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The influence of urinary flow rate in children on excretion of markers used for assessment of renal damage: albumin, γ-glutamyl transpeptidase, N-acetyl-β-D-glucosaminidase, and alpha1-microglobulin

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Abstract

The aim of the present study was to examine the influence of urinary flow rate on markers of renal function in children. A sub-study of the New England Children’s Amalgam Trial collected 82 pairs of urine samples from children aged 10–16 years: a timed overnight collection and a spot daytime sample collected the following day. These samples were analyzed for albumin, γ-glutamyl transpeptidase (γ-GT), N-acetyl-β-D-glucosaminidase (NAG), alpha1-microglobulin (A1M), and creatinine concentration. Regression analysis was used to model the effect of urinary flow rate in the timed overnight samples. A paired t-test compared concentrations and creatinine-corrected renal markers between overnight and daytime samples. Albumin, γ-GT, NAG, and A1M excretion rates increased significantly with urinary flow rate. Their corresponding creatinine-corrected markers did not vary significantly with urinary flow rate, but the creatinine-corrected excretions of albumin, γ-GT, and NAG were significantly higher in daytime samples than in overnight samples, with the same (non-significant) trend for A1M. The influence of urinary flow rate on creatinine-corrected markers of renal function was markedly less than its influence on excretion rates. Therefore, the use of creatinine-corrected markers seems to be a good choice in practice, with the caveat that daytime and overnight samples are not comparable.

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References

  1. World Health Organization (WHO) (2003) Concise international chemical assessment document 50. Elemental mercury and inorganic mercury compounds: human health aspects. WHO, Geneva

    Google Scholar 

  2. Cardenas A, Roels H, Bernard AM, Barbon R, Buchet JP, Lauwerys RR, Rosello J, Hotter G, Mutti A, Franchini I, Fels LM, Stolte H, De Broe ME, Nuyts GD, Taylor SA, Price RG (1993) Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapour. Br J Ind Med 50:17–27

    PubMed  CAS  Google Scholar 

  3. Boeniger MF, Lowry LK, Rosenberg J (1993) Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am Ind Hyg Assoc J 54:615–627

    PubMed  CAS  Google Scholar 

  4. Araki S, Aono H, Murata K (1986) Adjustment of urinary concentration to urinary volume in relation to erythrocyte and plasma concentrations: an evaluation of urinary heavy metals and organic substances. Arch Environ Health 41:171–177

    Article  PubMed  CAS  Google Scholar 

  5. Greenberg GN, Levine RJ (1989) Urinary creatinine excretion is not stable: a new method for assessing urinary toxic substance concentrations. J Occup Med 31:832–838

    Article  PubMed  CAS  Google Scholar 

  6. Araki S, Aono H (1989) Effects of water restriction and water loading on daily urinary excretion of heavy metals and organic substances in metal workers. Br J Ind Med 46:389–392

    PubMed  CAS  Google Scholar 

  7. Viberti GC, Mogensen CE, Keen H, Jacobsen FK, Jarrett RJ, Christensen CK (1982) Urinary excretion of albumin in normal man: the effect of water loading. Scand J Clin Lab Invest 42:147–157

    Article  PubMed  CAS  Google Scholar 

  8. Jespersen B, Pedersen EB, Danielsen H, Kornerup HJ, Knudsen F, Mogensen CE, Nielsen AH (1986) Urinary excretion of albumin and beta-2-microglobulin in hypertensive and normotensive renal transplant recipients during urinary diluting and concentrating tests. Scand J Clin Lab Invest 46:609–614

    Article  PubMed  CAS  Google Scholar 

  9. Jung K, Schulze G (1986) Diuresis-dependent excretion of multiple forms of renal brush-border enzymes in urine. Clin Chim Acta 156:77–83

    Article  PubMed  CAS  Google Scholar 

  10. Jung K, Schulze G, Reinholdt C (1986) Different diuresis-dependent excretions of urinary enzymes: N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, alkaline phosphatase, and gamma-glutamyltransferase. Clin Chem 32:529–532

