Urinary sediment analysis has not become less important as diagnostic procedures in medicine develop. In recent decades, because time-consuming manual methods were used, the majority of urinary sediment analyses were only carried out routinely if such an anlysis was requested by the nephrologist and urologist. Nowadays, as well as fully automated chemical examination, automated urinary sediment analysis is available. However, it is important to be aware that the general appearance of urine sediment, the presence of certain particles in the urine and the morphology of individual particles all provide a broader spectrum of information. This short overview of urinary sediment analysis should be useful for all healthcare workers involved in disease diagnosis.
by Dr Tibor Kovács, Dr Zsuzsanna Rékási and Prof. István Wittmann
Urinary examination was already part of the Hippocratic procedure more than 2500 years ago, but the examination was carried out by the naked eye at that time. [1]. After the construction of the first simple microscope in the 16th century, there were an increasing number of descriptions concerning the constituents of urinary sediment. In the early 20th century, Thomas Addis explored the connections between constituents of urinary sediment and different renal diseases using routine microscopic examination [2]. In recent years not only has the routine chemical examination of urine become automated, but an increasing number of clinical laboratories can provide detailed, electronically-transformed information on urinary sediment. Because fewer microscopic examinations are carried out by experts, the value of these examinations may decrease. This article summarises some important key points of urinary sediment examination in which the data are crucial in diagnosis.
Red blood cells – haematuria
Dipstick or chemical examinations are very sensitive for detecting red blood cells (RBC) in urine, but these methods are unable to differentiate between different forms of RBCs, or between RBCs and haemoglobin. On the basis of the different morphology of the RBCs, they can be categorised into three groups. Normal RBCs in urinary sediment are characteristic of non-immunological renal and urinary tract diseases, e.g., pyelonephritis, cystitis, calculi, tumours, as well as of extra-renal diseases, e.g., bleeding tendency, acute febrile episodes. Glomerular type RBCs - dysmorphic or distorted erythrocytes, (acanthocytes) are characteristic of glomerulonephritis. The membrane blebs seen on these RBCs may be caused by oxidative and carbonyl stress occurring while the RBCs are passing through the tubules [3]. The examination of urine sediment for dysmorphic RBCs is a first simple step towards making a diagnosis of glomerulonephritis. If more than 5% of RBCs in the urine sediment are dysmorphic, the specificity and sensitivity for glomerular disease is 98% and 52% respectively [4]. Crenated RBCs– due to a longer period that RBCs have remained in hyperosmolaric urine – is a sign of supravital damage and these RBCs should be differentiated from glomerular type RBCs. The characteristics of these RBCs may help clinicians to refer patients with haematuria to the appropriate clinic (eg. urology or nephrology).
White blood cells - leucocytes
Polymorphonuclear neutrophils are characteristic of bacterial infections include pyelonephritis, cystitis, prostatitis and urethritis, but these can also be observed in all renal diseases. Typically they appear as round granular cells about 12 µm in diameter. On the basis of large numbers of WBCs in the sediment, it can be assumed that a urinary tract infection is present and empirical antibiotic treatment can be started before bacterial culture results, which need at least two days to generate, are available. The efficacy of treatment can also be monitored by counting the number of WBCs per high power microscope field during the period of treatment.
Other constituents of the urinary sediment can only be observed by careful sediment analysis, whereas data on the presence of RBCs and WBCs can also be obtained from routine chemical examination of the urine.
Epithelial cells
In general, three different types of epithelial cells are found in urine sediment: renal tubular cells, transitional epithelial cells and squamous epithelial cells.
Increased numbers of renal tubular epithelial cells are found in the urine as a result of acute ischaemic or toxic renal tubular diseases (e.g. acute tubular necrosis), or associated with drug toxicity (non-steroid anti-inflammatory drugs, NSAIDs, aminoglycosides), heavy metals, immunosupressants and mushroom poisoning. Few transitional epithelial cells are present in the urine sediment from healthy individuals; increased numbers are often present in urine in cases of urinary tract infection. Squamous epithelial cells are the largest cells in the urine sediment. They have no diagnostic significance and are more common in urine from women.
