Renin-angiotensin-aldosterone system blockade in diabetes: Role of direct renin inhibitors

Postgraduate Medicine

Volumn 121, Issue 3, 2009, Pages 33-44

  Estacio, Raymond O ^a,b  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b NONE   (United States)

Author keywords

Aliskiren; Diabetes; Direct renin inhibitors; Organ protection; RAAS blockade

Indexed keywords

ALDOSTERONE; ALDOSTERONE ANTAGONIST; ALISKIREN; AMLODIPINE; ANGIOTENSIN; ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN 2 RECEPTOR; ANGIOTENSIN II; ATENOLOL; CANDESARTAN; CAPTOPRIL; CELECOXIB; CIMETIDINE; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HYDROCHLOROTHIAZIDE; IRBESARTAN; LISINOPRIL; LOSARTAN; METFORMIN; MEVINOLIN; PIOGLITAZONE; RAMIPRIL; RENIN; STREPTOZOCIN; TELMISARTAN; UNINDEXED DRUG; VALSARTAN; WARFARIN; AMIDE; FUMARIC ACID DERIVATIVE;

BLOOD PRESSURE REGULATION; CARDIOVASCULAR RISK; CLINICAL TRIAL; COMORBIDITY; DIABETES MELLITUS; DIABETIC NEPHROPATHY; HEART INFARCTION; HUMAN; HYPERKALEMIA; HYPERTENSION; HYPOKALEMIA; NONHUMAN; OUTCOME ASSESSMENT; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK REDUCTION; BLOOD; CARDIOVASCULAR DISEASE; DRUG ANTAGONISM; DRUG EFFECT; METABOLISM;

AMIDES; CARDIOVASCULAR DISEASES; DIABETES MELLITUS; FUMARATES; HUMANS; RENIN; RENIN-ANGIOTENSIN SYSTEM;

EID: 67549135974     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.3810/pgm.2009.05.2000     Document Type: Review

References (117)

