Microalbuminuria as a Target to Improve Cardiovascular and Renal Outcomes

American Journal of Kidney Diseases

Volumn 47, Issue 6, 2006, Pages 927-946

  Basi, Seema ^a   Lewis, Julia B ^a  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

angiotensin II receptor antagonist; angiotensin converting enzyme inhibitor; cardiovascular disease; kidney disease; Microalbuminuria

Indexed keywords

ALBUMIN; ALDOSTERONE ANTAGONIST; ALPHA TOCOPHEROL; AMLODIPINE; ANGIOTENSIN RECEPTOR ANTAGONIST; BENAZEPRIL; BENDROFLUMETHIAZIDE; CAPTOPRIL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DOXAZOSIN; ENALAPRIL; EPLERENONE; FOSINOPRIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IRBESARTAN; LOSARTAN; METOPROLOL; NICARDIPINE; PICOTAMIDE; RAMIPRIL; REMIKIREN; RENIN INHIBITOR; SULODEXIDE; THROMBOXANE RECEPTOR BLOCKING AGENT; TRANDOLAPRIL; VALSARTAN;

ALBUMINURIA; BLOOD PRESSURE REGULATION; CARDIOVASCULAR RISK; CLINICAL TRIAL; DRUG INHIBITION; HUMAN; HYPERTENSION; KIDNEY DISEASE; KIDNEY FUNCTION; META ANALYSIS; MICROALBUMINURIA; NONHUMAN; RENAL PROTECTION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK FACTOR; SYSTEMATIC REVIEW; TREATMENT OUTCOME;

ALBUMINS; ALBUMINURIA; ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; BLOOD PRESSURE; DIABETES COMPLICATIONS; DIABETES MELLITUS; DIABETIC ANGIOPATHIES; DIABETIC NEPHROPATHIES; DISEASE PROGRESSION; DRUG THERAPY, COMBINATION; HUMANS; HYPERTENSION; KIDNEY FAILURE, CHRONIC; PREDICTIVE VALUE OF TESTS; PROGNOSIS; RISK FACTORS; TREATMENT OUTCOME;

EID: 33646794442     PISSN: 02726386     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.ajkd.2006.02.182     Document Type: Review

References (105)

