Abstract
The kidney is one of the major target organs of hypertension.
Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).
ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.
Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.
Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.
These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.
The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m2 and 60 mL/min/1.73 m2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30–300 mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30–300 mg/g.
There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
ACE Inhibitors in Diabetic Nephropathy Trialist Group (2001) 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 134:370–379
Agrawal B, Berger A, Wolf K, Luft FC (1996) Microalbuminuria screening by reagent strip predicts cardiovascular risk in hypertension. J Hypertens 14:223–228
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus: provisional report of a WHO consultation. Diabet Med 15:539–553
Andronico G, Ferrara L, Mangano M, Mulè G, Cerasola G (1998) Insulin, sodium-lithium countertransport, and microalbuminuria in hypertensive patients. Hypertension 31:110–113
Andronico G, Romé M, Lo Cicero A, Parsi R, Seddio G, Ferraro-Mortellaro R et al (2005) Renal plasma flow, filtration fraction and microalbuminuria in hypertensive patients: effects of chronic smoking. Nephrology (Carlton) 10:483–486
Arnlov J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D 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
Asselbergs FW, Diercks GFH, Hillege HL, van Boven AJ, Janssen WM, Voors AA, et al. for the Prevention of Renal and Vascular Endstage Disease Intervention Trial investigators (2004) Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 110: 2809–2816
Astor BC, Hallan SI, Miller ER 3rd, Yeung E, Coresh J (2008) Glomerular filtration rate, albuminuria, and risk of cardiovascular and all-cause mortality in the US population. Am J Epidemiol 167:1226–1234
Astor BC, Matsushita K, Gansevoort RT, van der Velde M, Woodward M, Levey AS et al (2011) Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int 79:1331–1340
Bakris GL, Sarafidis PA, Weir MR, Dahlöf B, Pitt B, Jamerson K, ACCOMPLISH Trial Investigators et al (2010) Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet 375:1173–1181
Barzilay JI, Gao P, O’Donnell M et al (2011) Albuminuria and decline in cognitive function: the ONTARGET/TRANSCEND studies. Arch Intern Med 171:142–150
Bianchi S, Bigazzi R, Baldari G, Sgherri GP, Campese VM (1994) Diurnal variation of blood pressure and microalbuminuria in essential hypertension. Am J Hypertens 7:23–29
Bigazzi R, Bianchi S, Nenci R, Baldari D, Baldari G, Campese VM (1995) Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria. J Hum Hypertens 9:827–833
Bigazzi R, Bianchi S, Baldari S, Campese VM (1998) Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension. J Hypertens 16:1325–1333
Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95
Böhm M, Thoenes M, Danchin N, Bramlage P, La Puerta P, Volpe M (2007) Association of cardiovascular risk factors with microalbuminuria in hypertensive individuals: the i-SEARCH global study. J Hypertens 25:2317–2324
Bramlage P, Pittrow D, Lehnert H, Höfler M, Kirch W, Ritz E, Wittchen HU (2007) Frequency of albuminuria in primary care: a cross sectional study. Eur J Cardiovasc Prev Rehabil 14:107–113
Brantsma AH, Bakker SJ, de Zeeuw D, de Jong PE, Gansevoort RT (2008) Extended prognostic value of urinary albumin excretion for cardiovascular events. J Am Soc Nephrol 19:1785–1791
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH 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
Campese VM, Bianchi S, Bigazzi R (1999) Association between hyperlipidemia and microalbuminuria in essential hypertension. Kidney Int 56(Suppl 7):S10–S13
Cerasola G, Cottone S (1997) Microalbuminuria as a marker of vascular damage in hypertension: influence of blood pressure and metabolic patterns. Nutr Metab Cardiovasc Dis 7:92–95
Cerasola G, Cottone S, D’Ignoto G, Grasso L, Mangano MT, Andronico G (1989) Microalbuminuria as a predictor of cardiovascular damage in essential hypertension. J Hypertens 7(Suppl 6):S332–S333
