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Evidence for renoprotection by blockade of the renin–angiotensin–aldosterone system in hypertension and diabetes

Journal of Human Hypertension volume 20, pages 239–253 (2006)Cite this article

Abstract

The incidence of end-stage renal disease (ESRD) is rising worldwide, accompanied by corresponding increases in the risk of morbidity and mortality. Underlying this trend are increasing rates of hypertension and diabetes mellitus, the two most common causes of ESRD. In addition to the adverse haemodynamic effects of hypertension on the kidney, elevated blood pressure (BP) can activate components of the renin–angiotensin–aldosterone system (RAAS), which, in turn, activate mediators of inflammation, oxidative stress, cell growth, and matrix accumulation. Lowering BP reduces the risk of cardiovascular events and renal damage. Accumulating evidence from clinical and laboratory studies suggests that interrupting the RAAS with therapies such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone receptor blockers can interfere with the mechanisms that promote diabetic and non-diabetic renal damage. Moreover, clinical trials of RAAS blockade have demonstrated reductions in microalbuminuria, a predictor of increased cardiorenal risk and overt nephropathy in patients with and without diabetes and/or hypertension. In this way, agents that block the RAAS should be considered the drugs of first choice as they provide enhanced renoprotection compared with other classes of antihypertensive agents such as calcium channel blockers and β-blockers.

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References

  1. Weening JJ . Advancing nephrology around the globe: an invitation to contribute. J Am Soc Nephrol 2004; 15: 2761–2762.

    PubMed  Google Scholar 

  2. US Renal Data System. USRDS 2004 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. US Department of Health and Human Services, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, 2004.

  3. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. and the 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: 2560–2572.

    Article  CAS  PubMed  Google Scholar 

  4. Cooper ME, Gilbert RE, Epstein M . Pathophysiology of diabetic nephropathy. Metabolism 1998; 47(12, Suppl 1): 3–6.

    CAS  PubMed  Google Scholar 

  5. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R et al. for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis 2000; 36: 646–661.

    CAS  PubMed  Google Scholar 

  6. Nelson RG, Knowler WC, Pettitt DJ, Bennett PH . Kidney diseases in diabetes. In: National Diabetes Data Group (eds). Diabetes in America, 2nd edn. NIH Publication No. 95-1468. US Department of Health and Human Services, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, 1995 pp 349–400.

    Google Scholar 

  7. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2005; 28(Suppl 1): S4–S36.

  8. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–853.

  9. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703–713.

    PubMed Central  Google Scholar 

  10. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG et al. and Modification of Diet in Renal Disease (MDRD) Study Group. Blood pressure control, proteinuria, and the progression of renal disease: the Modification of Diet in Renal Disease (MDRD) Study. Ann Intern Med 1995; 123: 754–762.

    CAS  PubMed  Google Scholar 

  11. Hannedouche T, Albouze G, Chauveau P, Lacour B, Jungers P . Effects of blood pressure and antihypertensive treatment on progression of advanced chronic renal failure. Am J Kidney Dis 1993; 21(5, Suppl 2): 131–137.

    CAS  PubMed  Google Scholar 

  12. Long DA, Price KL, Herrera-Acosta J, Johnson RJ . How does angiotensin II cause renal injury? Hypertension 2004; 43: 722–723.

    CAS  PubMed  Google Scholar 

  13. Cooper ME . Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy. Diabetologia 2001; 44: 1957–1972.

    CAS  PubMed  Google Scholar 

  14. Ichihara A, Imig JD, Inscho EW, Navar LG . Interactive nitric oxide–angiotensin II influences on renal microcirculation in angiotensin II-induced hypertension. Hypertension 1998; 31: 1255–1260.

    CAS  PubMed  Google Scholar 

  15. Delles C, Klingbeil AU, Schneider MP, Handrock R, Schäufele T, Schmieder RE . The role of nitric oxide in the regulation of glomerular haemodynamics in humans. Nephrol Dial Transplant 2004; 19: 1392–1397.

