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Fogazzi GB, Garigali G, Abinti M, Lieti G, Verdesca S. An updated approach to the evaluation of the urinary sediment. Pediatr Nephrol 2025; 40:933-945. [PMID: 39377940 DOI: 10.1007/s00467-024-06545-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 08/23/2024] [Accepted: 09/16/2024] [Indexed: 10/09/2024]
Abstract
Examination of the urinary sediment (U-sed) is an important non-invasive, rapid, and inexpensive tool for the diagnosis and surveillance over time of renal diseases. In this Educational Review, we describe first how to collect, prepare, and examine urine samples in order to obtain reliable results. Then, we describe the U-sed findings in isolated microscopic hematuria, glomerular diseases, acute interstitial nephritis, acute kidney injury, reactivation of the BK virus in kidney transplant recipients, and crystalluric genetic diseases.
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Affiliation(s)
- Giovanni B Fogazzi
- Clinical and Research Laboratory On Urinary Sediment, SC Di Nefrologia, Dialisi e Trapianto Di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Giuseppe Garigali
- Clinical and Research Laboratory On Urinary Sediment, SC Di Nefrologia, Dialisi e Trapianto Di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Matteo Abinti
- SC Di Nefrologia, Dialisi e Trapianto Di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giulia Lieti
- USC Di Nefrologia E Dialisi, Ospedale Di Garbagnate Milanese, Garbagnate Milanese, Italy
| | - Simona Verdesca
- SC Di Nefrologia, Dialisi e Trapianto Di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Van Hoovels L, Vanhove B, Decavele AS, Capron A, Oyaert M. Current urinalysis practices in Belgian laboratories towards the 2023 EFLM European urinalysis guideline. Acta Clin Belg 2024:1-9. [PMID: 39392078 DOI: 10.1080/17843286.2024.2414155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 10/05/2024] [Indexed: 10/12/2024]
Abstract
OBJECTIVES/BACKGROUND We aimed to investigate routine urinalysis practices in Belgian laboratories and verify these findings against the 2023 European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Urinalysis Guideline. METHODS A questionnaire was developed to collect information on pre- to postanalytical aspects of urine test strip and particle analysis. The questionnaire was distributed by Sciensano to all Belgian laboratories, licensed to perform urine particle analysis. RESULTS Sixty-six percent of the Belgian laboratories (75/113) participated. The responding laboratories served physicians in private (25%), hospital (60%) and university hospital (15%) setting. All laboratories performed test strip and particle analysis, predominantly automatically (97% and 96%, respectively). In addition, most laboratories (87%) used intelligent verification criteria to optimize diagnostic accuracy. Almost all laboratories (≥90%) screened and reported a minimal biochemistry panel (glucose, protein, pH, ketones) and particle count (red and white blood cells). Independent of the technology, a notable variability was observed regarding medical cut-off values and advanced particle differentiation and reporting. Internal quality control was extensively performed for urine test strip (91%) and particle analysis (96%), while external QC was less common (32% and 36%, respectively). Consequently, only few laboratories were ISO15189 accredited for urine test strip (15%) and particle analysis (17%). CONCLUSION There is considerable variability in current urinalysis performed in Belgian laboratories. The 2023 EFLM urinalysis guideline has the potential to guide clinical laboratories towards improving their urinalysis practices. Additional efforts are required to implement these recommendations into clinical practice in Belgium.
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Affiliation(s)
- Lieve Van Hoovels
- Department of Laboratory Medicine, OLVZ Aalst, Aalst, Belgium
- Department of Microbiology, Immunology and Transplantation, Clinical and Diagnostic Immunology Research Group, KU Leuven, Belgium
| | - Bénédicte Vanhove
- Department of Laboratory Medicine, OLVZ Aalst, Aalst, Belgium
- Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
| | | | - Arnaud Capron
- Quality of Laboratories, Sciensano, Brussels, Belgium
| | - Matthijs Oyaert
- Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
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Gaggar P, Raju SB. Diagnostic Utility of Urine Microscopy in Kidney Diseases. Indian J Nephrol 2024; 34:213-221. [PMID: 39114391 PMCID: PMC11303840 DOI: 10.25259/ijn_362_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 11/03/2023] [Indexed: 08/10/2024] Open
Abstract
Urine sediment analysis is a highly valuable yet underutilized test in today's advanced medical landscape. The analysis of urine sediment is a simple, cost-effective, and powerful diagnostic tool in the hands of a skilled nephrologist, generally in all kidney diseases and particularly more so in the setting of acute kidney injury (AKI). The impact of AKI is far-reaching and encompasses elevated mortality rates, increased morbidity, longer hospital stays, and higher overall healthcare expenses. Timely and compartmental diagnosis of AKI with the use of a simple urine sediment analysis leads to targeted therapeutic strategies and also serves as a prognostic guide. The widespread use of automated analysis in recent times has its own set of limitations, as it fails to identify pathological casts, crystals, and dysmorphic red blood cells (RBCs). Hence, it is the need of the hour to learn this time-honored art of urine sediment analysis, to provide comprehensive patient care.
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Affiliation(s)
- Payal Gaggar
- Department of Nephrology, Medical Trust Hospital, Kochi, Kerala, India
| | - Sree B. Raju
- Department of Nephrology, NIMS, Hyderabad, Telangana, India
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Seigner S, Weber K, Dorsch R. [Urinalysis in dogs and cats, part 2: Urine sediment analysis]. TIERARZTLICHE PRAXIS. AUSGABE K, KLEINTIERE/HEIMTIERE 2023; 51:336-350. [PMID: 37956665 DOI: 10.1055/a-2122-5324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Examination of the urine sediment is part of a routine urinalysis and is undertaken in order to identify insoluble particles in the urine. This procedure is mainly used in the context of diagnostic evaluation of urinary tract diseases, but may also be useful for the diagnosis of systemic diseases and intoxications. Analysis of fresh urine is recommended as changes in cell morphology, cell lysis and in vitro crystal formation may occur in the course of its storage. Manual urine sediment analysis is still performed in many veterinary practices. Native wet-mount preparations are suitable for the identification and quantification of urine sediment particles. The examination of stained wet-mount preparations or air-dried smears may be necessary to further differentiate cells and to identify bacteria. For several years, automatic urine sediment analyzers have been available in veterinary medicine. These save considerable time and staff resources, however verification of the automatically generated results by an experienced observer remains necessary. Urine sediment particles that are frequently identified and clinically relevant include red blood cells, white blood cells, different types of epithelial cells, crystals, and casts as well as bacteria. Furthermore, parasite eggs, fungal hyphae, lipid droplets, spermatozoa, fibres, hair, mucus, plant parts or environmental contaminations may be found in the urine sediment and result in a complication of the result interpretation.
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Affiliation(s)
- Sandra Seigner
- Medizinische Kleintierklinik, Ludwig-Maximilians-Universität, München
| | - Karin Weber
- Medizinische Kleintierklinik, Ludwig-Maximilians-Universität, München
| | - Roswitha Dorsch
- Medizinische Kleintierklinik, Ludwig-Maximilians-Universität, München
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Delanghe J, Speeckaert M, Delanghe S, Oyaert M. Pitfalls in the diagnosis of hematuria. Clin Chem Lab Med 2023; 61:1382-1387. [PMID: 37079906 DOI: 10.1515/cclm-2023-0260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 04/14/2023] [Indexed: 04/22/2023]
Abstract
Detection of hemoglobin (Hb) and red blood cells in urine (hematuria) is characterized by a large number of pitfalls. Clinicians and laboratory specialists must be aware of these pitfalls since they often lead to medical overconsumption or incorrect diagnosis. Pre-analytical issues (use of vacuum tubes or urine tubes containing preservatives) can affect test results. In routine clinical laboratories, hematuria can be assayed using either chemical (test strips) or particle-counting techniques. In cases of doubtful results, Munchausen syndrome or adulteration of the urine specimen should be excluded. Pigmenturia (caused by the presence of dyes, urinary metabolites such as porphyrins and homogentisic acid, and certain drugs in the urine) can be easily confused with hematuria. The peroxidase activity (test strip) can be positively affected by the presence of non-Hb peroxidases (e.g. myoglobin, semen peroxidases, bacterial, and vegetable peroxidases). Urinary pH, haptoglobin concentration, and urine osmolality may affect specific peroxidase activity. The implementation of expert systems may be helpful in detecting preanalytical and analytical errors in the assessment of hematuria. Correcting for dilution using osmolality, density, or conductivity may be useful for heavily concentrated or diluted urine samples.
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Affiliation(s)
- Joris Delanghe
- Department of Diagnostic Sciences, Ghent University Hospital, Ghent, Belgium
| | - Marijn Speeckaert
- Department of Nephrology, Ghent University Hospital, Ghent, Belgium
- Research Foundation Flanders, Brussels, Belgium
| | | | - Matthijs Oyaert
- Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
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Saha MK, Massicotte-Azarniouch D, Reynolds ML, Mottl AK, Falk RJ, Jennette JC, Derebail VK. Glomerular Hematuria and the Utility of Urine Microscopy: A Review. Am J Kidney Dis 2022; 80:383-392. [PMID: 35777984 DOI: 10.1053/j.ajkd.2022.02.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 02/16/2022] [Indexed: 01/27/2023]
Abstract
Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.
