CONTINUING EDUCATION :: URINARY CASTS
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Urinary casts: Indicators of underlying
clinical pathology
By Paul R. Morris, MD, MA
T
he kidneys, two fist-sized, bean-shaped organs, reside world’s 13th leading cause of death to the 10th, and mortality
just below the rib cage in the back of the abdomen under has increased from 813,000 in 2000 to 1.3 million in 2019.2 Over
the liver. Properly functioning kidneys are essential for 6 million adults have been diagnosed with CKD in the United
maintaining overall health. Unfortunately, for millions of States alone, where it is also the 10th leading cause of death.3
people around the world, kidney diseases interrupt kidney Structural changes, genetics, and comorbidities all may
function, leading to high morbidity and mortality. play a role in determining CKD risk. More than 30% of adults
with diabetes and 20% of adults with hypertension may have
Kidney disease CKD.4 Other causes include heart disease, obesity, and a family
Chronic kidney disease (CKD), the most common type of kidney history of kidney failure.5
disease, occurs slowly over a long period of time, getting progres- One of the challenges with identifying and treating CKD, is
sively worse. Currently, an estimated 13.4% of the global popu- that early disease is often without symptoms—90% of patients
lation is affected by CKD at all stages and 10.6% for moderate to don’t know that their kidneys are damaged.6 Fortunately, most
advanced stages.1 Globally, kidney diseases have risen from the cases of CKD can be detected by simple urine and blood
tests. As with most medical conditions, early detection leads
to better patient outcomes.6
Earning CEUs
See test online at www.mlo-online.com under the Continuing The renal system
Education tab. Passing scores of 70 percent or higher are The kidneys, along with the ureters, bladder, and urethra,
eligible for 1 contact hour of P.A.C.E. credit. comprise the renal system. Kidneys serve several vital func-
LEARNING OBJECTIVES tions—they filter blood to remove wastes and toxins, remove
Upon completion of this article, the reader will be able to: excess water from the bloodstream and produce renin to help
maintain blood pressure, produce erythropoietin to maintain
1. List disease statistics of CKD in the global and U.S. a healthy level of red blood cells, balance salts in the body,
populations. and convert dietary vitamin D to its biologically active form,
2. Discuss the function and parts of the renal system. calcitriol, to regulate calcium. Kidneys filter about 200 quarts
3. Identify and define the components of a urinalysis. of fluid every day; 99% of that fluid is reused in the body,
4. Discuss key findings in a urinalysis that help to diagnose CKD. while the remaining 1% is converted to urine.7
8 | JANUARY 2024 MLO-ONLINE.COM
CONTINUING EDUCATION :: URINARY CASTS
Unfiltered blood enters the kidney through the renal artery, microbiology and cytology may also be performed. The presence
which then branches into progressively smaller blood vessels of crystals, casts, and blood cells in the urine sediment provides
until it reaches one of the more than 1 million nephrons in vital information for both diagnosis and prognosis.
the kidney. Nephrons are the microscopic functional unit of
the kidney, and each is comprised of a nephron and a tubule. Macroscopic examination
(See Figure 1.) Inside the nephron, the glomerulus, a network Macroscopic evaluation of urine is simply a visual exam-
of capillaries enclosed within a sac (Bowman’s capsule), filters ination. Macroscopic analysis of urine is done by visually
water and solutes from the blood. Smaller molecules, wastes, and inspecting the physical appearance of the urine. Normal urine
fluids pass through the glomerulus and into the tubules, which is light yellow and clear. Macroscopic urinalysis notes the
ultimately feed into the Loop of Henle, a U-shaped structure amount, color, and clarity of the urine as well as any other
where water and sodium chloride are resorbed from the filtrate. visible characteristics of the urine such as the presence of
Larger molecules and cells stay in the blood.8 Wastes from the blood or blood clots, precipitates, or sediments.
filtrate exit as concentrated urine through the ureter to the Unusual colors may indicate infection, liver dysfunction,
bladder and filtered blood returns to the body via the renal vein. or drug use,11 while turbidity may suggest infection or the
CKD and other kidney diseases can be identified on urinaly- presence of RBCs.12
sis. Acute kidney disease (AKI), which occurs over days or even
hours, results in the retention of nitrogenous wastes. Kidney Urine chemistry
stones and pyelonephritis (kidney infection) both cause severe Done to measure levels of certain substances such as proteins,
pain. Nephrotic syndrome presents with heavy proteinuria sugars, ketone, and bilirubin, urine chemistry can be used to
and lipuria. Others include glomerulonephritis, autoimmune help diagnose and monitor a variety of health conditions in-
conditions, kidney stones, and polycystic kidney disease. cluding diabetes, urinary tract infections, and kidney disease.
