Abstract
Background: Positive test strip results, pathological particles in urine and the presence of proteinuria are common findings in nephropathies. A comparison between these methods and renal biopsies became available with the introduction of quantitative measurement of marker proteins (albumin, transferrin, IgG, α1-microglobulin, retinol binding protein, α2-macroglobulin, Bence Jones proteins) and standardised urine sediment analysis by flow cytometry or microscopy.
Methods: A total of 400 urine samples were examined using marker protein patterns, test strips and quantitative sediment analyses.
Results: Results from standardised urine sediment analyses were compared with the excretion of renal marker proteins. Increased erythrocyte and leukocyte counts in urine were observed in only 29% and 39% of the samples for which pathological protein excretion was found. The sensitivity in detecting pathological particles in urine sediment, such as casts and/or dysmorphic erythrocytes, was only 19%. Renal biopsies from 65 patients who were classified as pathological were compared with proteinuria and sediment analyses. Increased excretion of marker proteins was found in all cases, whereas only 41% of the cellular urine sediments showed pathological results.
Conclusions: Quantitative measurement of marker proteins from both the glomerular and tubular sides should be used upfront as screening parameters for the early detection of renal disorders.
Clin Chem Lab Med 2006;44:1347–54.
References
1. Boesken WH, Batsford SR, Schmitz-Hubner U, Schneider G. Molecular weight analysis of proteinuria in experimental glomerulopathies. Res Exp Med (Berl) 1976; 167:23–30.10.1007/BF02180285Search in Google Scholar
2. Boesken WH. Diagnostic significance of SDS-PAA-electrophoresis of urinary proteins: different forms of proteinuria and their correlation to renal diseases. Curr Probl Clin Biochem 1979; 9:235–48.Search in Google Scholar
3. Birch DF, Fairley KF, Whitworth JA, Forbes I, Fairley JK, Cheshire GR, et al. Urinary erythrocyte morphology in the diagnosis of glomerular hematuria. Clin Nephrol 1983; 20:78–84.Search in Google Scholar
4. Pollock C, Liu PL, Gyory AZ, Grigg R, Gallery ED, Caterson R, et al. Dysmorphism of urinary red blood cells – value in diagnosis. Kidney Int 1989; 36:1045–9.10.1038/ki.1989.299Search in Google Scholar
5. Heine GH, Sester U, Girndt M, Kohler H. Acanthocytes in the urine: useful tool to differentiate diabetic nephropathy from glomerulonephritis? Diabetes Care 2004; 27:190–4.10.2337/diacare.27.1.190Search in Google Scholar
6. Froom P, Etzion R, Barak M. What is an abnormal test strip urinary erythrocyte concentration? Clin Chem 2004; 50:673–5.10.1373/clinchem.2003.028589Search in Google Scholar
7. Delanghe JR, Kouri TT, Huber AR, Hannemann-Pohl K, Guder WG, Lun A, et al. The role of automated urine particle flow cytometry in clinical practice. Clin Chim Acta 2000; 301:1–18.10.1016/S0009-8981(00)00342-9Search in Google Scholar
8. Ottiger C, Huber AR. Quantitative urine particle analysis: integrative approach for the optimal combination of automation with UF-100 and microscopic review with KOVA cell chamber. Clin Chem 2003; 49:617–23.10.1373/49.4.617Search in Google Scholar
9. Langlois MR, Delanghe JR, Steyaert SR, Everaert KC, De Buyzere ML. Automated flow cytometry compared with an automated dipstick reader for urinalysis. Clin Chem 1999; 45:118–22.10.1093/clinchem/45.1.118Search in Google Scholar
10. Hofmann W, Rossmuller B, Guder WG, Edel HH. A new strategy for characterizing proteinuria and haematuria from a single pattern of defined proteins in urine. Eur J Clin Chem Clin Biochem 1992; 30:707–12.Search in Google Scholar
11. Regeniter A, Haenni V, Risch L, Köchli HP, Colombo JP, Frei R, Huber AR. Urine analysis performed by flow cytometry: reference range determination and comparison to morphological findings, dipstick chemistry and bacterial culture results – a multicenter study. Clin Nephrol 2001; 55:384–92.Search in Google Scholar
12. Regeniter A, Siede WH, Seiffert UB. Computer assisted interpretation of laboratory test data with MDI-LabLink. Clin Chim Acta 1996; 248:107–8.10.1016/0009-8981(95)06271-8Search in Google Scholar
13. Regeniter A, Siede WH, Scholer A, Huber P, Frischmuth N, Steiger JU. Interpreting complex urinary patterns with MDI LABLINK: a statistical evaluation. Clin Chim Acta 2000; 297:261–73.10.1016/S0009-8981(00)00252-7Search in Google Scholar
14. Regeniter A, Steiger JU, Scholer A, Huber P, Siede WH. Windows to the ward: graphically oriented report forms. Presentation of complex, interrelated laboratory data for electrophoresis/immunofixation, cerebrospinal fluid, and urinary protein profiles. Clin Chem 2003; 49:41–50.10.1373/49.1.41Search in Google Scholar PubMed