    CAS  PubMed  Google Scholar 

  16. Hanes DS, Weir MR . Renal protection in chronic kidney disease. In: Oparil S, Weber MA (eds). Hypertension: A Companion to Brenner and Rector's The Kidney, 2nd edn. Elsevier Saunders: Philadelphia, PA, 2005 pp 281–294.

    Google Scholar 

  17. Loutzenhiser R, Epstein M . Effects of calcium antagonists on renal hemodynamics. Am J Physiol 1985; 249: F619–F629.

    CAS  PubMed  Google Scholar 

  18. Contreras G, Greene T, Agodoa LY, Cheek D, Junco G, Dowie D et al. for the African American Study of Kidney Disease and Hypertension (AASK) Study Group Investigators. Blood pressure control, drug therapy, and kidney disease. Hypertension 2005; 46: 44–50.

    CAS  PubMed  Google Scholar 

  19. Bidani AK, Schwartz MM, Lewis EJ . Renal autoregulation and vulnerability to hypertensive injury in remnant kidney. Am J Physiol 1987; 252: F1003–F1010.

    CAS  PubMed  Google Scholar 

  20. Ketteler M, Noble NA, Border WA . Transforming growth factor-beta and angiotensin II: the missing link from glomerular hyperfiltration to glomerulosclerosis? Annu Rev Physiol 1995; 57: 279–295.

    CAS  PubMed  Google Scholar 

  21. Gnudi L, Viberti G, Raij L, Rodriguez V, Burt D, Cortes P et al. GLUT-1 overexpression: link between hemodynamic and metabolic factors in glomerular injury? Hypertension 2003; 42: 19–24.

    CAS  PubMed  Google Scholar 

  22. Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA . Expression of transforming growth factorβ is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci USA 1993; 90: 1814–1818.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Tang W, Richards EM, Raizada MK, Sumners C . Angiotensin II increases glucose uptake and glucose transporter mRNA levels in astroglia. Am J Physiol 1995; 268: E384–E390.

    CAS  PubMed  Google Scholar 

  24. Ziyadeh FN, Snipes ER, Watanabe M, Alvarez RJ, Goldfarb S, Haverty TP . High glucose induces cell hypertrophy and stimulates collagen gene transcription in proximal tubule. Am J Physiol 1990; 259(4 Part 2): F704–F714.

    CAS  PubMed  Google Scholar 

  25. Xu Q, Liu Y, Gorospe M, Udelsman R, Holbrook NJ . Acute hypertension activates mitogen-activated protein kinases in arterial wall. J Clin Invest 1996; 97: 508–514.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Border WA, Noble NA . Transforming growth factor β in tissue fibrosis. N Engl J Med 1994; 331: 1286–1292.

    CAS  PubMed  Google Scholar 

  27. Boffa J-J, Lu Y, Placier S, Stefanski A, Dussaule J-C, Chatziantoniou C . Regression of renal vascular and glomerular fibrosis: role of angiotensin II receptor antagonism and matrix metalloproteinases. J Am Soc Nephrol 2003; 14: 1132–1144.

    CAS  PubMed  Google Scholar 

  28. Kato S, Luyckx VA, Ots M, Lee K-W, Ziai F, Troy JL et al. Renin–angiotensin blockade lowers MCP-1 expression in diabetic rats. Kidney Int 1999; 56: 1037–1048.

    CAS  PubMed  Google Scholar 

  29. Sjögren LS, Doroudi R, Gan L-M, Jungersten L, Hrafnkelsdóttir T, Jern S . Elevated intraluminal pressure inhibits vascular tissue plasminogen activator secretion and downregulates its gene expression. Hypertension 2000; 35: 1002–1008.

    PubMed  Google Scholar 

  30. Fogo AB . The role of angiotensin II and plasminogen activator inhibitor-1 in progressive glomerulosclerosis. Am J Kidney Dis 2000; 35: 179–188.

    CAS  PubMed  Google Scholar 

  31. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG . Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63: 1791–1800.