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Affiliation(s)
- Manish K Saha
- UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
| | - David Massicotte-Azarniouch
- UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Monica L Reynolds
- UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Amy K Mottl
- UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Ronald J Falk
- UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - J Charles Jennette
- Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Vimal K Derebail
- UNC Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
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Cho H, Yoo J, Kim H, Jang H, Kim Y, Chae H. Diagnostic Characteristics of Urinary Red Blood Cell Distribution Incorporated in UF-5000 for Differentiation of Glomerular and Non-Glomerular Hematuria. Ann Lab Med 2022; 42:160-168. [PMID: 34635609 PMCID: PMC8548254 DOI: 10.3343/alm.2022.42.2.160] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 06/17/2021] [Accepted: 09/17/2021] [Indexed: 11/29/2022] Open
Abstract
Background Automated urine sediment analysis has been developed to address the limitations of microscopic examination of dysmorphic red blood cells (RBCs). We evaluated the urinary RBC distribution (URD) parameter of a recently launched automated urinary flow cytometry analyzer, UF-5000 (Sysmex, Kobe, Japan), to differentiate glomerular hematuria (GH) from non-GH (NGH). Methods Samples submitted for urine sediment analysis from patients with hematuria (>20 RBCs/μL) were divided into derivation (N=156; 101 GH, 55 NGH) and validation cohorts (N=107; 60 GH, 47 NGH). The clinical diagnosis of GH or NGH was established based on clinical data review. Differences in UF-5000 parameters (URD, small RBC, lysed RBC, RBC-P70FSC, RBC-SF-FSC-W, mean forward-scattered light, and mean side-scattered light) between GH and NGH, and areas under the ROC curves (AUC) were analyzed in the derivation cohort. The derived ideal cut-off value was evaluated in the validation cohort. We applied the Kitasato criteria to compare the diagnostic performance. Results URD (%), differed significantly between GH and NGH (P<0.001) in the two cohorts. The AUC of URD was 0.814 and 0.806 in the derivation and validation cohorts, respectively. Using a cut-off of >20.1%, the sensitivity was 99.0%/89.4% and the specificity was 50.9%/63.3% in the derivation/validation cohort. When the Kitasato criteria were applied, the sensitivity and specificity were 80.2% and 52.7%, respectively. Conclusions URD is a rapid, objective, and quantitative measure that can be used to differentiate GH and NGH.
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Affiliation(s)
- Hanwool Cho
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jaeeun Yoo
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyunjung Kim
- Department of Laboratory Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyunsik Jang
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yonggoo Kim
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyojin Chae
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Kraus D, Köhler H, Weinmann-Menke J. Urine, doctors, and the acanthocyte’s 30th birthday. Kidney Int 2022; 101:196-200. [DOI: 10.1016/j.kint.2021.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/09/2021] [Accepted: 11/15/2021] [Indexed: 10/19/2022]
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9
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Ingelfinger JR. Hematuria in Adults. Reply. N Engl J Med 2021; 385:e51. [PMID: 34614343 DOI: 10.1056/nejmc2113014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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10
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Kortum AJ, Bazelle J, Gomez Selgas A, Kent ACC, Williams TL, Herrtage ME. A retrospective study of canine idiopathic renal haematuria: clinical findings and outcome following medical treatment. J Small Anim Pract 2021; 62:850-860. [PMID: 34075582 DOI: 10.1111/jsap.13352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 04/16/2021] [Accepted: 04/18/2021] [Indexed: 01/13/2023]
Abstract
OBJECTIVES To characterise and document the progression of idiopathic renal haematuria in a large cohort of medically managed UK dogs. MATERIALS AND METHODS Retrospective study of 41 client-owned dogs with confirmed (n=14), or suspected (n=27) idiopathic renal haematuria from 4 UK-based referral centres. Clinical findings and outcomes of dogs (2001 to 2018) were determined from the review of medical records and telephone follow-up. RESULTS Median survival time from diagnosis was long [1482 (152 to 1825) days] irrespective of treatment and clinical response. Only 1 case was euthanased due to idiopathic renal haematuria, and anaemia or azotaemia occurred infrequently. In total, 25 dogs received angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy, of which 23 received benazepril [0.44 (0.19 to 0.82) mg/kg/24 hours], two received enalapril (0.40 and 0.78 mg/kg/24 hours) and one received telmisartan (1 mg/kg/24 hours). In cases with follow-up urinalyses, complete resolution of haematuria was documented in eight of 19 (42%) dogs following angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker treatment, with partial improvement in five of 19 (26%) and no improvement in six of 19 (31%). Conversely, of the two untreated dogs where outcome was available, one had partial improvement and the other had no improvement. CLINICAL SIGNIFICANCE In this study, idiopathic renal haematuria was associated with a good prognosis and low complication rate. Resolution or improvement in haematuria occurred in both angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker-treated and untreated dogs, indicating that further studies are required to evaluate the effectiveness and safety of these interventions.
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Affiliation(s)
- A J Kortum
- The Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK
| | - J Bazelle
- Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, Hitchin, SG5 3HR, UK
| | - A Gomez Selgas
- Animal Health Trust, Lanwades Park, Kentford, Suffolk, CB8 7UU, UK
| | - A C C Kent
- Willows Veterinary Centre and Referral Service, Highlands Road, Shirley, Solihull, West Midlands, B90 4NH, UK
| | - T L Williams
- The Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK
| | - M E Herrtage
- The Queen's Veterinary School Hospital, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK
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Fang F, Li Y, Yang L, Li L, Yan Z, Sun Q. Sensitive and In Situ Hemoglobin Detection Based on a Graphene Oxide Functionalized Microfiber. NANOMATERIALS 2020; 10:nano10122461. [PMID: 33317010 PMCID: PMC7763212 DOI: 10.3390/nano10122461] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 12/07/2020] [Accepted: 12/07/2020] [Indexed: 01/22/2023]
Abstract
The determination of hemoglobin (Hb) level is indispensable in the pathological study of many blood diseases. Graphene oxide (GO), with its excellent optical properties and great biocompatibility, has attracted significant attention and been widely utilized in biochemical detection. Here, we report an ultrasensitive Hb sensor based on a graphene oxide (GO)-coated microfiber. The GO was utilized as a linking layer deposited on the microfiber surface, which can provide an enhanced local evanescent light field and abundant bonding sites for Hb molecules. The optical microfiber with a compact structure and a strong evanescent light field served as the platform for biosensing. The surface morphology characterized by optical microscope, scanning electron microscope, and Raman spectroscopy offers detailed evidence for the success of GO deposition. The dynamic bonding between GO and target Hb molecules was monitored in real-time through an optical spectrum analyzer. An ultrahigh sensitivity of 6.02 nm/(mg/mL) with a detection limit of 0.17 μg/mL was achieved by tracking the resonant wavelength shift of spectra. It is important to highlight that the detection limit of GO-coated microfiber is 1–2 orders of magnitude lower than other reported fiber optic Hb sensors. Benefiting from high sensitivity, low cost, small size, and fast response, the proposed sensing microfiber coated with GO could be a competitive alternative in the diagnosis of blood diseases and a subject of further research in the medical field.
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Affiliation(s)
| | | | | | | | | | - Qizhen Sun
- Correspondence: ; Tel.: +86-136-6718-7589
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Secchiero S, Fogazzi GB, Manoni F, Epifani M, Plebani M. The Italian External Quality Assessment (EQA) program on urinary sediment by microscopy examination: a 20 years journey. Clin Chem Lab Med 2020; 59:845-856. [PMID: 33554535 DOI: 10.1515/cclm-2020-1656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 11/24/2020] [Indexed: 11/15/2022]
Abstract
OBJECTIVES In spite of the introduction of automated systems for urinary sediment analysis, microscopy examination remains the gold standard, and it is more than ever important to perform it with a good and reliable quality. External Quality Assessment (EQA) programs on urinary sediment are rare. The present paper provides an analysis of results from 2001 to date of the EQA Italian program which involves today 230 laboratories. METHODS The program includes four surveys per year. Participants are asked the identification and clinical associations of urinary sediment particles, shown as phase contrast microscopy images in the website of the Center of Biomedical Research (CRB) (2 surveys), and the diagnosis of clinical cases presented by both images and a short clinical history (2 surveys). The results of each survey are then scored and commented. In 20 years, 298 images were presented: 90 cells (9 types), 23 lipids (5 types), 87 casts (21 types), 53 crystals (14 types), 22 microorganisms (5 types), and 23 contaminants (9 types). Moreover, 27 clinical cases, covering a wide spectrum of conditions with different degrees of complexity, were presented to participants. RESULTS Identification: among urinary particle categories, the correct identification rate (obtained for each particle from the sum of correct + partially correct answers) was very high for micro-organisms (mean ± SD: 96.2 ± 3.5%), high for lipids (88.0 ± 11.8%) and crystals (87.0 ± 16.5%) followed, in decreasing order, by cells (82.1 ± 15.9%), casts (81.8 ± 14.8%), and contaminants (76.7 ± 22.1%). Clinical associations (n=67): the rate of correct answers was 93.5 ± 5.7% ranging from 75.0 to 100% for all but one clinical association (i.e., acute glomerulonephritis: 55.4%). Clinical cases: throughout surveys, due to the overall rate of particle misidentification, only 59.8 ± 17.1%, (range 32.5-88.7%) of participants achieved access to clinical diagnosis. Of these, 88.7 ± 10.6% (range 59.9-99.3%) were able to indicate the correct diagnosis. CONCLUSIONS Our program can be used as a tool to improve the identification of urine particles and the knowledge of their clinical meaning and to encourage specialists of laboratory medicine to correlate urinary findings with other laboratory data and the clinical history, an aspect that improves the value of the day by day work.