    PubMed  CAS  Google Scholar 

  11. Wellwood JM, Ellis BG, Price RG, Hammond K, Thompson AE, Jones NF (1975) Urinary N-acetyl- beta-D-glucosaminidase activities in patients with renal disease. Br Med J 3:408–411

    Article  PubMed  CAS  Google Scholar 

  12. Harding S, Munro AJ (1978) Frusemide and renal enzyme excretion. Br Med J 2:1431

    PubMed  CAS  Google Scholar 

  13. Guarnieri G, Ianche M, Lin S (1979) Renal enzyme and protein excretion after induction of a diuresis. Br Med J 2:50–51

    PubMed  CAS  Google Scholar 

  14. Lockwood TD, Bosmann HB (1979) The use of urinary N-acetyl-beta-glucosaminidase in human renal toxicology. I. Partial biochemical characterization and excretion in humans and release from the isolated perfused rat kidney. Toxicol Appl Pharmacol 49:323–336

    Article  PubMed  CAS  Google Scholar 

  15. Houser MT (1986) The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man. Ann Clin Biochem 23:453–457

    PubMed  CAS  Google Scholar 

  16. Eshoj O, Feldt-Rasmussen B, Larsen ML, Mogensen EF (1987) Comparison of overnight, morning and 24-hour urine collections in the assessment of diabetic microalbuminuria. Diabet Med 4:531–533

    PubMed  CAS  Google Scholar 

  17. Davies AG, Postlethwaite RJ, Price DA, Burn JL, Houlton CA, Fielding BA (1984) Urinary albumin excretion in school children. Arch Dis Child 59:625–630

    PubMed  CAS  Google Scholar 

  18. Zuppi C, Baroni S, Scribano D, Di Salvo S, Musumeci V (1995) Choice of time for urine collection for detecting early kidney abnormalities in hypertensives. Ann Clin Biochem 32:373–378

    PubMed  Google Scholar 

  19. Chachati A, von Frenckell R, Foidart-Willems J, Godon JP, Lefebvre PJ (1987) Variability of albumin excretion in insulin-dependent diabetics. Diabet Med 4:441–445

    PubMed  CAS  Google Scholar 

  20. Vestbo E, Damsgaard EM, Froland A, Mogensen CE (1995) Urinary albumin excretion in a population based cohort. Diabet Med 12:488–493

    PubMed  CAS  Google Scholar 

  21. Feldmann D, Flandrois C, Jardel A, Phan TM, Aymard P (1989) Circadian variations and reference intervals for some enzymes in urine of healthy children. Clin Chem 35:864–867

    PubMed  CAS  Google Scholar 

  22. Lakatua DJ, Blomquist CH, Haus E, Sackett-Lundeen L, Berg H, Swoyer J (1982) Circadian rhythm in urinary N-acetyl-beta-glucosaminidase (NAG) of clinically healthy subjects. Timing and phase relation to other urinary circadian rhythms. Am J Clin Pathol 78:69–77

    Google Scholar 

  23. Cundy TF, Nixon D, Berkahn L, Baker J (1992) Measuring the albumin excretion rate: agreement between methods and biological variability. Diabet Med 9:138–143

    PubMed  CAS  Google Scholar 

  24. Bellinger DC, Trachtenberg F, Barregard L, Tavares M, Cernichiari E, Daniel D, McKinlay S (2006) Neuropsychological and renal effects of dental amalgam in children: a randomized clinical trial. JAMA 295:1775–1783

    Article  PubMed  CAS  Google Scholar 

  25. Children’s Amalgam Trial Study Group (2003) The Children’s Amalgam Trial: design and methods. Control Clin Trials 24:795–814

    Google Scholar 

  26. Jarup L, Hellstrom L, Alfven T, Carlsson MD, Grubb A, Persson B, Pettersson C, Spang G, Schütz A, Elinder CG (2000) Low level exposure to cadmium and early kidney damage: the OSCAR study. Occup Environ Med 57:668–672

    Article  PubMed  CAS  Google Scholar 

  27. Sanchez-Bayle M, Rodriguez-Cimadevilla C, Asensio C, Ruiz-Jarabo C, Baena J, Arnaiz P, Villa S, Cocho P (1995) Urinary albumin excretion in Spanish children. Nino Jesus Group. Pediatr Nephrol 9:428–430