1. Mogensen C.E., and Christensen C.K. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311 (1984) 89-93
2. Mogensen C.E. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310 (1984) 356-360
3. Parving H.H., Oxenboll B., Svendsen P.A., Christiansen J.S., and Andersen A.R. Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh) 100 (1982) 550-555
4. Ruggenenti P., Perna A., Gherardi G., et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 354 (1999) 359-364
5. Stuveling E.M., Hillege H.L., Bakker S.J., et al. C-Reactive protein and microalbuminuria differ in their associations with various domains of vascular disease. Atherosclerosis 172 (2004) 107-114
6. Verhave J.C., Gansevoort S.J., de Zeeuw D., and de Jong P.E. An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. Kidney Int Suppl 92 (2004) S18-S21
7. Brenner B.M., Cooper M.E., 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 (2001) 861-869
8. Lewis E.J., Hunsicker L.G., Clarke W.R., et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345 (2001) 851-860
9. Parving H.H., Lehnert H., Brochner-Mortensen J., Gomis R., Andersen S., and Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345 (2001) 870-878
10. Jones C.A., Francis M.E., Eberhardt M.S., et al. Microalbuminuria in the US population. Third National Health and Nutrition Examination Survey. Am J Kidney Dis 39 (2002) 445-459
11. Wu A.Y., Kong N.C., de Leon F.A., et al. An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients. The MicroAlbuminuria Prevalence (MAP) Study. Diabetologia 48 (2005) 17-26
12. Parving H.H., Lewis J.B., and Wajman A. Prevalence and risk factors for microalbuminuria in type 2 diabetic patients. A global perspective. Kidney Int (2006) (in press)
13. American Diabetes Association. Standards of Medical Care in Diabetes. [published erratum in Diabetes Care 28:990, 2005]. Diabetes Care 28 suppl 1 (2005) S4-S36
14. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease. Evaluation, Classification, and Stratification. Am J Kidney Dis 39 suppl 1 (2002) S1-S266
15. Connell S.J., Hollis S., Tieszen K.L., McMurray J.R., and Dornan T.L. Gender and the clinical usefulness of the albumin:creatinine ratio. Diabet Med 11 (1994) 32-36
16. Deckert T., Feldt-Rasmussen B., Borch-Johnsen K., Jensen T., and Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32 (1989) 219-226
17. Ritz E. Renal dysfunction as a novel risk factor. Microalbuminuria and cardiovascular risk. Kidney Int Suppl 93 (2005) S25-S28
18. Russo L.M., Comper W.D., and Osicka T.M. Mechanism of albuminuria associated with cardiovascular disease and kidney disease. Kidney Int Suppl 92 (2004) S67-S68
19. Myers B.D., Winetz J.A., Chui F., and Michaels A.S. Mechanisms of proteinuria in diabetic nephropathy. A study of glomerular barrier function. Kidney Int 21 (1982) 633-641
20. Deckert T., Feldt-Rasmussen B., Djurup R., and Deckert M. Glomerular size and charge selectivity in insulin-dependent diabetes mellitus. Kidney Int 33 (1988) 100-106
21. Vernier R.L., Steffes M.W., Sisson-Ross S., and Mauer S.M. Heparan sulphate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. Kidney Int 41 (1992) 1070-1080
22. Raats C.J., Van Den Born J., and Berden J.H. Glomerular heparan sulfate alterations. Mechanisms and relevance for proteinuria. Kidney Int 57 (2000) 385-400
23. Nickenig G. Central role of the AT(1)-receptor in atherosclerosis. J Hum Hypertens 16 suppl 3 (2002) S26-S33
24. Schieffer B., Schieffer E., Hilfiker-Kleiner D., et al. Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques. Potential implications for inflammation and plaque instability. Circulation 101 (2000) 1372-1378
25. Warnholtz A., Nickenig G., Schulz E., et al. Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis. Evidence for involvement of the renin-angiotensin system. Circulation 99 (1999) 2027-2033
26. Morawietz H., Rueckschloss U., Niemann B., et al. Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein. Circulation 100 (1999) 899-902
27. Graninger M., Reiter R., Drucker C., Minar E., and Jilma B. Angiotensin receptor blockade decreases markers of vascular inflammation. J Cardiovasc Pharmacol 44 (2004) 335-339
28. Miller J.A. Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus. J Am Soc Nephrol 10 (1999) 1778-1785
29. Taniwaki H., Ishimura E., Kawagishi T., et al. Intrarenal hemodynamic changes after captopril test in patients with type 2 diabetes. A duplex Doppler sonography study. Diabetes Care 26 (2003) 132-137