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Affiliation(s)
- Sandra Secchiero
- Centre of Biomedical Research for Quality in Laboratory Medicine, University-Hospital of Padova, Padova, Italy.,Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Giovanni B Fogazzi
- Clinical and Research Laboratory on Urinary Sediment, U.O.C. di Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Fabio Manoni
- Dipartimento Area Servizi di Diagnosi e Cura, Ospedali Riuniti "Madre Teresa di Calcutta", Monselice, Padova, Italy
| | - MariaGrazia Epifani
- Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Mario Plebani
- Centre of Biomedical Research for Quality in Laboratory Medicine, University-Hospital of Padova, Padova, Italy.,Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
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Luimstra JJ, Koçer RG, Jerman A, Klein Gunnewiek J, Gijzen K, Jacobs LHJ, Demir AY. Current state of the morphological assessment of urinary erythrocytes in The Netherlands: a nation-wide questionnaire. Clin Chem Lab Med 2020; 58:1891-1900. [PMID: 32335538 DOI: 10.1515/cclm-2020-0236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 03/28/2020] [Indexed: 01/03/2023]
Abstract
Background 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. Methods 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. Results 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. Conclusions In Dutch medical laboratories, results from morphological analysis of uRBC are heterogeneous, which point out the necessity for standardization and harmonization.
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Affiliation(s)
- Jolien J Luimstra
- Department of Clinical Chemistry and Hematology, Meander Medical Centre, Amersfoort, The Netherlands
| | - Rüya G Koçer
- Department of Clinical Chemistry and Hematology, Meander Medical Centre, Amersfoort, The Netherlands
| | - Alexander Jerman
- Department of Nephrology, University of Ljubljana, Ljubljana, Slovenia
| | - Jacqueline Klein Gunnewiek
- Section General Chemistry, Dutch Foundation for External Quality Assessment in Medical Laboratories (SKML), Nijmegen, The Netherlands
| | - Karlijn Gijzen
- Department of Clinical Chemistry and Hematology, Meander Medical Centre, Amersfoort, The Netherlands
| | - Leo H J Jacobs
- Department of Clinical Chemistry and Hematology, Meander Medical Centre, Amersfoort, The Netherlands
| | - Ayşe Y Demir
- Department of Clinical Chemistry and Hematology, Meander Medical Centre, Amersfoort, The Netherlands
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Forouzani-Haghighi B, Karimzadeh I. Isotretinoin and the Kidney: Opportunities and Threats. Clin Cosmet Investig Dermatol 2020; 13:485-494. [PMID: 32801824 PMCID: PMC7395703 DOI: 10.2147/ccid.s259048] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 07/08/2020] [Indexed: 11/26/2022]
Abstract
Retinoids are one of the most effective drugs in inducing complete or prolonged remission of severe acne vulgaris, but the adverse reactions associated with the use of them are raising a concern about the potential effect of these drugs on internal organs function such as the kidney. The aim of this review is to comprehensively gather data about isotretinoin, both potential adverse and beneficial effects on the kidney based on the current experimental and clinical findings. Very few studies, including five case reports, described that systemic oral isotretinoin within usual doses (40 mg/day or 0.5 mg/kg⁄day) within 1 to 4 months of treatment might be associated with different types of renal dysfunctions. These include acute interstitial nephritis, nephrotic syndrome, and hematuria with dysuria. The adverse reactions of systemic isotretinoin on the kidney and urinary system are unlikely and rare. In contrast, six experimental studies demonstrated the beneficial effects of either oral or parenteral low- (2 or 5 mg/kg/day) or high- (10, 20, 25, 40 mg/kg/day) dose isotretinoin on the kidney in the rat models of glomerulonephritis, obstructive nephropathy or allograft nephropathy. The nephroprotective functions of isotretinoin in these studies were attributed to its anti-proliferative, anti-fibrotic, and anti-inflammatory actions. However, clinical studies are warranted to elucidate the possible beneficial effects of isotretinoin in preventing or attenuating kidney injury in different settings.
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Affiliation(s)
- Bahareh Forouzani-Haghighi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Iman Karimzadeh
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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15
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Ronco P. Pathophysiology of the glomerulus: KI tells the story. Kidney Int 2020; 97:5-9. [PMID: 31901357 DOI: 10.1016/j.kint.2019.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 11/15/2019] [Indexed: 02/04/2023]
Affiliation(s)
- Pierre Ronco
- Sorbonne Université, Paris, France; Institut National de la Santé et de la Recherche Médicale (Inserm), Unité Mixte de Recherche S1155, Paris, France; Hôpital de jour - Néphrologie, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France.
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16
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Xiao M, Lv Q, Zhang Y, Tu L, Yang M, Lin Z, Liao Z, Jiang Y, Zheng X, Li X, Wei Q, Cao S, Gu J. Spondyloarthritis Patients Suffer Increased Risk of Renal Complications Compared With General Population: A Retrospective Observational Study. Front Pharmacol 2019; 10:1073. [PMID: 31620002 PMCID: PMC6759995 DOI: 10.3389/fphar.2019.01073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 08/22/2019] [Indexed: 01/01/2023] Open
Abstract
The objective of this study was to identify the prevalence and risk factors of renal complications of spondyloarthritis (SpA) patients, and to assess increased risks compared to general people. We conducted a retrospective study enrolled with consecutive SpA patients from an inpatient department and age, sex-matched general population (GP). The renal disorders investigated in this study contained decreased estimated glomerular filtration rate (eGFR), hematuria, proteinuria and nephrolithiasis. A total of 350 admitted SpA patients with complete medical records and 323 age and sex-matched GP were enrolled. Most SpA patients were male (n = 283, 80.9%) and the mean age was 31.61 ± 10.73 years old. Among 350 SpA patients, 29 (8.8%) suffered from hematuria, six (1.8%) suffered from proteinuria, one (0.3%) had decreased eGFR, and 27 (13.0%) presented with nephrolithiasis. The relative risk (RR) of nephrolithiasis in SpA compared to the GP was 2.24 (95% CI, 1.00-4.98), and the RR of renal insufficiency was 2.04 (95% CI, 1.11-3.77). In a univariate analysis, nephrolithiasis was significantly associated with age, age of onset, smoking, extra-articular manifestation and a bamboo spine. Renal insufficiency was significantly associated with age, peripheral manifestation, serum albumin, C-reactive protein and erythrocyte sedimentation rate. In a multivariable analysis, only extra-articular manifestation (OR = 8.43, 95% CI, 1.65-43.06, p = 0.010) and bamboo spine (OR = 3.47, 95% CI, 1.01-12.06, p = 0.049) remained significantly associated with nephrolithiasis. However, no variable was recognized as an independent risk factor for renal insufficiency. Renal complications are more common in SpA patients, with more than two-fold increased risk compared with GP. Extra-articular manifestation and bamboo spine are independent risk factors of renal disease in SpA patients.
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Affiliation(s)
- Min Xiao
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qing Lv
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yanli Zhang
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liudan Tu
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mingcan Yang
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhiming Lin
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zetao Liao
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yutong Jiang
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuqi Zheng
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaomin Li
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiujing Wei
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuangyan Cao
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jieruo Gu
- Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Enko D, Stelzer I, Böckl M, Derler B, Schnedl WJ, Anderssohn P, Meinitzer A, Herrmann M. Comparison of the diagnostic performance of two automated urine sediment analyzers with manual phase-contrast microscopy. ACTA ACUST UNITED AC 2019; 58:268-273. [DOI: 10.1515/cclm-2019-0919] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 09/22/2019] [Indexed: 11/15/2022]
Abstract
Abstract
Background
Recently, several manufacturers have launched automated urinalysis platforms. This study aimed to compare the diagnostic performance of the UF-5000 (Sysmex Corporation, Kobe, Japan) and the cobas® u 701 (Roche Diagnostics, Rotkreuz, Switzerland) urine sediment analyzers with manual phase-contrast microscopy as the reference method.
Methods
A total of 195 urine samples were analyzed on both automated platforms and subjected to manual microscopic examination. Agreement was assessed by Cohen’s kappa (κ) analysis. Sensitivities and specificities were calculated.