    CAS  PubMed  Google Scholar 

  32. Iglarz M, Touyz RM, Viel EC, Amiri F, Schiffrin EL . Involvement of oxidative stress in the profibrotic action of aldosterone: interaction with the rennin–angiotensin system. Am J Hypertens 2004; 17: 597–603.

    CAS  PubMed  Google Scholar 

  33. Brown NJ, Kim KS, Chen YQ, Blevins LS, Nadeau JH, Meranze SG et al. Synergistic effect of adrenal steroids and angiotensin II on plasminogen activator inhibitor-1 production. J Clin Endocrinol Metab 2000; 85: 336–344.

    CAS  PubMed  Google Scholar 

  34. The EUCLID Study Group. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet 1997; 349: 1787–1792.

  35. Mogensen CE . Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. J Intern Med 2003; 254: 45–66.

    CAS  PubMed  Google Scholar 

  36. Bakris GL . Clinical importance of microalbuminuria in diabetes and hypertension. Curr Hypertens Rep 2004; 6: 352–356.

    PubMed  Google Scholar 

  37. Gerstein HC, Mann JFE, Yi Q, Zinman B, Dinneen SF, Hoogwerf B et al. for the HOPE Study Investigators. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–426.

    CAS  PubMed  Google Scholar 

  38. Hillege HL, Fidler V, Diercks GFH, van Gilst WH, de Zeeuw D, van Veldhuisen DJ et al. for the Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106: 1777–1782.

    CAS  PubMed  Google Scholar 

  39. Messent JW, Elliott TG, Hill RD, Jarrett RJ, Keen H, Viberti GC . Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. Kidney Int 1992; 41: 836–839.

    CAS  PubMed  Google Scholar 

  40. Viberti G, Wheeldon NM, for the MicroAlbuminuria Reduction With VALsartan (MARVAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106: 672–678.

    CAS  PubMed  Google Scholar 

  41. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43(Suppl 1): S1–S290.

  42. Estacio RO, Jeffers BW, Gifford N, Schrier RW . Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care 2000; 23(Suppl 2): B54–B64.

    PubMed  Google Scholar 

  43. Wright Jr JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J et al. for the African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 2002; 288: 2421–2431.

    CAS  PubMed  Google Scholar 

  44. Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease study. Ann Intern Med 2005; 142: 342–351.

    PubMed  Google Scholar 

  45. Pohl MA, Blumenthal S, Cordonnier DJ, De Alvaro F, Deferrari G, Eisner G et al. Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the Irbesartan Diabetic Nephropathy Trial: clinical implications and limitations. J Am Soc Nephrol 2005; 16: 3027–3037.

    CAS  PubMed  Google Scholar 

  46. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S et al. for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998; 51: 1755–1762.

    Google Scholar 

  47. Mogensen CE, Cooper M . Diabetic renal disease: from recent studies to improved clinical practice. Diabet Med 2004; 21: 4–17.

    CAS  PubMed  Google Scholar 

  48. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD, for the Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–1462.

    CAS  PubMed  Google Scholar 

  49. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB et al. for the 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: 851–860.

    CAS  PubMed  Google Scholar 

  50. Maschio G, Alberti D, Janin G, Locatelli F, Mann JFE, Motolese M et al. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334: 939–945.

    CAS  PubMed  Google Scholar 

  51. Allen TJ, Cao Z, Youssef S, Hulthen UL, Cooper ME . Role of angiotensin II and bradykinin in experimental diabetic nephropathy: functional and structural studies. Diabetes 1997; 46: 1612–1618.

    CAS  PubMed  Google Scholar 

  52. Kasiske BL, Kalil RSN, Ma JZ, Liao M, Keane WF . Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med 1993; 118: 129–138.

    CAS  PubMed  Google Scholar 

  53. Bonnet F, Cooper ME, Kawachi H, Allen TJ, Boner G, Cao Z . Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. Diabetologia 2001; 44: 874–877.

    CAS  PubMed  Google Scholar 

  54. Gilbert RE, Cox A, Wu LL, Allen TJ, Hulthen UL, Jerums G et al. Expression of transforming growth factor-β1 and type IV collagen in the renal tubulointerstitium in experimental diabetes: effects of ACE inhibition. Diabetes 1998; 47: 414–422.