    Article  PubMed  CAS  Google Scholar 

  28. Bangstad HJ, Dahl-Jorgensen K, Kjaersgaard P, Mevold K, Hanssen KF (1993) Urinary albumin excretion rate and puberty in non-diabetic children and adolescents. Acta Paediatr 82:857–862

    PubMed  CAS  Google Scholar 

  29. Lorini R, d’Annunzio G, Vitali L, Scaramuzza A, Bacchella L, Zonta LA (1998) Normal values of overnight albumin excretion rate in a sample of healthy Italian children and adolescents. J Pediatr Endocrinol Metab 11:639–643

    PubMed  CAS  Google Scholar 

  30. Hjorth L, Helin I, Grubb A (2000) Age-related reference limits for urine levels of albumin, orosomucoid, immunoglobulin G and protein HC in children. Scand J Clin Lab Invest 60:65–73

    Article  PubMed  CAS  Google Scholar 

  31. Lehrnbecher T, Greissinger S, Navid F, Pfuller H, Jeschke R (1998) Albumin, IgG, retinol-binding protein, and alpha1-microglobulin excretion in childhood. Pediatr Nephrol 12:290–292

    Article  PubMed  CAS  Google Scholar 

  32. Oba K, Hirai M, Ajiro Y, Okazaki K, Sato S, Sasai K, Suzuki T, Nakano H, Metori S (1999) Effect of age on urinary excretion of N-acetyl-beta-D-glucosaminidase. Nippon Ika Daigaku Zasshi 66:33–36

    Article  PubMed  CAS  Google Scholar 

  33. Osborne J (1980) Urinary excretion of N-acetyl-beta-d-glucosaminidase in children. Arch Dis Child 55:719–721

    PubMed  CAS  Google Scholar 

  34. Remer T, Neubert A, Maser-Gluth C (2002) Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. Am J Clin Nutr 75:561–569

    PubMed  CAS  Google Scholar 

  35. Goldwasser P, Aboul-Magd A, Maru M (1997) Race and creatinine excretion in chronic renal insufficiency. Am J Kidney Dis 30:16–22

    PubMed  CAS  Google Scholar 

  36. Agirbasli M, Radhakrishnamurthy B, Jiang X, Bao W, Berenson GS (1996) Urinary N-acetyl-beta-D-glucosaminidase changes in relation to age, sex, race, and diastolic and systolic blood pressure in a young adult biracial population. The Bogalusa Heart Study. Am J Hypertens 9:157–161

    Article  PubMed  CAS  Google Scholar 

  37. Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, Kusek JW, Byrd-Holt D, Narayan KM, Herman WH, Jones CP, Salive M, Aodoa LY (2002) Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis 39:445–459

    PubMed  Google Scholar 

  38. Jung K, Hempel A, Grutzmann KD, Hempel RD, Schreiber G (1990) Age-dependent excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase in human urine. Enzyme 43:10–16

    PubMed  CAS  Google Scholar 

  39. Skinner AM, Addison GM, Price DA (1996) Changes in the urinary excretion of creatinine, albumin and N-acetyl-beta-D-glucosaminidase with increasing age and maturity in healthy schoolchildren. Eur J Pediatr 155:596–602

    PubMed  CAS  Google Scholar 

  40. Bakker AJ (1999) Detection of microalbuminuria. Receiver operating characteristic curve analysis favors albumin-to-creatinine ratio over albumin concentration. Diabetes Care 22:307–313

    Article  PubMed  CAS  Google Scholar 

  41. Jung K, Pergande M (1992) Sex- and age-dependent reference values of alpha-1-microglobulin in urine. Nephron 62:474–475

    PubMed  CAS  Google Scholar 

  42. Kesteloot H, Joossens JV (1996) On the determinants of the creatinine clearance: a population study. J Hum Hypertens 10:245–249

    PubMed  CAS  Google Scholar 

  43. Tencer J, Thysell H, Grubb A (1996) Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1-antitrypsin. Scand J Clin Lab Invest 56:691–700

