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Microalbuminuria in essential hypertension

1998; Elsevier BV; Volume: 54; Linguagem: Inglês

10.1046/j.1523-1755.1998.06813.x

1523-1755

José L. Rodicio, Carlos Campo, Luís M. Ruilope,

Sodium Intake and Health

Microalbuminuria in essential hypertension. Microalbuminuria is frequently seen in patients with established essential hypertension, and is a predictor of a higher risk for cardiovascular and probably renal dysfunction. The presence of microalbuminuria has been shown to correlate with the other cardiovascular risk factors commonly seen in hypertensive patients. This fact indicates that the detection of an increased urinary albumin excretion could probably be the best index of an increased global cardiovascular risk in a given patient. Blood pressure control is accompanied by a fall in the content of albumin in urine. Agents with the capacity to block the renin-angiotensin system have shown a capacity to decrease urinary albumin excretion, which is independent of their ability to lower blood pressure. Whether or not a decrease in urinary albumin excretion is accompanied by an improved renal and cardiovascular prognosis in hypertensive patients remains to be elucidated. Microalbuminuria in essential hypertension. Microalbuminuria is frequently seen in patients with established essential hypertension, and is a predictor of a higher risk for cardiovascular and probably renal dysfunction. The presence of microalbuminuria has been shown to correlate with the other cardiovascular risk factors commonly seen in hypertensive patients. This fact indicates that the detection of an increased urinary albumin excretion could probably be the best index of an increased global cardiovascular risk in a given patient. Blood pressure control is accompanied by a fall in the content of albumin in urine. Agents with the capacity to block the renin-angiotensin system have shown a capacity to decrease urinary albumin excretion, which is independent of their ability to lower blood pressure. Whether or not a decrease in urinary albumin excretion is accompanied by an improved renal and cardiovascular prognosis in hypertensive patients remains to be elucidated. The term microalbuminuria is defined by a urinary albumin excretion (UAE) rate higher than normal but lower than 200 μg/min, the lowest detection limit of proteinuria as measured by standard laboratory methods1.Viberti G.C. Mackintosh D. Bilous R.W. Pickup J.C. Keen H. Proteinuria in diabetes mellitus: Role of spontaneous and experimental variations of glycemia.Kidney Int. 1982; 21: 714-720Abstract Full Text PDF PubMed Scopus (107) Google Scholar,2.Ruilope L.M. Rodicio J.L. Clinical relevance of proteinuria and microalbuminuria.Curr Opin Nephrol Hypertens. 1993; 2: 962-967Crossref PubMed Scopus (57) Google Scholar in the absence of urinary tract infection and acute illness including myocardial infarction3.Marshall S.M. Screening for microalbuminuria: Which measurement?.Diabetic Med. 1991; 8: 706-711Crossref PubMed Scopus (117) Google Scholar. A diagnosis of microalbuminuria can be made by measuring its excretion rate during 24 hours or in an overnight urine collection, or by measuring albumin/creatinine ratio or albumin concentration in the morning or a random urine sample (Table 1). Determination of UAE in the morning urine sample constitutes the ideal test for screening, and overnight urine collection might be the best choice for monitoring microalbuminuria. The normal urinary excretion of albumin oscillates between 1 and 22 mg/day and varies with posture, exercise, and blood pressure; however, the day-to-day variation is in the range of 31% to 52%4.Poulsen P.E. Microalbuminuria-techniques of measurement,.in: Mogensen C.E. Microalbuminuria, A Marker for Organ Damage. Science Press Ltd., London1993: 10-19Google Scholar,5.Mogensen C.E. Microalbuminuria as a predictor of clinical diabetic nephropathy.Kidney Int. 1987; 31: 673-689Abstract Full Text PDF PubMed Scopus (486) Google Scholar. Therefore, a mean of three urine collections has been recommended to determine the