15. Watanabe N, Kamei N, Ohkubo A, Yamanaka M, Ohsawa S, Makino K, et al. Urinary protein as measured with a pyrogallol red-molybdate complex, manually and in a Hitachi 726 automated analyzer. Clin Chem 1986; 32:1544–51.10.1093/clinchem/32.8.1551Search in Google Scholar
16. Orsonneau JL, Douet P, Massoubre C, Lustenberger P, Bernard S. An improved pyrogallol red-molybdate method for determining total urinary protein. Clin Chem 1989; 35:2233–6.10.1093/clinchem/35.11.2233Search in Google Scholar
17. Morales JV, Weber R, Wagner MB, Barros EJ. Is morning urinary protein/creatinine ratio a reliable estimator of 24-hour proteinuria in patients with glomerulonephritis and different levels of renal function? J Nephrol 2004; 17:666–72.Search in Google Scholar
18. Hofmann W, Guder WG. A diagnostic programme for quantitative analysis of proteinuria. J Clin Chem Clin Biochem 1989; 9:589–600.10.1515/cclm.1989.27.9.589Search in Google Scholar PubMed
19. Hofmann W, Regenbogen C, Edel H, Guder WG. Diagnostic strategies in urinalysis. Kidney Int 1994; 46(Suppl 47):111–4.Search in Google Scholar
20. Guder WG, Ivandic M, Hofmann W. Physiopathology of proteinuria and laboratory diagnostic strategy based on single protein analysis. Clin Chem Lab Med 1998; 36:935–9.10.1515/CCLM.1998.162Search in Google Scholar PubMed
21. Boege F, Kohler B, Liebermann F. Identification and quantification of Bence-Jones proteinuria by automated nephelometric screening. J Clin Chem Clin Biochem 1990; 28:37–42.Search in Google Scholar
22. Thut MT, Uehlinger D, Steiger J, Mihatsch MJ. Renal biopsy – standard procedure of modern nephrology. Ther Umschau 2002; 59:110–6.10.1024/0040-5930.59.3.110Search in Google Scholar PubMed
23. Tischer CC, Brunner BM. Renal pathology with clinical and functional correlation, 2nd ed. Philadelphia, PA: JB Lippincott, 1994.Search in Google Scholar
24. Fassett RG, Owen JE, Fairley J, Birch DF, Fairley KF. Urinary red-cell morphology during exercise. Br Med J 1982; 285:1455–7.10.1136/bmj.285.6353.1455Search in Google Scholar PubMed PubMed Central
25. Everaert K, Delanghe J, Vanderkelen M, Cornelis K, De Wachter S, Viaene A, et al. Urinary plasma protein patterns in acute prostatitis. Clin Chem Lab Med 2003; 41:79–84.10.1515/CCLM.2003.014Search in Google Scholar PubMed
26. Svanborg Eden C, Kulhavy R, Marild S, Prince SJ, Mestecky J. Urinary immunoglobulins in healthy individuals and children with acute pyelonephritis. Scand J Immunol 1985; 21:305–13.10.1111/j.1365-3083.1985.tb01435.xSearch in Google Scholar PubMed
27. Nicolle LE, Brunka J. Urinary IgG and IgA antibodies in elderly individuals with bacteriuria. Gerontology 1990; 36:345–55.10.1159/000213220Search in Google Scholar PubMed
28. Col M, Ocaktan E, Ozdemir O, Yalcin A, Tuncbilek A. Microalbuminuria: prevalence in hypertensives and diabetics. Acta Med Austriaca 2004; 31:23–9.Search in Google Scholar
29. Kutter D. Dry chemistry urinalysis of pathological proteinuria. Clin Chem Lab Med 1998; 36:929–33.10.1515/CCLM.1998.161Search in Google Scholar PubMed
30. Gerc V, Schubert A, Burnier M. Differentiation between glomerular and non-glomerular erythrocyturia: what is the value of differential microhematuria diagnosis? Schweiz Rundsch Med Prax 1997; 86:1198–203.Search in Google Scholar
31. Corso A, Serricchio G, Zappasodi P, Klersy C, Bosoni T, Moratti R, et al. Assessment of renal function in patients with multiple myeloma: the role of urinary proteins. Ann Hematol 1999; 78:371–5.10.1007/s002770050531Search in Google Scholar
32. Nicastri AL, Prado MJ, Dominguez WV, Prado EB. Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification. Braz J Med Biol Res 2002; 35:357–60.10.1590/S0100-879X2002000300011Search in Google Scholar
33. Hofmann W, Garbrecht M, Bradwell AR, Guder WG. A new concept for detection of Bence Jones proteinuria in patients with monoclonal gammopathy. Clin Lab 2004; 50:181–5.Search in Google Scholar
34. Tencer J, Thysell H, Grubb A. Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, κ- and λ-immunoreactivity, orosomucoid and α1-antitrypsin. Scand J Clin Lab Invest 1996; 56:691–700.10.3109/00365519609088816Search in Google Scholar
35. Nowrousian MR, Brandhorst D, Sammet C, Kellert M, Daniels R, Schuett P, et al. Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma. Clin Cancer Res 2005; 11:8706–14.10.1158/1078-0432.CCR-05-0486Search in Google Scholar
36. Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003; 361:489–91.10.1016/S0140-6736(03)12457-9Search in Google Scholar
37. Balow JE. Clinical presentation and monitoring of lupus nephritis. Lupus 2005; 14:25–30.10.1191/0961203305lu2055oaSearch in Google Scholar PubMed
38. Thakkar H, Lowe PA, Price CP, Newman DJ. Measurement of the kinetics of protein uptake by proximal tubular cells using an optical biosensor. Kidney Int 1998; 54:1197–205.10.1046/j.1523-1755.1998.00098.xSearch in Google Scholar PubMed
©2006 by Walter de Gruyter Berlin New York