CKD is divided into five stages based on the estimated
Urinalysis glomerular filtration rate (eGFR) and urine albumin-creati-
Laboratory testing can provide timely information for iden- nine ratio (uACR). Albumin, a protein normally found in the
tification and comprehensive therapeutic interventions to blood, is involved in building muscles, repairing tissues, and
help drastically improve patient outcomes. Cost-effective9 fighting infections. In a normal kidney, albumin cannot pass
and usually noninvasive,10 urinalysis provides critical infor- through the kidney’s filter and into the urine, but in a diseased
mation in the early detection of many diseases, including kidney, albumin leaks through the filter. Creatinine is a waste
kidney disease. Considered to be the first developed laboratory product of protein metabolism—from food or from normal
test,10 routine urinalysis can be used to screen for underlying muscle cell turnover and is normally found in both serum
health conditions such as diabetes, urinary tract infections, and urine. If the kidneys are not functioning properly, the
and kidney disease. It can also be used to monitor disease urine level of creatinine decreases. To ensure that the urine
and disease treatment. concentration doesn’t interfere with the determination of
The three main components of urinalysis are macroscopic albumin levels, the uACR test is done. The uACR is a ratio
examination of the sample, chemical analysis, and microscopic between urine albumin and serum creatinine; a uACR greater
examination of the urine sediment. Additional tests including than 30 mg(albumin)/g(creatinine) is indicative of albumin-
uria—excessive protein in the urine.13 eGFR
is a calculation based on serum creatinine
levels and shows how well the kidneys are
filtering toxins and wastes from the blood.14
A normal eGFR is above 60 mL/min/1.73m2,
and a normal uACR is below 30 mg/g.14 Falling
eGFR numbers and rising uACR numbers are
indicators of progressing disease.
Urine microscopy
Urine microscopy is a common test in the
clinical laboratory and is used to evaluate
cells, casts, and crystals in the urine. While
it is not uncommon to find some epithelial
cells in the urine, an increased number may
be a sign of trauma, inflammation, or infec-
tion in the urinary tract. Similarly, bacterial
or yeast in the sample suggest an underlying
renal system infection. Blood cells in the urine
may be benign—for example, as a result of
heavy exercise—but may also indicate a more
serious disorder such as a severe infection or
urinary tract cancer.15 The presence of urine
casts often portend a more serious underlying
Figure 1. Microscopic images courtesy of Sorin Gîju, Ph.D., Clinical Emergency Hospital kidney condition and may be one of the first
Timisoara, Romania. early indicators of underlying kidney disease.
MLO-ONLINE.COM JANUARY 2024 | 9
CONTINUING EDUCATION :: URINARY CASTS
Casts urinalysis systems with automated urine microscopy and
Urinary casts are cylindrical mucoprotein particles that arise auto-particle recognition software provide numeric counts
from the distal convoluted tubule or collecting duct during and digital image results and can also auto-classify parti-
periods of urinary concentration or stasis. All casts have cles based on size, shape, contrast, and texture and assist
a core matrix glycoprotein, uromodulin, that is secreted with particle sub-categorization. The insights gained from
by renal tubular cells in the ascending arm of the Loop urinalysis with sensitive cast identification are facilitating
of Henle.12 Trapped contents in the tubule lumen intermix partnerships between laboratorians and clinicians to identify
with the uromodulin, and eventually, the tubule-shaped kidney disease in a timely manner—allowing them to focus
cast is excreted in the urine. Different casts are comprised of their time on the most critical patients.
different components and are formed in different areas of the
tubule (See Figure 1), which may be helpful in determining REFERENCES
clinical significance. Urine cast formation is influenced by the 1. Hill NR, Fatoba ST, Oke JL, et al. Global Prevalence of Chronic Kid-
pH, concentration, and temperature of the urine—as well as ney Disease - A Systematic Review and Meta-Analysis. PLoS ONE.
2016;11(7):e0158765. doi:10.1371/journal.pone.0158765.
by the presence of drugs or underlying genetic conditions.
2. World Health Organization. The Top 10 Causes of Death. Fact Sheet | The
And while having some casts in the urine sediment may
Top 10 Causes of Death. December 9, 2020. Accessed October 31, 2023. https://
be normal, the type and number of casts may indicate the www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
presence of renal disease12 and can be detected and charac- 3. National Center for Health Statistics. FastStats - Kidney Disease. Center
terized using automated urinalysis. The clinical significance for Disease Control and Prevention. January 17, 2023. Accessed November
of some of the most common casts is shown in Table 1 below. 1, 2023. https://www.cdc.gov/nchs/fastats/kidney-disease.htm.
