(10), 918–929 (2010).
  • Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann. Intern. Med.148(1), 30–48 (2008).
  • Jennings DL, Kalus JS, Coleman CI, Manierski C, Yee J. Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis. Diabet. Med.24(5), 486–493 (2007).
  • Yusuf S, Teo KK, Pogue J et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N. Engl. J. Med.358(15), 1547–1559 (2008).
  • Cowan BR, Young AA, Anderson C et al. Left ventricular mass and volume with telmisartan, ramipril, or combination in patients with previous atherosclerotic events or with diabetes mellitus (from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET]). Am. J. Cardiol.104(11), 1484–1489 (2009).
  • Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet372(9638), 547–553 (2008).
  • Tobe SW, Clase CM, Gao P et al. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. Circulation123(10), 1098–1107 (2011).
  • Vergaro G, Emdin M, Iervasi A et al. Prognostic value of plasma renin activity in heart failure. Am. J. Cardiol.108(2), 246–251 (2011).
  • Verma S, Gupta M, Holmes DT et al. Plasma renin activity predicts cardiovascular mortality in the Heart Outcomes Prevention Evaluation (HOPE) study. Eur. Heart J.32(17), 2135–2142 (2011).
  • Ribeiro-Oliveira A Jr, Nogueira AI, Pereira RM et al. The renin–angiotensin system and diabetes: an update. Vasc. Health Risk Manag.4(4), 787–803 (2008).
  • Atlas SA. The renin–angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J. Manag. Care Pharm.13(8 Suppl. SB), S9–S20 (2007).
  • Steckelings UM, Rompe F, Kaschina E, Unger T. The evolving story of the RAAS in hypertension, diabetes and CV disease: moving from macrovascular to microvascular targets. Fundam. Clin. Pharmacol.23(6), 693–703 (2009).
  • Strain WD, Chaturvedi N. The renin–angiotensin–aldosterone system and the eye in diabetes. J. Renin Angiotensin Aldosterone Syst.3(4), 243–246 (2002).
  • Lai KN, Leung JC, Lai KB et al. Gene expression of the renin–angiotensin system in human kidney. J. Hypertens.16(1), 91–102 (1998).
  • Danser AH, Deinum J. Renin, prorenin and the putative (pro)renin receptor. Hypertension46(5), 1069–1076 (2005).
  • Toma I, Kang JJ, Sipos A et al. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. J. Clin. Invest.118(7), 2526–2534 (2008).
  • Colucci JA, Arita DY, Cunha TS et al. Renin–angiotensin system may trigger kidney damage in NOD mice. J. Renin Angiotensin Aldosterone Syst.12(1), 15–22 (2011).
  • Bonnet F, Candido R, Carey RM et al. Renal expression of angiotensin receptors in long-term diabetes and the effects of angiotensin Type 1 receptor blockade. J. Hypertens.20(8), 1615–1624 (2002).
  • Reinemund J, Seidel K, Steckelings UM et al. Poly(ADP-ribose) polymerase-1 (PARP-1) transcriptionally regulates angiotensin AT2 receptor (AT2R) and AT2R binding protein (ATBP) genes. Biochem. Pharmacol.77(12), 1795–1805 (2009).
  • Singh VP, Le B, Khode R, Baker KM, Kumar R. Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes57(12), 3297–3306 (2008).
  • Singh VP, Baker KM, Kumar R. Activation of the intracellular renin–angiotensin system in cardiac fibroblasts by high glucose: role in extracellular matrix production. Am. J. Physiol. Heart Circ. Physiol.294(4), H1675–H1684 (2008).
  • Saris JJ, ‘t Hoen PA, Garrelds IM et al. Prorenin induces intracellular signaling in cardiomyocytes independently of angiotensin II. Hypertension48(4), 564–571 (2006).
  • Lavrentyev EN, Malik KU. High glucose-induced Nox1-derived superoxides downregulate PKC-βII, which subsequently decreases ACE2 expression and ANG(1–7) formation in rat VSMCs. Am. J. Physiol. Heart Circ. Physiol.296(1), H106–H118 (2009).
  • Ebrahimian TG, Tamarat R, Clergue M et al. Dual effect of angiotensin-converting enzyme inhibition on angiogenesis in Type 1 diabetic mice. Arterioscler. Thromb. Vasc. Biol.25(1), 65–70 (2005).
