Health  Vol.5 No.4 A , April 2013
Microalbuminuria in pediatric patients with hypertension

Microalbuminuria in adults has been found to be an early indicator of both renal and systemic vascular disease, as well as significant cardiovascular risk predictor and therapeutic marker. Its role in essential hypertension in adults has also been well established. As diseases like hypertension and obesity have their roots in childhood and are already present in children, influencing the morbidity in adulthood, the role of microalbuminuria has been extensively investigated in children as well. Most investigations have been performed in diabetic children, confirming its clinical significance. There is also enough evidence to suggest that microalbuminuria in obese children should be taken as seriously as in children with diabetes. In children with hypertension rare studies also indicate that its presence identifies hypertensive children with higher risk, although the exact role has to be confirmed in prospective and larger studies. The mechanisms of microalbuminuria onset could be the result of renal damage secondary to hypertension or underlying renal and systemic endothelial dysfunction. Evidence from small intervention studies in children with microalbuminuria also suggests that early intervention with antihypertensive drugs is likely to be beneficial, pointing out the role of microalbuminuria as a therapeutic marker in children too. In addition, we have to stress the importance of follow-up of children with microalbuminuria, confirmation of its persistence and identification of progression. However, longitudinal prospective studies in children, investigating its future cardiovascular risk, are still lacking.

Cite this paper: Varda, N. (2013) Microalbuminuria in pediatric patients with hypertension. Health, 5, 40-46. doi: 10.4236/health.2013.54A006.

[1]   Vasan, R.S., Larson, M.G., Leip, E.P., Evans, J.C., O’Donnell, J.C., Kannel, W.B. and Levy, D. (2001) Impact of high-normal blood pressure on the risk of cardiovascular disease. The New England Journal of Medicine, 345, 1291-1297. doi:10.1056/NEJMoa003417

[2]   Berenson, G.S. (2002) Childhood risk factors predict adult risk associated with subclinical cardiovascular disease: The Bogalusa heart study. American Journal of Cardiology, 90, 3L-7L. doi:10.1016/S0002-9149(02)02953-3

[3]   McNiece, K.L., Poffenbarger, T.S., Turner, J.L., Franco, K.D., Sorof, J.M. and Portman, R.J. (2007) Prevalence of hypertension and pre-hypertension among adolescents. Journal of Pediatrics, 150, 640-644. doi:10.1016/j.jpeds.2007.01.052

[4]   Assadi, F. (2012) The growing epidemic of hypertension among children and adolescents: A challenging road ahead. Pediatric Cardiology, 33, 1013-1020. doi:10.1007/s00246-012-0333-5

[5]   Sorof, J. and Daniels, S. (2002) Obesity hypertension in children: A problem of epidemic proportions. Hypertension, 40, 441-447. doi:10.1161/01.HYP.0000032940.33466.12

[6]   Lauer, R.M., Clarke, W.R., Mahoney, L.T. and Witt, J. (1993) Childhood predictors for high adult blood pressure. The Muscatine Study. Pediatric Clinics of North America, 40, 23-40.

[7]   Lawes, C.M., Vander Hoorn, S., Law, M.R., Elliott, P., MacMahon, S. and Rodgers, A. (2006) Blood pressure and the global burden of disease 2000. Part II: Estimates of attributable burden. Journal of Hypertension, 24, 423- 430. doi:10.1097/01.hjh.0000209973.67746.f0

[8]   Assadi, F. (2008) Relation of left ventricular hypertrophy to microalbuminuria and C-reactive protein in children and adolescents with essential hypertension. Pediatric Cardiology, 29, 580-584. doi:10.1007/s00246-007-9153-4

[9]   Seeman, T., Pohl, M., Palyzova, D. and John, U. (2012) Microalbuminuria in children with primary and white- coat hypertension. Pediatric Nephrology, 27, 461-467. doi:10.1007/s00467-011-2019-2

[10]   Hoq, S., Chen, W., Srinivasan, S.R. and Berenson, G.S. (2002) Childhood blood pressure predicts adult microalbuminuria in African Americans, but not in whites: The Bogalusa heart study. American Journal of Hypertension, 15, 1036-1041. doi:10.1016/S0895-7061(02)03066-2

[11]   Antoniewicz, J., Litwin, M., Daszkoska, J., Nemirska, A., Sladowska, J., Wierzbicka, A., Wawer, Z. and Grenda, R. (2006) Target organ damage in children with newly diagnosed and untreated essential hypertension. Przegl Lek, 63, 101-106.