Results
The agreement of the UF-5000 with manual microscopy was almost perfect (κ > 0.8) for red (RBC) and white blood cells (WBC), renal tubular epithel cells, hyaline casts, bacteria (BACT) and yeast (YLC), substantial (κ = 0.61–0.80) for squamous epithel cells (SEC) and pathologic casts, and moderate (κ = 0.41–0.60) for transitional epithel cells. The cobas® u 701 showed substantial agreement (κ = 0.61–0.80) for WBC, moderate agreement (κ = 0.41–0.60) for hyaline casts, and fair agreement (κ = 0.21–0.40) for RBC, SEC, non-squamous epithel (NEC), pathologic casts, BACT and YLC. The UF-5000 sensitivities ranged between 98.5% for RBC and 83.3% for pathological casts. The cobas® u 701 showed sensitivities between 83.0% for WBC and 31.6% for YLC.
Conclusions
The UF-5000 (Sysmex) analyzer showed a better diagnostic agreement with manual phase-contrast microscopy compared to the cobas® u 701 (Roche) module. The Sysmex platform showed reliable results for urine sediment analysis. However, pathological samples should be verified with manual microscopy.
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Affiliation(s)
- Dietmar Enko
- Clinical Institute of Medical and Chemical Laboratory Diagnostics , Medical University of Graz , Graz , Austria
- Institute of Clinical Chemistry and Laboratory Medicine , General Hospital Hochsteiermark , Leoben , Austria
| | - Ingeborg Stelzer
- Institute of Clinical Chemistry and Laboratory Medicine , General Hospital Hochsteiermark , Leoben , Austria
| | - Michael Böckl
- Institute of Clinical Chemistry and Laboratory Medicine , General Hospital Hochsteiermark , Leoben , Austria
| | - Brigitta Derler
- Institute of Clinical Chemistry and Laboratory Medicine , General Hospital Hochsteiermark , Leoben , Austria
| | | | - Petra Anderssohn
- Institute of Clinical Chemistry and Laboratory Medicine , General Hospital Hochsteiermark , Leoben , Austria
| | - Andreas Meinitzer
- Clinical Institute of Medical and Chemical Laboratory Diagnostics , Medical University of Graz , Graz , Austria
| | - Markus Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics , Medical University of Graz , Graz , Austria
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Kim H, Kim YO, Kim Y, Suh JS, Cho EJ, Lee HK. Small Red Blood Cell Fraction on the UF-1000i Urine Analyzer as a Screening Tool to Detect Dysmorphic Red Blood Cells for Diagnosing Glomerulonephritis. Ann Lab Med 2019; 39:271-277. [PMID: 30623619 PMCID: PMC6340839 DOI: 10.3343/alm.2019.39.3.271] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 06/28/2018] [Accepted: 11/07/2018] [Indexed: 11/22/2022] Open
Abstract
Background Dysmorphic red blood cells (dRBCs) are first-line biomarkers for detecting glomerulonephritis (GN) in patients with hematuria. The UF-1000i system (Sysmex, Kobe, Japan), based on flow cytometry, provides small red blood cell (RBC) values (UF-1000i [UF]-%sRBCs). We evaluated the clinical application of UF-%sRBCs for detecting %dRBCs and GN. Methods Urine samples of 103 patients (47 with GN; 56 without GN [NGN]) were analyzed using UF-1000i urinalysis, phase-contrast microscopy (PCM), and urine chemistry. Serum creatinine (mg/dL), serum albumin (g/dL), serum protein (mg/dL), urine protein (mg/dL), and urea nitrogen (mg/dL) levels were measured using an automated chemical analyzer. To determine the cut-off level of predicting GN, ROC curve was analyzed. Results UF-%sRBCs, %dRBCs, urine protein, serum creatinine, and estimated-glomerular filtration rate differed between the GN and NGN groups, with the greatest differences detected for UF-%sRBCs and %dRBCs (P<0.0001). In ROC curve analysis, urine protein had the highest area under the curve (0.828), followed by %dRBCs (0.771) and UF-%sRBCs (0.745). To screen for GN, the best cut-off values of UF-%sRBCs and %dRBCs were >40.5% and >6.7%, respectively. %dRBCs (P=0.0001) and UF-%sRBCs (P=0.0006) differed between the GN and NGN groups in patients with isolated hematuria but without proteinuria. Conclusions UF-%sRBCs had similar diagnostic power to %dRBCs determined by PCM for identifying patients with GN. UF-%sRBCs may be more useful for diagnosing GN in patients with isolated hematuria. Predicting %dRBCs using UF-1000i will provide information on possible GN in patients presenting with asymptomatic hematuria.
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Affiliation(s)
- Hyunjung Kim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Ok Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yonggoo Kim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Soon Suh
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun Jung Cho
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hae Kyung Lee
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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19
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Falbo R, Sala MR, Bussetti M, Cappellini F, Giacobone C, Fania C, Brambilla P. Performance evaluation of a new and improved cuvette-based automated urinalysis analyzer with phase contrast microscopy. Clin Chim Acta 2019; 491:126-131. [DOI: 10.1016/j.cca.2019.01.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 01/14/2019] [Accepted: 01/27/2019] [Indexed: 10/27/2022]
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20
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Kouri T, Fogazzi G, Gant V, Hallander H, Hofmann W, Guder WG. European Urinalysis Guidelines. Scandinavian Journal of Clinical and Laboratory Investigation 2019. [DOI: 10.1080/00365513.2000.12056993] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Bellincioni C, Garigali G, Fogazzi GB. Glomerular isolated microscopic hematuria: urinary features and long term follow-up of a selected cohort of patients. J Nephrol 2018; 32:253-258. [PMID: 30535632 DOI: 10.1007/s40620-018-0560-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 11/12/2018] [Indexed: 11/28/2022]
Abstract
BACKGROUND Isolated microscopic hematuria is a condition characterized by the presence in the urine of an "abnormal" number of erythrocytes in the absence of proteinuria. Several studies have been published on this condition, but with heterogeneous inclusion criteria and variable outcomes at follow-up. In this retrospective study, we describe a selected and homogenous cohort of patients who presented with isolated microscopic hematuria of glomerular origin. METHODS We included in the study patients with isolated microscopic hematuria of glomerular origin (> 1 erythrocyte/high power field at 400× and ≥ 40% dysmorphic erythrocytes and/or ≥ 5% acanthocytes and proteinuria ≤ 150 mg/24 h) with a follow-up of > 60 months from the first documentation of microscopic hematuria. RESULTS Forty-two patients (M 12, F 30, age at presentation 14-68 years, eGFR < 60 ml/min/1.73 m2: 1 patient) were included. During a medium term follow-up, microscopic hematuria was persistent in 25 patients (59.5%), transiently absent in 17 (40.5%), always glomerular in 16 patients (38.1%), and occasionally non-glomerular in 26 (61.9%); proteinuria, observed in 16 patients (38.1%), was always transient and < 500 mg/24 h. At the end of a follow-up of 181.8 ± 97.9 (median 168) months, only 2 patients (4.8%) had eGFR < 60 ml/min/1.73 m2, one of whom had reduced eGFR already at presentation. CONCLUSIONS This study on a small but selected and homogeneous cohort of patients with isolated microscopic hematuria of glomerular origin demonstrates that urinary features can transiently change over time and that the renal outcome is good.
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Affiliation(s)
- Cecilia Bellincioni
- Clinical and Research Laboratory on Urinary Sediment, U.O.C. di Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda, 15, Milan, Italy
| | - Giuseppe Garigali
- Clinical and Research Laboratory on Urinary Sediment, U.O.C. di Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda, 15, Milan, Italy
| | - Giovanni B Fogazzi
- Clinical and Research Laboratory on Urinary Sediment, U.O.C. di Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda, 15, Milan, Italy.
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22
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Fogazzi G, Delanghe J. Microscopic examination of urine sediment: Phase contrast versus bright field. Clin Chim Acta 2018; 487:168-173. [DOI: 10.1016/j.cca.2018.09.036] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 09/21/2018] [Accepted: 09/24/2018] [Indexed: 10/28/2022]
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23
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Jiang S, Wang Y, Zhang Z, Dai P, Yang Y, Li W. Accuracy of hematuria for predicting non-diabetic renal disease in patients with diabetes and kidney disease: A systematic review and meta-analysis. Diabetes Res Clin Pract 2018; 143:288-300. [PMID: 30059756 DOI: 10.1016/j.diabres.2018.07.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 06/24/2018] [Accepted: 07/23/2018] [Indexed: 11/18/2022]
Abstract
AIMS To clarify the predictive value of hematuria in patients with diabetes and non-diabetic renal disease (NDRD). METHODS The databases of Medline, Embase and the Cochrane Library were searched up to November 22, 2017. The pooled sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated using a bivariate mixed-effects regression model. RESULTS Thirty-eight articles were eligible, of which 35 articles with 4005 patients investigated hematuria. The pooled sensitivity and specificity of hematuria to predict NDRD were 0.42 (95% CI 0.35-0.49) and 0.72 (95% CI 0.64-0.79), respectively. The pooled PLR and NLR were 1.49 (95% CI 1.28-1.75) and 0.81 (95% CI 0.75-0.87), respectively. The DOR was 1.85 (95% CI 1.49-2.30). The pooled AUC was 0.59 (95% CI 0.54-0.63). For dysmorphic erythrocytes, the pooled sensitivity was 0.27 (95% CI 0.23-0.32), while the specificity was 0.94 (95% CI 0.91-0.97). There was heterogeneity among studies (p < 0.001), and no publication bias was identified. CONCLUSIONS Type 2 diabetes patients presenting with hematuria are slightly more likely to develop NDRD. Dysmorphic erythrocytes may be more useful than microhematuria in diagnosing for NDRD in type 2 diabetes with proteinuria.