Cerasola G, Cottone S, Nardi E, D’Ignoto G, Volpe V, Mulé G, Carollo C (1995) White-coat hypertension and cardiovascular risk. J Cardiovasc Risk 2:545–549
Cerasola G, Cottone S, Mulè G, Nardi E, Mangano MT, Andronico G, Contorno A et al (1996) Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension. J Hypertens 14:915–920
Cerasola G, Mulè G, Nardi E, Cottone S, Andronico G, Mongiovì R et al (2004) Usefulness of microalbuminuria in cardiovascular risk stratification of essential hypertensive patients. Nephron Clin Pract 96:c23–c30
Cerasola G, Mulè G, Cottone S, Nardi E, Cusimano P (2008) Hypertension, microalbuminuria and renal dysfunction: the Renal Dysfunction in Hypertension (REDHY) study. J Nephrol 21:368–373
Cerasola G, Mulè G, Nardi E, Cusimano P, Palermo A, Arsena R et al (2010) Clinical correlates of renal dysfunction in hypertensive patients without cardiovascular complications: the REDHY study. J Hum Hypertens 24:44–50
Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V et al (2004) The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 140:167–174
Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R et al (1998) Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: The Gubbio Population Study. Arch Intern Med 158:1933–1939
Cirillo M, Laurenzi M, Mancini M, Zanchetti A, De Santo NG (2006) Low muscular mass and overestimation of microalbuminuria by urinary albumin/creatinine ratio. Hypertension 47:56–61
Cirillo M, Lanti MP, Menotti A, Laurenzi M, Mancini M, Zanchetti A, De Santo NG (2008) Definition of kidney dysfunction as a cardiovascular risk factor: use of urinary albumin excretion and estimated glomerular filtration rate. Arch Intern Med 168:617–624
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047
Cottone S, Cerasola G (1992) Microalbuminuria fractional clearance and early renal permselectivity changes in essential hypertension. Am J Nephrol 12:326–329
Cottone S, Vadalà A, Mangano MT, Vella MC, Riccobene R, Neri AL et al (2000) Endothelium-derived factors in microalbuminuric and nonmicroalbuminuric essential hypertensives. Am J Hypertens 13:172–176
Cottone S, Mulè G, Nardi E, Lorito MC, Guarneri M, Arsena R, Cerasola G (2007) Microalbuminuria and early endothelial activation in essential hypertension. J Hum Hypertens 21:167–172
Cuspidi C, Meani S, Fusi V, Severgnini B, Valerio C, Catini E et al (2004) Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens 22:1991–1998
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
Diercks GF, van Boven AJ, Hillege HL, Janssen WM, Kors JA, de Jong PE et al (2000) Microalbuminuria is independently associated with ischaemic electrocardiographic abnormalities in a large nondiabetic population. The PREVEND (Prevention of Renal and Vascular ENdstage Disease) study. Eur Heart J 21:1922–1927
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
Dworkin LD, Ichikawa I, Brenner BM (1983) Hormonal modulation of glomerular function. Am J Physiol 244:F95–F104
Festa A, D’Agostino R, Howard G, Mykkanen L, Tracy RP, Haffner SM (2000) Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: the Insulin Resistance Atherosclerosis Study. Kidney Int 58:1703–1710
Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW et al (2005) Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 16:489–495
Fox CS, Matsushita K, Woodward M, Bilo HJG, Chalmers J, Heerspink HJL et al (2012) Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 380:1662–1673
Furtner M, Kiechl S, Mair A, Seppi K, Weger S, Oberhollenzer F et al (2005) Urinary albumin excretion is independently associated with carotid and femoral artery atherosclerosis in the general population. Eur Heart J 26:279–287
Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJL, Mann JF et al (2013) Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382:339–352
Geraci G, Mulè G, Geraci C, Mogavero M, D’Ignoto F, Morreale M et al (2015a) Association of renal resistive index with aortic pulse wave velocity in hypertensive patients. Eur J Prev Cardiol 22:415–422
Geraci G, Mulè G, Mogavero M, Geraci C, D’Ignoti D, Guglielmo C et al (2015b) Renal haemodynamics and severity of carotid atherosclerosis in hypertensive patients with and without impaired renal function. Nutr Metab Cardiovasc 25:160–166