Atypical or a large number of epithelial cells recognised by urine sediment analysis may indicate that further cytological examination is necessary.
Casts
Urinary casts, with a core matrix of Tamm-Horsfall protein, are formed in the distal and collecting renal tubules. Any nephron component, whether a chemical or a formed component, can be found incorporated into a cast (e.g. RBCs, WBCs, pigments, fat globules). Degradation processes occurring within the casts can transform leukocytes or tubular cell casts into coarse granular casts. Hyalin and finely granular casts can also be observed in the urine of healthy individuals. However, different cells (e.g. RBCs, WBCs, epithelial cells, bacteria), pigments (e.g. bilirubin, haemoglobin) and other inclusions (e.g. crystals, granular structures) in the casts may indicate glomerular or tubulointerstitial diseases. The presence of RBC casts is diagnostic for glomerular bleeding in proliferative/necrotising glomerulonephritis. Leukocyte casts can be observed in acute interstitial nephritis, acute pyelonephritis and proliferative glomerulonephritis. Fatty casts may indicate marked proteinuria and nephrotic syndrome.
Crystals
Urinary sediment contains many types of crystals resulting from the precipitation of urinary solutes out of solution. Several factors influence crystal formation including the concentration of the solute in the urine, its pH, the flow of the primary urine through the tubules and urine storage. Examination of the urine crystals is informative in assessing individuals with kidney stone disease, in some rare inherited metabolic disorders and with suspected drug nephrotoxicity. Most of the different crystals are formed in acidic urine (e.g. amorphous urate, uric acid, calcium oxalate, bilirubin, cystine, and crystals from medications including ampicillin and sulphonamides. Amorphous phosphate, triple phosphate and calcium carbonate are typically formed in alkaline urine.
Bacteria & yeast
Detecting bacteria in the sediment of freshly voided urine suggests a type of urinary tract infection before the result of bacterial culture is available. During urinary tract infections, bacteruria are accompanied by WBCs (pyuria) in the urine sediment. Both rod-shaped (bacilli) and coccoid forms may be identified, although those most commonly encountered are gram-negative rods.
Yeasts are ovoid, colourless cells often present with budding forms. Yeast in the urine sediment often results from a vaginal infection, more usually in immuno-compromised patients (e.g. treated immune disease, diabetes mellitus); yeasts may also indicate urinary tract infection.
Conclusion
On the basis of this brief summary on the importance of urine sediment analysis, we can conclude that careful and accurate urine sediment examination should provide more information about the patient’s state of health than simple chemical or urine test strip analysis. The automated analysis of the urine sediment by digital imaging software can provide rapid, accurate results, and evaluation can be carried out on screen any time after the examination; there is no need for a manual microscopic investigation.
References
1. Fine LG. Circle of urine glasses: art of uroscopy. Am J Nephrol 1986;6(4):307-11.
2. Piccoli GB. Patient-based continuum of care in nephrology: why read Thomas Addis’ "Glomerular Nephritis" in 2010? J Nephrol 2010 Mar-Apr;23(2):164-7.
3. Degrell P, Wagner Z, Szijarto IA, Wagner L, Marko L, Mohas M, Cseh J, Wittmann I. Morphology of glomerular hematuria is reproduced in vitro by carbonyl stress. Nephron Exp Nephrol 2008;110(1):e25-30.
4. Köhler H, Wandel E, Brunck B: Acanthocyturia--a characteristic marker for glomerular bleeding. Kidney Int 1991 Jul;40(1):115-20.
5. Fogazzi GB, Pirovano B. Urinalysis In. Feehally, Floege, Johnson eds. Comprehensive Clinical Nephrology p.35-50, Mosby/Elsevier 2007.