  • Nguyen G, Delarue F, Burckle C et al. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J. Clin. Invest.109(11), 1417–1427 (2002).
  • Ichihara A, Sakoda M, Kurauchi-Mito A, Kaneshiro Y, Itoh H. Renin, prorenin and the kidney: a new chapter in an old saga. J. Nephrol.22(3), 306–311 (2009).
  • Siragy HM, Huang J. Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity. Exp. Physiol.93(5), 709–714 (2008).
  • Matavelli LC, Huang J, Siragy HM. (Pro)renin receptor contributes to diabetic nephropathy by enhancing renal inflammation. Clin. Exp. Pharmacol. Physiol.37(3), 277–282 (2010).
  • Huang J, Matavelli LC, Siragy HM. Renal (pro)renin receptor contributes to development of diabetic kidney disease through transforming growth factor-b1-connective tissue growth factor signalling cascade. Clin. Exp. Pharmacol. Physiol.38(4), 215–221 (2011).
  • Ichihara A, Hayashi M, Kaneshiro Y et al. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the ‘handle’ region for nonproteolytic activation of prorenin. J. Clin. Invest.114(8), 1128–1135 (2004).
  • Uddin MN, Nabi AH, Nakagawa T et al. Non-proteolytic activation of prorenin: activation by (pro)renin receptor and its inhibition by a prorenin prosegment, ‘decoy peptide’. Front. Biosci.13, 745–753 (2008).
  • Feldt S, Maschke U, Dechend R, Luft FC, Muller DN. The putative (pro)renin receptor blocker HRP fails to prevent (pro)renin signaling. J. Am. Soc. Nephrol.19(4), 743–748 (2008).
  • Muller DN, Klanke B, Feldt S et al. (Pro)renin receptor peptide inhibitor ‘handle-region’ peptide does not affect hypertensive nephrosclerosis in Goldblatt rats. Hypertension51(3), 676–681 (2008).
  • Athyros VG, Mikhailidis DP, Kakafika AI, Tziomalos K, Karagiannis A. Angiotensin II reactivation and aldosterone escape phenomena in renin–angiotensin–aldosterone system blockade: is oral renin inhibition the solution? Expert Opin. Pharmacother.8(5), 529–535 (2007).
  • Ferrario CM. Addressing the theoretical and clinical advantages of combination therapy with inhibitors of the renin–angiotensin–aldosterone system: antihypertensive effects and benefits beyond BP control. Life Sci.86(9–10), 289–299 (2010).
  • Azizi M. Direct renin inhibition: clinical pharmacology. J. Mol. Med.86(6), 647–654 (2008).
  • Fisher ND, Jan Danser AH, Nussberger J, Dole WP, Hollenberg NK. Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans. Circulation117(25), 3199–3205 (2008).
  • Uresin Y, Taylor AA, Kilo C et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J. Renin Angiotensin Aldosterone Syst.8(4), 190–198 (2007).
  • Persson F, Rossing P, Reinhard H et al. Renal effects of aliskiren compared to and in combination with irbesartan in patients with Type 2 diabetes, hypertension and albuminuria. Diabetes Care32(10), 1873–1879 (2009).
  • Feldman DL, Jin L, Xuan H et al. Effects of aliskiren on blood pressure, albuminuria, and (pro)renin receptor expression in diabetic TG(mRen-2)27 rats. Hypertension52(1), 130–136 (2008).
  • Durvasula RV, Shankland SJ. Activation of a local renin angiotensin system in podocytes by glucose. Am. J. Physiol. Renal Physiol.294(4), F830–F839 (2008).
  • Sakoda M, Ichihara A, Kurauchi-Mito A et al. Aliskiren inhibits intracellular angiotensin II levels without affecting (pro)renin receptor signals in human podocytes. Am. J. Hypertens.23(5), 575–580 (2010).
  • Kelly DJ, Zhang Y, Moe G, Naik G, Gilbert RE. Aliskiren, a novel renin inhibitor, is renoprotective in a model of advanced diabetic nephropathy in rats. Diabetologia50(11), 2398–2404 (2007).
  • Dong YF, Liu L, Lai ZF et al. Aliskiren enhances protective effects of valsartan against Type 2 diabetic nephropathy in mice. J. Hypertens.28(7), 1554–1565 (2010).