[12]   Rowe, D.J., Dawnay, A. and Watts, G.F. (1990) Microalbuminuria in diabetic subjects. Annals of Clinical Biochemistry, 27, 297-312.

[13]   Donnelly, R. and Rea, R. (2003) Microalbuminuria: How informative and reliable are individual measurements? Journal of Hypertension, 21, 1229-1233. doi:10.1097/00004872-200307000-00003

[14]   Chae, H.W., Shin, J.I., Kwon, A.R., Kim, H.S. and Kim, D.H. (2012) Spot urine albumin to creatinine ratio and serum cystatin C are effective for detection of diabetic nephropathy in childhood diabetic patients. Journal of Korean Medical Science, 27, 784-787. doi:10.3346/jkms.2012.27.7.784

[15]   Assadi, F.K. (2002) Quantitation of microalbuminuria using random urine samples. Pediatric Nephrology, 17, 107-110. doi:10.1007/s00467-001-0762-5

[16]   Singh, A. and Satchell, S.C. (2011) Microalbuminuria: Causes and implications. Pediatric Nephrology, 26, 1957- 1965. doi:10.1007/s00467-011-1777-1

[17]   De Zeeuw, D., Parving, H.H. and Henning, R.H. (2006) Microalbuminuria as an early marker for cardiovascular disease. Journal of the American Society of Nephrology, 17, 2100-2105. doi:10.1681/ASN.2006050517

[18]   Viberti, G.C., Hill, R.D., Jarret, R.J., Argyropoulos, A., Mahmud, U. and Keen, H. (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet, 1, 1430-1432. doi:10.1016/S0140-6736(82)92450-3

[19]   Weir, M.R. (2004) Microalbuminuria in type 2 diabetes: An important, overlooked cardiovascular risk factor. The Journal of Clinical Hypertension, 6, 134-143. doi:10.1111/j.1524-6175.2004.02524.x

[20]   Gerstein, H.C., Mann, J.F., Yi, Q., Zinman, B., Dinneen, S.F., Hoogwerf, B., Hallé, J.P., Young, J., Rashkow, A., Joyce, C., Nawaz, S., Yusuf, S. and HOPE Study Investigators (2001) Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA, 286, 421-426. doi:10.1001/jama.286.4.421

[21]   Brantsma, A.H., Bakker, S.J., de Zeeuw, D., de Jong, P.E. and Gansevoort, R.T. (2006) Urinary albumin excretion as a predictor of the development of hypertension in the general population. Journal of the American Society of Nephrology, 17, 331-335.

[22]   Brantsma, A.H., Bakker, S.J., Hillege, H.L., de Zeeuw, D., de Jong, P.E., Gansevoort, R.T. and PREVEND Study Group (2005) Urinary albumin excretion and its relation with C-reactive protein and metabolic syndrome in the prediction of type 2 diabetes. Diabetes Care, 28, 2525- 2530. doi:10.2337/diacare.28.10.2525

[23]   Asselbergs, F.W., Diercks, G.F.H., Hillenge, H., van Boven, A.J., Janssen, W.M., Voors, A.A., de Zeeuw, D., de Jong, P.E., van Veldhuisen, D.J. and van Gilst, W.H. and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators (2004) Prevention of renal and vascular endstage disease intervention trial (PREVEND IT) investigators. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation, 110, 2809- 2816. doi:10.1161/01.CIR.0000146378.65439.7A

[24]   Crippa, G. (2002) Microalbuminuria in essential hypertension. Journal of Human Hypertension, 16, S74-S77. doi:10.1038/sj.jhh.1001348

[25]   Sellers, E.A.C., Blydt-Hansen, T.D., Dean, H.J., Gibson, I.W., Birk, P.E. and Ogborn, M. (2009) Microalbuminuria and renal pathology in first nation youth with type 2 diabetes. Diabetes Care, 32, 786-790. doi:10.2337/dc08-1828

[26]   Alleyn, C.R., Volkening, L.K., Wolfson, J., Rodriguez- Ventura, A., Wood, J.R. and Laffel, L.M.B. (2010) Occurrence of microalbuminuria in young people with type 1 diabetes: Importance of age and diabtes duration. Diabetic Medicine, 27, 532-537. doi:10.1111/j.1464-5491.2010.02983.x