UAE level of a given subject1.Viberti G.C. Mackintosh D. Bilous R.W. Pickup J.C. Keen H. Proteinuria in diabetes mellitus: Role of spontaneous and experimental variations of glycemia.Kidney Int. 1982; 21: 714-720Abstract Full Text PDF PubMed Scopus (107) Google Scholar. Different assays can be used to measure UAE including several semiquantitative tests that bring the test closer for general practioners4.Poulsen P.E. Microalbuminuria-techniques of measurement,.in: Mogensen C.E. Microalbuminuria, A Marker for Organ Damage. Science Press Ltd., London1993: 10-19Google Scholar,6.Pedersen E.B. Mogensen C.E. Larsen J.S. Effects of exercise on urinary excretion of albumin and beta2-microglobulin in young patients with mild essential hypertension without treatment and during long-term propranolol treatment.Scand J Clin Lab Invest. 1981; 41: 493-498Crossref PubMed Scopus (26) Google Scholar. The Micral-test is a test-strip method in which the color reaction is mediated by an antibody-bound enzyme. Nycocard U-albumin is a three drop test based on a solid phase enzyme-linked immunosorbent assay. Both methods have shown good correlations with radioimmunoassay and can be readily used for screening. The accepted cut-off values for detection of microalbuminuria are 20 μg/min when assessed in 24-hour urine collection5.Mogensen C.E. Microalbuminuria as a predictor of clinical diabetic nephropathy.Kidney Int. 1987; 31: 673-689Abstract Full Text PDF PubMed Scopus (486) Google Scholar,7.Mimran A. Ribstein J. Ducailar G. Halimi J.M. Albuminuria in normals and essential hypertension.J Diab Complic. 1994; 8: 150-156Abstract Full Text PDF Scopus (95) Google Scholar. However, a recent study suggest that the risk for cardiovascular disease in arterial hypertension is increased at even lower UAE levels of 15 μg/min8.Jensen J.S. Feldt-Rasmussen B. Borch-Johnsen K. Clausen P. Appleyard M. Jensen G. Microalbuminuria and its raltion to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals.J Hum Hypertens. 1997; 11: 727-732Crossref PubMed Scopus (94) Google Scholar.Table 1Definition of microalbuminuria Open table in a new tab It is now apparent that between 5 and 10% of nondiabetic individuals have a UAE within the microalbuminuric range9.Yudkin J.S. Microalbuminuria in vascular disease,.in: Mogensen C.E. Microalbuminuria, A Marker for Organ Damage. Science Press Ltd., London1993: 69-80Google Scholar. Initial studies indicated that microalbuminuria may be a strong predictor of mortality of cardiovascular origin10.Yudkin J.S. Forrest R.D. Jackson C.A. Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey.Lancet. 1998; II: 530-533Google Scholar, 11.Damsgaard E.M. Froland A. Jorgensen O.D. Mogensen C.E. Microalbuminuria as predictor of increased mortality in elderly people.Br Med J. 1990; 300: 297-300Crossref PubMed Scopus (549) Google Scholar, 12.Hahhner S.M. Stern M.P. Gruber M.K.K. Microalbuminuria-potential marker for increased cardiovascular risk factors in nondiabetic subjects?.Arteriosclerosis. 1990; 10: 727-731Crossref PubMed Scopus (264) Google Scholar, 13.Winocour P.H. Harland J.O. Millar J.P. Laker M.F. Alberti K.G. Microalbuminuria and associated cardiovascular risk factors in the community.Atherosclerosis. 1992; 93: 71-81Abstract Full Text PDF PubMed Scopus (149) Google Scholar. Nevertheless, it could not be concluded whether microalbuminuria is a predictor in its own value, or whether it is the association with other risk factors that is of importance. In this sense, elevated UAE has been shown to be related to elevated serum triglycerides and low high-density lipoprotein cholesterol, obesity, glucose intolerance, insulin resistance and uric acid levels7.Mimran A. Ribstein J. Ducailar G. Halimi J.M. Albuminuria in normals and essential hypertension.J Diab Complic. 