Geraci G, Mulè G, Costanza G, Mogavero M, Geraci C, Cottone S (2016) Relationship between carotid atherosclerosis and pulse pressure with renal hemodynamics in hypertensive patients. Am J Hypertens 29:519–527
Gerstein HC, Mann JF, Pogue J, Dinneen SF, Hallé JP, Hoogwerf B et al (2000) Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators. Diabetes Care 23(Suppl 2):B35–B39
Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP et al (2001) Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286:421–426
Go A, Chertow G, Fan D, Mcculloch CE, Hsu C (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. New Eng J Med 351:1296–1305
Halbesma N, Kuiken DS, Brantsma AH, Bakker SJL, Wetzels JFM, de Zeeuw D et al (2006) Macroalbuminuria is a better risk marker than low estimated GFR to identify individuals at risk for accelerated GFR loss in population screening. J Am Soc Nephrol 17:2582–2590
Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR (2009) Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 20:1069–1077
Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A et al (2012) Age and association of kidney measures with mortality and end-stage renal disease. JAMA 308:2349–2360
Haller H, Ito S, Izzo JL Jr, Januszewicz A, Katayama S, Menne J, ROADMAP Trial Investigators et al (2011) Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 364:907–917
Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR et al (2010) Relation between kidney function, proteinuria, and adverse outcomes. JAMA 303:423–429
Hermans MM, Henry R, Dekker JM, Kooman JP, Kostense PJ, Nijpels G et al (2007) Estimated glomerular filtration rate and urinary albumin excretion are independently associated with greater arterial stiffness: the Hoorn Study. J Am Soc Nephrol 18:1942–1952
Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ 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
Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ et al (2002) Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106:1777–1782
Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM (1981) Hyperfiltration in remnant nephrons: A potential adverse response to renal ablation. Am J Physiol 241:F85–F93
Hsu CC, Brancati FL, Astor BC, Kao WH, Steffes MW, Folsom AR, Coresh J (2009) Blood pressure, atherosclerosis, and albuminuria in 10,113 participants in the Atherosclerosis Risk in Communities Study. J Hypertens 27:397–409
Ibsen H, Wachtell K, Olsen MH, Borch-Johnsen K, Lindholm LH, Mogensen CE et al (2004) Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy. J Hypertens 22:1805–1811
Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE 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
Investigators ONTARGET, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H et al (2008) Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 358:1547–1559
Jager A, Kostense PJ, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD (1998) Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study. Diabetologia 41:694–700
Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD (2002) C-reactive protein and soluble vascular cell adhesion molecule-1 are associated with elevated urinary albumin excretion but do not explain its link with cardiovascular risk. Arterioscler Thromb Vasc Biol 22:593–598
Jørgensen L, Jenssen T, Johnsen SH, Mathiesen EB, Heuch I, Joakimsen O et al (2007) Albuminuria as risk factor for initiation and progression of carotid atherosclerosis in non-diabetic persons: the Tromsø Study. Eur Heart J 28:363–369
Keen H, Chlouverakis C (1963) An immunoassay method for urinary albumin at low concentrations. Lancet 2:913–914
Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, Scharling H et al (2004) Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 110:32–35
Klausen KP, Parving HH, Scharling H, Jensen JS (2007) The association between metabolic syndrome, microalbuminuria and impaired renal function in the general population: impact on cardiovascular disease and mortality. J Intern Med 262:470–478
Klausen KP, Parving HH, Scharling H, Jensen JS (2009) Microalbuminuria and obesity: impact on cardiovascular disease and mortality. Clin Endocrinol (Oxf) 71:40–45