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Affiliation(s)
- Shimin Jiang
- China-Japan Friendship Institute of Clinical Medicine, Graduate School of Peking Union Medical College, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yining Wang
- Department of Clinical Medicine, Peking University Health Science Center, Beijing 100191, China
| | - Zheng Zhang
- China-Japan Friendship Institute of Clinical Medicine, Graduate School of Peking Union Medical College, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Peilin Dai
- Department of Clinical Medicine, Peking University Health Science Center, Beijing 100191, China
| | - Yue Yang
- Department of Nephrology, China-Japan Friendship Hospital, No. 2 East Yinghuayuan Street, Chaoyang District, Beijing 100029, China.
| | - Wenge Li
- China-Japan Friendship Institute of Clinical Medicine, Graduate School of Peking Union Medical College, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Department of Nephrology, China-Japan Friendship Hospital, No. 2 East Yinghuayuan Street, Chaoyang District, Beijing 100029, China.
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Hamadah AM, Gharaibeh K, Mara KC, Thompson KA, Lieske JC, Said S, Nasr SH, Leung N. Urinalysis for the diagnosis of glomerulonephritis: role of dysmorphic red blood cells. Nephrol Dial Transplant 2017; 33:1397-1403. [DOI: 10.1093/ndt/gfx274] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2017] [Accepted: 08/16/2017] [Indexed: 12/17/2022] Open
Affiliation(s)
| | - Kamel Gharaibeh
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Kristin C Mara
- Division of Biostatistics, Mayo Clinic, Rochester, MN, USA
| | - Katherine A Thompson
- Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA
| | - John C Lieske
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Samar Said
- Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA
| | - Samih H Nasr
- Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
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Löbig N, Wezel F, Martini T, Schröppel B, Bolenz C. [Microscopic hematuria : Reasonable and risk-adapted diagnostic evaluation]. Urologe A 2017. [PMID: 28643107 DOI: 10.1007/s00120-017-0432-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Microscopic hematuria that is not explained by an obvious underlying condition is a frequent and often an incidental finding that commonly triggers urological or nephrological evaluation. Potential underlying conditions range from benign to severe malignant diseases of the kidneys and urinary tract. MATERIALS AND METHODS A nonsystematic literature search was performed, focusing on potential urological and nephrological causes of hematuria. National and international guidelines were considered and diagnostic as well as follow-up strategies are discussed. We provide a recommendation for practices in the clinical evaluation of hematuria. RESULTS The overall prevalence for microscopic hematuria is estimated at approximately 2%, whereas risk populations show an increase to around 30%. In 13-35% of patients presenting with microscopic hematuria, a medical or surgical intervention is required. Malignant tumors of the kidneys or urinary tract can be diagnosed in 2.6-4% of all patients and in up to 25.8% of at-risk populations. "Idiopathic microscopic hematuria" without an obvious underlying medical condition accounts for approximately 80% of patients with asymptomatic hematuria. After exclusion of nephrological diseases, standard diagnostic procedures by means of medical history, physical and laboratory examination as well as ultrasound of the kidneys and the urinary tract should be performed. In the presence of risk factors, an extended diagnostic work-up using cystoscopy, urinary cytology, and cross-sectional imaging of the upper urinary tract is indicated. CONCLUSION Evidence-based strategies of a risk-adapted diagnostic evaluation for microscopic hematuria are not available. The development of reliable clinical and molecular markers offers great potential for the identification of patients at higher risk for harboring severe diseases.
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Affiliation(s)
- N Löbig
- Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Prittwitzstraße 43, 89075, Ulm, Deutschland
| | - F Wezel
- Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Prittwitzstraße 43, 89075, Ulm, Deutschland
| | - T Martini
- Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Prittwitzstraße 43, 89075, Ulm, Deutschland
| | - B Schröppel
- Klinik für Innere Medizin I, Sektion Nephrologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Deutschland
| | - C Bolenz
- Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Prittwitzstraße 43, 89075, Ulm, Deutschland.
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Chu-Su Y, Shukuya K, Yokoyama T, Lin WC, Chiang CK, Lin CW. Enhancing the Detection of Dysmorphic Red Blood Cells and Renal Tubular Epithelial Cells with a Modified Urinalysis Protocol. Sci Rep 2017; 7:40521. [PMID: 28074941 PMCID: PMC5225455 DOI: 10.1038/srep40521] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 12/07/2016] [Indexed: 11/19/2022] Open
Abstract
Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis.
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Affiliation(s)
- Yu Chu-Su
- Institute of Biomedical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei City 10617, Taiwan.,Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Taipei City 10002, Taiwan
| | - Kenichi Shukuya
- Department of Clinical Laboratory, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Takashi Yokoyama
- Department of Central Clinical Laboratory, Tokyo Women's Medical University Hospital, 8-1, Kawada-cho, Shinjyuku-ku, Tokyo 162-8666, Japan
| | - Wei-Chou Lin
- Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, No. 7, Zhongshan S. Rd., Taipei City 10002, Taiwan
| | - Chih-Kang Chiang
- Graduate Institute of Toxicology, College of Medicine, No. 1, Jen-Ai Rd., Taipei City 10002, Taiwan.,Department of Integrated Diagnostics &Therapeutics, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Taipei City 10002, Taiwan
| | - Chii-Wann Lin
- Institute of Biomedical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei City 10617, Taiwan
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Ajith Y, Rajeswari T, Siji SR, Dilip C. Case report on babesiosis associated pre-hepatic jaundice in a malabari goat. Vet Anim Sci 2017; 3:1-3. [PMID: 32734034 PMCID: PMC7386767 DOI: 10.1016/j.vas.2017.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 01/06/2017] [Accepted: 01/09/2017] [Indexed: 11/23/2022] Open
Abstract
Pre-hepatic jaundice associated with babesiosis in a malabari goat and its successful management is described. The animal was presented with muco-purulent nasal discharge, dyspnoea, coughing, icteric sclera and oral mucosa, bloated abdomen, diarrhoea, hematochezia and coffee coloured urine. History of tick infestation was reported by the owner. Clinical examination revealed pyrexia, tachycardia, tachypnea, pre-scapular and pre-femoral lymphadenopathy and respiratory wheezes. Laboratory investigations revealed anaemia, neutrophilia, thrombocytopaenia, hypoproteinemia, hyperbilirubinemia and haemoglobinuria. On microscopic examination, small pyriform Babesia sp. (probably B. ovis) could be detected in Giemsa stained peripheral blood smear. The animal had undergone babesicidal therapy using diminazene aceturate (3.5 mg/kg bodyweight deep IM, two doses at 48hr interval) and oxytetracycline (10 mg/kg body weight once daily for 5 days), and supportive therapy using NSAIDs, polyionic isotonic fluids, antihistamines, B complex vitamins, stomachic and iron supplements. The animal made an uneventful clinical recovery after two weeks.
Rare acute febrile form of small Babesia sp. infection in a goat. Unconjugated hyperbilirubinemia, suggestive of pre-hepatic jaundice, in a goat infected by small Babesia sp. Elimination of parasitemia achieved by day 5 using a combination therapy of Diminazine aceturate and Oxytetracycline.
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Affiliation(s)
- Y. Ajith
- District Veterinary Hospital, AHD, Thiruvanathapuram, Kerala, India
- Corresponding author. Present address: Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243122, India.
| | - T.U. Rajeswari
- District Veterinary Hospital, AHD, Thiruvanathapuram, Kerala, India
| | - S. Raj Siji
- District Veterinary Hospital, AHD, Thiruvanathapuram, Kerala, India
- College of Veterinary and Animal Sciences, Mannuthy, Thrissur, Kerala, India
| | - Chandran Dilip
- District Veterinary Hospital, AHD, Thiruvanathapuram, Kerala, India
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Becker GJ, Garigali G, Fogazzi GB. Advances in Urine Microscopy. Am J Kidney Dis 2016; 67:954-64. [DOI: 10.1053/j.ajkd.2015.11.011] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 11/03/2015] [Indexed: 11/11/2022]
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Moreno JA, Yuste C, Gutiérrez E, Sevillano ÁM, Rubio-Navarro A, Amaro-Villalobos JM, Praga M, Egido J. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review. Pediatr Nephrol 2016; 31:523-33. [PMID: 25980470 DOI: 10.1007/s00467-015-3119-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 04/15/2015] [Accepted: 04/20/2015] [Indexed: 12/18/2022]
Abstract
Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.