30. Buter H., Navis G., Dullaart R.P., de Zeeuw D., and de Jong P.E. Time course of the antiproteinuric and renal haemodynamic responses to losartan in microalbuminuric IDDM. Nephrol Dial Transplant 16 (2001) 771-775
31. Viberti G., and Wheeldon N.M. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus. A blood pressure-independent effect. Circulation 106 (2002) 672-678
32. Kopyt N.P. Slowing progression along the renal disease continuum. J Am Osteopath Assoc 105 (2005) 207-215
33. Jafar T.H., Stark P.C., Schmid C.H., et al. Progression of chronic kidney disease: The role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: A patient-level meta-analysis. Ann Intern Med 139 (2003) 244-252
34. Atkins R.C., Briganti E.M., Lewis J.B., et al. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis 45 (2005) 281-287
35. Locatelli F., Marcelli D., Comelli M., et al., Northern Italian Cooperative Study Group. Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Nephrol Dial Transplant 11 (1996) 461-467
36. Iseki K., Ikemiya Y., Iseki C., and Takishita S. Proteinuria and the risk of developing end-stage renal disease. Kidney Int 63 (2003) 1468-1474
37. Keane W.F., Brenner B.M., de Zeeuw D., et al. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy. The RENAAL Study. Kidney Int 63 (2003) 1499-1507
38. de Zeeuw D., Remuzzi G., Parving H.H., et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy. Lessons from RENAAL. Kidney Int 65 (2004) 2309-2320
39. Chan J.C., Wat N.M., So W.Y., et al. Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes. An Asian perspective from the RENAAL Study. Diabetes Care 27 (2004) 874-879
40. Viberti G.C., Hill R.D., Jarrett R.J., Argyropoulos A., Mahmud U., and Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1 (1982) 1430-1432
41. Mogensen C.E. Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int 31 (1987) 673-689
42. Berrut G., Bouhanick B., Fabbri P., et al. Microalbuminuria as a predictor of a drop in glomerular filtration rate in subjects with non-insulin-dependent diabetes mellitus and hypertension. Clin Nephrol 48 (1997) 92-97
43. Nosadini R., and Tonolo G. Blood glucose and lipid control as risk factors in the progression of renal damage in type 2 diabetes. J Nephrol 16 suppl 7 (2003) S42-S47
44. Agodoa L.Y., Appel L., Bakris G.L., et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis. A randomized controlled trial. JAMA 285 (2001) 2719-2728
45. Pontremoli R., Leoncini G., Ravera M., et al. Microalbuminuria, cardiovascular, and renal risk in primary hypertension. J Am Soc Nephrol 13 suppl 3 (2002) S169-S172
46. Bigazzi R., Bianchi S., Baldari D., and Campese V.M. Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. J Hypertens 16 (1998) 1325-1333
47. Dell'Omo G., Penno G., Giorgi D., Di Bello V., Mariani M., and Pedrinelli R. Association between high-normal albuminuria and risk factors for cardiovascular and renal disease in essential hypertensive men. Am J Kidney Dis 40 (2002) 1-8
48. Pontremoli R., Sofia A., Ravera M., et al. Prevalence and clinical correlates of microalbuminuria in essential hypertension: The MAGIC Study. Microalbuminuria: A Genoa Investigation on Complications. Hypertension 30 (1997) 1135-1143
49. Ahmad J., Shafique S., Abidi S.M., and Parwez I. Effect of 5-year enalapril therapy on progression of microalbuminuria and glomerular structural changes in type 1 diabetic subjects. Diabetes Res Clin Pract 60 (2003) 131-138
50. De Boer E., Navis G., Tiebosch A.T., De Jong P.E., and de Zeeuw D. Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in Adriamycin nephrotic rats. J Am Soc Nephrol 10 (1999) 2359-2366
51. 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 349 (1997) 1857-1863
52. Ciavarella A., Mustacchio A., Silletti A., et al. Low-dose angiotensin converting enzyme inhibitors. Effect on renal function in normo- and hypertensive type 1 diabetic patients. Eur J Med 1 (1992) 268-272
53. Lewis E.J., Hunsicker L.G., Bain R.P., and Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 329 (1993) 1456-1462
54. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus. Results of the HOPE Study and MICRO-HOPE Substudy. [erratum in Lancet 356:860, 2000]. Lancet 355 (2000) 253-259
55. Rossing K., Schjoedt K.J., Jensen B.R., Boomsma F., and Parving H.H. Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int 68 (2005) 1190-1198
56. Crippa G. Microalbuminuria in essential hypertension. J Hum Hypertens 16 suppl 1 (2002) S74-S77