Kshirsagar AV, Bomback AS, Bang H, Gerber LM, Vupputuri S, Shoham DA et al (2008) Association of C-reactive protein and microalbuminuria (from the National Health and Nutrition Examination Surveys, 1999 to 2004). Am J Cardiol 101:401–406
Leoncini G, Viazzi F, Agabiti Rosei E, Ambrosioni E, Costa FV, Leonetti G et al (2010) Chronic kidney disease in hypertension under specialist care: the I-DEMAND study. J Hypertens 28:156–162
Levey AS, Cattran D, Friedman A, Miller WG, Sedor J, Tuttle K et al (2009) Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 54:205–226
Levin A, Stevens PE, Bilous RW, Coresh J, De Francisco ALM, de Jong PE, Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group et al (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:4
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB 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
Lieb W, Mayer B, Stritzke J, Doering A, Hense HW, Loewel H, Erdmann J et al (2006) Association of low-grade urinary albumin excretion with left ventricular hypertrophy in the general population: the MONICA/KORA Augsburg Echocardiographic Substudy. Nephrol Dial Transplant 21:2780–2787
Mafham M, Emberson J, Landray MJ, Wen C-P, Baigent C (2011) Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: a meta-analysis. PLoS ONE 6:e25920
Mahmoodi BK, Matsushita K, Woodward M, Blankestijn PJ, Cirillo M, Ohkubo T et al (2012) Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis. Lancet 380:1649–1661
Malik AR, Sultan S, Turner ST, Kullo IJ (2007) Urinary albumin excretion is associated with impaired flow- and nitroglycerin-mediated brachial artery dilatation in hypertensive adults. J Hum Hypertens 21:231–238
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bhöm M (2013) et al; Task Force Members. 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 31:1281–1357
Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, ONTARGET investigators et al (2008) Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 372:547–553
Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE et al (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375:2073–2081
Meccariello A, Buono F, Verrengia E, Orefice G, Grieco F, Romeo F et al (2016) Microalbuminuria predicts the recurrence of cardiovascular events in patients with essential hypertension. J Hypertens 34:646–665
Menne J, Ritz E, Ruilope LM, Chatzikyrkou C, Viberti G, Haller H (2014) The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) observational follow-up study: benefits of RAS blockade with olmesartan treatment are sustained after study discontinuation. J Am Heart Assoc 3:e000810
Miller WG, Bruns DE, Hortin GL, Sandberg S, Aakre KM, McQueen MJ et al (2009) Current issues in measurement and reporting of urinary albumin excretion. Clin Chem 55:24–38
Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity onset diabetes. N Engl J Med 310:356–360
Mogensen CE (2003) Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. J Intern Med 254:45–66
Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. New Eng J Med 31:89–93
Mogensen CE, Vestbo E, Poulsen PL, Christiansen C, Damsgaard EM, Eiskjaer H et al (1995) Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion. Diabetes Care 18:572–581
Morreale M, Mulè G, Ferrante A, D’ignoto F, Cottone S (2016) Association of renal resistive index with markers of extrarenal vascular changes in patients with systemic lupus erythematosus. Ultrasound Med Biol 42:1103–1110. doi:10.1016/j.ultrasmedbio.2015.12.025
Mountokalakis TD (1997) The renal consequences of hypertension. Kidney Int 51:1639–1653
Moynihan R, Glassock R, Doust J (2013) Chronic kidney disease controversy: how expanding definitions are unnecessarily labelling many people as diseased. BMJ 347:f4298
Mulè G, Cottone S, Vadalà A, Volpe V, Mezzatesta G, Mongiovì R et al (2004) Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients. J Intern Med 256:22–29
Mulè G, Nardi E, Cottone S, Cusimano P, Volpe V, Piazza G et al (2005) Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med 257:503–513
Mulè G, Cottone S, Mongiovì R, Cusimano P, Mezzatesta G, Seddio G et al (2006) Influence of metabolic syndrome on aortic stiffness in never treated hypertensive patients. Nutr Metab Cardiovasc Dis 16:54–59