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Affiliation(s)
- Juan Antonio Moreno
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain.
| | - Claudia Yuste
- Department of Nephrology, Gregorio Marañon Hospital, 28007, Madrid, Spain
| | - Eduardo Gutiérrez
- Department of Nephrology, 12 de Octubre Hospital, 28041, Madrid, Spain
| | - Ángel M Sevillano
- Department of Nephrology, 12 de Octubre Hospital, 28041, Madrid, Spain
| | - Alfonso Rubio-Navarro
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain
| | - Juan Manuel Amaro-Villalobos
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain
| | - Manuel Praga
- Department of Nephrology, 12 de Octubre Hospital, 28041, Madrid, Spain
| | - Jesús Egido
- Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, Av. Reyes Católicos 2, 28040, Madrid, Spain.,Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
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30
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Diagnostic impact of dysmorphic red blood cells on evaluating microscopic hematuria: the urologist’s perspective. Int Urol Nephrol 2016; 48:1021-7. [DOI: 10.1007/s11255-016-1265-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 03/09/2016] [Indexed: 10/22/2022]
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31
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Yuste C, Rivera F, Moreno JA, López-Gómez JM. Haematuria on the Spanish Registry of Glomerulonephritis. Sci Rep 2016; 6:19732. [PMID: 26818712 PMCID: PMC4730139 DOI: 10.1038/srep19732] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 12/15/2015] [Indexed: 12/24/2022] Open
Abstract
Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.
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Affiliation(s)
| | | | - Juan Antonio Moreno
- Renal,Vascular and Diabetes Research Lab. IIS-Fundación Jiménez Díaz. Autonóma University, Madrid, Spain
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Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Ortiz A, Egido J, Praga M, Moreno JA. Pathogenesis of glomerular haematuria. World J Nephrol 2015; 4:185-95. [PMID: 25949932 PMCID: PMC4419128 DOI: 10.5527/wjn.v4.i2.185] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Revised: 12/19/2014] [Accepted: 12/29/2014] [Indexed: 02/06/2023] Open
Abstract
Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidney disease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells (RBCs) with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological findings.
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Martinez MG, dos S. Silva V, do Valle AP, Amaro CR, Corrente JE, Martin LC. Comparison of Different Methods of Erythrocyte Dysmorphism Analysis to Determine the Origin of Hematuria. ACTA ACUST UNITED AC 2014; 128:88-94. [DOI: 10.1159/000367848] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Accepted: 08/15/2014] [Indexed: 11/19/2022]
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Fogazzi GB, Pallotti F, Garigali G. Atypical/malignant urothelial cells in routine urinary sediment: worth knowing and reporting. Clin Chim Acta 2014; 439:107-11. [PMID: 25451946 DOI: 10.1016/j.cca.2014.10.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Accepted: 10/13/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND Urinary cytology (Ucytol), which is performed in pathology laboratories on fixed and stained samples, represents the gold standard for the identification of atypical/malignant urothelial cells (A/MUC) due to urothelial carcinoma. In this paper we describe three patients in whom A/MUC, due to a bladder carcinoma, were identified with conventional urine sediment (Used) examination on unfixed and unstained samples. METHODS Included are urine samples prepared with conventional and standardized techniques as currently used in general clinical laboratories. Samples were examined with phase contrast microscopy. A/MUC were identified according to the criteria currently used for Ucytol. RESULTS A/MUC (i.e., cells with unusual and pleomorphic size and shape, increased nuclear/cytoplasmic ratio, increased number of nuclei, irregular nuclear borders and irregular chromatin patterns, either isolated or in clusters) were identified in the urine of three patients, all of whom were found to have bladder carcinoma by cystoscopy. CONCLUSIONS At variance with the common and widespread view, A/MUC can also be identified with conventional Used examination, even though Ucytol still represents the gold standard method.
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Affiliation(s)
- G B Fogazzi
- Clinical and Research Laboratory on Urinary Sediment, U.O. di Nefrologia e Dialisi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
| | - F Pallotti
- U.O. di Anatomia Patologica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - G Garigali
- Clinical and Research Laboratory on Urinary Sediment, U.O. di Nefrologia e Dialisi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
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35
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Muto S, Sugiura SI, Nakajima A, Horiuchi A, Inoue M, Saito K, Isotani S, Yamaguchi R, Ide H, Horie S. Isomorphic red blood cells using automated urine flow cytometry is a reliable method in diagnosis of bladder cancer. Int J Clin Oncol 2013; 19:928-34. [PMID: 24105457 DOI: 10.1007/s10147-013-0623-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 09/16/2013] [Indexed: 11/28/2022]
Abstract
BACKGROUND We aimed to identify patients with a chief complaint of hematuria who could safely avoid unnecessary radiation and instrumentation in the diagnosis of bladder cancer (BC), using automated urine flow cytometry to detect isomorphic red blood cells (RBCs) in urine. METHODS We acquired urine samples from 134 patients over the age of 35 years with a chief complaint of hematuria and a positive urine occult blood test or microhematuria. The data were analyzed using the UF-1000i (®) (Sysmex Co., Ltd., Kobe, Japan) automated urine flow cytometer to determine RBC morphology, which was classified as isomorphic or dysmorphic. The patients were divided into two groups (BC versus non-BC) for statistical analysis. Multivariate logistic regression analysis was used to determine the predictive value of flow cytometry versus urine cytology, the bladder tumor antigen test, occult blood in urine test, and microhematuria test. RESULTS BC was confirmed in 26 of 134 patients (19.4 %). The area under the curve for RBC count using the automated urine flow cytometer was 0.94, representing the highest reference value obtained in this study. Isomorphic RBCs were detected in all patients in the BC group. On multivariate logistic regression analysis, only isomorphic RBC morphology was significantly predictive for BC (p < 0.001). Analytical parameters such as sensitivity, specificity, positive predictive value, and negative predictive value of isomorphic RBCs in urine were 100.0, 91.7, 74.3, and 100.0 %, respectively. CONCLUSION Detection of urinary isomorphic RBCs using automated urine flow cytometry is a reliable method in the diagnosis of BC with hematuria.
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Affiliation(s)
- Satoru Muto
- Department of Urology, Teikyo University School of Medicine, Tokyo, Japan
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36
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Mach AJ, Adeyiga OB, Di Carlo D. Microfluidic sample preparation for diagnostic cytopathology. LAB ON A CHIP 2013; 13:1011-26. [PMID: 23380972 PMCID: PMC4041400 DOI: 10.1039/c2lc41104k] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
The cellular components of body fluids are routinely analyzed to identify disease and treatment approaches. While significant focus has been placed on developing cell analysis technologies, tools to automate the preparation of cellular specimens have been more limited, especially for body fluids beyond blood. Preparation steps include separating, concentrating, and exposing cells to reagents. Sample preparation continues to be routinely performed off-chip by technicians, preventing cell-based point-of-care diagnostics, increasing the cost of tests, and reducing the consistency of the final analysis following multiple manually-performed steps. Here, we review the assortment of biofluids for which suspended cells are analyzed, along with their characteristics and diagnostic value. We present an overview of the conventional sample preparation processes for cytological diagnosis. We finally discuss the challenges and opportunities in developing microfluidic devices for the purpose of automating or miniaturizing these processes, with particular emphases on preparing large or small volume samples, working with samples of high cellularity, automating multi-step processes, and obtaining high purity subpopulations of cells. We hope to convey the importance of and help identify new research directions addressing the vast biological and clinical applications in preparing and analyzing the array of available biological fluids. Successfully addressing the challenges described in this review can lead to inexpensive systems to improve diagnostic accuracy while simultaneously reducing overall systemic healthcare costs.
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Affiliation(s)
- Albert J. Mach
- University of California, Los Angeles - Bioengineering, 5121E Engineering V University of California, Los Angeles, California 90095-1600, United States
| | - Oladunni B. Adeyiga
- University of California, Los Angeles - Bioengineering, 5121E Engineering V University of California, Los Angeles, California 90095-1600, United States
| | - Dino Di Carlo
- University of California, Los Angeles - Bioengineering, 5121E Engineering V University of California, Los Angeles, California 90095-1600, United States
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Mandal SN, Jha R, Fatima R, Swarnalata G. Non-nephronal hematuria misdiagnosed as C1q nephropathy: Look before you leap. Indian J Nephrol 2012; 22:206-9. [PMID: 23087557 PMCID: PMC3459526 DOI: 10.4103/0971-4065.98761] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 19-year-old male presented with persistent macroscopic hematuria for last 3 months. On initial evaluation, he was found to have minimal proteinuria, normal renal function, and normal complement with negative lupus serology. Light microscopy, immunofluorescence and electron microscopy of renal tissue confirmed the presence of C1q nephropathy. Because of poor response to immunosuppressive agent (prednisolone and mycophenolate mofetil), passage of urinary clot once and vexing persistent macroscopic hematuria, alternative diagnosis was considered. Cystourethroscopy showed urethritis of prostatic urethra. Immunosuppressives were stopped and doxycycline started to which hematuria responded dramatically. This case report illustrates that hematuria in this patient was because of undiagnosed urethritis rather than incidental C1q nephropathy.
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Affiliation(s)
- S N Mandal
- Department of Nephrology, Medwin Hospital, Nampally, India
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38
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Tesser Poloni JA, Bosan IB, Garigali G, Fogazzi GB. Urinary red blood cells: not only glomerular or nonglomerular. Nephron Clin Pract 2011; 120:c36-41; discussion c41. [PMID: 22205019 DOI: 10.1159/000330286] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Two main types of red blood cells, isomorphic and dysmorphic, are found in the urine sediment, indicating nonglomerular and glomerular hematuria, respectively. Occasionally, however, other types of red blood cells such as sickle cells, anisocytes, poikilocytes, elliptocytes and dacryocytes can be seen in the urine sediment of patients with hematuria. This paper describes such cases reported in the literature in which such unusual urinary red blood cells have been found and the experience of the authors on this subject.