4. Diabetes and Chronic Kidney Disease. Centers for Disease Control and
Conclusion Prevention. December 30, 2022. Accessed November 7, 2023. https://www.
Advancements in automation are streamlining the urinalysis cdc.gov/diabetes/managing/diabetes-kidney-disease.html.
laboratory workflow and improving laboratory efficiency to 5. National Institute of Diabetes and Digestive and Kidney Diseases.
take the subjectivity out of urinalysis. Integrated automated Chronic Kidney Disease (CKD) - NIDDK. Accessed November 7,
2023. https://www.niddk.nih.gov/health-information/kidney-disease/
chronic-kidney-disease-ckd.
Casts Clinical significance
6. National Kidney Foundation. Kidney Disease: The Basics. Kidney Disease:
Hyaline Hyaline casts, the most common type of urinary casts, The Basics. 2023. Accessed November 2, 2023. https://www.kidney.org/
are composed of mucoproteins. Like granular casts news/newsroom/fsindex.
and RBC casts, hyaline casts may be a normal finding 7. National Kidney Foundation. Top 5 Jobs Kidneys Do. 2023. Accessed Novem-
following strenuous exercise. They are also found in ber 3, 2023. https://www.kidney.org/kidneydisease/top-5-jobs-kidneys-do.
those using diuretics. Clinically, though, hyaline casts are 8. NIH. Your Kidneys & How They Work - NIDDK. National Institute of
indicative of pyelonephritis and CKD. Diabetes and Digestive and Kidney Diseases. June 2018. Accessed October
Granular Granular casts are a key indicator of acute tubular 31, 2023. https://www.niddk.nih.gov/health-information/kidney-disease/
necrosis or advanced renal disease. The granules inside kidneys-how-they-work.
the casts are formed after decomposition of cells in the 9. Cusick MM, Tisdale RL, Chertow GM, Owens DK, Goldhaber-Fiebert JD.
cast or a tubule. The appearance of granular casts may Population-Wide Screening for Chronic Kidney Disease : A Cost-Effective-
vary from coarse granules including cell particles to fine ness Analysis. Ann Intern Med. 2023;176(6):788-797. doi:10.7326/M22-3228.
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Butterworths; 1990.
Cellular Cellular casts include those comprised of red blood
cells (RBCs), white blood cells (WBCs), and epithelial 12. Brunzel NA. Fundamentals of Urine & Body Fluid Analysis. 4th ed.
cells. RBC and WBC casts are implicated in glomerular (Bellinger KG, Briski M, Crawford C, et al., eds.). Elsevier; 2018.
dysfunction and nephron inflammation or kidney infection, 13. National Institute of Diabetes and Digestive and Kidney Diseases. Urine
respectively. Epithelial casts, which form by inclusion Albumin-to-Creatinine Ratio (UACR) In Evaluating Patients with Diabetes for
or adherence of desquamated epithelial cells to the Kidney Disease. 2010. Accessed November 7, 2023. https://www.niddk.nih.
tubule lining, have a broad range of clinical significance gov/-/media/Files/Health-Information/Health-Professionals/Kidney-Disease/
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nephropathy from heavy metal ingestion. 14. American Kidney Fund. Blood test: eGFR (estimated glomerular filtration
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Waxy Waxy casts, the largest of the casts, occur in patients Accessed October 31, 2023. https://www.kidneyfund.org/all-about-kidneys/
with chronic kidney diseases and are indicative of tubule tests/blood-test-egfr.
damage. These casts are comprised of a variety of cell 15. Johns Hopkins Medicine. Hematuria (Blood in the Urine). Johns
types but have a homogenous structure. Occasionally, Hopkins Medicine Conditions and Diseases. 2023. Accessed November
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are often seen as broad casts, having a greater diameter hematuria-blood-in-the-urine.
than most casts.
Dr. Paul R. Morris earned his medical degree from Boston
Fatty Fatty casts are comprised of fat- or lipid-laden cells. They University. He completed his residency in Pathology at Duke
are formed by the breakdown of lipid-rich epithelial cells and fellowship in Blood Banking/Transfusion Medicine at the
and have a Maltese cross pattern under polarized light. University of North Carolina. Dr. Morris has over twenty years
Fatty casts are clinically significant for nephrotic syndrome, of experience in blood and tissue banking, reference
kidney disease, hypothyroidism, or toxic renal poisoning. laboratories, and the in-vitro diagnostics industry. He currently
is the Medical Director for Beckman Coulter Diagnostics and
Table 1. Most common urinary casts. Life Sciences focusing on risk management and new product development.
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