1. Wild S, Roglic G, Green A. Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-1053.
2. American Heart Association. Heart Disease and Stroke Statistics 2008 update. http://www.americanheart.org/downloadable/heart/1200082005246HS- Stats%202008.final.pdf. Accessed April 11, 2008.
3. Hairis MI. Noninsulin-dependent diabetes mellitus in black and white Americans. Diabetes Metab Rev. 1990;6(2):71-90. (Pubitemid 20331561)
4. Carter JS, Pugh JA, Monterrosa A. Non-insulin-dependent diabetes mellitus in minorities in the United States. Ann Intern Med. 1996; 125(3):221-232. (Pubitemid 126449266)
5. Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289(1):76-79.
6. American Diabetes Association. Economic costs of diabetes in the US in 2007. Diabetes Care. 2008;31(3):596-615.
7. Kannel WB, McGee DL. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes Care. 1979:2(2):120-126. (Pubitemid 9238733)
8. Krolewski AS, Kosinski EJ, Warram JH, et al. Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. Am J Cardiol. 1987;59(8):750-755. (Pubitemid 17061281)
9. Pyörälä K. Diabetes and heart disease. In: Mogensen CE, Standl E, eds. Prevention and Treatment of Diabetic Late Complications. New York, NY: Walter de Gruyter, 1989:151-168.
10. Fuller JH, Stevens LK. Epidemiology of hypertension in diabetic patients and implications for treatment. Diabetes Care. 1991;14(suppl 4):8-12.
11. Satterfield S, Cutler JA, Langford HG, et al. Trials of hypertension prevention. Phase I design. Ann Epidemiol. 1991;1(5):455-471.
12. Walker WG, Hermann J, Murphy R, Patz A. Elevated blood pressure and angiotensin II are associated with accelerated loss of renal function in diabetic nephropathy. Trans Am Clin Climatol Assoc. 1986;97:94-104.
13. Christensen CK, Mogensen CE. The course of incipient diabetic nephropathy: studies of albumin excretion and blood pressure. Diabet Med. 1985;2(2):97-102. (Pubitemid 15109132)
14. Parving HH, Andersen AR, Smidt UM, Oxenbøll B, Edsberg B, Christiansen JS. Diabetic nephropathy and arterial hypertension. Diabetologia. 1983;24(1):10-12. (Pubitemid 13167151)
15. Christlieb AR, Warram JH, Królewski AS, et al. Hypertension: the major risk factor in juvenile-onset insulin-dependent diabetics. Diabetes. 1981;30(suppl 2):90-96.
16. Savage S, Schrier RW. Progressive renal insufficiency: the role of angiotensin converting enzyme inhibitors. Adv Intern Med. 1992:37:85-101.
17. Kuowler WC, Bennett PH, Ballintine EJ. Increased incidence of retinopathy in diabetics with elevated blood pressure. A six-year follow-up study in Pima Indians. N Engl J Med. 1980;302(12):645-650. (Pubitemid 10132146)
18. Ishihara M, Yukimura Y, Aizawa T, Yamada T, Ohto K, Yoshizawa K. High blood pressure as risk factor in diabetic retinopathy development in NIDDM patients. Diabetes Care. 1987;10(1):20-25. (Pubitemid 17069062)
19. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med. 1989;149(11):2427-2432.
20. Maser RE, Steenkiste AR, Dorman JS, et al. Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes. 1989:38(11):1456-1461.
21. Dupree EA, Meyer MB. Role of risk factors in complications of diabetes mellitus. Am J Epidemiol. 1980;112(1):100-112. (Pubitemid 10019006)
22. Nelson RG, Newman JM, Knowler WC, et al. Incidence of end-stage renal disease in type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians. Diabetologia. 1988;3l(10):730-736.
23. Ferrario CM. Role of angiotensin II in cardiovascular disease: therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst. 2006;7(1):3-14. (Pubitemid 43891239)
24. Brewster UC, Setaro JF, Perazella MA. The renin-angiotensin-aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states. Ant J Med Sci. 2003;326(1):15-24. (Pubitemid 36870293)
25. Cooper ME. The role of the renin-angiotensin-aldosterone system in diabetes and its vascular complications. Am J Hypertens. 2004;17(11 pt2):16S-20S. (Pubitemid 39469911)
26. Touyz RM. Molecular and cellular mechanisms in vascular injury in hypertension: role of angiotensin II. Curr Opin Nephrol Hypertens. 2005;14(2):125-131. (Pubitemid 40396865)
27. Siragy MM, Carey RM. Protective role of the angiotensin AT2 receptor in a renal wrap hypertension model. Hypertension. 1999;33(5):1237-1242. (Pubitemid 29230980)
28. Yamada T, Akishita M, Pollman MJ, Gibbons GH, Dzau VJ, Horiuchi M. Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagonizes angiotensin II type 1 receptor action: an in vitro gene transfer study. Life Sci. 1998;63(19):PL289-PL295. (Pubitemid 28494164)
