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Use of Urinalysis in the Diagnosis of Kidney Disease

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Published: April 2013

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A well-performed urinalysis is a critical component of the evaluation of all patients with possible kidney disease. Dr. Lieske and Ms. Miller present technical methods and case studies to illustrate the diagnostic value of urinalysis.

Presenter: John C. Lieske, MD

Presenter: Ms. Rachel Miller

  • Education Specialist in the Renal Testing Laboratory

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This presentation will discuss how the longstanding test of urinalysis can still play a key role in the diagnosis of kidney disease. We will pay particular attention to the microscopic interpretation.

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Elements that are reported from microscopic urinalysis are listed on this slide and include: white blood cells, red blood cells, transitional epithelial cells, renal epithelial cells, squamous epithelial cells, various forms of casts, free fat, free oval fat bodies, bacteria, yeast, crystals, trichomonas, and sperm.

There are 3 types of microscopy:  Brightfield, Phase, and Polarized. Brightfield produces images that appear dark against a bright background. Phase microscopy allows the tech to view detailed images of low-refractile elements. Phase is especially usefully when looking for hyaline casts and dysmorphic red blood cells. Polarized microscopy is especially useful when identifying elements that are birefringent. It is particularly helpful when looking at fat and crystals. Polarized microscopy can be used to help differentiate between casts and fibers. Fibers will polarize whereas casts will not.

White blood cells are 12 to 15 mcm in diameter. They have a multilobed nucleus, grainy cytoplasm, and about a 1 to 2  nucleus to cytoplasm ratio.

Red blood cells are smaller at about 8 mcm in diameter. They have no nucleus and appear as smooth biconcave discs.

Sometimes we see dysmorphic RBCs. When dysmorphic RBCs are seen, this is an indication that the bleeding is coming from the kidney rather than the bladder, namely that the patient has a glomerular defect that allows red blood cells through. Dysmorphic RBCs look different from normal RBCs since they can have holes through them, protrusions, or both. If the patient does have this so-called “glomerular bleeding” you might also see a RBC cast in their urine along with the dysmorphic RBCs. Therefore, anytime dysmorphic RBCs are seen, check carefully for RBC casts. Dysmorphic RBCs can look a lot like budding yeast. Acetic acid can be added to the slide. This will lyse the RBCs but keep yeast intact. That way you will be able to tell if you have dysmorphic RBCs or yeast.

This image shows a normal RBC along with a dysmorphic under phase microscopy. As you can see, the dysmorphic RBC has a hole through the center of it, while the normal one does not.

This slide shows another example of dysmorphic RBCs. You can see holes through the cells and some of them have protrusions.

Renal tubular epithelial cells are the cells that line the nephron. They are 15 to 25 mcm in size. They are usually mononuclear with a grainy cytoplasm. They have about a 1 to 1 nuclear to cytoplasm ratio. Renal cells can vary greatly in size depending on what part of the nephron they were sloughed off from. When renal cells are in a cast, the cast is called an epithelial cell cast.

This slide shows a few more examples of renal epithelial cells. The variation in the cell shape and size is really evident from these images. But they still have the 1 to 1 nucleus to cytoplasm ratio.

Transitional epithelial cells line the ureters and the bladder. These are usually larger than white blood cells and transitional cells are about 20 to 30 mcm in size. They have a smooth cytoplasm and a defined cell wall. They have a 1 to 3 nuclear to cytoplasm ratio.

Squamous epithelial cells are the largest of the epithelial cells at 30 to 50 mcm, and are derived from the skin. They are mononuclear with smooth cytoplasm. They have a 1 to 5 nuclear to cytoplasm ratio. Squamous cells are a sign of contamination of the urine during collection via contact with the skin. Thus, they indicate that the sample was probably not a clean catch.

Casts can be seen in healthy and unhealthy urine. They are held together by a specific protein called Tamm Horsfall protein that easily forms gels and is made in the thick ascending limb of the nephron. They have parallel sides and rounded ends from having formed inside the nephron. Their size and shape varies depending on what part of the nephron they are sloughed off from. If there are cells present in the nephron when a cast forms they will be trapped inside it. To safely identify a cellular cast, one-third of its volume should be made up of the cell type you want to call it.

Any amount of hyaline casts are normal. They are made up of Tamm Horsfall protein without cells. Hyaline casts are colorless and transparent.

Granular casts are degraded cellular casts. Often these are degraded renal epithelial cells. Any amount of granular casts is considered abnormal.

A leukocyte cast contains white blood cells in the hyaline matrix. These are abnormal and could mean that the patient has pyelonephritis. They can also be seen in acute interstitial nephritis.

Epithelial casts have renal epithelial cells incorporated into the cast matrix. They are typically seen when the patient has a condition that results in acute tubular necrosis. Causes include ischemia, sepsis, drugs, toxins, or very high levels of bilirubin.

Red blood cell casts contain red blood cells incorporated into the cast matrix. These are typically seen along with free floating red cells, some of which may be dysmorphic. These are very diagnostic. The only way red cell casts can form is when blood is free in the nephron, having leaked through a defective glomerular barrier. The only circumstance when this occurs is during glomerulonephritis.