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Affiliation(s)
- José Antonio Tesser Poloni
- Central Laboratory of Clinical Analysis, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
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Barros Silva GE, Costa RS, Ravinal RC, Saraiva e Silva J, Dantas M, Coimbra TM. Evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens: A simple and efficient method. Nephrology (Carlton) 2010; 15:171-7. [PMID: 20470275 DOI: 10.1111/j.1440-1797.2009.01197.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIM To demonstrate that the evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens (LMLC) is useful to identify patients with a haematuria of glomerular or non-glomerular origin. METHODS A comparative double-blind study between phase contrast microscopy (PCM) and LMLC is reported to evaluate the efficacy of these techniques. Urine samples of 39 patients followed up for 9 months were analyzed, and classified as glomerular and non-glomerular haematuria. The different microscopic techniques were compared using receiver-operator curve (ROC) analysis and area under curve (AUC). Reproducibility was assessed by coefficient of variation (CV). RESULTS Specific cut-offs were set for each method according to their best rate of specificity and sensitivity as follows: 30% for phase contrast microscopy and 40% for standard LMLC, reaching in the first method the rate of 95% and 100% of sensitivity and specificity, respectively, and in the second method the rate of 90% and 100% of sensitivity and specificity, respectively. In ROC analysis, AUC for PCM was 0.99 and AUC for LMLC was 0.96. The CV was very similar in glomerular haematuria group for PCM (35%) and LMLC (35.3%). CONCLUSION LMLC proved to be effective in contributing to the direction of investigation of haematuria, toward the nephrological or urological side. This method can substitute PCM when this equipment is not available.
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Affiliation(s)
- Gyl Eanes Barros Silva
- Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil
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40
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Fogazzi GB, Secchiero S, Consonni D, Sciacovelli L, Zardo L, Garigali G, Verdesca S, Messa P, Plebani M. An Italian external quality assessment (EQA) program on urinary sediment. Clin Chim Acta 2010; 411:859-67. [PMID: 20214893 DOI: 10.1016/j.cca.2010.02.073] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2009] [Revised: 02/01/2010] [Accepted: 02/28/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND EQA programs on urinary sediment are rare. We describe an EQA Italian program which started in 2001 and involves today more than 300 laboratories. METHODS The program, which started with a questionnaire about the methodological aspects on urinary sediment, includes today four surveys per year. These ask the participants the identification and clinical associations of urinary sediment particles shown by colour images (surveys 1 and 3) and the diagnosis of clinical cases presented by both images and a short clinical history (surveys 2 and 4). The results of each survey are then scored and commented. RESULTS Questionnaire (participants = 287): most methodological aspects were not dealt with properly. IDENTIFICATION cells, lipids, casts and some contaminants were poorly known. However, when 27 particles were presented for the second time and 16 particles for the third time, the correct identification rate for most of them increased significantly. Clinical associations (No presented = 16): a correct answer was indicated by > or = 84% of participants for all particles but one. Clinical cases (No presented=4): lowest correct identification for urine contamination from genital secretion (77.3%), highest for ureteric stone (94.4%). CONCLUSIONS Our program shows that EQA programs are both useful and needed.
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Affiliation(s)
- Giovanni B Fogazzi
- Research Laboratory on Urine, Unità Operativa di Nefrologia, Dialisi, Trapianto, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy.
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41
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Chen YL, Chang MK, Chen YJ, Chang BC. Comparing Neubauer Hemacytometer, SY Conventional, SY Located, and Automated Flow Cytometer F–100 Methods for Urinalysis. Lab Med 2009. [DOI: 10.1309/lm8poktmiqxsstho] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Wald R, Bell CM, Nisenbaum R, Perrone S, Liangos O, Laupacis A, Jaber BL. Interobserver reliability of urine sediment interpretation. Clin J Am Soc Nephrol 2009; 4:567-71. [PMID: 19261816 DOI: 10.2215/cjn.05331008] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Urine sediment interpretation is frequently used in the evaluation of patients with kidney disease. There has been no systematic evaluation of the reliability of this diagnostic maneuver. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Digital photographs of urine sediment images were acquired from 165 consecutive patients being evaluated by the nephrology consultation service at a tertiary care hospital. Urine sediment images of 100 patients were randomly selected; 86 patients had images that were deemed to be of sufficient quality, and one image per patient was chosen for inclusion in an internet-based questionnaire. For each image, the presence or absence of 14 potential urinary structures was ascertained. Ten nephrologists (senior readers [n = 3]: >10 yr of experience; intermediate readers [n = 3]: 1 to 10 yr of experience; and junior readers [n = 4]: first year of practice) completed the questionnaire. For each urinary structure, we measured the rate of complete agreement among the readers as well as the kappa statistic as a marker of agreement beyond chance. RESULTS Unanimous agreement was highest (79.1%) regarding the presence of broad and fatty casts and poorest (31.4%) for the identification of dysmorphic red blood cells and white blood cells. Interobserver agreement was best for squamous epithelial cells (kappa = 0.54) and hyaline casts (kappa = 0.52) and worst for transitional epithelial cells (kappa = 0.14) and fatty casts (kappa = 0.06). When assessed within strata of physician experience, interobserver agreement was not associated with seniority. CONCLUSIONS Nephrologists achieved slight to moderate agreement in the identification of structures that are commonly observed in the urine sediment.
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Affiliation(s)
- Ron Wald
- Department of Medicine, Division of Nephrology, St Michael's Hospital, Toronto, ON, Canada.
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43
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Tonna S, Wang YY, Wilson D, Rigby L, Tabone T, Cotton R, Savige J. The R229Q mutation in NPHS2 may predispose to proteinuria in thin-basement-membrane nephropathy. Pediatr Nephrol 2008; 23:2201-7. [PMID: 18726620 DOI: 10.1007/s00467-008-0934-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2007] [Revised: 05/15/2008] [Accepted: 05/31/2008] [Indexed: 10/21/2022]
Abstract
Thin-basement-membrane nephropathy (TBMN) is characterized by persistent dysmorphic hematuria, and the presence of proteinuria is a risk factor for renal impairment. TBMN is often due to mutations in the COL4A3 and COL4A4 genes, and this study determined whether additional mutations in genes encoding other structures in the glomerular filtration barrier contributed to the development of proteinuria. Fifty-six unrelated individuals with TBMN including 18 (32%) with proteinuria > or = 300 mg/L and ten (18%) with proteinuria > or = 500 mg/L were studied. Deoxyribonucleic acid (DNA) was screened for NPHS2 mutations and variants (R138Q and P375L) using single-stranded conformational analysis (SSCA) and for the R229Q mutation by sequencing. DNA was also screened for ACTN4 mutations. R229Q was more common in patients with TBMN and proteinuria > or = 500 mg/L (p < 0.05), and a possible NPHS2 mutation (671G>A, R224H) was identified in one patient with proteinuria 700 mg/L. No other NPHS2 variants correlated with proteinuria, and no ACTN4 mutations were found. Individuals with TBMN and R229Q are carriers of the autosomal recessive forms of both Alport syndrome and familial focal segmental glomerulosclerosis (FSGS). The early demonstration of R229Q in individuals with TBMN may indicate those at increased risk of proteinuria and renal impairment.
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Affiliation(s)
- Stephen Tonna
- Department of Medicine, The Northern Hospital, The University of Melbourne, Epping, VIC 3076, Australia
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Abstract
There is an intimate relationship between the kidney and pregnancy. Renal plasma flow increases by 50–70% during a normal pregnancy and the glomerular filtration rate by about 50%.1These changes commence in the first trimester and fall in the last trimester reaching normal levels within about four weeks postpartum. These physiological changes are accompanied by striking anatomical changes which consist of dilatation of the ureter, pelvis and calyces, together with an increase in renal parenchymal size. The dilatation i s more marked on the right and may appear in the first trimester. At term, 90% of pregnant women show this change.2
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Seccia TM, Rossi GP. Clinical Use and Pathogenetic Basis of Laboratory Tests for the Evaluation of Primary Arterial Hypertension. Crit Rev Clin Lab Sci 2008; 42:393-452. [PMID: 16390680 DOI: 10.1080/10408360500295600] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
This review focuses on the laboratory biochemical tests that are useful in the diagnostic approach to the hypertensive patient. A "minimal" diagnostic laboratory work-up, including a small number of tests that are simple and relatively inexpensive, is first described. Because these tests provide basic information on the presence of major cardiovascular (CV) risk factors and target organ damage, and might give some clues to the presence of a secondary form of hypertension (HT), they should be performed on all patients presenting with HT. Other tests that are aimed at assessing the overall CV risk, a major determinant of prognosis that dictates the therapeutic strategy in the individual HT patient, are then discussed. They allow identification of major CV risk factors and associated clinical conditions which, if present, lead to a substantial change of therapeutic strategy. The role of C-reactive protein as a marker of atherosclerosis and its predictive value for CV events are also discussed. Finally, a section is devoted to tests that are currently confined to research purposes, such as markers of endothelial function including endothelin-1, homocysteine and genetic analysis.