Mulè G, Cottone S, Cusimano P, Riccobene R, Palermo A, Geraci C et al (2009) The association of microalbuminuria with aortic stiffness is independent of C-reactive protein in essential hypertension. Am J Hypertens 22:1041–1047
Mulè G, Cottone S, Cusimano P, Palermo A, Geraci C, Nardi E et al (2010) Unfavourable interaction of microalbuminuria and mildly reduced creatinine clearance on aortic stiffness in essential hypertension. Int J Cardiol 145:372–375. http://dx.doi.org/10.1016/j.ijcard.2010.02.047
Mulè G, Calcaterra I, Costanzo M, Geraci G, Guarino L, Foraci L et al (2015a) Relationship between short-term blood pressure variability and subclinical renal damage in essential hypertensive patients. J Clin Hypertens (Greenwich) 17:473–480
Mulè G, Geraci G, Geraci C, Morreale M, Cottone S (2015b) The renal resistive index: is it a misnomer. Intern Emerg Med 10:889–891. doi:10.1007/s11739-015-1323-1324
Mulè G, Calcaterra I, Costanzo M, Morreale M, Castiglia A, D’Ignoto F et al (2016) Average real variability of 24-h systolic blood pressure is associated with microalbuminuria in patients with primary hypertension. J Hum Hypertens 30:164–170
Munakata M, Miura Y, Yoshinaga K, J-TOPP study group (2009) Higher brachial-ankle pulse wave velocity as an independent risk factor for future microalbuminuria in patients with essential hypertension: the J-TOPP study. J Hypertens 27:1466–1471
Newman DJ, Mattock MB, Dawnay AB, Kerry S, McGuire A, Yaqoob M et al (2005) Systematic review on urine albumin testing for early detection of diabetic complications. Health Technol Assess 9:iii–vi, xiii–163
Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, et al on behalf of the ADVANCE Collaborative Group (2009) Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 20: 1813–1821
Ninomiya T, Perkovic V, Verdon C, Barzi F, Cass A, Gallagher M, Jardine M, Anderson C, Chalmers J, Craig JC, Huxley R (2009b) Proteinuria and stroke: a meta-analysis of cohort studies. Am J Kidney Dis 53:417–425
Nitsch D, Grams M, Sang Y, Black C, Cirillo M, Djurdjev O et al (2013) Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis. BMJ 346:f324
O’Hare AM, Choi AI, Bertenthal D, Bacchetti P, Garg AX, Kaufman JS et al (2007) Age affects outcomes in chronic kidney disease. J Am Soc Nephrol 18:2758–2765
Palaniappan L, Carnethon M, Fortmann SP (2003) Association between microalbuminuria and the metabolic syndrome: NHANES III. Am J Hypertens 16:952–958
Palatini P, Graniero GR, Canali C, Santonastaso M, Mos L, Piccolo D et al (1995) Relationship between albumin excretion rate, ambulatory blood pressure and left ventricular hypertrophy in mild hypertension. J Hypertens 13:1796–1800
Palatini P, Mormino P, Santonastaso M, Mos L, Dal Follo M, Zanata G, Pessina AC (1998) Target-organ damage in stage I hypertensive subjects with white coat and sustained hypertension: results from the HARVEST study. Hypertension 31:57–63
Parving HH, Lehnert H, Brochner-Mortenson J, Gomis R, Andersen S, Arner P. for the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group (2001) The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345: 870–878
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
Pascual JM, Rodilla E, Miralles A, Gonzalez C, Redon J (2006) Determinants of urinary albumin excretion reduction in essential hypertension: a long-term follow-up study. J Hypertens 24:2277–2284
Pascual JM, Rodilla E, Costa JA, Garcia-Escrich M, Gonzalez C, Redon J (2014) Prognostic value of microalbuminuria during antihypertensive treatment in essential hypertension. Hypertension 64:1228–1234
Pedrinelli R, Giampietro O, Cammassi F, Melillo E, Dell’Olmo G, Catapano G (1994) Microalbuminuria and endothelial dysfunction in essential hypertension. Lancet 344:14–18
Pedrinelli R, Dell’Omo G, Di Bello V, Pontremoli R, Mariani M (2002) Microalbuminuria an integrated marker of cardiovascular risk in essential hypertension. J Hum Hypertens 16:79–89
Pedrinelli R, Dell’Omo G, Di Bello V, Pellegrini G, Pucci L, Del Prato S, Penno G (2004) Low-grade inflammation and microalbuminuria in hypertension. Arterioscler Thromb Vasc Biol 24:2414–2419
Perkovic V, Verdon C, Ninomiya T, Barzi F, Cass A, Patel A, Jardine M, Gallagher M, Turnbull F, Chalmers J, Craig J, Huxley R (2008) The relationship between proteinuria and coronary risk: a systematic review and meta-analysis. PLoS Med 5(10):e207