[27]   Nguyen, S., McCulloch, C., Brakeman, P., Portale, A. and Hsu, C. (2008) Being overweight modifies the association between cardiovascular risk factors and microalbuminuria in adolescents. Pediatrics, 121, 37-45. doi:10.1542/peds.2007-3594

[28]   Sanad, M. and Gharib, A. (2011) Evaluation of microalbuminuria in obese children and its relation to metabolic syndrome. Pediatric Nephrology, 26, 2193-2319. doi:10.1007/s00467-011-1931-9

[29]   Salgado, C.M., Jardim, P.C., Teles, F.B. and Nures, M.C. (2009) Influence of low birth weight on microalbuminuria and blood pressure of school children. Clinical Nephrology, 71, 367-374.

[30]   Becton, L.J., Kalpatthi, R.V., Rackoff, E., Disco, D., Orak, J.K., Jackson S.M. and Shatat, I.F. (2010) Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease. Pediatric Nephrology, 25, 1505-1511. doi:10.1007/s00467-010-1536-8

[31]   Rudberg, S., Aperia, A., Freyschuss, U. and Persson, B. (1990) Enalapril reduces microalbuminuria in young normotensive type 1 (insulin-dependent) diabetic patients irespective of its hypotensive effect. Diabetologia, 33, 470-476. doi:10.1007/BF00405108

[32]   Adolescent Type 1 Diabetes Cardio-renal Intervention Trial Research Group (2009) Adolescent type 1 diabetes cardio-renal intervention trial (AdDIT). BMC Pediatrics, 9, 79.

[33]   Jones, C.A., Francis, M.E., Eberhardt, M.S., Chavers, B., Coresh, J., Engelgau, M., Kusek, J.W., Byrd-Holt, D., Narayan, K.M., Herman, W.H., Jones, C.P., Salive, M. and Agodoa, L.Y. (2002) Microalbuminuria in the US popualtion: Third national health and nutrition examination survey. American Journal of Kidney Diseases, 39, 445- 459. doi:10.1053/ajkd.2002.31388

[34]   Brandt, J.R., Jacobs, A., Raissy, H.H., Kelly, F.M., Staples, A.O., Kaufman, E. and Wong, C.S. (2010) Orthostatic proteinuria and the spectrum of diurnal variability of urinary protein excretion in healthy children. Pediatric Nephrology, 25, 1131-1137. doi:10.1007/s00467-010-1451-z

[35]   Tsioufis, C., Mazaraki, A., Dimitriadis, K., Stefanidis, C.J. and Stefanadis, C. (2011) Microalbuminuria in the paediatric age: Current knowledge and emerging questions. Acta Paediatrica, 100, 1180-1184. doi:10.1111/j.1651-2227.2011.02291.x

[36]   Kwak, B.O., Lee, S.T., Chung, S. and Kim, K.S. (2011) Microalbuminuria in normal Korean children. Yonsei Medical Journal, 52, 476-481. doi:10.3349/ymj.2011.52.3.476

[37]   Kim, N.H., Pavkov, M.E., Knowler, W.C., Hanson, R.L., Weil, E.J., Curtis, J.M., Bennett, P.H. and Nelson, R.G. (2010) Predictive value of albuminuria in American Indian youth with or without type 2 diabetes. Pediatrics, 125, e844-e851. doi:10.1542/peds.2009-1230

[38]   Rademacher, E., Mauer, M., Jacobs Jr., D.R., Chavers, B., Steinke, J. and Sinaiko, A. (2008) Albumin excretion rate in normal adolescents: Relation to insulin resistance and cardiovascular risk factors and comparisons to type 1 diabetes mellitus patients. Clinical Journal of the American Society of Nephrology, 3, 998-1005. doi:10.2215/CJN.04631007

[39]   Rademacher, E.R. and Sinaiko, A.R. (2009) Albuminuria in children. Current Opinion in Nephrology and Hypertension, 18, 246-251. doi:10.1097/MNH.0b013e3283294b98

[40]   Klausen, K., Borch-Johnsen, K., Feldt-Rasmussen, B., Jensen, G., Clausen, P., Scharling, H., Appleyard, M. and Jensen, J.S. (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. doi:10.1161/01.CIR.0000133312.96477.48

[41]   Chronic Kidney Disease Prognosis Consortium, Matsushita, K., Velde, M., Astor, B.C., Woodward, M., Levey, A.S., Jong, P.E., Coresh, J. and Gansevoort, R.T. (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. doi:10.1016/S0140-6736(10)60674-5

[42]   Salgado, P.P., Silva, I.N, Vieira, E.C. and Simäes e Silva, A.C. (2010) Risk factors for early onset of diabetic nephropathy in pediatric type 1 diabetes. Journal of Pediatric Endocrinology & Metabolism, 23, 1311-1320.