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Affiliation(s)
- Teresa M Seccia
- Department of Clinical Methodology and Medical-Surgical Technologies, University of Bari, Bari, Italy
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The use of ocular abnormalities to diagnose X-linked Alport syndrome in children. Pediatr Nephrol 2008; 23:1245-50. [PMID: 18343956 DOI: 10.1007/s00467-008-0759-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2007] [Revised: 12/10/2007] [Accepted: 12/14/2007] [Indexed: 10/22/2022]
Abstract
The diagnosis of X-linked Alport syndrome is often difficult, but the demonstration of lenticonus and retinopathy may facilitate the diagnosis in adult patients. The aim of this study was to determine the diagnostic usefulness of ocular examination in children. Fourteen families with at least one affected child were studied clinically, and COL4A5 mutations were determined. The families included 15 affected boys (median age 11 years, range 4-19 years). Two boys (13%) had renal failure, nine (60%) had a known hearing loss, one (7%) had lenticonus and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy. Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively. All boys with retinopathy had a hearing loss. The early onset retinopathy was associated with a severe mutation (Q1383X). Eight families (8/14, 57%) comprised only sons and mothers, and two mothers (2/12, 17%) had the retinopathy. Six boys (40%) would have been diagnosed with Alport syndrome on the basis of their own or their mother's ocular examinations. None of the six girls (median age 8 years, range 7-14 years) had ocular abnormalities. Hearing loss is usually highly sensitive for the diagnosis of Alport syndrome, but ocular examination of boys and their mothers at the initial consultation is a non-invasive test that is helpful in up to 40% cases.
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Fogazzi GB, Edefonti A, Garigali G, Giani M, Zolin A, Raimondi S, Mihatsch MJ, Messa P. Urine erythrocyte morphology in patients with microscopic haematuria caused by a glomerulopathy. Pediatr Nephrol 2008; 23:1093-100. [PMID: 18324420 DOI: 10.1007/s00467-008-0777-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2007] [Revised: 12/24/2007] [Accepted: 01/17/2008] [Indexed: 12/01/2022]
Abstract
The evaluation of urinary erythrocyte morphology (UEM) has been proposed for patients with isolated microscopic haematuria (IMH) to early orientate the diagnosis towards a glomerular or a nonglomerular disease. However, to date, the role of this test in patients with IMH has very rarely been investigated. Sixteen patients (ten children, six adults) with persistent IMH classified as glomerular on the basis of repeated UEM evaluations (55 urine samples, two to eight per patient) were submitted to renal biopsy. This showed a glomerular disease in 14/16 patients (87.5%) (nine thin basement membrane disease; three Alport syndrome; two other), whereas in two patients, no abnormalities were found. Of four microscopic criteria investigated to define a IMH as glomerular, >80% dysmorphic erythrocytes were not found in any sample, >or=40% dysmorphic erythrocytes alone were seen in seven samples (12.7%), >or=5% acanthocytes alone in 15 samples (27.3%) and erythrocytic casts in six samples (10.9%). There was >or=40% dysmorphic erythrocytes associated with >or=5% acanthocytes in 25 samples (45.5%). Sensitivity and positive predictive values in diagnosing a glomerular haematuria were 59.2% and 90.6%, respectively, for >or=40% dysmorphic erythrocytes, 69.4% and 85% for >or=5% acanthocytes/G1 cells and 12.2% and 100% for erythrocytic casts. Our findings demonstrate that the evaluation of UEM is useful to identify patients with an IMH of glomerular origin.
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Affiliation(s)
- Giovanni Battista Fogazzi
- Unità Operative di: Nefrologia-Laboratorio di ricerca sulle urine, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Commenda 15, Milano, Italy.
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Fogazzi GB, Garigali G, Pirovano B, Muratore MT, Raimondi S, Berti S. How to improve the teaching of urine microscopy. Clin Chem Lab Med 2007; 45:407-12. [PMID: 17378742 DOI: 10.1515/cclm.2007.079] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Urinary microscopy is difficult to teach. This paper describes a 1-day course on urine microscopy, which was based on both theoretical and practical sessions at the microscope, during which real urine samples were examined. METHODS The course was based on: a) an introductory presentation with slides on the main components of urinary sediments and their clinical correlates; b) examination of fixed urine samples under the guidance of two experts; and c) the use of two microscopes, each equipped with a co-observation device for up to 15 observers. RESULTS Throughout 2005, four courses were held in four Italian towns. Altogether, there were 97 participants (20-27 per course) from 75 laboratories, all graduates with wide but variable experience in the field. During each course, 17-22 urinary sediment components were shown by both bright-field and phase-contrast microscopy and, when indicated, by polarized light. Tests set before and after the course showed a significant improvement (p<0.01) in the identification of erythrocyte subtypes, epithelial cells, fatty components, various types of casts and drug crystals. A questionnaire conducted with participants by phone several months after the course demonstrated that 51.6% and 32.3% of laboratories have introduced or formally requested phase-contrast and polarized-light microscopy, respectively; 45.2% have changed the terminology for urinary epithelial cells; and 87.1% have identified for the first time urinary sediment components that were not recognized or not considered before the course. CONCLUSIONS Our course demonstrates that it is possible to improve the teaching of urinary microscopy.
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Affiliation(s)
- Giovanni B Fogazzi
- Urine Research Laboratory, Unità Operativa di Nefrologia, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
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Zhang KW, Tonna S, Wang YY, Rana K, Padavarat S, Savige J. Do mutations in COL4A1 or COL4A2 cause thin basement membrane nephropathy (TBMN)? Pediatr Nephrol 2007; 22:645-51. [PMID: 17216253 DOI: 10.1007/s00467-006-0391-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2006] [Revised: 10/20/2006] [Accepted: 10/26/2006] [Indexed: 11/25/2022]
Abstract
Thin basement membrane nephropathy (TBMN) is the commonest cause of persistent glomerular haematuria and often presents in childhood. Only 40% of affected individuals have mutations identified in the COL4A3 and COL4A4 genes, but mutations in the genes for other COL4A isoforms also result in thinned membranes in humans (COL4A5) and mice (COL4A1). This study examined whether COL4A1/COL4A2 represented a further genetic locus for TBMN. Nine families with TBMN in whom haematuria did not segregate with COL4A3/COL4A4, were examined for linkage to COL4A1/COL4A2 using five micro-satellite markers. In addition, index cases from these families plus a further 14 unrelated individuals with TBMN that was not due to COL4A3 or COL4A4 mutations (n=23) were screened for mutations in each of the 52 exons of COL4A1 and the 47 exons of COL4A2 using single stranded conformational analysis (SSCA). DNA samples that demonstrated bandshifts were sequenced. Haplotype analysis demonstrated that haematuria segregated with the COL4A1/COL4A2 locus in only two small families (2/9, 22%). No definite COL4A1 or COL4A2 mutations were identified in the 23 unrelated individuals with TBMN although novel polymorphisms were demonstrated. This study indicates that COL4A1/COL4A2 does not represent a further major genetic locus for TBMN.
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Affiliation(s)
- Ke Wei Zhang
- Department of Medicine, Austin Health and Northern Health, The Northern Hospital, The University of Melbourne, Epping, VIC, 3076, Australia
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Rana K, Tonna S, Wang YY, Sin L, Lin T, Shaw E, Mookerjee I, Savige J. Nine novel COL4A3 and COL4A4 mutations and polymorphisms identified in inherited membrane diseases. Pediatr Nephrol 2007; 22:652-7. [PMID: 17216251 DOI: 10.1007/s00467-006-0393-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2006] [Revised: 10/18/2006] [Accepted: 10/31/2006] [Indexed: 11/28/2022]
Abstract
Both thin basement membrane nephropathy (TBMN) and autosomal recessive Alport syndrome result from mutations in the COL4A3 and COL4A4 genes, and this study documents further mutations and polymorphisms in these genes. Thirteen unrelated children with TBMN and five individuals with autosomal recessive Alport syndrome were examined for mutations in the 52 exons of COL4A3 and the 47 coding exons of COL4A4 using single-stranded conformation polymorphism (SSCP) analysis. Amplicons producing different electrophoretic patterns were sequenced, and mutations were defined as variants that changed an amino acid but were not present in 50 non-hematuric normals. Three further novel mutations were identified. These were IVS 22-5 T>A in the COL4A3 gene in a consanguineous family with autosomal recessive Alport syndrome, and R1677C and R1682Q in the COL4A4 gene. In addition, six novel polymorphisms (G455G, I462I, G736G and IVS 38-8 G>A in COL4A3, and L658L and A1577A in COL4A4) were demonstrated.Many different COL4A3 and COL4A4 mutations cause TBMN and autosomal recessive Alport syndrome. The identification of polymorphisms in these genes is particularly important to enable diagnostic laboratories to distinguish mutations from uncommon normal variants.
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Affiliation(s)
- Kesha Rana
- Department of Medicine (AH/NH), The Northern Hospital, University of Melbourne, Epping, VIC, 3076, Australia
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