29. Tone A, Shikata K, Ogawa D, et al. Changes of gene expression profiles in macrophages stimulated by angiotensin II-angiotensin II induces MCP-2 through AT1-receptor. J Renin Angiotensin Aldosterone Syst. 2007;8(1):45-50, (Pubitemid 46779549)
30. D'Amore A, Black MJ, Thomas WG. The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy. Hypertension. 2005;46(6):1347-1354. (Pubitemid 43189734)
31. Reudelhuber TL. The continuing saga of the AT2 receptor: a case of the good, the bad, and the innocuous. Hypertension. 2005;46(6):1261-1262. (Pubitemid 43189720)
32. Yan X, Schuldt AJ, Price RL, et al. Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Am J Physiol Heart Circ Physiol. 2008;294(3):H1274-H1281.
33. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev. 2003;24(3):261-271. (Pubitemid 36733542)
34. Hilgers KF, Mann JF. ACE inhibitors versus AT(1) receptor antagonists in patients with chronic renal disease. J Am Soc Nephrol. 2002;13(4):1100-1108.
35. Chobanian AV, Bakris GL, Black BR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.
36. Riley D, Lang AE, Blair RD, Birnbaum A, Reid B. Frozen shoulder and other shoulder disturbances in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1989;52(1):63-66. (Pubitemid 19043872)
37. Hunt SA, Baker DW, Chin MH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure); International Society for Heart and Lung Transplantation; Heart Failure Society of America. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation. 2001;104(24):2996-3007.
38. United States Renal Data System. 2007 USRDS Annual Data Report: Chronic Kidney Disease. Bethesda. MD: United States Renal Data System; 2007:64-80.
39. Striker GE, Agodoa LL, Held P, Doi T, Conti F, Striker LJ. Kidney disease of diabetes mellitus (diabetic nephropathy): perspectives in the United States. J Diabet Complications. 1991;5(2-3):51-52.
40. Nelson RG, Bennett PH, Beck GJ, et al. Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus: Diabetic Renal Disease Study Group. N Engl J Med. 1996;335(22):1636-1642. (Pubitemid 26392728)
41. Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 2005;28(1):164-176. (Pubitemid 40095801)
42. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984;310(6):356-360. (Pubitemid 14179541)
43. Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001;134(8):629-636. (Pubitemid 32322240)
44. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63(1):225-232. (Pubitemid 35463925)
45. Wolf G, Ziyadeh FN. The role of angiotensin II in diabetic nephropathy: emphasis on nonhemodynamic mechanisms. Am J Kidney Dis. 1997;29(1):153-163. (Pubitemid 27020811)
46. Leehey DJ, Singh AK, Alavi N, Singh R. Role of angiotensin II in diabetic nephropathy. Kidney Int Suppl. 2000;77:S93-S98. (Pubitemid 30681197)
47. Rosenberg ME, Smith LJ, Correa-Rotter R, Hostetter TH. The paradox of the renin-angiotensin system in chronic renal disease. Kidney Int. 1994;45(2):403-4l0. (Pubitemid 24065073)
48. Wolf G. Angiotensin II is involved in the progression of renal disease: importance of non-hemodynamic mechanisms. Nephrologie. 1998;19(7):451-456. (Pubitemid 28547242)
49. Lewis EJ, Hunsicker LO, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329(20):1456-1462.
50. Taguma V, Kitamoto Y, Futaki G, et al. Effect of captopril on heavy proteinuria in azotemic diabetics. N Engl J Med. 1985;313(26):1617-1620. (Pubitemid 16155665)
51. Björck S, Mulec H, Johnsen SA, Nordén G, Aurell M. Renal protective effect of enalapril in diabetic nephropathy. BMJ. 1992;304(6823):339-343.
52. Viberti G, Mogensen CE, Groop LC, Pauls JF. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria: European Microalbuminuria Captopril Study Group. JAMA. 1994;271(4):275-279.
53. Brenner BM, Cooper ME, de Zeeuw D, et al; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. (Pubitemid 34940825)
54. Lewis FJ, Hunsicker LG, Clarke WR, et al; Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851-860. (Pubitemid 34940824)
55. Barnett AH, Bain SC, Bouter P, et al; Diabetics Exposed to Telmisartan and Enalapril Study Group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351(19):1952-1961.
56. Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366(9502):2026-2033. (Pubitemid 41773378)
57. 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. 2008;148(1):30-48. (Pubitemid 351688350)
58. Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321(7274):1440-1444.
59. Rossing K, Jacobsen P, Pietraszek L, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care. 2003;26(8):2268-2274. (Pubitemid 36993311)