  • Kang YS, Lee MH, Song HK et al. Aliskiren improves insulin resistance and ameliorates diabetic vascular complications in db/db mice. Nephrol. Dial. Transplant.26(4), 1194–1204 (2011).
  • Dong YF, Liu L, Kataoka K et al. Aliskiren prevents cardiovascular complications and pancreatic injury in a mouse model of obesity and Type 2 diabetes. Diabetologia53(1), 180–191 (2010).
  • Iwai M, Kanno H, Tomono Y et al. Direct renin inhibition improved insulin resistance and adipose tissue dysfunction in Type 2 diabetic KK-A(y) mice. J. Hypertens.28(7), 1471–1481 (2010).
  • Scheen AJ. Renin–angiotensin system inhibition prevents Type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab.30(6), 498–505 (2004).
  • Ernsberger P, Koletsky RJ. Metabolic actions of angiotensin receptor antagonists: PPAR-γ agonist actions or a class effect? Curr. Opin. Pharmacol.7(2), 140–145 (2007).
  • Zhao C, Vaidyanathan S, Yeh CM, Maboudian M, Armin DH. Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with Type 2 diabetes mellitus. Clin. Pharmacokinet.45(11), 1125–1134 (2006).
  • Vaidyanathan S, Maboudian M, Warren V et al. A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin, pioglitazone and fenofibrate in healthy subjects. Curr. Med. Res. Opin.24(8), 2313–2326 (2008).
  • Townsend RR, Forker A, Rumpelt P, Papst CC, Yadao A. Initial combination therapy with aliskiren/hydrochlorothiazide is more effective than amlodipine in patients with stage 2 systolic hypertension and diabetes mellitus. J. Clin. Hypertens.12(7), 534 (2010) (Abstract LB-PO-03).
  • Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in Type 2 diabetes and nephropathy. N. Engl. J. Med.358(23), 2433–2446 (2008).
  • Persson F, Lewis JB, Lewis EJ et al. Aliskiren in combination with losartan reduces albuminuria independent of baseline blood pressure in patients with Type 2 diabetes and nephropathy. Clin. J. Am. Soc. Nephrol.6(5), 1025–1031 (2011).
  • Persson F, Lewis JB, Lewis EJ et al. Impact of baseline renal function on the efficacy and safety of aliskiren added to losartan in patients with Type 2 diabetes and nephropathy. Diabetes Care33(11), 2304–2309 (2010).
  • Persson F, Rossing P, Schjoedt KJ et al. Time course of the antiproteinuric and antihypertensive effects of direct renin inhibition in Type 2 diabetes. Kidney Int.73(12), 1419–1425 (2008).
  • Persson F, Rossing P, Reinhard H et al. Optimal antiproteinuric dose of aliskiren in Type 2 diabetes mellitus: a randomised crossover trial. Diabetologia53(8), 1576–1580 (2010).
  • Cherney DZ, Lai V, Scholey JW et al. Effect of direct renin inhibition on renal hemodynamic function, arterial stiffness, and endothelial function in humans with uncomplicated Type 1 diabetes: a pilot study. Diabetes Care33(2), 361–365 (2010).
  • Pool JL, Schmieder RE, Azizi M et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am. J. Hypertens.20(1), 11–20 (2007).
  • Solomon SD, Hee SS, Shah A et al. Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction. Eur. Heart J.32(10), 1227–1234 (2011).
  • Danser AH. The increase in renin during renin inhibition: does it result in harmful effects by the (pro)renin receptor? Hypertens. Res.33(1), 4–10 (2010).
  • Stanton AV, Gradman AH, Schmieder RE et al. Aliskiren monotherapy does not cause paradoxical blood pressure rises: meta-analysis of data from 8 clinical trials. Hypertension55(1), 54–60 (2010).
  • Parving HH, Brenner BM, McMurray JJ et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol. Dial. Transplant.24(5), 1663–1671 (2009).
  • Delea TE, Sofrygin O, Palmer JL et al. Cost–effectiveness of aliskiren in Type 2 diabetes, hypertension, and albuminuria. J. Am. Soc. Nephrol.20(10), 2205–2213 (2009).
  • Bader M. Tissue renin–angiotensin–aldosterone systems: targets for pharmacological therapy. Annu. Rev. Pharmacol. Toxicol.50, 439–465 (2010).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.