    Article  PubMed  CAS  Google Scholar 

  44. Harvey JN, Hood K, Platts JK, Devarajoo S, Meadows PA (1999) Prediction of albumin excretion rate from albumin-to-creatinine ratio. Diabetes Care 22:1597–1598

    Article  PubMed  CAS  Google Scholar 

  45. Jacobs DR Jr, Murtaugh MA, Steffes M, Yu X, Roseman J, Goetz FC (2002) Gender- and race-specific determination of albumin excretion rate using albumin-to-creatinine ratio in single, untimed urine specimens: The Coronary Artery Risk Development in Young Adults Study. Am J Epidemiol 155:1114–1119

    Article  PubMed  Google Scholar 

  46. Mattix HJ, Hsu CY, Shaykevich S, Curhan G (2002) Use of the albumin/creatinine ratio to detect microalbuminuria: implications of sex and race. J Am Soc Nephrol 13:1034–1039

    PubMed  CAS  Google Scholar 

  47. Lindeman RD, Romero L, Liang HC, Hundley R, Baumgartner R, Koehler K, Garry P (1998) Prevalence of proteinuria/microalbuminuria in an elderly urban, biethnic community. Geriatr Nephrol Urol 8:123–130

    Article  PubMed  CAS  Google Scholar 

  48. Metcalf PA, Baker JR, Scragg RK, Dryson E, Scott AJ, Wild CJ (1993) Microalbuminuria in a middle-aged workforce. Effect of hyperglycemia and ethnicity. Diabetes Care 16:1485–1493

    Article  PubMed  CAS  Google Scholar 

  49. Summerson JH, Bell RA, Konen JC (1995) Racial differences in the prevalence of microalbuminuria in hypertension. Am J Kidney Dis 26:577–579

    PubMed  CAS  Google Scholar 

  50. Hara F, Nakazato K, Shiba K, Shimoda J, Kojima T, Fukumura Y, Kobayashi I (1994) Studies of diabetic nephropathy. I. Effects of storage time and temperature on microalbuminuria. Biol Pharm Bull 17:1241–1245

    PubMed  CAS  Google Scholar 

  51. Loeb WF, Das SR, Trout JR (1997) The effect of erythritol on the stability of gamma-glutamyl transpeptidase and N-acetyl glucosaminidase in human urine. Toxicol Pathol 25:264–267

    PubMed  CAS  Google Scholar 

  52. Manley SE, Burton ME, Fisher KE, Cull CA, Turner RC (1992) Decreases in albumin/creatinine and N-acetylglucosaminidase/creatinine ratios in urine samples stored at −20 degrees C. Clin Chem 38:2294–2299

    PubMed  CAS  Google Scholar 

  53. Matteucci E, Gregori G, Pellegrini L, Navalesi R, Giampietro O (1991) How can storage time and temperature affect enzymic activities in urines? Enzyme 45:116–120

    PubMed  CAS  Google Scholar 

  54. Matteucci E, Pellegrini L, Uncini-Manganelli C, Cecere M, Saviozzi M, Giampietro O (1992) More on effects of storage time and temperature on urinary enzymes: a 1-year study. Enzyme 46:249–251

    PubMed  CAS  Google Scholar 

  55. Osberg I, Chase HP, Garg SK, DeAndrea A, Harris S, Hamilton R, Marshall G (1990) Effects of storage time and temperature on measurement of small concentrations of albumin in urine. Clin Chem 36:1428–1430

    PubMed  CAS  Google Scholar 

  56. Schultz CJ, Dalton RN, Turner C, Neil HA, Dunger DB (2000) Freezing method affects the concentration and variability of urine proteins and the interpretation of data on microalbuminuria. The Oxford Regional Prospective Study Group. Diabet Med 17:7–14

    Article  PubMed  CAS  Google Scholar 

  57. Shield JP, Hunt LP, Morgan JE, Pennock CA (1995) Are frozen urine samples acceptable for estimating albumin excretion in research? Diabet Med 12:713–716

    Article  PubMed  CAS  Google Scholar 

  58. Tencer J, Thysell H, Andersson K, Grubb A (1994) Stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at various conditions. Scand J Clin Lab Invest 54:199–206