60. Jacobsen P, Andersen S, Rossing K, Hansen BV, Parving HH. Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. Nephrol Dial Transplant. 2002;17(6):1019-1024. (Pubitemid 34746204)
61. Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int. 2003;63(5):1874-1880. (Pubitemid 36513336)
62. Tütüncü NB, Gürlek A, Gedik O. Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study. Acta Diabetol. 2001;38(4):157-16l. (Pubitemid 34145694)
63. Andersen NH, Poulsen PL, Knudsen ST, et al. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study. Diabetes Care. 2005;28(2):273-277. (Pubitemid 40170925)
64. van den Meiracker AH, Man in 't Veld AJ, Admiraal PJ, et al. Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response? J Hypertens. 1992;10(8):803-812.
65. The ONTARGET Investigators; Yusuf S. Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547-1559.
66. Mann JF, Schmieder RE, McQueen M, et al; ONTARGET investigators. 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(9638):547-553.
67. Andersen NH, Poulsen PL, Knudsen ST, et al. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study. Diabetes Care. 2005;28(2):273-277. (Pubitemid 40170925)
68. Jacobsen P, Andersen S, Rossing K, Hansen BV, Parving HH. Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. Nephrol Dial Transplant. 2002;17(6):1019-1024. (Pubitemid 34746204)
69. Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int. 2003;63(5):1874-1880. (Pubitemid 36513336)
70. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351(6):585-592. (Pubitemid 39025174)
71. Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3):646-661.
72. US National Institutes of Health. VA NEPHRON-D study (CSP#565). www.clinicaltrials.gov/ct2/show/NCT005552l7. Accessed May 7, 2008.
73. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229-234. (Pubitemid 28350165)
74. Bell DS. Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care. 2003;26(8):2433-2441. (Pubitemid 36993339)
75. Zuanetti G, Latini R, Maggioni AP, Franzosi M, Santoro L, Tognoni G. Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study. Circulation. 1997;96(12):4239-4245. (Pubitemid 28007450)
76. Effects of ramipril on cardiovascular and microascular outcomes in people with diabetes mellitus: results of the HOPE study and MICROHOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355(9200):253-259.
77. Lindholm LH, Ibsen H, Dahlöf B, et al; LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):1004-1010.
78. Pourdjabbar A, Lapointe N, Rouleau JL. Angiotensin receptor blockers: powerful evidence with cardiovascular outcomes? Can J Cardiol. 2002;18(suppl A):7A-14A.
79. de Zeeuw D, Remuzzi G, Parving HH, et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulalion. 2004;110(8):921-927. (Pubitemid 39128617)
80. Deinum J, Rønn B, Mathiesen E, Derkx FH, Hop WC, Schalekamp MA. Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus. Diaberologia. 1999;42(8):1006-1010. (Pubitemid 29369610)
81. Luetscher JA, Kraemer FR, Wilson DM, Schwartz HC, Bryer-Ash M. Increased plasma inactive renin in diabetes mellitus. A marker of microvascular complications. N Engl J Med. 1985;312(22):1412-1417. (Pubitemid 15083658)
82. Packer M, Poole-Wilson PA. Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999;100(23):2312-2318.
83. ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547-1559.
84. Allan DR, Hui KY, Coletti C, Hollenberg NK. Renin vs angiotensin- converting enzyme inhibition in the rat: consequences for plasma and renal tissue angiotensin. J Pharmacol Exp Ther. 1997;283(2):661-665. (Pubitemid 27514624)
85. Nguyen G, Delarue F, Burckle C, Bouzhir L, Giller T, Sraer JD. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 2002;109(11):1417-1427. (Pubitemid 34596167)
86. Nguyen G, Danser AH. Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents. Exp Physiol. 2008;93(5):557-563. (Pubitemid 351595066)
87. Danser AH, Deinum J. Renin, prorenin and the putative (pro)renin receptor. Hypertension. 2005;46(5):1069-1076. (Pubitemid 41533004)
88. Danser AH. Novel drugs targeting hypertension: renin inhibitors. J Cardiovasc Pharmacol. 2007;50(2):105-111. (Pubitemid 47267735)
89. Danser AH, van den Dorpel MA, Deinum J, et al. Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy. J Clin Endocrinol Metab. 1989;68(1):160-167. (Pubitemid 19028740)
90. 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. 2004;114(8):1128-1135.