    CAS  PubMed  Google Scholar 

  55. Plum J, Bunten B, Nemeth R, Grabensee B . Effects of the angiotensin II antagonist valsartan on blood pressure, proteinuria, and renal hemodynamics in patients with chronic renal failure and hypertension. J Am Soc Nephrol 1998; 9: 2223–2234.

    CAS  PubMed  Google Scholar 

  56. The ACE Inhibitors in Diabetic Nephropathy Trialist Group. Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med 2001; 134: 370–379.

  57. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving H-H et al. for the 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: 861–869.

    CAS  PubMed  Google Scholar 

  58. Parving H-H, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P, for the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–878.

    CAS  PubMed  Google Scholar 

  59. Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V et al. and the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004; 351: 1941–1951.

    CAS  PubMed  Google Scholar 

  60. Fogari R, Preti P, Zoppi A, Rinaldi A, Corradi L, Pasotti C et al. Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients. Am J Hypertens 2002; 15: 1042–1049.

    CAS  PubMed  Google Scholar 

  61. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J et al. for the 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: 1952–1961.

    CAS  PubMed  Google Scholar 

  62. Atkins RC, Briganti EM, Lewis JB, Hunsicker LG, Braden G, Champion de Crespigny PJ et al. for the Collaborative Group. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis 2005; 45: 281–287.

    PubMed  Google Scholar 

  63. Schrier RW, Estacio RO, Esler A, Mehler P . Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy, and strokes. Kidney Int 2002; 61: 1086–1097.

    PubMed  Google Scholar 

  64. Marre M, Puig JG, Kokot F, Fernandez M, Jermendy G, Opie L et al. Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR study. J Hypertens 2004; 22: 1613–1622.

    CAS  PubMed  Google Scholar 

  65. Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW et al. for the CALM Study Group. 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: 1440–1444.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Andersen NH, Poulsen PL, Knudsen ST, Poulsen SH, Eiskjaer H, Hansen KW et al. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study. Diabetes Care 2005; 28: 273–277.

    CAS  PubMed  Google Scholar 

  67. Tarnow L, Rossing P, Jensen C, Hansen BV, Parving H-H . Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy. Diabetes Care 2000; 23: 1725–1730.

    CAS  PubMed  Google Scholar 

  68. Mogensen CE, Viberti G, Halimi S, Ritz E, Ruilope L, Jermendy G et al. Effect of low-dose perindopril/indapamide on albuminuria in diabetes: Preterax in albuminuria regression: PREMIER. Hypertension 2003; 41: 1063–1071.

    CAS  PubMed  Google Scholar 

  69. Krimholtz MJ, Karalliedde J, Thomas S, Bilous R, Viberti G . Targeting albumin excretion rate in the treatment of the hypertensive diabetic patient with renal disease. J Am Soc Nephrol 2005; 16(Suppl 1): S42–S47.

    CAS  PubMed  Google Scholar 

  70. Rachmani R, Slavachevsky I, Amit M, Levi Z, Kedar Y, Berla M et al. The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study. Diabet Med 2004; 21: 471–475.

    CAS  PubMed  Google Scholar 

  71. Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving H-H . Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy. Diabetes Care 2005; 28: 2106–2112.

    CAS  PubMed  Google Scholar 

  72. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000; 355: 253–259.

  73. Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: Losartan Intervention for Endpoint Reduction in Hypertension study. Hypertension 2005; 45: 198–202.

    CAS  PubMed  Google Scholar 

  74. Parving H-H, Hovind P . Microalbuminuria in type 1 and type 2 diabetes mellitus: evidence with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers for treating early and preventing clinical nephropathy. Curr Hypertens Rep 2002; 4: 387–393.

    PubMed  Google Scholar 

  75. Slataper R, Vicknair N, Sadler R, Bakris GL . Comparative effects of different antihypertensive treatments on progression of diabetic renal disease. Arch Intern Med 1993; 153: 973–980.

