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Licensed Unlicensed Requires Authentication Published by De Gruyter April 25, 2020

Current state of the morphological assessment of urinary erythrocytes in The Netherlands: a nation-wide questionnaire

Jolien J. Luimstra , Rüya G. Koçer , Alexander Jerman , Jacqueline Klein Gunnewiek , Karlijn Gijzen , Leo H.J. Jacobs and Ayşe Y. Demir EMAIL logo



The morphological assessment of urinary erythrocytes (uRBC) is a convenient screening tool for the differentiation of nephrological (dysmorphic) and urological (isomorphic) causes of hematuria. Considering the morphological heterogeneity, this analysis is often perceived as difficult. There is no clear (inter)national consensus and there is a lack of external quality assessment programs. To gain insight into the heterogeneity within and between laboratories, we scrutinized the current state of this analysis in Dutch medical laboratories.


The laboratories, affiliated with the Dutch Foundation for Quality Assessment in Medical Laboratories, were invited to participate in a web-based survey, consisting of two questionnaires. The first one provided information about the institution and laboratory organization, and the second explored the variability in the morphological analysis of uRBC on the basis of categorization of 160 uRBC images. Statistical analysis was premised on binomial significance testing and principal component analysis.


Nearly one third of the Dutch medical laboratories (65/191) with 167 staff members participated in the survey. Most of these laboratories (83%) were an integral part of secondary care. The statistical analysis of the evaluations of the participants in comparison to the consensus (three experts from two different medical laboratories) suggested a great degree of heterogeneity in the agreement. Nearly half of the participants consciously disagreed with the consensus, whereas one fifth demonstrated a random relationship with it.


In Dutch medical laboratories, results from morphological analysis of uRBC are heterogeneous, which point out the necessity for standardization and harmonization.

Corresponding author: Ayşe Y. Demir, MD, PhD, Department of Clinical Chemistry and Hematology, Meander Medical Centre, Postbus 1502, 3800 BM Amersfoort, The Netherlands, Phone: 0031-33-8504344


The authors thank Prof. Dr. Giovanni B. Fogazzi and Dr. Giuseppe Garigali (Research Laboratory on Urine, Nephrology Unit, Fondazione IRCCS, Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milano, Italy) for their contribution to the questionnaire, including the preparation of the images.

  1. Author contributions: J.J. Luimstra, manuscript preparation; A. Jerman, concept and study design, data collection; R.G. Koçer, data collection and analysis; J. Klein Gunnewiek, concept and study design; K. Gijzen, manuscript preparation; L.H.J. Jacobs, manuscript preparation; A.Y. Demir, concept and study design, conduction of experiments, data analysis, manuscript preparation. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: Authors state no conflict of interest.

  6. Informed consent: Informed consent was obtained from all individuals included in this study.

  7. Ethical approval: None.


1. Birch DF, Fairley KF. Haematuria: glomerular or non-glomerular? Lancet 1979;2:845–6.10.1016/S0140-6736(79)92191-3Search in Google Scholar

2. Fairley KF, Birch DF. Hematuria: a simple method for identifying glomerular bleeding. Kidney Int 1982;21:105–8.10.1038/ki.1982.16Search in Google Scholar

3. Mohr DN, Offord KP, Owen RA, Melton 3rd LJ. Asymptomatic microhematuria and urologic disease. A population-based study. J Am Med Assoc 1986;256:224–9.10.1001/jama.256.2.224Search in Google Scholar

4. Woolhandler S, Pels RJ, Bor DH, Himmelstein DU, Lawrence RS. Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders. I. Hematuria and proteinuria. J Am Med Assoc 1989;262:1214–9.10.1001/jama.262.9.1214Search in Google Scholar

5. 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

6. Martinez MG, dos SS, do Valle AP, Amaro CR, Corrente JE, Martin LC. Comparison of different methods of erythrocyte dysmorphism analysis to determine the origin of hematuria. Nephron Clin Pract 2014;128:88–94.10.1159/000367848Search in Google Scholar

7. Huussen J, Koene RA, Meuleman EJ, Hilbrands LB. Diagnostic approach in patients with asymptomatic haematuria: efficient or not? Int J Clin Pract 2006;60:557–61.10.1111/j.1368-5031.2006.00910.xSearch in Google Scholar

8. Roth S, Renner E, Rathert P. Microscopic hematuria: advances in identification of glomerular dysmorphic erythrocytes. J Urol 1991;146:680–4.10.1016/S0022-5347(17)37892-8Search in Google Scholar

