OJPed  Vol.3 No.2 , June 2013
Urine albumin excretion: Characterization of normal variability in healthy children
Abstract: Objective: Elevated urine albumin to creatinine ratio (ACR) of >30 mg/gm is a widely agreed upon indicator of pathologic albuminuria in children. However, the most reliable specimen to measure ACR in children remains undefined. We assess the range and limits of upright and supine total albumin and ACR in healthy children. Methods: Healthy children age 6 - 18 years completed 24-hour and split upright and supine urine collections. Upright, supine and 24-hour protein, albumin and creatinine were measured. Primary outcomes are range and variation in urine albumin by diurnal status, age, gender, BMI percentile and Tanner stage. Results: In healthy children, with mean age 12.9 year (sd 3.2), upright ACR was 2-fold greater than supine (13.9 vs 6.8 mg/gm, p = 0.02). The range of ACR was much greater in the upright (2 - 323 mg/gm) compared to the supine (1.7 - 76 mg/gm) samples. The average total 24-hour urine albumin was 8.4 mg (sd 9.8) and the mean ACR was 8.9 mg/gm (sd 11.7). The 24-hour albumin increased with age and Tanner stage, but this relationship was not significant after adjusting for BSA or urine creatinine. A supine or upright ACR of >30 mg/gm was found in 5.4% of each group. However, in all subjects with an elevated ACR on an individual upright or supine sample, a second 1st am ACR sample was normal. Conclusions: In healthy children there is a marked diurnal variability in ACR with a higher value from a daytime sample compared to 1st morning specimen. Screening for pathologic albuminuria should always use a first morning urine specimen.
Cite this paper: Brandt, J. , Wong, C. , Jacobs, A. and Staples, A. (2013) Urine albumin excretion: Characterization of normal variability in healthy children. Open Journal of Pediatrics, 3, 58-64. doi: 10.4236/ojped.2013.32012.

[1]   Wong, C.S., Pierce, C.B., Cole, S.R., Warady, B.A., Mak, R.H., Benador, N.M., Kaskel, F., Furth, S.L. and Schwartz, G.J. (2009) Association of proteinuria with race, cause of chronic kidney disease, and glomerular filtration rate in the chronic kidney disease in children study. Clinical Journal of American Society of Nephrology, 4, 812-819. doi:10.2215/CJN.01780408

[2]   Levey, A.S., Atkins, R., Coresh, J., Cohen, E.P., Collins, A.J., Eckardt, K.U., Nahas, M.E., Jaber, B.L., Jadoul, M., Levin, A., Powe, N.R., Rossert, J., Wheeler, D.C., Lameire, N. and Eknoyan, G. (2007) Chronic kidney disease as a global public health problem: approaches and initiatives—A position statement from kidney disease improving global outcomes. Kidney International, 72, 247-259. doi:10.1038/

[3]   Rademacher, E.R. and Sinaiko, A.R. (2009) Albuminuria in children. Current Opinion in Nephrology and Hypertension, 18, 246-251.

[4]   Gerstein, H.C., Mann, J.F., Yi, Q., Zinman, B., Dinneen, S.F., Hoogwerf, B., Halle, J.P., Young, J., Rashkow, A., Joyce, C., Nawaz, S. and Yusuf, S. (2001) Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. Journal of the American Medical Association, 286, 421-426. doi:10.1001/jama.286.4.421

[5]   Din-Dzietham, R., Liu, Y., Bielo, M.V. and Shamsa, F. (2007) High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. Circulation, 116, 1488-1496. doi:10.1161/CIRCULATIONAHA.106.683243

[6]   Ogden, C.L., Carroll, M.D. and Flegal, K.M. (2008) High body mass index for age among US children and adolescents, 2003-2006. Journal of the American Medical Association, 299, 2401-2405. doi:10.1001/jama.299.20.2401

[7]   Levey, A.S., de Jong, P.E., Coresh, J., El Nahas, M., Astor, B.C., Matsushita, K., Gansevoort, R.T., Kasiske, B.L. and Eckardt, K.U. (2011) The definition, classification, and prognosis of chronic kidney disease: A KDIGO controversies conference report. Kidney International, 80, 17-28. doi:10.1038/ki.2010.483

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

[9]   Cowell, C.T., Rogers, S. and Silink, M. (1986) First morning urinary albumin concentration is a good predictor of 24-hour urinary albumin excretion in children with type 1 (insulin-dependent) diabetes. Diabetologia, 29, 97-99. doi:10.1007/BF00456117

[10]   Bangstad, H.J., Dahl-Jorgensen, K., Kjaersgaard, P., Mevold, K. and Hanssen, K.F. (1993) Urinary albumin excretion rate and puberty in non-diabetic children and adolescents. Acta Paediatrica, 82, 857-862.