1994; 8: 150-156Abstract Full Text PDF Scopus (95) Google Scholar, 14.Ferrannini E. The metabolic syndrome,.in: Mogensen C.E. Target Organ Damage in the Mature Hypertensive. Science Press Ltd., London1993: 31-49Google Scholar, 15.Metcalf P. Baker J. Scott A. Wild C. Scragg R. Dryson E. Albuminuria in people at least 40 years old: Effect of obesity, hypertension and hyperlipidemia.Clin Chem. 1992; 38: 1802-1808PubMed Google Scholar, 16.Vestbo E, Damsgaard EM, Froland A,Mogensen CE: Microalbuminuria in a population based cohort. J Diab Compl (in press)Google Scholar, 17.Pontremoli R. Sofia A. Ravera M. Nicolella C. Viazzi F. Tirotta A. Ruello N. Tomolillo C. Castello C. Grillo G. Sacchi G. Deferrari G. Prevalence and clinical correlates of microalbuminuria in essential hypertension. The MAGIC study.Hypertension. 1997; 30: 1135-1143Crossref PubMed Scopus (190) Google Scholar, 18.Wasada T. Katsumori K. Saeki A. Saito S. Omori Y. Urinary albumin excretion rate is related to insulin resistance in normotensive subjects with impaired glucose tolerance.Diabetes Res Clin Pract. 1997; 34: 157-162Abstract Full Text PDF PubMed Scopus (14) Google Scholar. An association between smoking, alcohol intake and microalbuminuria has also been shown7.Mimran A. Ribstein J. Ducailar G. Halimi J.M. Albuminuria in normals and essential hypertension.J Diab Complic. 1994; 8: 150-156Abstract Full Text PDF Scopus (95) Google Scholar, 19.Ticket J. Vol S. Hallab M. Caces F. Marre M. Epidemiology of microalbuminuria in a french population.J Diab Compl. 1994; 8: 294-295Google Scholar, 20.Metcalf P.A. Baker J.R. Scragg R.K.R. Dryson E. Scott A.J. Wild C.J. Albuminuria in people at least 40 years old: Effect of alcohol consumption, regular exercise and cigarrette smoking.Clin Chem. 1993; 39: 1793-1797PubMed Google Scholar. Patients with microalbuminuria are older and exhibit predominant male gender, as compared with normoalbuminuric subjects8.Jensen J.S. Feldt-Rasmussen B. Borch-Johnsen K. Clausen P. Appleyard M. Jensen G. Microalbuminuria and its raltion to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals.J Hum Hypertens. 1997; 11: 727-732Crossref PubMed Scopus (94) Google Scholar,17.Pontremoli R. Sofia A. Ravera M. Nicolella C. Viazzi F. Tirotta A. Ruello N. Tomolillo C. Castello C. Grillo G. Sacchi G. Deferrari G. Prevalence and clinical correlates of microalbuminuria in essential hypertension. The MAGIC study.Hypertension. 1997; 30: 1135-1143Crossref PubMed Scopus (190) Google Scholar. Finally, a correlation between systemic blood pressure and UAE has been found not only in hypertensive patients7.Mimran A. Ribstein J. Ducailar G. Halimi J.M. Albuminuria in normals and essential hypertension.J Diab Complic. 1994; 8: 150-156Abstract Full Text PDF Scopus (95) Google Scholar, 8.Jensen J.S. Feldt-Rasmussen B. Borch-Johnsen K. Clausen P. Appleyard M. Jensen G. Microalbuminuria and its raltion to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals.J Hum Hypertens. 1997; 11: 727-732Crossref PubMed Scopus (94) Google Scholar, 17.Pontremoli R. Sofia A. Ravera M. Nicolella C. Viazzi F. Tirotta A. Ruello N. Tomolillo C. Castello C. Grillo G. Sacchi G. Deferrari G. Prevalence and clinical correlates of microalbuminuria in essential hypertension. The MAGIC study.Hypertension. 1997; 30: 1135-1143Crossref PubMed Scopus (190) Google Scholar, but in the general population21.Mogensen C.E. Systemic blood pressure and glomerular leakage with particular reference to diabetes and hypertension.J Int Med. 1994; 235: 297-316Crossref PubMed Scopus (72) Google Scholar,22.Jiang X. Srinivasan S.R. Radhakrishnamurthy B. Dalferes E.R. Bao Weihang B. Berenson G.S. Microalbuminuria in young adults related to blood pressure in a biracial (black-white) population.Am J Hypertens. 1994; 7: 794-800PubMed Google Scholar. Interestingly, recent data by Jiang et al indicate that the association between blood pressure and UAE is stronger in blacks than in whites22.Jiang X. Srinivasan S.R. Radhakrishnamurthy B. Dalferes E.R. Bao Weihang B. Berenson G.S. Microalbuminuria in young adults related to blood pressure in a biracial (black-white) population.Am J Hypertens. 