This can be a corrected model of the article that appeared in print.
JEFF A. SIMERVILLE, M.D., WILLIAM C. MAXTED, M.D., and JOHN J. PAHIRA, M.D., Georgetown College College of Medication, Washington, D.C
Urinalysis is invaluable within the prognosis of urologic situations resembling calculi, urinary tract an infection (UTI), and malignancy. It can also alert the doctor to the presence of systemic illness affecting the kidneys. Though urinalysis shouldn’t be really helpful as a routine screening device besides in girls who could also be pregnant, physicians ought to know easy methods to interpret urinalysis outcomes accurately. This text opinions the right methodology for performing urinalysis and the differential prognosis for a number of irregular outcomes.
A whole urinalysis contains bodily, chemical, and microscopic examinations. Midstream clear assortment is suitable in most conditions, however the specimen ought to be examined inside two hours of assortment. Cloudy urine typically is a results of precipitated phosphate crystals in alkaline urine, however pyuria additionally could be the trigger. A robust odor could also be the results of a concentrated specimen relatively than a urinary tract an infection. Dipstick urinalysis is handy, however false-positive and false-negative outcomes can happen. Particular gravity supplies a dependable evaluation of the affected person’s hydration standing. Microhematuria has a variety of causes, from benign to life threatening. Glomerular, renal, and urologic causes of microhematuria typically could be differentiated by different components of the urinalysis. Though transient proteinuria usually is a benign situation, persistent proteinuria requires additional work-up. Uncomplicated urinary tract infections identified by constructive leukocyte esterase and nitrite exams could be handled with out tradition.
A = constant, good-quality patient-oriented proof; B = inconsistent or limited-quality patient-oriented proof; C = consensus, disease-oriented proof, normal observe, opinion, or case sequence. See web page 1046 for extra data.
A = constant, good-quality patient-oriented proof; B = inconsistent or limited-quality patient-oriented proof; C = consensus, disease-oriented proof, normal observe, opinion, or case sequence. See web page 1046 for extra data.
Specimen Assortment
A midstream clean-catch approach often is sufficient in women and men. Though prior cleaning of the exterior genitalia typically is really helpful in girls, it has no confirmed profit. In reality, a current study1 discovered that contamination charges had been comparable in specimens obtained with and with out prior cleaning (32 versus 29 p.c). Urine should be refrigerated if it can’t be examined promptly; delays of greater than two hours between assortment and examination typically trigger unreliable outcomes.2
Bodily Properties: Shade and Odor
Meals, medicines, metabolic merchandise, and an infection could cause irregular urine colours (Desk 1).3 Cloudy urine typically is a results of precipitated phosphate crystals in alkaline urine, however pyuria additionally could be the trigger.
The conventional odor of urine is described as urinoid; this odor could be sturdy in concentrated specimens however doesn’t suggest an infection. Diabetic ketoacidosis could cause urine to have a fruity or candy odor, and alkaline fermentation could cause an ammoniacal odor after extended bladder retention. Individuals with UTIs typically have urine with a pungent odor. Different causes of irregular odors embrace gastrointestinal-bladder fistulas (related to a fecal scent), cystine decomposition (related to a sulfuric scent), and medicines and food plan (e.g., asparagus).
Dipstick Urinalysis
False-positive and false-negative outcomes will not be uncommon in dipstick urinalysis (Desk 2). The accuracy of this take a look at in detecting microscopic hematuria, important proteinuria, and UTI is summarized in Desk 3.4–13
SPECIFIC GRAVITY
Urinary particular gravity (USG) correlates with urine osmolality and provides vital perception into the affected person’s hydration standing. It additionally displays the concentrating capacity of the kidneys. Regular USG can vary from 1.003 to 1.030; a worth of lower than 1.010 signifies relative hydration, and a worth better than 1.020 signifies relative dehydration.14 Elevated USG is related to glycosuria and the syndrome of inappropriate antidiuretic hormone; decreased USG is related to diuretic use, diabetes insipidus, adrenal insufficiency, aldosteronism, and impaired renal perform.14 In sufferers with intrinsic renal insufficiency, USG is fastened at 1.010—the particular gravity of the glomerular filtrate.
