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Stefan G Kiessling MD FAAPStefan G Kiessling, MD, FAAP
To briefly review the anatomy and physiology of the urinary system
To review the basics of urinalysis and urine sediment in children pertinent to a primary care provider’s needschildren pertinent to a primary care provider s needs
To review normal and abnormal findings of the urinalysis and urine sediment and correlation with clinical pathology
To discuss a further diagnostic approach based on findings of urinalysis and microscopy
Easy inexpensive tool to diagnose illnesses that could otherwise remain undiagnosed and to follow therapy response to certain diseases Diabetes mellitusDiabetes mellitus Glomerulonephritis Hypertension related renal injury Non‐symptomatic UTIs Non‐symptomatic UTIs
AAP News 2010(12):31 ‐ UA should only be done in children at risk or with certain medical conditions but NOT used as a routine tool
In the office setting, clean catch midstream voided specimen are collected most commonlyspecimen are collected most commonly
Make sure to label properly with name, MR#, DOB to avoid mix up with sample from another patientS i h ld b i d ithi i t t h Specimen should be examined within 30 minutes to 1 hour after voiding either in the office or set to the lab
Collect new sample if >1 hr at room temperature or >4 hr in f i trefrigerator
Urine sediment should be reviewed in certain cases: Spin 5‐10 ml of urine at 2500‐3000r/min for 3‐5 minutes Discard the supernatant and resuspend sediment in remaining Discard the supernatant and resuspend sediment in remaining
amount of urine Transfer one drop of urine to a slide and coverglass
Analysis Of The Urine SedimentAnalysis Of The Urine Sedimentyy
►► Take minimum of 8Take minimum of 8‐‐10 cc of urine (if available); spin at 10 cc of urine (if available); spin at 20002000‐‐3000 3000 RPM for 3RPM for 3‐‐5 minutes with 5 minutes with >> 5 RBC/HPF5 RBC/HPFRPM for 3RPM for 3 5 minutes with 5 minutes with >> 5 RBC/HPF5 RBC/HPF
►► Discard supernatant and Discard supernatant and resuspendresuspend pellet in remaining urinepellet in remaining urine►► Put the cover glass on in Put the cover glass on in an an angle so that possible casts get washed to angle so that possible casts get washed to
the opposite sidethe opposite sidethe opposite sidethe opposite side
Casts
►► If there is microscopic hematuria on an initial clean catch urine, If there is microscopic hematuria on an initial clean catch urine, repeat at least one more repeat at least one more time 2time 2‐‐3weeks later 3weeks later since high (>50since high (>50‐‐70) “false 70) “false positive” rate (Dodge et al., 1976) positive” rate (Dodge et al., 1976)
Remember: In adolescent and obese females, the labia must be spread apart to
get a proper clean sample – MOST girls don’t do that
Eileen Brewer (Peds Nephrologist at Baylor) :Eileen Brewer (Peds Nephrologist at Baylor) : Her husband urologist says that if your hands are not wet after you
collect the sample, you did not do it right
Do not squeeze the diaper in infants except if you look for Do not squeeze the diaper in infants except if you look for protein
Uncircumcised male with difficult to retract foreskin: Best method of collection is suprapubic tap
Consider In/Out cath
Clear Cloudy Color (red/brown/yellow) Smell
Yellow: normal Amber to reddish brown:
RBC – hemoglobin – myoglobin – hemosiderin Bright red:Bright red:
Fresh blood, urates (infant diapers), porphyrins, pyridium, adriamycin, food coloring, beets
Brown‐Black:Brown Black: Alkaptonuria, melanin, methyldopa
Bright orange: Rifampin Rifampin
Dark orange: Bilirubin, carotin
Brewer E.
