Current Hypertension Reports

, Volume 11, Issue 5, pp 354–362 | Cite as

Should albuminuria be a focus of antihypertensive therapy goals?

  • Radica Z. Alicic
  • Sandeep A. Saha
  • Robert A. Short
  • Katherine R. Tuttle


Albuminuria has been recognized as a risk marker for both chronic kidney disease and cardiovascular disease in large observational cohorts. In addition, post hoc analyses of many large randomized trials have found a positive relationship between albu minuria and adverse renal and cardiovascular outcomes, leading some to suggest that albuminuria may be a potential therapeutic target for antihypertensive treatment. However, direct clinical evidence linking albuminuria reduction to reduction in adverse renal and cardiovascular events is scarce. This paper reviews the evidence in the current literature to address whether albuminuria can be used as a credible predictor of risk for chronic kidney disease and cardiovascular disease and also reviews the clinical trial evidence to appraise the prospect of using albuminuria as a therapeutic target to prevent adverse renal and cardiovascular events.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    United States Renal Data System, USRDS 2008 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2008.Google Scholar
  2. 2.
    Lea J, Greene T, Hebert L, et al.: 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 2005, 165:947–953.PubMedCrossRefGoogle Scholar
  3. 3.
    Ruggenenti P, Perna A, Mosconi L, et al.: Urinary protein excretion in rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. Kidney Int 1998, 53:1209–1216.PubMedCrossRefGoogle Scholar
  4. 4.
    Lambers Heerspink HJ, Brantsma AH, de Zeeuw D, et al.; PREVEND Study Group: Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality. Am J Epidemiol 2008, 168:897–905.PubMedCrossRefGoogle Scholar
  5. 5.
    Lewis EJ, Hunsicker LG, Clarke WR, et al.: Renoprotective effects of the angiotensin-receptor antagonist irbesartan on nephropathy due to type 2 diabetes. N Engl J Med 2001, 345:851–860.PubMedCrossRefGoogle Scholar
  6. 6.
    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, nondiabetic nephropathy. Lancet 1997, 349:1857–1863.CrossRefGoogle Scholar
  7. 7.
    de Zeeuw D, Remuzzi G, Parving HH, et al.: Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 2004, 65:2309–2320.PubMedCrossRefGoogle Scholar
  8. 8.
    de Zeeuw D, Remuzzi G, Parving HH, et al.: Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004, 110:921–927.PubMedCrossRefGoogle Scholar
  9. 9.
    Atkins RC, Briganti EM, Lewis JB, et al.: 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.PubMedCrossRefGoogle Scholar
  10. 10.
    Kambiz ZN, Allison AE, Richard JG, et al.: Why is proteinuria an ominous biomarker of progressive kidney disease? Kidney Int 2004, 66:S76–S89.CrossRefGoogle Scholar
  11. 11.
    Morelli E, Loon N, Meye TW, et al.: Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy. Diabetes 1990, 39:76–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Remuzzi A, Ruggenenti P, Mosconi L, et al.: Effect of low-dose enalapril on glomerular size selectivity in human diabetic nephropathy. J Nephrol 1993, 6:36–43.Google Scholar
  13. 13.
    Velbert G, Wheeldon NM: Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002, 106:672–678.CrossRefGoogle Scholar
  14. 14.
    Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993, 352:1456–1462.CrossRefGoogle Scholar
  15. 15.
    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 2001, 345:861–869.PubMedCrossRefGoogle Scholar
  16. 16.
    Wright JT, Bakris G, Greene T, et al.: Effect of blood pressure lowering and antihypertensive drug class on progression of antihypertensive kidney disease: results of AASK trial. JAMA 2002, 288:2421–2431.PubMedCrossRefGoogle Scholar
  17. 17.
    Mann JF, Schmieder RE, McQuen M, et al.: Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicenter, randomized, double-blind, controlled trial. Lancet 2008, 372:547–553.PubMedCrossRefGoogle Scholar
  18. 18.