Pinto-Sietsma SJ, Mulder J, Janssen WM, Hillege HL, De Zeeuw D, De Jong PE (2000) Smoking is related to albuminuria and abnormal renal function in nondiabetic persons. Ann Int Med 133:585–591
Pinto-Sietsma SJ, Navis G, Janssen WM, de Zeeuw D, Gans RO, de Jong PE, PREVEND Study Group (2003) A central body fat distribution is related to renal function impairment, even in lean subjects. Am J Kidney Dis 41:733–741
Pontremoli R, Sofia A, Ravera M, Nicolella C, Viazzi F, Tirotta A et al (1997) Prevalence and clinical correlates of microalbuminuria in essential hypertension: the MAGIC Study. Microalbuminuria: A Genoa Investigation on Complications. Hypertension 30:1135–1143
Pontremoli R, Ravera M, Bezante GP, Viazzi F, Nicolella C, Berruti V et al (1999) Left ventricular geometry and function in patients with essential hypertension and microalbuminuria. J Hypertens 17:993–1000
Ratto E, Leoncini G, Viazzi F, Bezante GP, Falqui V, Parodi A et al (2008) Inappropriate left ventricular mass is associated with microalbuminuria independently of left ventricular hypertrophy in primary hypertension. J Hypertens 26:345–350
Ravera M, Ratto E, Vettoretti S, Viazzi F, Leoncini G, Parodi D et al (2002) Microalbuminuria and subclinical cerebrovascular damage in essential hypertension. J Nephrol 15:519–524
Redon J (1998) Renal protection by antihypertensive drugs: insights from microalbuminuria studies. J Hypertens 16:2091–2100
Redon J, Williams B (2002) Microalbuminuria in essential hypertension. Redefining the threshold. J Hypertens 20:353–355
Redon J, Liao Y, Lozano JV, Miralles A, Pasqual JM, Cooper RS (1994) Ambulatory blood pressure and microalbuminuria in essential hypertension: role of circadian variability. J Hypertens 12:947–953
Rodondi N, Yerly P, Gabriel A, Riesen WF, Burnier M, Paccaud F et al (2007) Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults. Nephrol Dial Transplant 22:1107–1114
Ruggenenti P, Remuzzi G (2006) Time to abandon microalbuminuria? Kidney Int 70:1214–1222
Ruilope LM (2002) The kidney as a sensor of cardiovascular risk in essential hypertension prevalence of mild renal insufficiency in essential hypertension. J Am Soc Nephrol Suppl 3: S165–S168.
Savarese G, Dei Cas A, Rosano G, D’Amore C, Musella F, Mosca S et al (2014) Reduction of albumin urinary excretion is associated with reduced cardiovascular events in hypertensive and/or diabetic patients. A meta-regression analysis of 32 randomized trials. Int J Cardiol 172:403–410
Schmieder RE, Mann JF, Schumacher H, Gao P, Mancia G, Weber MA et al (2011) ONTARGET Investigators. Changes in albuminuria predict mortality and morbidity in patients with vascular disease. J Am Soc Nephrol 22:1353–1364
Sciarretta S, Pontremoli R, Rosei EA, Ambrosioni E, Costa V, Leonetti G et al (2009) Independent association of ECG abnormalities with microalbuminuria and renal damage in hypertensive patients without overt cardiovascular disease: data from Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease study. J Hypertens 27:410–417
Smilde TD, Asselbergs FW, Hillege HL, Voors AA, Kors JA, Gansevoort RT et al (2005) Mild renal dysfunction is associated with electrocardiographic left ventricular hypertrophy. Am J Hypertens 18:342–347
Smith A, Karalliedde J, De Angelis L, Goldsmith D, Viberti G (2005) Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes. J Am Soc Nephrol 16:1069–1075
Srinivasan SR, Myers L, Berenson GS (2000) Risk variables of insulin resistance syndrome in African American and Caucasian young adults with microalbuminuria: the Bogalusa Heart Study. Am J Hypertens 13:1274–1279
Stehouwer CDA, Henry RMA, Dekker JM, Nijpels G, Heine RJ, Bouter LM (2004) Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: Further evidence for a link between microalbuminuria and endothelial dysfunction—The Hoorn Study. Kidney Int 66(Suppl 92):S42–S44
Svendsen PA, Oxenball B, Christiansen JS (1981) Microalbuminuria in diabetic patients: a longitudinal study. Acta Endocrinol Suppl (Copenh) 242:53–54
The Chronic Kidney Disease Prognosis Consortium (2011) Association of estimated glomerular filtration rate and albuminuria with mortality and end-stage renal disease: a collaborative meta-analysis of kidney disease cohorts. Kidney Int 79:1331–1340
