Microscopic examination of urine epithelial cells
|
Heidi Andersen (born 1980) Biomedical laboratory scientist with Master’s degree in molecular bioscience and a certificate of Completion of Specialist Training in medical morphology. She works at the Department of Medical Biochemistry, Diakonhjemmet Hospital. Show The author has completed the ICMJE form and reports the following conflicts of interest: She has copyright on 188 images in a urine micro application (4). Email: [email protected] See All Articles Ludvig N.W. Daae Ludvig N.W. Daae (born 1934) MD, PhD and senior consultant at the Department of Medical Biochemistry, Diakonhjemmet Hospital. He has previously written a number of articles on urine testing. The author has completed the ICMJE form and reports no conflicts of interest. See All Articles Tale Norbye Wien Tale Norbye Wien (born 1968) MD, PhD, Consultant in internal medicine and speciality registrar in renal diseases at the Department of Renal Diseases, Oslo University Hospital. The author has completed the ICMJE form and reports no conflicts of interest. () sporsmal_grey_rgbArticle Microscopy of urine sediment is a simple and inexpensive, but often overlooked procedure. With practice, it can contribute to swift, correct diagnosis of suspected kidney and urinary tract disease. With the development of a wide range of blood tests and multiple test strips (dipsticks) for testing urine, urine microscopy often seems to be forgotten both in everyday use and in the literature on diagnosis of kidney and urinary tract disease. However, existing European guidelines stress the importance of urine examination, including the use of microscopy (1). In the following, a brief summary of these guidelines is illustrated with case histories showing what we may miss by not using a microscope on urine samples. European guidelinesEuropean guidelinesAccording to the guidelines from the European Confederation of Laboratory Medicine (ECLM) (1) there are three important indications for strip testing and microscopy of urine:
The guidelines operate with two levels of knowledge of urine microscopy. The basic level is the minimum for anyone examining urine samples and consists of description and identification of erythrocytes, leukocytes, epithelial cells, hyaline/non-hyaline casts, bacteria, Trichomonas, spermatozoa, artefacts (hairs/fibres etc.), lipid droplets and crystals. At the advanced level, these elements are studied in detail; for example, isomorphic/dysmorphic erythrocytes, subclassification of epithelial cells, casts, bacteria etc. We should point out here that if the strip test is positive, it is important to distinguish between real disease and sample contamination (Fig. 1), which can be determined by microscopy.  Illustrative case historiesPatient 1. The patient was hospitalised with increasing dyspnoea, oedema of the legs, a general sense of malaise and macroscopic haematuria. The patient had a previous medical history of atrial fibrillation, hypertension, ischaemic heart disease and type 2 diabetes. The patient’s clinical status on admission was normal – apart from atrial fibrillation, pitting oedema of the lower extremities and overweight. Blood tests revealed elevated creatinine, 114 μmol/l, with an estimated glomerular filtration rate (eGFR) of 42 ml/min/1.73 m². Urine dipsticks showed abundant leukocytes (> 500 leukocytes/μl urine), a moderate quantity of erythrocytes (≈ 80 erythrocytes/μl) and slight albuminuria (0.3 g/l). Urine microscopy revealed a moderate quantity of isomorphic (intact) erythrocytes (7 – 25 erythrocytes per field of view enlarged 40 ×) (Fig. 2), a moderate quantity of hyaline casts (findings of hyaline casts in every second field of view with an enlargement of 40 ×) and some squamous epithelial cells (1 – 5 squamous epithelial cells per field of view with an enlargement of 40 ×). Further examination with chest X-ray and echocardiogram revealed heart failure, and therapy commenced. A CT abdomen showed localised wall thickening in the urinary bladder, and the patient was referred to a urologist with suspected bladder tumour as the cause of the haematuria. Urine dipsticks react to both intact and damaged erythrocytes and to free haemoglobin and myoglobin, while microscopy may help to determine the source of the erythrocytes in the