Ammonia: bacteria Fruity: ketones (DM, starvation) Maple Syrup: maple syrup disease Musty: PKU Ingested foods: asparagusE t d D tibi ti Excreted Drugs: antibiotics
Should be read as soon as dipstick is taken out of urine specimen Alk li H d t l f l til ( i f t Alkaline pH due to loss of volatile gases (conversion of urea to ammonia in the presence of bacteria and loss of CO2)
Range quite wide from 4.5 to 7 in normal individuals but usually id ( 6) d t b idi i d f ti f d il acid (5‐6); needs to be acidic given need for excretion of daily
acid load of 2mEQ/kg/day Usually of little importance pH>7.5 in vegetarian (vegan) diet or urease producing organisms
(Proteus; nitrite usually also positive) Urine pH below 5.3 in the setting of metabolic acidosis, if not,
think about RTA Excess urine runover from protein reagent can falsely lower urine
pH
Range seen usually is between 1.003 and 1.035 Reflects number and size of particles in solution Expected value:
L i l l di d hi h i l d fi i b h fl i Low in volume loading and high in volume deficit both reflecting appropriate tubular function
Unexpected value: Low SG in ARF or oliguria reflecting tubular dysfunction
Normally not seen unless serum glucose passes renal threshold (>180mg/dl)
Dipstick is specific for glucose (need other testing for galactose fructose lactose)galactose, fructose, lactose)
Not a good indicator for diabetes control Glucose in the urine does not always reflect hyperglycemia G y yp g ybut can be a sign of abnormal tubular reabsorption (need concomitant serum glucose to rule out renal glucosuria)F l i i i h f b i Vi i C d False positive in the presence of bacteria, Vitamin C and ASA (acetylsalicylic acid)
Normal in children as a rule of thumb is <100mg/day Normal small amounts are either filtered by the glomerulus albumin or
secreted by the tubule Tamm Horsfallsecreted by the tubule Tamm‐Horsfall Dipstick tests ONLY for albumin Urine albumin concentration influenced by rate of protein excretion and
urine volume In case of concerns of non‐glomerular proteinuria, need to consider special
testing (Beta2‐microglobulin, sulfosalicylic acid precipitation) Dipstick:
0: 0 mg/dl 0: 0 mg/dl Trace: 1‐10 mg/dl 1+: 15‐30 mg/dl 2+: 40‐100 mg/dl 3+: 150‐350 mg/dl 4+: >500 mg/dl
< 1 g per day Transient – postural – tubular – glomerularTransient postural tubular glomerular
> 3 g per day Glomerular
False positive results Macroscopic hematuria Pyridium (phenazopyridine)y (p py ) Urine pH >8 Vaginal secretions chlorhexidinechlorhexidine
Normal < 3 RBC per high power field (HPF) Results are trace to 3+ Results are trace to 3+ Positive dipstick does not exclude pigmenturia true hematuria needs to be confirmed by RBCs on t ue e atu a eeds to be co ed by R Cs ourine microscopy
Can spin urine down – if supernatant clear hhematuria
Can originate from anywhere in the urinary tract RBC morphology can help to determine glomerular RBC morphology can help to determine glomerular vs. non‐glomerular hematuria
False positives: Betadine, hypochlorite cleansers (oxidize dip‐stick reagent) Other chemicals Positive dipstick without RBCs ‐> dilute urine (SG<1.006) leading to p ( ) g
red cell lysis Excess bacterial peroxidase in urine, bacterial overgrowth Menstruating femaleg
Take home message: A positive dipstick for blood should always be followed by the assessment for presence or absence of red blood be followed by the assessment for presence or absence of red blood cells
Product of fat metabolism (largely β hydroxybutyric acid but Product of fat metabolism (largely β‐hydroxybutyric acid but also acetoacetic acid and acetone)
Dipstick only detects acetoacetic acid and acetone thus p yunderestimating true ketone excretion
Positive in DKA, starvation, anorexia, dieting, vomitingd Reported as trace to 4+
Caveat: false negative in delayed reading of the urine sample false negative in delayed reading of the urine sample False positive in highly pigmented urine, mesna and levodopa
metabolites
Reported as 1+ to 3+ Reported as 1+ to 3+ May indicate abnormal liver function tests or biliary obstruction
Is quite unstable and should be read in a timely fashion to avoid false negative readingl f l f Also false negative in presence of Vitamin C
Degradation product from bilirubin formed by intestinal Degradation product from bilirubin formed by intestinal bacteria