URINARY PH
Urinary pH can vary from 4.5 to eight however usually is barely acidic (i.e., 5.5 to six.5) due to metabolic exercise. Ingestion of proteins and acidic fruits (e.g., cranberries) could cause acidic urine, and diets excessive in citrate could cause alkaline urine.15–17 Urinary pH typically displays the serum pH, besides in sufferers with renal tubular acidosis (RTA). The lack to acidify urine to a pH of lower than 5.5 regardless of an in a single day quick and administration of an acid load is the hallmark of RTA. In kind I (distal) RTA, the serum is acidic however the urine is alkaline, secondary to an incapability to secrete protons into the urine. Kind II (proximal) RTA is characterised by an incapability to reabsorb bicarbonate. This case initially ends in alkaline urine, however because the filtered load of bicarbonate decreases, the urine turns into extra acidic.
Dedication of urinary pH is helpful within the prognosis and administration of UTIs and calculi. Alkaline urine in a affected person with a UTI suggests the presence of a urea-splitting organism, which can be related to magnesium-ammonium phosphate crystals and might kind staghorn calculi. Uric acid calculi are related to acidic urine.
HEMATURIA
In accordance with the American Urological Affiliation, the presence of three or extra pink blood cells (RBCs) per high-powered discipline (HPF) in two of three urine samples is the commonly accepted definition of hematuria.18–20 The dipstick take a look at for blood detects the peroxidase exercise of erythrocytes. Nonetheless, myoglobin and hemoglobin additionally will catalyze this response, so a constructive take a look at end result could point out hematuria, myoglobinuria, or hemoglobinuria. Visualization of intact erythrocytes on microscopic examination of the urinary sediment can distinguish hematuria from different situations. Microscopic examination additionally could detect RBC casts or dysmorphic RBCs. Hematuria is split into glomerular, renal (i.e., nonglomerular), and urologic etiologies (Desk 4).21
Glomerular Hematuria
Glomerular hematuria usually is related to important proteinuria, erythrocyte casts, and dysmorphic RBCs. Nonetheless, 20 p.c of sufferers with biopsy-proven glomerulonephritis current with hematuria alone.22 IgA nephropathy (i.e., Berger’s illness) is the commonest reason for glomerular hematuria.
Renal (Nonglomerular) Hematuria
Nonglomerular hematuria is secondary to tubulointerstitial, renovascular, or metabolic problems. Like glomerular hematuria, it typically is related to important proteinuria; nonetheless, there aren’t any related dysmorphic RBCs or erythrocyte casts. Additional analysis of sufferers with glomerular and nonglomerular hematuria ought to embrace dedication of renal perform and 24-hour urinary protein or spot urinary protein-creatinine ratio.
Urologic Hematuria
Urologic causes of hematuria embrace tumors, calculi, and infections. Urologic hematuria is distinguished from different etiologies by the absence of proteinuria, dysmorphic RBCs, and erythrocyte casts. Even important hematuria won’t elevate the protein focus to the two+ to three+ vary on the dipstick take a look at.23 As much as 20 p.c of sufferers with gross hematuria have urinary tract malignancy; a full work-up with cystoscopy and upper-tract imaging is indicated in sufferers with this situation.24 In sufferers with asymptomatic microscopic hematuria (with out proteinuria or pyuria), 5 to 22 p.c have critical urologic illness, and 0.5 to five p.c have a genitourinary malignancy.25–29
Train-induced hematuria is a comparatively widespread, benign situation that always is related to long-distance working. Outcomes of repeat urinalysis after 48 to 72 hours ought to be adverse in sufferers with this situation.30
PROTEINURIA
In wholesome individuals, the glomerular capillary wall is permeable solely to substances with a molecular weight of lower than 20,000 Daltons. As soon as filtered, low–molecular-weight proteins are reabsorbed and metabolized by the proximal tubule cells. Regular urinary proteins embrace albumin, serum globulins, and proteins secreted by the nephron. Proteinuria is outlined as urinary protein excretion of greater than 150 mg per day (10 to twenty mg per dL) and is the hallmark of renal illness. Microalbuminuria is outlined because the excretion of 30 to 150 mg of protein per day and is an indication of early renal illness, significantly in diabetic sufferers.