urine. Isomorphic erythrocytes in the urine mean that the red blood cells are of natural size and shape, in contrast to dysmorphic erythrocyctes, which are deformed after passing through glomerular capillary walls in cases of glomerular disease. They can be detected in the urine as acanthocytes, pencil cells, elliptocytes or fragments. Isomorphic erythrocytes have a regular, biconcave shape, are the result of post-glomerular bleeding and stem from kidney tubules, renal pelvis, ureter, bladder or urethra. Common causes of isomorphic haematuria are pronounced venous congestion in the urinary tract, urinary infections and cancer. These were all possibilities in the patient in question, and a rational test programme was initiated as a result of the urine microscopy. Patient 2. The patient was hospitalised after a clinical history of 24 hours of abdominal pain with intermittent episodes of exacerbation, lethargy and nausea. The clinical examination was normal, apart from hypertension (blood pressure 195/140 mm Hg). In the blood sample, the creatinine value was elevated at 183 μmol/l; the other blood test results were within the normal range. Urine on admission showed the following dipstick levels: leukocytes moderate (≈ 70 – 125 leukocytes/μl), nitrite negative, glucose moderate (14 – 28 mmol/l), albumin moderate (0.3 – 1 g/l), abundant erythrocytes (≈ 200 per μl). Microscopy showed very large numbers of tubular epithelial cells (large flakes) (Fig. 3), a moderate number of cellular casts of tubular epithelium (4 – 10 in the whole slide), moderate numbers of erythrocytes and leukocytes (7 – 25 per field of view with an enlargement of 40 ×) (Fig. 4). The findings were consistent with acute tubular necrosis. X-rays of the abdomen and thorax and a CT without contrast of the urinary tract provided no explanation for the patient’s symptoms. The abdominal pain was interpreted as possible constipation, and the patient received intravenous fluid and antihypertensives. The following day, serum creatinine had risen to 551μmol/l and urine production was falling despite infusion of intravenous fluid. The patient was therefore transferred to the Renal Department. A kidney biopsy showed ischaemic kidney damage (acute tubular necrosis). Three months later the patient was still dependent on dialysis. If the patient’s urine findings had been considered at the time of admission, the renal damage would have been detected before the creatinine value and other blood variables had risen alarmingly. Acute tubular necrosis is acute renal failure where tubular epithelial cells are lost due to ischaemic and/or toxic damage. Microscopy of urine is helpful for distinguishing acute tubular necrosis from prerenal kidney failure, where there is no structural renal damage. In acute tubular necrosis, the urine typically contains tubular epithelial cells and cell casts of tubular epithelium, as in our patient. Patient 3. The patient was hospitalised after some weeks of fatigue and chills, in the last few days with dark urine and pruritus. Blood tests showed a highly elevated creatinine level of 2 449 μmol/l, urea 46.2 mmol/l and potassium 6.4 mmol/l. Urine dipsticks showed considerable proteinuria and haematuria (> 20 g/l and ≈ 200 erythrocytes per μl, respectively). Microscopy showed a nephritic sediment characterised by glomerular haematuria with a moderate quantity of dysmorphic erythrocytes (7 – 25 erythrocytes per field of view with enlargement 40 ×), abundant waxy casts (> 4 in the whole slide). There were also abundant tubular epithelial cells, a moderate presence of granular casts (4 – 10 in the whole slide) and some cellular casts (1 – 3 in the whole slide) (Fig. 5). The patient was transferred the same day to the Renal Department on suspicion of acute glomerulonephritis, which was confirmed by renal biopsy. Appropriate treatment was initiated. Waxy casts are always a serious sign and are only present in patients with pathological conditions. A patient with as high a serum creatinine level as in this case would have been promptly transferred to the Renal Department under any circumstances, but in the present case urine microscopy provided important supplementary information about the urgent need for further diagnostics and treatment. Potential for improvement:Potential for