57. Bigazzi R., Bianchi S., Baldari D., Sgherri G., Baldari G., and Campese V.M. Long-term effects of a converting enzyme inhibitor and a calcium channel blocker on urinary albumin excretion in patients with essential hypertension. Am J Hypertens 6 (1993) 108-113
58. Bianchi S., Bigazzi R., Baldari G., and Campese V.M. Microalbuminuria in patients with essential hypertension. Effects of several antihypertensive drugs. Am J Med 93 (1992) 525-528
59. Bianchi S., Bigazzi R., Baldari G., and Campese V.M. Microalbuminuria in patients with essential hypertension. Effects of an angiotensin converting enzyme inhibitor and of a calcium channel blocker. Am J Hypertens 4 (1991) 291-296
60. Shionoiri H., Sugimoto K., Kosaka T., et al. Long-term therapy with an ACE inhibitor, temocapril, reduces microalbuminuria in essential hypertension. Hypertens Res 21 (1998) 81-87
61. Monster T.B., Janssen W.M., de Jong P.E., and de Jong-van den Berg L.T. The impact of antihypertensive drug groups on urinary albumin excretion in a non-diabetic population. Br J Clin Pharmacol 53 (2002) 31-36
62. Lea J., Greene T., and Hebert L. The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease. Results of the African American Study of Kidney Disease and Hypertension. Arch Intern Med 165 (2005) 947-953
63. Maschio G., Alberti D., Janin G., 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 334 (1996) 939-945
64. Marre M., Lievre M., Chatellier G., Mann J.F., Passa P., and Menard J. Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin. Randomised, double blind, placebo controlled trial (the DIABHYCAR Study). [erratum in BMJ 328:686, 2004]. BMJ 328 (2004) 495
65. Vaur L., Gueret P., Lievre M., Chabaud S., and Passa P. Development of congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria. Observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) Study. [erratum in Diabetes Care 26:2489, 2003]. Diabetes Care 26 (2003) 855-860
66. Yuyun M.F., Khaw K.T., Luben R., et al. Microalbuminuria and stroke in a British population. The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. J Intern Med 255 (2004) 247-256
67. Yuyun M.F., Khaw K.T., Luben R., et al. A prospective study of microalbuminuria and incident coronary heart disease and its prognostic significance in a British population. The EPIC-Norfolk study. Am J Epidemiol 159 (2004) 284-293
68. Yuyun M.F., Khaw K.T., Luben R., et al. Microalbuminuria independently predicts all-cause and cardiovascular mortality in a British population. The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. Int J Epidemiol 33 (2004) 189-198
69. Culleton B.F., Larson M.G., Parfrey P.S., Kannel W.B., and Levy D. Proteinuria as a risk factor for cardiovascular disease and mortality in older people. A prospective study. Am J Med 109 (2000) 1-8
70. Gerstein H.C., Mann J.F., Yi Q., et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286 (2001) 421-426
71. Mann J.F., Lonn E.M., Yi Q., et al. Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency. Results of the HOPE Study. Kidney Int 65 (2004) 1375-1380
72. Anavekar N.S., Gans D.J., and Berl T. Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension. A case for albuminuria. Kidney Int Suppl 92 (2004) S50-S55
73. Wachtell K., Ibsen H., Olsen M.H., et al. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy. The LIFE Study. Ann Intern Med 139 (2003) 901-906
74. Olsen M.H., Wachtell K., Bella J.N., et al. Effect of losartan versus atenolol on aortic valve sclerosis (a LIFE substudy). Am J Cardiol 94 (2004) 1076-1080
75. Miettinen H., Haffner S.M., Lehto S., Ronnemaa T., Pyorala K., and Laakso M. Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects. Stroke 27 (1996) 2033-2039
76. Jensen J.S., Feldt-Rasmussen B., Strandgaard S., Schroll M., and Borch-Johnsen K. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension 35 (2000) 898-903
77. Nakamura S., Kawano Y., Inenaga T., et al. Microalbuminuria and cardiovascular events in elderly hypertensive patients without previous cardiovascular complications. Hypertens Res 26 (2003) 603-608
78. Rachmani R., Levi Z., Lidar M., Slavachevski I., Half-Onn E., and Ravid M. Considerations about the threshold value of microalbuminuria in patients with diabetes mellitus. Lessons from an 8-year follow-up study of 599 patients. Diabetes Res Clin Pract 49 (2000) 187-194
79. Damsgaard E.M., Froland A., Jorgensen O.D., and Mogensen C.E. Microalbuminuria as predictor of increased mortality in elderly people. BMJ 300 (1990) 297-300