The reagent on most dipstick exams is delicate to albumin however could not detect low concentrations of γ-globulins and Bence Jones proteins. Dipstick exams for hint quantities of protein yield constructive outcomes at concentrations of 5 to 10 mg per dL—decrease than the edge for clinically important proteinuria.15 A results of 1+ corresponds to roughly 30 mg of protein per dL and is taken into account constructive; 2+ corresponds to 100 mg per dL, 3+ to 300 mg per dL, and 4+ to 1,000 mg per dL.31,32 Dipstick urinalysis reliably can predict albuminuria with sensitivities and specificities of better than 99 p.c.4 Asymptomatic proteinuria is related to important renal illness in lower than 1.5 p.c of sufferers.4,33
Proteinuria could be categorized as transient or persistent (Desk 5).21 In transient proteinuria, a brief change in glomerular hemodynamics causes the protein extra; these situations comply with a benign, self-limited course.34,35 Orthostatic (postural) proteinuria is a benign situation that may end result from extended standing; it’s confirmed by acquiring a adverse urinalysis end result after eight hours of recumbency.
Persistent proteinuria is split into three common classes: glomerular, tubular, and overflow. In glomerular proteinuria, the commonest kind, albumin is the first urinary protein. Tubular proteinuria outcomes when malfunctioning tubule cells not metabolize or reabsorb usually filtered protein. On this situation, low–molecular-weight proteins predominate over albumin and barely exceed 2 g per day. In overflow proteinuria, low–molecular-weight proteins overwhelm the flexibility of the tubules to reabsorb filtered proteins.
Additional analysis of persistent proteinuria often contains dedication of 24-hour urinary protein excretion or spot urinary protein-creatinine ratio, microscopic examination of the urinary sediment, urinary protein electrophoresis, and evaluation of renal perform.32
GLYCOSURIA
Glucose usually is filtered by the glomerulus, however it’s virtually utterly reabsorbed within the proximal tubule. Glycosuria happens when the filtered load of glucose exceeds the flexibility of the tubule to reabsorb it (i.e., 180 to 200 mg per dL). Etiologies embrace diabetes mellitus, Cushing’s syndrome, liver and pancreatic illness, and Fanconi’s syndrome.
KETONURIA
Ketones, merchandise of physique fats metabolism, usually will not be present in urine. Dipstick reagents detect acetic acid via a response with sodium nitroprusside or nitro-ferricyanide and glycine. Ketonuria mostly is related to uncontrolled diabetes, but it surely can also happen throughout being pregnant, carbohydrate-free diets, and hunger.
NITRITES
Nitrites usually will not be present in urine however end result when micro organism cut back urinary nitrates to nitrites. Many gram-negative and a few gram-positive organisms are able to this conversion, and a constructive dipstick nitrite take a look at signifies that these organisms are current in important numbers (i.e., greater than 10,000 per mL). This take a look at is particular however not extremely delicate. Thus, a constructive result’s useful, however a adverse end result doesn’t rule out UTI.6 The nitrite dipstick reagent is delicate to air publicity, so containers ought to be closed instantly after eradicating a strip. After one week of publicity, one third of strips give false-positive outcomes, and after two weeks, three fourths give false-positive outcomes.36 Non-nitrate–lowering organisms additionally could trigger false-negative outcomes, and sufferers who devour a low-nitrate food plan could have false-negative outcomes.
LEUKOCYTE ESTERASE
Leukocyte esterase is produced by neutrophils and will sign pyuria related to UTI. [
corrected] To detect important pyuria precisely, 30 seconds to 2 minutes ought to be allowed for the dipstick reagent strip to alter shade, relying within the model used. Leukocyte casts within the urinary sediment will help localize the realm of irritation to the kidney.
