Abstract
Microalbuminuria (MA), conventionally defined as a urinary albumin excretion (UAE) of 30–300 mg/day, is recognised as a marker of endothelial dysfunction. Furthermore, it represents an established risk factor for cardiovascular morbidity and mortality and for end-stage renal disease in individuals with an adverse cardiovascular risk profile. It is common in the general population, particularly in patients with diabetes mellitus or arterial hypertension. There is growing evidence from prospective observational trials that UAE levels well below the current MA threshold (“lowgrade MA”) are also associated with an increased risk of incident cardiovascular disease and allcause mortality. Even in apparently healthy individuals (without diabetes or hypertension), such an association has been shown. As albuminuria screening assays that are reliable even in the lower ranges are commercially available, there may be an important clinical role for MA in disease screening, comparable to the role of blood pressure and lipid screening. MA is modifiable, and the inhibition of the renin-angiotensin system by ACE inhibitors and AT1 receptor antagonists has been shown to result in a lower incidence of cardiovascular events.
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Amonymous (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 39:S1–S266
Knight EL, Curhan GC (2003) Albuminuria: moving beyond traditional microalbuminuria cut-points. Curr Opin Nephrol Hypertens 12:283–284
Anonymous (1994) Plan and operation of the Third National Health and Nutrition Examination Survey, 1988– 1994. Series 1: programs and collection procedures. Vital Health Stat 1 32:1–407
Hillege H, Janssen W, Bak A, et al (2001) Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 249:519–526
Bramlage P, Pittrow D, Lehnert H, et al (2007) Frequency of albuminuria in primary care: a cross sectional study. Eur J Cardiovasc Prev Rehabil (in press)
Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG (2006) Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int 69:2057–2063
de Zeeuw D, Parving HH, Henning RH (2006) Microalbuminuria as an early marker for cardiovascular disease. J Am Soc Nephrol 17:2100–2105
Volpe M, Cosentino F, Ruilope LM (2003) Is it time to measure microalbuminuria in hypertension? J Hypertens 21:1213–1220
Deckert T, Feldt-Rasmussen B, Borch- Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32:219–226
Mogensen CE (1994) Systemic blood pressure and glomerular leakage with particular reference to diabetes and hypertension. J Intern Med 235:297–316
Yuyun MF, Khaw KT, Luben R, et al (2004) 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 159:284–293
Jensen JS (1995) Renal and systemic transvascular albumin leakage in severe atherosclerosis. Arterioscler Thromb Vasc Biol 15:1324–1329
Sarnak MJ, Levey AS, Schoolwerth AC, et al (2003) Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 108:2154–2169
Gerstein HC, Mann JF, Yi Q, et al (2001) Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286:421–426
Diercks GF, Hillege HL, van Boven AJ, et al (2002) Microalbuminuria modifies the mortality risk associated with electrocardiographic ST-T segment changes. J Am Coll Cardiol 40:1401–1407
Grimm RH Jr, Svendsen KH, Kasiske B, Keane WF, Wahi MM (1997) Proteinuria is a risk factor for mortality over 10 years of follow-up. MRFIT Research Group. Multiple Risk Factor Intervention Trial. Kidney Int Suppl 63:S10–S14
De Leeuw PW, Thijs L, Birkenhager WH, et al (2002) Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial. J Am Soc Nephrol 13:2213–2222
Ljungman S, Wikstrand J, Hartford M, Berglund G (1996) Urinary albumin excretion – a predictor of risk of cardiovascular disease. A prospective 10-year follow-up of middle-aged nondiabetic normal and hypertensive men. Am J Hypertens 9:770–778
Agewall S, Wikstrand J, Ljungman S, Fagerberg B (1997) Usefulness of microalbuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Risk Factor Intervention Study Group. Am J Cardiol 80:164–169
Wang TJ, Evans JC, Meigs JB, et al (2005) Low-grade albuminuria and the risks of hypertension and blood pressure progression. Circulation 111:1370–1376
Berton G, Cordiano R, Palmieri R, Cucchini F, De Toni R, Palatini P (2001) Microalbuminuria during acute myocardial infarction; a strong predictor for 1-year mortality. Eur Heart J 22:1466–1475
Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, Schroll M, Jensen JS (1999) Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol 19:1992–1997
Romundstad S, Holmen J, Kvenild K, Hallan H, Ellekjaer H (2003) Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord- Trondelag Health Study (HUNT), Norway. Am J Kidney Dis 42:466–473
Hillege HL, Fidler V, Diercks GF, et al (2002) Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106:1777–1782
Arnlov J, Evans JC, Meigs JB, et al (2005) Low-Grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: The Framingham Heart Study. Circulation 112:969–975