1994; 7: 794-800PubMed Google Scholar, which supports the notion that blacks may be more susceptible to renal damage from relatively low levels of blood pressure increase. Increased UAE could be the consequence of an augmented intraglomerular capillary pressure, it could reflect the existence of intrinsic glomerular damage that causes changes in glomerular barrier filtration, or it could be the consequence of a tubular alteration that impedes the normal reabsorption of filtered albumin. However, it has been suggested that microalbuminuria may represent the renal manifestation of generalized, genetically-conditioned vascular endothelial dysfunction that may underlie the link between an increased UAE and an elevated risk for cardiovascular disease23.Stehouwer C.D. Nauta J.J. Zeldenrust G.C. Hackeng W.H. Donker A.J. den Ottolander G.J. Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus.Lancet. 1992; 340: 319-323Abstract PubMed Scopus (536) Google Scholar,24.Pedrinelli R. Giampietro O. Carmassi F. Melillo E. Dell'olmo G. Catapano G. Matteucci E. Talarico L. Morale M. De Negri F. Di Bello V. Microalbuminuria and endothelial dysfunction in essential hypertension.Lancet. 1994; 344: 14-18Abstract PubMed Scopus (359) Google Scholar. In this sense, it has been described that microalbuminuria is associated with a decreased size- and charge-selectivity of the glomerular vessel wall in clinically healthy subjects25.Jensen J.S. Borch-Johnsen K. Deckert T. Deckert M. Jensen G. Feldt-Rasmussen B. Reduced glomerular size- and charge-selectivity in clinically healthy individuals with microalbuminuria.Eur J Clin Invest. 1995; 25: 608-614Crossref PubMed Scopus (31) Google Scholar, and is an independent marker of systemic transvascular albumin leakiness26.Jensen J.S. Borch-Johnsen K. Jensen G. Feldt-Rasmussen B. Microalbuminuria reflects a generalized transvascular albumin leakiness in clinically healthy subjects.Clin Sci. 1995; 88: 629-633Crossref PubMed Scopus (191) Google Scholar. Furthermore, atherosclerotic vascular disease is associated with renal and systemic transvascular leakiness for albumin27.Jensen J.S. Renal and systemic transvascular albumin leakage in severe atherosclerosis.Arterioscler Thromb Vasc Biol. 1995; 15: 1324-1329Crossref PubMed Scopus (80) Google Scholar. A defective endothelial permeability could then be the origin of microalbuminuria in the general population. Some recent findings support an eventual relationship between microalbuminuria and endothelial dysfunction in hypertension that includes a positive correlation of UAE and circulating von Willebrand Factor antigen, Factor VII hyperactivity, fibrinogen and endothelial cell damage24.Pedrinelli R. Giampietro O. Carmassi F. Melillo E. Dell'olmo G. Catapano G. Matteucci E. Talarico L. Morale M. De Negri F. Di Bello V. Microalbuminuria and endothelial dysfunction in essential hypertension.Lancet. 1994; 344: 14-18Abstract PubMed Scopus (359) Google Scholar, 28.Kario K. Matsuo T. 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Such mechanisms include renal hemodynamic changes due to the direct transmission of increased systemic pressure to the glomeruli31.Parving H.H. Jensen H.A.E. Mogensen C.E. Evrin P.E. Increased urinary albumin excretion rate in benign essential hypertension.Lancet. 1974; i: 1190-1192Abstract Scopus (349) Google Scholar, 32.Ljungman S. Microalbuminuria in essential hypertension.Am J Hypertens. 1990; 3: 956-960PubMed Google Scholar, 33.Ruilope L.M. Alcazar J.M. Rodicio J.L. Renal consequences of arterial hypertension.J Hypertens. 1992; 10: S85-S90Google Scholar, permselectivity changes of the glomerular filter and/or insufficient tubular reabsorption of albumin32.Ljungman S. Microalbuminuria in essential hypertension.Am J Hypertens. 1990; 3: 956-960PubMed Google Scholar,34.Cottone S. Cerasola G. Microalbuminuria fractional clearance and early renal permselectivity changes in essential hypertension.Am J Nephrol. 1992; 12: 326-329Crossref PubMed Scopus (17) Google Scholar, and structural damage to the glomeruli and arterioles33.Ruilope L.M. Alcazar J.M. Rodicio J.L. Renal consequences of arterial hypertension.J Hypertens. 