9. Wandel E, Kohler H. Acanthocytes in urinary sediment–a pathognomonic marker? Nephrol Dial Transplant 1998;13:206–7.10.1093/ndt/13.1.206Search in Google Scholar PubMed

10. Rodgers M, Nixon J, Hempel S, Aho T, Kelly J, Neal D, et al. Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation. Health Technol Assess 2006;10:iii–iv, xi–259.10.3310/hta10180Search in Google Scholar PubMed

11. Offringa M, Benbassat J. The value of urinary red cell shape in the diagnosis of glomerular and post-glomerular haematuria. A meta-analysis. Postgrad Med J 1992;68:648–54.10.1136/pgmj.68.802.648Search in Google Scholar PubMed PubMed Central

12. Venkat Raman G, Pead L, Lee HA, Maskell R. A blind controlled trial of phase-contrast microscopy by two observers for evaluating the source of haematuria. Nephron 1986;44:304–8.10.1159/000184011Search in Google Scholar PubMed

13. 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 PubMed

14. Fassett RG, Horgan B, Gove D, Mathew TH. Scanning electron microscopy of glomerular and non glomerular red blood cells. Clin Nephrol 1983;20:11–6.Search in Google Scholar

15. Tomita M, Kitamoto Y, Nakayama M, Sato T. A new morphological classification of urinary erythrocytes for differential diagnosis of glomerular hematuria. Clin Nephrol 1992;37:84–9.Search in Google Scholar

16. Kohler H, Wandel E. Acanthocyturia detects glomerular bleeding. Nephrol Dial Transplant 1993;8:879.Search in Google Scholar

17. Kitamoto Y, Tomita M, Akamine M, Inoue T, Itoh J, Takamori H, et al. Differentiation of hematuria using a uniquely shaped red cell. Nephron 1993;64:32–6.10.1159/000187274Search in Google Scholar PubMed

18. Nguyen GK. Urine cytology in renal glomerular disease and value of g1 cell in the diagnosis of glomerular bleeding. Diagn Cytopathol 2003;29:67–73.10.1002/dc.10320Search in Google Scholar PubMed

19. Nagahama D, Yoshiko K, Watanabe M, Morita Y, Iwatani Y, Matsuo S. A useful new classification of dysmorphic urinary erythrocytes. Clin Exp Nephrol 2005;9:304–9.10.1007/s10157-005-0380-9Search in Google Scholar PubMed

20. The Dutch College of General Practitioners (NHG). Guideline on chronic kidney disease, 2018. Accessed 02-03-2020.Search in Google Scholar

21. Dutch Society for Internal Medicine (NIV) Guideline on diagnosis and policy for chronic kidney disease in adults,2018. Accessed 02-03-2020.Search in Google Scholar

22. Dutch Society for Urology (NVU). Guideline on hematuria, 2010. Accessed 02-03-2020.Search in Google Scholar

23. CLSI. Urinalysis; approved guideline, 2nd ed. CLSI document gp16-a3. Wayne, PA: Clinical and Laboratory Standards Institute, 2009.Search in Google Scholar

24. European Confederation of Laboratory M. European urinalysis guidelines. Scand J Clin Lab Invest Suppl 2000;231:1–86.10.1080/00365513.2000.12056993Search in Google Scholar

25. Boven LA, Kemperman H, Demir A. A comparative analysis of the iris iq200 with manual microscopy as a diagnostic tool for dysmorphic erythrocytes in urine. Clin Chem Lab Med 2012;50:751–3.10.1515/cclm.2011.813Search in Google Scholar

26. Bignardi GE. Validation and verification of automated urine particle analysers. J Clin Pathol 2017;70:94–101.10.1136/jclinpath-2016-203958Search in Google Scholar PubMed

27. Poloni JA, da Silva Carpeggiani FP, da Silva IA, de Oliveira JA, Tobler JB, Saldanha EM, et al. External quality assessment program on urinary dysmorphic erythrocytes. Clin Chim Acta 2017;475:20–1.10.1016/j.cca.2017.10.003Search in Google Scholar PubMed

28. Tsai JJ, Yeun JY, Kumar VA, Don BR. Comparison and interpretation of urinalysis performed by a nephrologist versus a hospital-based clinical laboratory. Am J Kidney Dis 2005;46:820–9.10.1053/j.ajkd.2005.07.039Search in Google Scholar PubMed