[43]   Roy, M.S., Affouf, M. and Roy, A. (2007) Six-year incidence of proteinuria in type 1 diabetic African Americans. Diabetes Care, 30, 1807-1812. doi:10.2337/dc06-2534

[44]   Stone, M.L., Craig, M.E., Chan, A.K., Lee, J.W., Verge, C.F. and Donaghue, K.C. (2006) Natural history and risk factors for microalbuminuria in adolescents with type 1 diabetes: A longitudinal study. Diabetes Care, 29, 2072- 2077. doi:10.2337/dc06-0239

[45]   Galler, A., Haberland, H., Näke, A., Hofer, S., Holder, M., Raile, K. and Holl, R.W. and German Federal Ministry for Education and Research BMBF Competence Network of Diabetes Mellitus (2012) Natural course of untreated microalbuminuria in children and adolescents with type 1 diabetes and the importance of diabetes duration and immigrant status: Longitudinal analysis from the prospective nationwide German and Austrian diabetes survey DPV. European Journal of Endocrinology, 166, 493-501. doi:10.1530/EJE-11-0695

[46]   Amin, R., Widmer, B., Prevost, A.T., Schwarze, P., Cooper, J., Edge, J., Marcovecchio, L., Neil, A., Dalton, R.N. and Dunger, D.B. (2008) Risk of microalbuminuria and progresson to macroalbuminuria in a cohort with childhood onset type 1 diabetes: Prospective observational study. BMJ, 336, 697-701. doi:10.1136/bmj.39478.378241.BE

[47]   Basiratnia, M., Abadi, F.S., Amirhakimi, G.H., Karamizadeh, Z. and Karamifar, H. (2012) Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria. Saudi Journal of Kidney Diseases and Transplantation, 23, 311-315.

[48]   Dost, A., Klinkert, C., Kapellen, T., Lemmer, A., Naeke, A., Grabert, M., Kreuder, J. and Holl, R.W., DPV Science Initiative (2008) Arterial hypertension determined by ambulatory blood pressure profiles. Contribution to microalbuminuria risk in a multicenter investigation in 2105 children and adolescents with type 1 diabetes. Diabetes Care, 31, 720-725. doi:10.2337/dc07-0824

[49]   Marcovecchio, M.L., Tossavainen, P.H., Acerini, C.L., Barrett, T.G., Edge, J., Neil, A., Shield, J., Widmer, B., Dalton, R.N. and Dunger, D.B. (2010) Maternal but not paternal association of ambulatory blood pressure with albumin excretion in young offspring with type 1 diabetes. Diabetes Care, 33, 366-371. doi:10.2337/dc09-1152

[50]   Salardi, S., Balsamo, C., Zucchini, S., Maltoni, G., Scipione, M., Rollo, A., Gualandi, S. and Cicognani, A. (2011) High rate of regression from micro-macroal- buminuria to normoalbuminuria in children and adolescents with type 1 diabetes treated or not with enalapril: The influence of HDL cholesterol. Diabetes Care, 34, 424-429. doi:10.2337/dc10-1177

[51]   Gheissari, A., Javanmard, S.H., Shirzadi, R., Amini, M. and Khalili, N. (2012) The effects of blocking angiotensin receptors an early stages of diabetic nephropathy. International Journal of Preventive Medicine, 3, 477-482.

[52]   Burgert, T.S., Dziura, J., Yeckel, C., Taksali, S.E., Weiss, R., Tamborlane, W. and Caprio, S. (2006) Microalminuria in pediatric obesity: Prevalence and relation to other cardiovascular risk factors. International Journal of Obesity, 30, 273-280. doi:10.1038/sj.ijo.0803136

[53]   Ariceta, G. (2011) Clinical practice: Proteinuria. European Journal of Pediatrics, 170, 15-20. doi:10.1007/s00431-010-1334-0

[54]   Cosentino, F., Hishikawa, K., Katusic, Z.S. and Luscher, T.F. (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation, 96, 25-28. doi:10.1161/01.CIR.96.1.25

[55]   Franks, P.W., Hanson, R.L., Knowler, W.C., Sievers, M.L., Bennet, P.H. and Looker, H.C. (2010) Childhood obesity, other cardiovascular risk factors, and premature death. The New England Journal of Medicine, 362, 485-493. doi:10.1056/NEJMoa0904130

[56]   Assadi, F.K. (2005) Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria. Pediatric Nephrology, 20, 1131-1135. doi:10.1007/s00467-005-1928-3

[57]   Imuetinyan, B.A., Okoeguale, M.I. and Egberue, G.O. (2011) Microalbuminuria in children with sickle cell anemia. Saudi Journal of Kidney Diseases and Transplantation, 22, 733-738.