1992; 10: S85-S90Google Scholar. In favor of a significant role of elevated systemic blood pressure facilitating the transglomerular passage of albumin is the significant positive correlation found between office blood pressure levels and UAE by most groups20.Metcalf P.A. Baker J.R. Scragg R.K.R. Dryson E. Scott A.J. Wild C.J. Albuminuria in people at least 40 years old: Effect of alcohol consumption, regular exercise and cigarrette smoking.Clin Chem. 1993; 39: 1793-1797PubMed Google Scholar, 31.Parving H.H. Jensen H.A.E. Mogensen C.E. Evrin P.E. 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Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions in mild hypertension.Am J Hypertens. 1994; 7: 965-974Crossref PubMed Scopus (32) Google Scholar. The correlation is more pronounced when UAE values are plotted against ambulatory blood pressure values37.Hoegholm A. Bang L.E. Kristensen K.S. Nielsen J.W. Holm J. Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension and normotension.Hypertension. 1994; 24: 101-105Crossref PubMed Scopus (157) Google Scholar, 39.Bianchi S. Bigazzi R. Baldari G. Sgherri G. Campese V.M. Diurnal variations of blood pressure and microalbuminuria in essential hypertension.Am J Hypertens. 1994; 7: 23-29Crossref PubMed Scopus (351) Google Scholar, 40.Redon J. Liao Y. Lozano J.V. Miralles A. Pascual J.M. Cooper R.S. Ambulatory blood pressure and microalbuminuria in essential hypertension: Role of circadian variability.J Hypertens. 1994; 12: 947-953Crossref PubMed Google Scholar. In this sense systolic blood pressure has been shown to be one of the most relevant determinants of microalbuminuria in the early stages of hypertensive disease41.Palatini P. Graniero G.R. Mormino P. Mattarei M. Sanzuol F. Cignacco G.B. Gregori S. Garavelli G. Pegoraro F. Maraglino G. Bortolazzi A. Accurso V. Dorigatti F. Graniero F. Gelisio R. Businaro R. Vriz O. Dalfollo M. Camarotto A. Pessina A.C. on behalf of the Harvest Study group Prevalence and clinical correlates of microalbuminuria in Stage I hypertension. Results from the Hypertension and Ambulatory reccording Venetia Study (HARVEST Study).Am J Hypertens. 1996; 9: 334-341Crossref PubMed Scopus (85) Google Scholar. On the other hand, higher levels of UAE have been described in those patients not exhibiting a nocturnal fall in blood pressure (non-dippers), indicating that a greater degree of renal involvement could be present in this particular group of patients39.Bianchi S. Bigazzi R. Baldari G. Sgherri G. Campese V.M. 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Pessina A.C. on behalf of the Harvest Study group Prevalence and clinical correlates of microalbuminuria in Stage I hypertension. Results from the Hypertension and Ambulatory reccording Venetia Study (HARVEST Study).Am J Hypertens. 1996; 9: 334-341Crossref PubMed Scopus (85) Google Scholar,43.Agrawal B. Berger A. Wolf K. Luft F. Microalbuminuria screening by reagent strip predicts cardiovascular risk in hypertension.J Hypertens. 1996; 14: 223-228Crossref PubMed Scopus (165) Google Scholar. In treated patients prevalence can be as high as 25% when diuretics and beta-blockers are used33.Ruilope L.M. Alcazar J.M. Rodicio J.L. Renal consequences of arterial hypertension.J Hypertens. 1992; 10: S85-S90Google Scholar,44.Agewall S. Persson B. Samuelsson O. Ljungman S. Herlitz H. 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Microalbuminuria and body fat distribution in obese subjects.Int J Obes. 1994; 18: 806-811PubMed Google Scholar. In conclusion, microalbuminuria seems to constitute a simple and accurate method to detect a hypertensive patient at a high risk for cardiovascular and probably renal damage. While a decrease in UAE in essential hypertension is currently thought to be beneficial for the patient, this assertion remains to be proven. In this sense, antihypertensive therapy of any kind is able to lower UAE in essential hypertensives by simply lowering blood pressure2.Ruilope L.M. Rodicio J.L. Clinical relevance of proteinuria and microalbuminuria.Curr Opin Nephrol Hypertens. 1993; 2: 962-967Crossref PubMed Scopus (57) Google Scholar, and both systolic and diastolic blood pressure reductions are the most important factors associated with a UAE decrease61.Agrawal B. Wolf K. Berger A. Luft F.C. 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