Hemoglobin casts are degenerated red blood cell casts. Hemoglobin casts are yellow to brown in color and are accompanied by hematuria. When these are seen, diagnostically, they indicate the same thing as a red blood cell cast. A hemoglobin cast with one visible red cell in the cast should be reported as a RBC cast.

Waxy casts get their name because of their waxy appearance. They are very refractive and very easy to see on brightfield and phase. They are homogeneous, have well defined edges, and uneven ends. Another characteristic of waxy casts are cracks along the edges, caused because the protein in them becomes weak and begins to crack and break. Waxy casts are formed when hyaline or granular casts sit in the tubules for long periods of time, which means the patient has urinary stasis. Waxy casts are most commonly seen in patients with chronic kidney disease.

As their name implies, broad casts have a wide diameter. They are formed in a distal convoluted tubule that is dilated. Broad casts can be of any type but they are typically granular or waxy in appearance. When these are seen, it usually is a sign that the patient has dilated tubules and urinary stasis, which is seen in patients with chronic kidney disease.

Fat can be seen in several forms in the urine. It can be free floating, within oval fat bodies, or within casts. Fat is highly refractive and spherical in shape. Patients with high urinary protein levels, termed the nephrotic syndrome, develop blood lipid abnormalities that spill over into the urine. Therefore, seeing fat in the urine indicates proteinuria or the nephrotic syndrome. Under polarized light, urinary fat has a characteristic Maltese cross-like appearance.  Now that we have discussed the technical aspects of urinalysis, Dr. Lieske will describe circumstances in which these assays are useful for diagnosis.

Thank you, Rachel. A mother notices that her 5-year-old boy has seemed lethargic for several weeks. Normally, he is very active, driving his mother crazy running around the house. She also notices that he has some puffiness around his face and eyes. She takes him to the doctor. They perform a urinalysis and obtain the following results.

On the chemical portion of the urinalysis, a very high protein of 786 mg/dL stands out. On the microscopic, free fat, oval fat bodies, fat in casts, and waxy casts are seen.  Given the urinalysis results and the boy’s clinical presentation, what could be wrong with him?

The periorbital puffiness in a young child indicates edema. He also has a markedly high urinary protein excretion. These findings indicate nephrotic syndrome. In a young child, minimal change disease would be most common. The lack of cells and cellular casts also makes glomerulonephritis less likely. A 24-hour urine protein should be collected to establish the diagnosis of nephrotic syndrome. A serum creatinine or glomerular filtration rate should also be tested to establish renal function. The waxy casts are somewhat concerning since these can indicate a decline in glomerular filtration rate, namely chronic kidney disease.

A 30-year-old man is admitted to the hospital with headache, anorexia, and red urine (gross hematuria). Examination reveals 1-plus pedal edema and hypertension (150/100). The patient’s daughter had strep throat that resolved with antibiotics 1 month previously. The patient himself developed a sore throat that lasted a few days, but he did not seek treatment.

Here are the man’s urinalysis results. Key findings indicate the red appearance, high protein concentrations of 1256 mg/dL and 41 to 50 RBC’s per high power field with >25% of them being dysmorphic. He also had an occasional granular cast, and an occasional red blood cell cast. Based off his urinalysis results and clinical presentation what could be wrong with this gentleman?

The combination of high urinary protein levels, red blood cells, dysmorphic red blood cells, and red cell casts indicate glomerulonephritis. Given the history of exposure to strep and the sore throat, poststreptococcal glomerulonephritis is possible. In this circumstance, tests could be ordered to confirm the diagnosis, including serum complements C3, C4 both of which should be low and an antistreptolysin O titre which should be positive. Poststreptococcal glomerulonephritis is often self-limited. However other causes of glomerulonephritis can rapidly progress to end stage kidney failure, and a kidney biopsy might be indicated to rule out other causes.

One more case study:

A 26-year-old woman is seen by her physician. She has a temperature of 101 degrees ahrenheit and complains of nausea, headache, flank tenderness, and pain. When asked, she states that urination is sometimes painful, that she must urinate much more frequently than usual, and that she has a sensation of urgency. A midstream urine is collected for urinalysis and culture.

The presence of 51 to 100 white blood cells per high power field in the urinalysis stands out. The white blood cell casts in the presence of bacteria are also noteworthy. What is the diagnosis?

The white blood cells and bacteria indicate that this woman has a urinary tract infection. The presence of white blood cell casts suggests that the infection is present in the kidney, so she has pyelonephritis. Most often acute pyelonephritis occurs when bacteria ascend from the lower urinary tract or bladder to the kidney via the ureter.

In summary, a well-performed urinalysis is a critical component of the evaluation of all patients with possible kidney disease. For this reason the urinalysis has been called a “poor man’s kidney biopsy”.

The presence of specific formed elements in the urine provides valuable clues regarding the type of renal pathology a patient is likely to have. For example, the presence of red cell casts makes glomerulonephritis very likely. Conversely, the absence of specific elements in the urine makes certain kidney diseases less likely. Glomerular disease is not likely when proteinuria, casts, and red cells are all absent. Thank you.