    Article  PubMed  CAS  Google Scholar 

  59. Tencer J, Thysell H, Andersson K, Grubb A (1997) Long-term stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain-immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at −20 degrees C. Scand J Urol Nephrol 31:67–71

    Article  PubMed  CAS  Google Scholar 

  60. MacNeil ML, Mueller PW, Caudill SP, Steinberg KK (1991) Considerations when measuring urinary albumin: precision, substances that may interfere, and conditions for sample storage. Clin Chem 37:2120–2123

    PubMed  CAS  Google Scholar 

  61. Klasen IS, Reichert LJ, de Kat Angelino CM, Wetzels JF (1999) Quantitative determination of low and high molecular weight proteins in human urine: influence of temperature and storage time. Clin Chem 45:430–432

    PubMed  CAS  Google Scholar 

  62. Grogan CB, Ekvall SM (1999) Body composition of children with myelomeningocele, determined by 40K, urinary creatinine and anthropometric measures. J Am Coll Nutr 18:316–323

    PubMed  CAS  Google Scholar 

  63. Forbes GB, Bruining GJ (1976) Urinary creatinine excretion and lean body mass. Am J Clin Nutr 29:1359–1366

    PubMed  CAS  Google Scholar 

  64. Ebner A, Manz F (2002) Sex difference of urinary osmolality in German children. Am J Nephrol 22:352–355

    Article  PubMed  Google Scholar 

  65. Hong CY, Chia KS (1998) Markers of diabetic nephropathy. J Diabetes Complications 12:43–60

    Article  PubMed  CAS  Google Scholar 

  66. Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, 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

    Article  PubMed  CAS  Google Scholar 

  67. Basturk T, Altuntas Y, Kurklu A, Aydin L, Eren N, Unsal A (2006) Urinary N-acetyl B glucosaminidase as an earlier marker of diabetic nephropathy and influence of low-dose perindopril/indapamide combination. Ren Fail 28:125–128

    Article  PubMed  CAS  Google Scholar 

  68. Gibb DM, Shah V, Preece M, Barratt TM (1989) Variability of urine albumin excretion in normal and diabetic children. Pediatr Nephrol 3:414–419

    Article  PubMed  CAS  Google Scholar 

  69. Skinner AM, Clayton PE, Price DA, Addison GM, Mui CY (1993) Variability in the urinary excretion of growth hormone in children: a comparison with other urinary proteins. J Endocrinol 138:337–343

    PubMed  CAS  Google Scholar 

  70. Gaspari F, Perico N, Remuzzi G (2006) Timed urine collections are not needed to measure urine protein excretion in clinical practice. Am J Kidney Dis 47:1–7

    Article  PubMed  Google Scholar 

  71. Shidham G, Hebert LA (2006) Timed urine collections are not needed to measure urine protein excretion in clinical practice. Am J Kidney Dis 47:8–14

    Article  PubMed  Google Scholar 

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Acknowledgments

We acknowledge Elsa Cernichiari for the laboratory analyses of creatinine and γ-GT. The study was supported by the National Institute of Dental and Craniofacial research, USA (U01 DE11886), which also participated in the design and conduct of the study.

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Authors and Affiliations

  1. New England Research Institutes, 9 Galen St., Watertown, MA, 02472, USA

    Felicia Trachtenberg & Sonja McKinlay

  2. Department Occupational and Environmental Medicine, Sahlgrenska University Hospital and Academy, Gothenburg, Sweden

    Lars Barregard

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  1. Felicia Trachtenberg
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Correspondence to Felicia Trachtenberg.

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This study was supported by a cooperative agreement (U01 DE11886) between the New England Research Institutes and the National Institute of Dental and Craniofacial Research, National Institutes of Health.

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Trachtenberg, F., Barregard, L. & McKinlay, S. The influence of urinary flow rate in children on excretion of markers used for assessment of renal damage: albumin, γ-glutamyl transpeptidase, N-acetyl-β-D-glucosaminidase, and alpha1-microglobulin. Pediatr Nephrol 23, 445–456 (2008). https://doi.org/10.1007/s00467-007-0568-1

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