[58]   Puddu, M., Podda, M.F., Mussap, M., Tumbarello, R. and Fanos, V. (2009) Early detection of microalbuminuria and hypertension in children of very low birthweight. Journal of Maternal-Fetal and Neonatal Medicine, 22, 83-88. doi:10.1080/14767050802360809

[59]   Schreuder, M.F., Langemeijer M.E., Bökenkamp, A., Delemarre-Van de Waal, H.A. and Van Wijk, J.A. (2008) Hypertension and microalbuminuria in children with congenital solitary kidneys. Journal of Paediatrics and Child Health, 44, 363-368. doi:10.1111/j.1440-1754.2008.01315.x

[60]   Jensen, J.S., Feldt-Rasmussen, B., Strandgaard, S., Schroll, M. and Borch-Johnsen, K. (2000) Atrerial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension, 35, 898-903. doi:10.1161/01.HYP.35.4.898

[61]   Muiesan, M.L., Ambrosioni, E., Costa, F.V., Leonetti, G., Pessina, A.C., Salvetti, M., Trimarco, B., Volpe, M., Pontremoli, R., Deferrari, G. and Rosei, E.A. (2012) Sex differences in hypertension-related renal and cardiovascular diseases in Italy: The I-DEMAND study. Journal of Hypertension, 30, 2378-2386. doi:10.1097/HJH.0b013e328359b6a9

[62]   Karpettas, N., Nasothimiou, E., Kollias, A., Vazeou, A., and Stergiou, G.S. (2013) Ambulatory and home blood pressure monitoring in children and adolescents: Diagnosis of hypertension and assessment of target-organ damage. Hypertension Research, 36, 285-292. doi:10.1038/hr.2012.220

[63]   Hillenge, H.L., Janssen, W.M., Bak, A.A., Diercks, G.F., Grobbee, D.E., Crijns, H.J., Van Gilst, W.H., De Zeeuw D., De Jong, P.E. and Prevend Study Group (2001) Microalbuminuria is common, also in nondiabetic, non- hypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. Journal of Internal Medicine, 249, 519-526. doi:10.1046/j.1365-2796.2001.00833.x

[64]   Wachtell, K., Palmieri, V., Olsen, M.H., Bella, J.N., Aalto, T., Dahlof, B., Gerdts, E., Wright Jr., J.T., Papademetriou, V., Mogensen, C.E., Borch-Johnsen, K., Ibsen, H. and Devereux, R.B. (2002) 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. American Heart Journal, 43, 319-326. doi:10.1067/mhj.2002.119895

[65]   Okpere, A.N., Anochie, I.C. and Eke, F.U. (2012) Prevalence of microalbuminuria among secondary school children. African Health Sciences, 12, 140-147. doi:10.4314/ahs.v12i2.10

[66]   Assadi, F. (2007) Effect of microalbuminuria lowering on regression of left ventricular hypertrophy in children and adolescents with essential hypertension. Pediatric Cardiology, 28, 27-33. doi:10.1007/s00246-006-1390-4

[67]   National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics, 144, 555-576.

[68]   Lurbe, E., Cifkova, R., Cruickshank, J.K., Dillon, M.J., Ferreira, I., Invitti, C., Kuznetsova, T., Laurent, S., Mancia, G., Morales-Olivas, F., Rascher, W., Redon, J., Schaefer, F., Seeman, T., Stergiou, G., Wühl, E., Zanchetti, A. and European Society of Hypertension (2009) Management of high blood pressure in children and adolescents: Recommendations of the European society of hypertension. Journal of Hypertension, 27, 1719-1742. doi:10.1097/HJH.0b013e32832f4f6b

[69]   Varda, N.M. and Gregoric, A. (2005) A diagnostic approach for the child with hypertension. Pediatric Nephrology, 20, 499-506. doi:10.1007/s00467-004-1737-0