improvement:Although urine microscopy can provide essential and conclusive information in the assessment of a patient’s illness, our impression is that microscopy is often omitted from both literature and practice. For example, a recently published Nordic article on kidney function variables in cases of acute kidney failure did not mention urine microscopy at all (2). Some hospital laboratories do not offer urine microscopy any longer. In our experience, urine microscopy is not as widely used as we think it should be. A study of urine morphology conducted at Diakonhjemmet Hospital in 2008 revealed a great potential for improvement among doctors and biomedical laboratory scientists in satisfying the European guidelines’ minimum requirements for basic knowledge of urine morphology (1, 3). There may be a number of reasons for this. Urinalysis requires a relatively long, thorough training, and the expertise must be maintained. Two Norwegian tools providing support and training in this field were introduced in 2012 (4, 5). Since creatinine, eGFR and cystatin C are widely discussed concerning suspected kidney and urinary disease, it is easy to forget that urine microscopy can provide faster and in many cases more appropriate information. Contaminated samplesContaminated samplesAs mentioned in the introduction, urine microscopy is the only means of determining whether a urine sample is contaminated or not. Urine samples may be contaminated during sampling by vaginal secretions and skin flora if procedures for washing prior to sample collection and mid-stream urine are not properly followed (1, 4, 5). We regard the presence of five or more epithelial cells on microscopy with 40 × enlargement as a sign of contamination. We do not send such a sample for microbiological culture, but report that it is contaminated and recommend new, correct sampling. Contaminated urine samples are a widespread problem (1, 4, 5). We have analysed the samples in our laboratory and found by urine microscopy that approximately 25 % of the over 300 urine samples received each month are contaminated. Cultures of contaminated samples yield results with no clinical relevance and may lead to patients receiving unnecessary antimicrobial treatment if an assumed urinary infection is treated on the basis of a positive strip test without microscopic verification. Culture of contaminated samples will also lead to extra costs for the health service. If the contaminated samples at our hospital had been forwarded for culture at the current rate of NOK 104 per urine sample, it would have resulted in an annual cost of about NOK 100 000 for the hospital. Useful toolUseful toolAs illustrated by the above case histories, urine microscopy can help the clinician to distinguish between glomerular and post-glomerular haematuria (patient 1), detect acute renal damage earlier than a rise in creatinine would allow (patient 2) and detect acute nephritis where the initiation of appropriate treatment is urgent (patient 3). Acute renal failure is a relatively common condition, and is associated with increased mortality in hospitalised patients (6). Prerenal disease and acute tubular necrosis are the most usual causes of acute renal failure (6, 7). The diagnosis must be made in light of the clinical history, somatic examination, blood and urine tests, including urine microscopy (8). Several articles report good correlation between various findings in urine sediments and disease, such as the presence of granular and cellular casts of tubular epithelia in cases of acute tubular necrosis (9, 10). Despite this, urine microscopy is still variably used (2, 11), and there is inadequate emphasis on and description of the role and importance of urine microscopy in modern clinical practice (12). It is well known that the serum creatinine level alone does not necessarily reflect the degree of renal damage in a patient, as we saw with patient 2. This applies to acute renal failure in particular. Urine microscopy is a useful diagnostic tool which meets all the requirements that can be made of an ideal prognostic test: it is simple and inexpensive to perform, readily available, capable of distinguishing between different conditions and of predicting a diagnosis prior to manifest disease. A number of scoring systems developed for urine