    Marussi M, Baglio P, Gross JL, et al.: Risk factors for microalbuminuria and macroalbuminuria in type 2 diabetic patients: a 9-year follow-up study. Diabetes Care 2002, 25:1101–1103.CrossRefGoogle Scholar
  19. 19.
    Retnakaran R, Cull CA, Thorne KI, et al.: Risk factors for renal dysfunction in type 2 diabetes. U.K. prospective diabetes study 74. Diabetes 2006, 55:1832–1839.PubMedCrossRefGoogle Scholar
  20. 20.
    Rossing K, Christensen PK, Hovind P, et al.: Progression of nephropathy in type 2 diabetic patients. Kidney Int 2004, 66:1596–1605.PubMedCrossRefGoogle Scholar
  21. 21.
    Gaede P, Lund-Anderson H, Parving HH, et al.: Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008, 358:580–591.PubMedCrossRefGoogle Scholar
  22. 22.
    Sarafidis PA, Bakris GL: Renin-angiotensin blockade and kidney disease. Lancet 2008, 372:511–512.PubMedCrossRefGoogle Scholar
  23. 23.
    Fried LF, Duckworth W, Zhang JH, et al.: Design of combination angiotensin receptor blocker and angio tensinconverting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). Clin J Am Soc Nephrol 2009, 4:361–368.PubMedCrossRefGoogle Scholar
  24. 24.
    Hillege HL, Fidler V, Diercks GF, et al., for the Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group: Urinary albumin excretion predicts cardio vascular and noncardiovascular mortality in general population. Circulation 2002, 106:1777–1782.PubMedCrossRefGoogle Scholar
  25. 25.
    Astor BC, Hallan SI, Miller ER 3rd, et al.: Glomerular filtration rate, albuminuria, and risk of cardiovascular and all-cause mortality in the US population. Am J Epidemiol 2008, 167:1226–1234.PubMedCrossRefGoogle Scholar
  26. 26.
    Arnlöv J, Evans JC, Meigs JB, et al.: Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation 2005, 112:969–975.PubMedCrossRefGoogle Scholar
  27. 27.
    Ibsen H, Olsen MH, 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 2005, 45:198–202.PubMedCrossRefGoogle Scholar
  28. 28.
    Anavekar NS, Gans DJ, Berl T, et al.: Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. Kidney Int 2004, 66:S50–S55.CrossRefGoogle Scholar
  29. 29.
    Brantsma AH, Bakker SJL, de Zeeuw D, et al., for the PREVEND Study Group: Extended prognostic value of urinary albumin excretion for cardiovascular events. J Am Soc Nephrol 2008, 19:1785–1791.PubMedCrossRefGoogle Scholar
  30. 30.
    Ibsen H, Wachtell K, Olsen MH, et al.: Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy. J Hypertens 2004, 22:1805–1811.PubMedCrossRefGoogle Scholar
  31. 31.
    Parving HH, Lehnert H, Brochner-Mortenson J, et al., for The Irbesartan in Patients With Type 2 Diabetes and Micro-Albuminuria 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Kowey PR, Dickson TZ, Zhang Z, et al., for the RENAAL investigators: Losartan and end-organ protection—lessons from the RENAAL study. Clin Cardiol 2005, 28:136–142.PubMedCrossRefGoogle Scholar
  33. 33.
    Berl T, Hunsicker LG, Lewis JB, et al.: Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003, 138:542–549.PubMedGoogle Scholar
  34. 34.
    Steines W, Piehlmeier W, Schenkirsch G, et al.: Effectiveness of a disease management programme for patients with type 2 diabetes mellitus and albuminuria in primary care—the PROSIT project (Proteinuria Screening and Intervention). Exp Clin Endocrinol Diabetes 2004, 112:88–94.PubMedCrossRefGoogle Scholar
  35. 35.
    Gaede P, Vedel P, Larsen N, et al.: Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003, 348:383–393.PubMedCrossRefGoogle Scholar
  36. 36.
    The ONTARGET Investigators: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008, 358:1547–1559.CrossRefGoogle Scholar
  37. 37.
    Asselbergs FW, Diercks GFH, Hillege HL, et al., for the Prevention of Renal and Vascular Endstage Disease Intervention Trial investigators: Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 2004, 110:2809–2816.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  • Radica Z. Alicic
  • Sandeep A. Saha
    • 1
  • Robert A. Short
  • Katherine R. Tuttle
  1. 1.Providence Medical Research CenterSpokaneUSA

Personalised recommendations