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin- converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) 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 342:145–153
Asselbergs FW, Diercks GF, Hillege HL, et al (2004) Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 110:2809–2816
Ruggenenti P, Fassi A, Ilieva AP, et al (2004) Preventing microalbuminuria in type 2 diabetes. N Engl J Med 351:1941–1951
Parving HH, Lehnert H, Brochner- Mortensen J, Gomis R, Andersen S, Arner P (2001) The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345:870–878
Lewis EJ, Hunsicker LG, Clarke WR, et al (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860
Ibsen H, Olsen MH, Wachtell K, et al (2005) Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension 45:198–202
Brenner BM, Cooper ME, de Zeeuw D, et al (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869
Parving HH, Lehnert H, Brochner- Mortensen J, Gomis R, Andersen S, Arner P (2001) The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345:870–878
Berl T, Hunsicker LG, Lewis JB, et al (2003) Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 138:542–549
Kaplan NM (2001) Management of hypertension in patients with type 2 diabetes mellitus: guidelines based on current evidence. Ann Intern Med 135:1079–1083
Lindholm LH, Ibsen H, Dahlof B, et al (2002) 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 359:1004–1010
Cohn JN, Tognoni G (2001) A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 345:1667– 1675
de Zeeuw D, Remuzzi G, Parving HH, et al (2004) Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 65:2309–2320
Pourdjabbar A, Lapointe N, Rouleau JL (2002) Angiotensin receptor blockers: powerful evidence with cardiovascular outcomes? Can J Cardiol 18 Suppl A:7A–14A
Schrader J, Luders S, Kulschewski A, et al (2006) Microalbuminuria and tubular proteinuria as risk predictors of cardiovascular morbidity and mortality in essential hypertension: final results of a prospective long-term study (MARPLE Study)*. J Hypertens 24:541–548
Rossing K, Schjoedt KJ, Jensen BR, Boomsma F, Parving HH (2005) Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int 68:1190–1198
Andersen S, Rossing P, Juhl TR, Deinum J, Parving HH (2002) Optimal dose of losartan for renoprotection in diabetic nephropathy. Nephrol Dial Transplant 17:1413–1418
Laverman GD, Henning RH, de Jong PE, Navis G, de Zeeuw D (2001) Optimal antiproteinuric dose of losartan in nondiabetic patients with nephrotic range proteinuria. Am J Kidney Dis 38:1381–1384
Wright JT Jr, Bakris G, Greene T, et al (2002) Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. Jama 288:2421–2431
Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH (2002) Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes 51:1157–1165
Stephenson JM, Kenny S, Stevens LK, Fuller JH, Lee E (1995) Proteinuria and mortality in diabetes: the WHO Multinational Study of Vascular Disease in Diabetes. Diabet Med 12:149–155
Dinneen SF, Gerstein HC (1997) The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med 157:1413–1418
Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356–360
Valmadrid CT, Klein R, Moss SE, Klein BE (2000) The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with olderonset diabetes mellitus. Arch Intern Med 160:1093–1100
Miettinen H, Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1996) Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects. Stroke 27:2033–2039
Messent JW, Elliott TG, Hill RD, Jarrett RJ, Keen H, Viberti GC (1992) Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. Kidney Int 41:836–839
Rossing P, Hougaard P, Borch-Johnsen K, Parving HH (1996) Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study. BMJ 313:779–784
Gall MA, Borch-Johnsen K, Hougaard P, Nielsen FS, Parving HH (1995) Albuminuria and poor glycemic control predict mortality in NIDDM. Diabetes 44:1303–1309
Uusitupa MI, Niskanen LK, Siitonen O, Voutilainen E, Pyorala K (1993) Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Diabetologia 36:1175–1184
Romundstad S, Holmen J, Hallan H, Kvenild K, Ellekjaer H (2003) Microalbuminuria and all-cause mortality in treated hypertensive individuals: does sex matter? The Nord-Trondelag Health Study (HUNT), Norway. Circulation 108:2783–2789
de Zeeuw D, Remuzzi G, Parving HH, et al (2004) Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 110:921–927
Marre M, Lievre M, Chatellier G, Mann JF, Passa P, Menard J (2004) 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). BMJ 328:495
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Schmieder, R.E., Schrader, J., Zidek, W. et al. Low-grade albuminuria and cardiovascular risk. Clin Res Cardiol 96, 247–257 (2007). https://doi.org/10.1007/s00392-007-0510-3
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DOI: https://doi.org/10.1007/s00392-007-0510-3