Tsioufis C, Stefanadis C, Antoniadis D, Toutouza M, Kallikazaros I, Pitsavos C et al (2002) Microalbuminuria is associated with unfavorable left ventricular geometry patterns in untreated, non-diabetic, patients with essential hypertension. J Hum Hypertens 16:249–254
Tsioufis C, Thomopoulos C, Dimitriadis K, Amfilochiou A, Tsiachris D, Selima M et al (2008) Association of obstructive sleep apnea with urinary albumin excretion in essential hypertension: a cross-sectional study. Am J Kidney Dis 52:285–293
Tuttle KR, Puhlman ME, Cooney SK, Short R (1999) Urinary albumin and insulin as predictors of coronary artery disease: an angiographic study. Am J Kidney Dis 34:918–925
Upadhyay A, Hwang SJ, Mitchell GF, Vasan RS, Vita JA, Stantchev PI, Meigs JB, Larson MG, Levy D, Benjamin EJ, Fox CS (2009) Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol 20:2044–2053
van der Velde M, Halbesma N, de Charro FT, Bakker SJ, de Zeeuw D, de Jong PE, Gansevoort RT (2009) Screening for albuminuria identifies individuals at increased renal risk. J Am Soc Nephrol 20:852–862
van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey AS et al (2011) Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 79:1341–1352
Viazzi F, Leoncini G, Conti N, Tomolillo C, Giachero G, Vercelli M et al (2010) Microalbuminuria is a predictor of chronic renal insufficiency in patients without diabetes and with hypertension: the MAGIC study. Clin J Am Soc Nephrol 5:1099–1106
Viazzi F, Leoncini G, Derchi LE, Pontremoli R (2015) Ultrasound Doppler renal resistive index: a useful tool for the management of the hypertensive patient. J Hypertens 32:149–153
Viazzi F, Muiesan ML, Schillaci G, Salvetti M, Pucci G, Bonino B et al (2016) Changes in albuminuria and cardiovascular risk under antihypertensive treatment: a systematic review and meta-regression analysis. J Hypertens 34:1689–1697. [Epub ahead of print] doi: 10.1097/HJH.0000000000000991
Viberti GC, Hill RD, Jarret RJ, Argyropoulos A, Mahmud U, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1:1430–1432
Viberti GC, Wheelden NM, for the MicroAlbuminuria Reduction with VALsartan (MARVAL) Study Investigators (2002) Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 106: 672–678
Wachtell K, Palmieri V, Olsen MH, Bella JN, Aalto T, Dahlof B et al (2002a) Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE study. Losartan Intervention for Endpoint Reduction. Am Heart J 143:319–326
Wachtell K, Olsen MH, Dahlöf B, Devereux RB, Kjeldsen SE, Nieminen MS et al (2002b) Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. J Hypertens 20:405–412
Wada M, Nagasawa H, Kurita K, Koyama S, Arawaka S, Kawanami T, Tajima K et al (2007) Microalbuminuria is a risk factor for cerebral small vessel disease in community-based elderly subjects. J Neurol Sci 255:27–34
Yokoyama H, Aoki T, Imahori M, Kuramitsu M (2004) Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity. Kidney Int 66:448–454
Yuyun MF, Khaw KT, Luben R, Welch A, Bingham S, Day NE, Wareham NJ (2004) Microalbuminuria, cardiovascular risk factors and cardiovascular morbidity in a British population: The EPIC-Norfolk Population-based Study. Eur J Cardiovasc Prev Rehabil 11:207–213
Zoungas S, de Galan BE, Ninomiya T, Grobbee D, Hamet P, Heller S, ADVANCE Collaborative Group et al (2009) Combined effects of routine blood pressure lowering and intensive glucose control on macrovascularand microvascular outcomes in patients with type 2 diabetes: new results from the ADVANCE trial. Diabetes Care 32:2068–2074
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing AG
About this chapter
Cite this chapter
Mulè, G. et al. (2016). Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the Cardiovascular System. Focus on Microalbuminuria. In: Islam, M.S. (eds) Hypertension: from basic research to clinical practice. Advances in Experimental Medicine and Biology(), vol 956. Springer, Cham. https://doi.org/10.1007/5584_2016_85
Download citation
DOI: https://doi.org/10.1007/5584_2016_85
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-44250-1
Online ISBN: 978-3-319-44251-8
eBook Packages: MedicineMedicine (R0)