80. Yudkin J.S., Forrest R.D., and Jackson C.A. Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey. Lancet 2 (1988) 530-533
81. Hillege H.L., Fidler V., Diercks G.F., et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106 (2002) 1777-1782
82. Arnlov J., Evans J.C., Meigs J.B., et al. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals. The Framingham Heart Study. Circulation 112 (2005) 969-975
83. Wang T.J., Evans J.C., Meigs J.B., et al. Low-grade albuminuria and the risks of hypertension and blood pressure progression. Circulation 111 (2005) 1370-1376
84. Klausen K., Borch-Johnsen K., Feldt-Rasmussen B., et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 110 (2004) 32-35
85. HOPE Study Investigators. The HOPE (Heart Outcomes Prevention Evaluation) Study. The design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. Can J Cardiol 12 (1996) 127-137
86. Jose P., Tomson C., and Skali H. Influence of proteinuria on outcomes and response to ACE inhibitor therapy after myocardial infarction. Eur Heart J 26 suppl 1 (2005) S48A abstr
87. Arnold J.M., Yusuf S., Young J., et al. Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 107 (2003) 1284-1290
88. Ibsen H., Olsen M.H., Wachtell K., et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients. Losartan intervention for endpoint reduction in hypertension study. Hypertension 45 (2005) 198-202
89. Asselbergs F.W., Diercks G.F., Hillege H.L., et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 110 (2004) 2809-2816
90. Jacobsen P., Andersen S., Jensen B.R., and Parving H.H. Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy. J Am Soc Nephrol 14 (2003) 992-999
91. Jacobsen P., Andersen S., Rossing K., Jensen B.R., and Parving H.H. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 63 (2003) 1874-1880
92. Nakao N., Yoshimura A., Morita H., Takada M., Kayano T., and Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE). A randomised controlled trial. [erratum in Lancet 361:1230, 2003]. Lancet 361 (2003) 117-124
93. Sinzinger H., Kritz H., and Furberg C.D. Atorvastatin reduces microalbuminuria in patients with familial hypercholesterolemia and normal glucose tolerance. Med Sci Monit 9 (2003) PI88-PI92
94. de Zeeuw D. Albuminuria, not only a cardiovascular/renal risk marker, but also a target for treatment?. Kidney Int Suppl 92 (2004) S2-S6
95. Gambaro G., Kinalska I., Oksa A., et al. Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients. The Di.N.A.S. randomized trial. J Am Soc Nephrol 13 (2002) 1615-1625
96. Giustina A., Perini P., Desenzani P., et al. Long-term treatment with the dual antithromboxane agent picotamide decreases microalbuminuria in normotensive type 2 diabetic patients. Diabetes 47 (1998) 423-430
97. Lewis E.J., Lewis J.B., and Hunsicker L.G. Interim analysis of a pilot trial of sulodexide in type 2 diabetic nephropathy with microalbuminuria. Free communication. Novel clinical markers and therapy in diabetes (2005). http://www.abstracts2view.com/asn Abstract presented at: American Society of Nephrology 38th Annual Renal Week. F-FC092 Available at: www.abstracts2view.com/asn. Accessed January 1, 2006.
98. Azizi M., and Menard J. Combined blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists. Circulation 109 (2004) 2492-2499
99. van Paassen P., de Zeeuw D., Navis G., and de Jong P.E. Renal and systemic effects of continued treatment with renin inhibitor remikiren in hypertensive patients with normal and impaired renal function. Nephrol Dial Transplant 15 (2000) 637-643
100. Pilz B., Shagdarsuren E., Wellner M., et al. Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats. Hypertension 46 (2005) 569-576
101. Epstein M. Aldosterone receptor blockade and the role of eplerenone. Evolving perspectives. Nephrol Dial Transplant 18 (2003) 1984-1992
102. Cerasola G., Cottone S., Mule G., et al. Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension. J Hypertens 14 (1996) 915-920
103. Bigazzi R., Bianchi S., Nenci R., Baldari D., Baldari G., and Campese V.M. Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria. J Hum Hypertens 9 (1995) 827-833
104. Mule G., Cottone S., Vadala A., et al. Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients. J Intern Med 256 (2004) 22-29
105. Fisher N.D., and Hollenberg N.K. Renin inhibition. What are the therapeutic opportunities?. J Am Soc Nephrol 16 (2005) 592-599