[11]   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 population: Third national health and nutrition examination survey. American Journal of Kidney Diseases, 39, 445-459. doi:10.1053/ajkd.2002.31388

[12]   Ferris, M., Hogan, S.L., Chin, H., Shoham, D.A., Gipson, D.S., Gibson, K., Yilmaz, S., Falk, R.J. and Jennette, J.C. (2007) Obesity, albuminuria, and urinalysis findings in US young adults from the add health wave III study. Clinical Journal of the American Society of Nephrology, 2, 1207-1214. doi:10.2215/CJN.00540107

[13]   Davies, A.G., Postlethwaite, R.J., Price, D.A., Burn, J.L., Houlton, C.A. and Fielding, B.A. (1984) Urinary albumin excretion in school children. Archives of Disease in Childhood, 59, 625-630. doi:10.1136/adc.59.7.625

[14]   Sanchez-Bayle, M., Rodriguez-Cimadevilla, C., Asensio, C., Ruiz-Jarabo, C., Baena, J., Arnaiz, P., Villa, S. and Cocho, P. (1995) Urinary albumin excretion in Spanish children. Nino Jesus Group. Pediatric Nephrology, 9, 428-430. doi:10.1007/BF00866717

[15]   Taylor, S.J., Whincup, P.H., Hindmarsh, P.C., Lampe, F., Odoki, K. and Cook, D.G. (2001) Performance of a new pubertal self-assessment questionnaire: A preliminary study. Paediatric and Perinatal Epidemiology, 15, 88-94. doi:10.1046/j.1365-3016.2001.00317.x

[16]   Hogg, R.J., Portman, R.J., Milliner, D., Lemley, K.V., Eddy, A. and Ingelfinger, J. (2000) Evaluation and management of proteinuria and nephrotic syndrome in children: Recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics, 105, 1242-1249. doi:10.1542/peds.105.6.1242

[17]   Haycock, G.B., Schwartz, G.J. and Wisotsky, D.H. (1978) Geometric method for measuring body surface area: A height-weight formula validated in infants, children, and adults. Journal of Pediatrics, 93, 62-66. doi:10.1016/S0022-3476(78)80601-5

[18]   Kuczmarski, R.J., Ogden, C.L., Guo, S.S., Grummer-Strawn, L.M., Flegal, K.M., Mei, Z., Wei, R., Curtin, L.R., Roche, A.F. and Johnson, C.L. (2002) 2000 CDC growth charts for the United States: Methods and development. Vital and Health Statistics Series, 11, 1-190.

[19]   Odeh, R.E., Chou, Y.M. and Owen, D.B. (1989) Sample size determination for two-sided beta-expectetion tolerance intervals for a normal distribution. Technometrics, 31, 461-468. doi:10.1080/00401706.1989.10488594

[20]   Schreuder, M.F., Langemeijer, M.E., Bokenkamp, 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

[21]   Lou-Meda, R., Gilstrap, J., et al. (2007) Prognostic significance of microalbuminuria in postdiarrheal hemolytic uremic syndrome. Pediatric Nephrology, 22, 117-120. doi:10.1007/s00467-006-0283-3

[22]   Maahs, D.M., Bell, M.S., et al. (2007) Higher prevalence of elevated albumin excretion in youth with type 2 than type 1 diabetes: The SEARCH for diabetes in youth study. Diabetes Care, 30, 2593-2598. doi:10.2337/dc07-0450

[23]   Houser, M.T. (1987) Characterization of recumbent, ambulatory, and postexercise proteinuria in the adolescent. Pediatric Research, 21, 442-446. doi:10.1203/00006450-198705000-00004

[24]   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.

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

[26]   Skinner, A.M., Addison, G.M. and Price, D.A. (1996) Changes in the urinary excretion of creatinine, albumin and N-acetyl-beta-D-glucosaminidase with increasing age and maturity in healthy schoolchildren. European Journal of Pediatrics, 155, 596-602.

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