    CAS  PubMed  Google Scholar 

  76. Ferder L, Daccordi H, Martello M, Panzalis M, Inserra F . Angiotensin converting enzyme inhibitors versus calcium antagonists in the treatment of diabetic hypertensive patients. Hypertension 1992; 19(2, Suppl): II237–II242.

    CAS  PubMed  Google Scholar 

  77. Bakris GL . The effects of calcium antagonists on renal hemodynamics, urinary protein excretion, and glomerular morphology in diabetic states. J Am Soc Nephrol 1991; 2(Suppl 1): S21–S29.

    CAS  PubMed  Google Scholar 

  78. Delles C, Klingbeil AU, Schneider MP, Handrock R, Weidinger G, Schmieder RE . Direct comparison of the effects of valsartan and amlodipine on renal hemodynamics in human essential hypertension. Am J Hypertens 2003; 16: 1030–1035.

    CAS  PubMed  Google Scholar 

  79. Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O . Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348: 383–393.

    PubMed  Google Scholar 

  80. Gaede P, Tarnow L, Vedel P, Parving H-H, Pedersen O . Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant 2004; 19: 2784–2788.

    PubMed  Google Scholar 

  81. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–1863.

  82. Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999; 354: 359–364.

    CAS  PubMed  Google Scholar 

  83. Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP et al. for the African American Study of Kidney Disease and Hypertension (AASK) Study Group. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285: 2719–2728.

    CAS  PubMed  Google Scholar 

  84. The PROCOPA Study Group. Dissociation between blood pressure reduction and fall in proteinuria in primary renal disease: a randomized double-blind trial. J Hypertens 2002; 20: 729–737.

  85. Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T . Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003; 361: 117–124.

    CAS  PubMed  Google Scholar 

  86. White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003; 41: 1021–1026.

    CAS  PubMed  Google Scholar 

  87. Boero R, Rollino C, Massara C, Berto IM, Perosa P, Vagelli G et al. The Verapamil Versus Amlodipine in Nondiabetic Nephropathies Treated with Trandolapril (VVANNTT) study. Am J Kidney Dis 2003; 42: 67–75.

    CAS  PubMed  Google Scholar 

  88. Ruggenenti P, Perna A, Loriga G, Ganeva M, Ene-Iordache B, Turturro M et al. for the REIN-2 Study Group. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. Lancet 2005; 365: 939–946.

    PubMed  Google Scholar 

  89. Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G et al. for the ACE Inhibition in Progressive Renal Disease Study Group. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med 2001; 135: 73–87.

    CAS  PubMed  Google Scholar 

  90. Rahman M, Pressel S, Davis BR, Nwachuku C, Wright Jr JT, Whelton PK et al. Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 2005; 165: 936–946.

    CAS  PubMed  Google Scholar 

  91. Rossing P, Hommel E, Smidt UM, Parving HH . Reduction in albuminuria predicts diminished progression in diabetic nephropathy. Kidney Int Suppl 1994; 45: S145–S149.

    CAS  PubMed  Google Scholar 

  92. Weir MR . Angiotensin II receptor blockers: the importance of dose in cardiovascular and renal risk reduction. J Clin Hypertens (Greenwich) 2004; 6: 315–323.

    CAS  Google Scholar 

  93. Schmieder RE, Klingbeil AU, Fleischmann EH, Veelken R, Delles C . Additional antiproteinuric effect of ultrahigh dose candesartan: a double-blind, randomized, prospective study. J Am Soc Nephrol 2005; 16: 3038–3045.

    CAS  PubMed  Google Scholar 

  94. Mangrum AJ, Bakris G . Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues. Semin Nephrol 2004; 24: 168–175.

    CAS  PubMed  Google Scholar 

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  1. Department of Diabetes, Cardiovascular Division, Unit for Metabolic Medicine, Endocrinology and Internal Medicine, King's College London School of Medicine, King's College London, London, UK

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Karalliedde, J., Viberti, G. Evidence for renoprotection by blockade of the renin–angiotensin–aldosterone system in hypertension and diabetes. J Hum Hypertens 20, 239–253 (2006). https://doi.org/10.1038/sj.jhh.1001982

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