sediment have proved capable of predicting exacerbation of acute renal failure (10) – (13). New biomarkers are being tested, and in several places cystatin C, for example, has been introduced into the diagnosis of renal diseases. However, it is known that the levels of both creatinine and cystatin C often increase relatively late in acute renal diseases, as in patient 2. The European guidelines for urinary analysis are therefore justified in continuing to recommend test strips and urine microscopy as important supplements to biochemical testing on suspicion of or symptoms of renal disease (1). Literature1. European Confederation of Laboratory Medicine. European urinalysis guidelines. Scand J Clin Lab Invest Suppl 2000; 231: 1 – 86. [PubMed] 2. Mårtensson J, Bell M. Njurfunktionsmätningar inom intesivvården. Klinisk Biokemi i Norden 2014; 26: 36 – 9. 3. Andersen H. Urinmorfologi på lokalsykehusnivå. Bioingeniøren 2009; 44: 12 – 4. 4. Andersen H, Wien TN, Daae LNW. Urinemicro. Mobile app for Iphone and Android. Search word «urinemicro». Oslo: Diakonhjemmet Sykehus, 2012. 5. Vinje BU. Urinmikroskopi – praktisk utførelse og bildeatlas. Kristiansand: Capppelen Damm Høyskoleforlaget, 2012. 6. Mehta RL, Pascual MT, Soroko S et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int 2004; 66: 1613 – 21. [PubMed] [CrossRef] 7. Rabb H. Evaluation of urinary markers in acute renal failure. Curr Opin Nephrol Hypertens 1998; 7: 681 – 5. [PubMed] [CrossRef] 8. Marcussen N, Schumann J, Campbell P et al. Cytodiagnostic urinalysis is very useful in the differential diagnosis of acute renal failure and can predict the severity. Ren Fail 1995; 17: 721 – 9. [PubMed] [CrossRef] 9. Schentag JJ, Gengo FM, Plaut ME et al. Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides. Antimicrob Agents Chemother 1979; 16: 468 – 74. [PubMed] [CrossRef] 10. Chawla LS, Dommu A, Berger A et al. Urinary sediment cast scoring index for acute kidney injury: a pilot study. Nephron Clin Pract 2008; 110: c145 – 50. [PubMed] [CrossRef] 11. Perazella MA, Coca SG, Hall IE et al. Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol 2010; 5: 402 – 8. [PubMed] [CrossRef] 12. Perazella MA, Coca SG. Traditional urinary biomarkers in the assessment of hospital-acquired AKI. Clin J Am Soc Nephrol 2012; 7: 167 – 74. [PubMed] [CrossRef] 13. Macedo E, Mehta RL. Biomarkers for acute kidney injury: combining the new silver with the old gold. Nephrol Dial Transplant 2013; 28: 1064 – 7. [PubMed] [CrossRef] This article was published more than 12 months ago and we have therefore closed it for new comments. Published: 30 September 2014 Tidsskr Nor Legeforen 30 September 2014 doi: 10.4045/tidsskr.14.0174
PlumX 134 :1765-7 Published: 30 September 2014 Tidsskr Nor Legeforen 2014 134 :1765-7 doi: 10.4045/tidsskr.14.0174
Plum Print visual indicator of research metrics PlumX Metrics If you do not see the PDF file or want to save the file, you can right-click on the PDF icon. Select «Save target / file as ...» and then retrieve the PDF file in, for example, Acrobat Reader. How many epithelial cells in urine is normal?It's normal to have one to five squamous epithelial cells per high power field (HPF) in your urine. Having a moderate number or many cells may indicate: a yeast or urinary tract infection (UTI) kidney or liver disease.
What does epithelial cells positive mean?If there are more than the specified number of epithelial cells in your urine test, it indicates the presence of any of the following conditions: Urinary tract infections, such as: Urethritis (urethral infection) Cystitis (urinary bladder infection) Kidney infection.
What diseases cause epithelial cells in urine?If urinalysis results show a moderate or high number of epithelial cells it may indicate the following medical conditions: Kidney disease Liver disease Yeast infections Urinary tract infections Certain types of cancer In addition, the type of epithelial cells in the urine can also signal certain diseases.
What is the normal range for urine microscopy?Microscopic examination/urine sediment. WBCs, RBCs, epithelial cells, and, rarely, tumor cells are the cellular elements found in the urinary sediment. The number of WBCs considered normal is typically 2-5 WBCs/hpf or less. A high number of WBCs indicates infection, inflammation, or contamination.
|