29. Fogazzi GB, Passerini P, Bazzi M, Bogetic J, Barletta L. Use of high power field in the evaluation of formed elements of urine. J Nephrol 1989;2:107–12.Search in Google Scholar

30. Fassett RG, Horgan BA, Mathew TH. Detection of glomerular bleeding by phase-contrast microscopy. Lancet 1982;1: 1432–34.10.1016/S0140-6736(82)92451-5Search in Google Scholar

31. Martinez-Martinez MU, Llamazares-Azuara LM, Martinez-Galla D, Mandeville PB, Valadeze-Castillo F, Román-Acosta S, et al. Urinary sediment suggests lupus nephritis histology. Lupus 2017;26:580–7.10.1177/0961203316669241Search in Google Scholar

32. Favaro S, Bonfante L, D’Angelo A, Giacomini A, Normanno M, Calo L, et al. Is the red cellmorphology really useful to detect the source of hematuria? Am J Nephrol 1997;17:172–5.10.1159/000169093Search in Google Scholar

33. Ward JF, Kaplan GW, Mevorach R, Sock JA, Cilento BG. Refined microscopic urinalysis for red blood cell morphology in the evaluation of asymptomatic microscopic hematuria in a pediatric population. J Urol 1998;160:1492–5.10.1016/S0022-5347(01)62600-4Search in Google Scholar

34. Crop MJ, de Rijke YB, Verhagen PC, Cransberg C, Zietse R. Diagnostic value of urinary dysmorphic erythrocytes in clinical practice. Nephron Clin Pract 2010;115:c203–12.10.1159/000313037Search in Google Scholar PubMed

35. Ottiger C, Savoca R, Yurtsever H, Huber AR. Increased sensitivity in detecting renal impairments by quantitative measurement of marker protein excretion compared to detection of pathological particles in urine sediment analysis. Clin Chem Lab Med 2006;44:1347–54.10.1515/CCLM.2006.237Search in Google Scholar PubMed

36. Delanghe J. New screening diagnostic techniques in urinalysis. Acta Clin Belg 2007;62:155–61.10.1179/acb.2007.026Search in Google Scholar PubMed

37. L’Imperio V, Smith A, Chinello C, Pagni F, Magni F. Proteomics and glomerulonephritis: a complementary approach in renal pathology for the identification of chronic kidney disease related markers. Proteomics Clin Appl 2016;10: 371–83.10.1002/prca.201500075Search in Google Scholar PubMed

38. Sathianathen NJ, Butaney M, Weight CJ, Kumar R, Konety BR. Urinary biomarkers in the evaluation of primary hematuria: a systematic review and meta-analysis. Bladder Cancer 2018;4:353–63.10.3233/BLC-180179Search in Google Scholar PubMed PubMed Central

39. Martinez Valenzuela L, Draibe J, Quero Ramos M, Fulladosa Oliveras X, Melilli E, Cruzado Garrit JM, et al. Calprotectin as a smoldering activity detection tool and renal prognosis biomarker in ANCA associated vasculitis. PLoS One 2018;13:e0205982.10.1371/journal.pone.0205982Search in Google Scholar PubMed PubMed Central

40. Taherkhani A, Farrokhi Yekta R, Mohseni M, Saidijam M, Arefi Oskouie A. Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers. Proteome Sci 2019;17:7.10.1186/s12953-019-0155-ySearch in Google Scholar PubMed PubMed Central

41. Horie S, Ito S, Okada H, Kikuchi H, Narita I, Nishiyama T, et al. Japanese guideline of the management of hematuria 2013. Clin Exp Nephrol 2014;18:679–89.10.1007/s10157-014-1001-2Search in Google Scholar PubMed

42. Fogazzi GB, Secchiero S, Consonni D, Sciacovelli L, Zardo L, Garibali G, et al. An Italian External Quality Assessment (EQA) program on urinary sediment. Clin Chim Acta 2010; 411:859–67.10.1016/j.cca.2010.02.073Search in Google Scholar PubMed

43. Fogazzi GB, Secchiero S, Garigali G, Plebani M. Evaluation of clinical cases in External Quality Assessment Scheme (EQAS) for the urinary sediment. Clin Chem Lab Med 2014;52:845–52.10.1515/cclm-2013-0785Search in Google Scholar PubMed

Received: 2020-03-02
Accepted: 2020-03-28
Published Online: 2020-04-25
Published in Print: 2020-10-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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