91. Eder J, Hommel U, Cumin F, Martoglio B, Gerhartz B. Aspartic proteases in drug discovery. Curr Pharm Des. 2007;13(3):271-285. (Pubitemid 46085279)
92. Nussberger J, Wuerzner G, Jensen C, Brunner HR. Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension. 2002;39(1):E1-E8.
93. Tekturna [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; March 2007.
94. Tekturna HCT [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corp; January 2008.
95. Vaidyanathan S, Valencia J, Kemp C, et al. Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. Int J Clin Prod. 2006;60(11):1343-1356. (Pubitemid 44560330)
96. Waldmeier F, Glaenzel U, Wirz B, et al. Absorption, distribution, metabolism, and elimination of the direct renin inhibitor aliskiren in healthy volunteers. Drug Metab Dispos. 2007;35(8):1418-1428. (Pubitemid 47121784)
97. Zhao C, Vaidyanathan S, Yeh CM, Maboudian M, Armin Dieterich H. Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with type 2 diabetes mellitus. Clin Pharmacokinet. 2006;45(11):1125-1134. (Pubitemid 44631391)
98. Vaidyanathan S, Bigler H, Yeh C, et al. Pharmacokinetics of the oral direct renin inhibitor aliskiren alone and in combination with irbesartan in renal impairment. Clin Pharmacokinet. 2007;46(8):661-675. (Pubitemid 47204852)
99. Vaidyanathan S, Warren V, Yeh C, Bizot MN, Dieterich HA, Dole WP. Pharmacokinetics, safety, and tolerability of the oral renin inhibitor aliskiren in patients with hepatic impairment. J Clin Pharmacol. 2007;47(2):192-200. (Pubitemid 46146485)
100. Vaidyanathan S. Lick of pharmacokinetic interaction with the direct renin inhibitor aliskiren with metformin, pioglitazone, and fenofibrate in healthy subjects. Curr Med Res Opin. In press.
101. Dieterle W, Corynen S, Mann J. Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects. Br J Clin Pharmacol. 2004;58(4):433-436. (Pubitemid 39312468)
102. Dieterle W, Corynen S, Vaidyanathan S, Mann J. Pharmacokinetic interactions of the oral renin inhibitor aliskiren with lovastatin, atenolol, celecoxib and cimetidine. Int J Clin Pharmacol Ther. 2005;43(11):527-535. (Pubitemid 41684265)
103. Castells L, Vargas V, Allende H, et al. Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation. J Hepatol. 2005;43(1):53-59. (Pubitemid 40805272)
104. Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007;370(9583):221-229. (Pubitemid 47069535)
105. 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. 2007;8(4):190-198. (Pubitemid 351166266)
106. Villamil A, Chrysant SG, Calhoun D, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens. 2007;25(1):217-226. (Pubitemid 44885684)
107. American Diabetes Association. Standards of medical care in diabetes - 2008. Diabetes Care. 2008;31(suppl 1):S12-S54.
108. Pilz B, Shagdarsuren E, Wellner M, et al. Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats. Hypertension. 2005;46(3):569-576. (Pubitemid 41376839)
109. 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. Hypertension. 2008;52(1):130-136.
110. 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. 2008;73(12):1419-1425. (Pubitemid 351770494)
111. Persson FP, Rossing H, Reinhard T, et al. Renoprotective effects of direct renin inhibition compared to and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria. Diabetologia, 2008;51(suppl 1):S492.
112. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK; AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008;358(23):2433-2446. (Pubitemid 351793017)
113. Parving HH, Brenner BM, McMurray JJV, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Disease Endpoints (ALTITUDE): rationale and study design. Paper presented at: American Society of Nephrology Renal Week 2007; October 31 to November 5, 2007; San Francisco, CA. Abstract PUB557.
114. US National Institutes of Health. Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (ALTITUDE). www.clinicaltrials.gov/ct2/show/NCT00549757. Accessed May 7, 2008.
115. O'Brien E, Barton J, Nussberger J, et al. Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker. Hypertension. 2007;49(2):276-284. (Pubitemid 46143002)
116. Yarows SA, Oparil S, Patel S, Fang H, Zhang J. Aliskiren and valsartan in stage 2 hypertension: subgroup analysis of a randomized, double-blind study. Adv Ther. 2008;25(12):1288-1302.
117. Chrysant SG, Murray AV, Hoppe UC, et al. Long-term safety, tolerability and efficacy of aliskiren in combination with valsartan in patients with hypertension: a 6-month interim analysis. Curr Med Res Opin. 2008;24(4):1039-1047. (Pubitemid 351579161)