Organisms resembling Chlamydia and Ureaplasma urealyticum ought to be thought-about in sufferers with pyuria and adverse cultures. Different causes of sterile pyuria embrace balanitis, urethritis, tuberculosis, bladder tumors, viral infections, nephrolithiasis, overseas our bodies, train, glomerulonephritis, and corticosteroid and cyclophosphamide (Cytoxan) use.
BILIRUBIN AND UROBILINOGEN
Urine usually doesn’t include detectable quantities of bilirubin. Unconjugated bilirubin is water insoluble and can’t go via the glomerulus; conjugated bilirubin is water soluble and signifies additional analysis for liver dysfunction and biliary obstruction when it’s detected within the urine.
Regular urine incorporates solely small quantities of urobilinogen, the top product of conjugated bilirubin after it has handed via the bile ducts and been metabolized within the gut. Urobilinogen is reabsorbed into the portal circulation, and a small quantity ultimately is filtered by the glomerulus. Hemolysis and hepatocellular illness can elevate urobilinogen ranges, and antibiotic use and bile duct obstruction can lower urobilinogen ranges.
Microscopic Urinalysis
Microscopic examination is an indispensable a part of urinalysis; the identification of casts, cells, crystals, and micro organism aids within the prognosis of quite a lot of situations. To arrange a urine specimen for microscopic evaluation, a recent pattern of 10 to fifteen mL of urine ought to be centrifuged at 1,500 to three,000 rpm for 5 minutes. The supernatant then is decanted and the sediment resuspended within the remaining liquid.37 A single drop is transferred to a clear glass slide, and a canopy slip is utilized.
CELLS
Leukocytes could also be seen underneath low- and high-power magnification (Determine 1). Males usually have fewer than two white blood cells (WBCs) per HPF; girls usually have fewer than 5 WBCs per HPF.
Epithelial cells typically are current within the urinary sediment. Squamous epithelial cells are giant and irregularly formed, with a small nucleus and superb granular cytoplasm; their presence suggests contamination. The presence of transitional epithelial cells is regular. These cells are smaller and rounder than squamous cells, and so they have bigger nuclei. The presence of renal tubule cells signifies important renal pathology (Determine 2). Erythrocytes are finest visualized underneath high-power magnification. Dysmorphic erythrocytes, which have odd shapes due to their passage via an irregular glomerulus, counsel glomerular illness.
CASTS
Casts within the urinary sediment could also be used to localize illness to a selected location within the genitourinary tract (Desk 6).38 Casts, that are a coagulum of Tamm-Horsfall mucoprotein and the trapped contents of tubule lumen, originate from the distal convoluted tubule or gathering duct during times of urinary focus or stasis, or when urinary pH may be very low. Their cylindrical form displays the tubule by which they had been shaped and is retained when the casts are washed away. The predominant mobile components decide the kind of forged: hyaline, erythrocyte, leukocyte, epithelial, granular, waxy, fatty, or broad (Determine 3).
CRYSTALS
Crystals could also be seen within the urinary sediment of wholesome sufferers (Determine 4). Calcium oxalate crystals have a refractile sq. “envelope” form that may range in dimension. Uric acid crystals are yellow to orange-brown and could also be diamond- or barrel-shaped. Triple phosphate crystals could also be regular however typically are related to alkaline urine and UTI (usually related to Proteus species). These crystals are colorless and have a attribute “coffin lid” look. Cystine crystals are colorless, have a hexagonal form, and are current in acidic urine, which is diagnostic of cystinuria.
BACTERIURIA
[
corrected] Underneath high-powered magnification, gram-negative rods, streptococci, and staphylococci could be distinguished by their attribute look.
Gram staining will help information antibiotic remedy, however it’s not indicated in routine outpatient observe. Clear-catch specimens from feminine sufferers incessantly are contaminated by vaginal flora. In these sufferers, 5 micro organism per HPF represents roughly 100,000 colony-forming models (CFU) per mL, the traditional diagnostic criterion for asymptomatic bacteriuria and positively suitable with a UTI. In symptomatic sufferers, a colony depend as little as 100 CFU per mL suggests UTI, and antibiotics ought to be thought-about. The presence of micro organism in a correctly collected male urine specimen is suggestive of an infection, and a tradition ought to be obtained.
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