Trace amounts are considered normal since <5% of bili i t d i th i ( / h )urobilinogen is excreted in the urine (1‐4mg/24hr)
Presence can indicate hemolysis, intestinal obstruction or abnormal LFTs but not biliary obstructiony
If dipstick is positive for bilirubin but negative for urobilinogen, think about biliary obstruction (absence of bilirubin in the intestine, no bacterial metabolism) bilirubin in the intestine, no bacterial metabolism)
Dietary nitrate is normally excreted in the urine Dietary nitrate is normally excreted in the urine Useful as a screen for presence of bacteria (if there is adequate contact time), usually gram negative rods which q ) y g greduce nitrate to nitrite
False negative results in the presence of Vitamin C, yeast or iti b t i d i t i (l it t gram positive bacteria and in vegetarians (low nitrate
production)
Essentially confirms presence of polymorph nuclear cells Essentially confirms presence of polymorph nuclear cells (PMN)
False positive with eosinophilia and trichomonas False negative with Vitamin C and large amounts of albumin
Sensitive for UTI but need to think about others in the Sensitive for UTI but need to think about others in the differential diagnosis:
Resolving UTI Glomerulonephritis Renal stone Tubulo‐interstitial nephritis TB (Interstitial cystitis)
PKD PKD
Red blood cells Red blood cells White blood cells Renal tubular epithelial cells Transitional epithelial cells Squamous epithelial cellsC t l Crystals
Casts Bacteria Artifacts (Fiber, starch crystals, air bubbles) Mucous threads (normal in low quantity, high quantity in i f ti /i it ti f th i t t)infammation/irritation of the urinary tract)
Small smooth no nucleus Small, smooth, no nucleus Normal <3 RBC per HPF They lyse in dilute, alkaline and non‐fresh urine samplesThey lyse in dilute, alkaline and non fresh urine samples Dysmorphic RBCs ‐ acanthocytes
Spherical larger than RBCs dull gray characteristic granules Spherical, larger than RBCs, dull gray, characteristic granules and lobulation of the nucleus (0‐4/HPF)
Normal urine contains up to 2000 leukocytes/mlp y
Slighly larger than WBCs with a large round nucleus that can be eccentric
Cuboidal, Columnar or teardrop shapedS i ATN d t h t i Seen in ATN and exposure to nephrotoxins
Oval fat bodies: tubular cells with lipid particles (seen often in urine sediment in nephrotic syndrome) p y )
Normal urine component If present in large quantities need to think about neoplasm
Usually less than one if the urine is a clean catch Larger numbers indicate vaginal contamination
In acidic urine Calcium oxalate – normal after intake of oxalate‐rich foods
(spinach, tomatoes, oranges, asparagus, garlic, rhubarb) – Calcium oxalate calculi, ethylene glycol intoxication, large amounts od Vit C
Uric acid – normal or associated with gout, febrile illness, Lesch‐Nyhan syndrome, tumor lysis syndrome
Cystine – Cystinuria or cystinosis
In alkaline urine Ammonium Magnesium Phosphates (Struvite) – coffin lid; UTI
with urease producing orgamismwith urease producing orgamism Calcium phosphate Amorphous Phosphate: phosphate salts
Calcium OxalateCalcium Oxalate
Often seen after urine is refrigerated Of little clinical value Can mimic brownish casts of ATN Occur in acid pH and can be dissolved by adding an alkali like 2% ammonia solution
Usually formed by precipitation of Tamm‐Horsfall mucoprotein (which is secreted by the tubules) and the mucoprotein (which is secreted by the tubules) and the clumping of cells or other materials within the protein matrix; they reflect renoparenchymal injury
Thin or broad (often correlating with duration of Thin or broad (often correlating with duration of underlying disease)
Hyaline casts: found in very concentrated urine found in very concentrated urine Exercise or stress induced Proteinuria
Cellular casts:Cellular casts: RBC casts: Glomerulonephritis and vasculitis WBC casts: pyelonephritis and tubulointerstitial disease Tubular casts: ATN or other renal tubular damage
Granular casts: Coarse or fine Degenerating cellular casts Aggregated proteingg g p
Fatty casts: Heavy proteinuria as in nephrotic syndrome
W Waxy: Advance renal failure
Red blood cell cast White blood cell cast
Only few bacteria in UNSPUN urine are essentially diagnostic of a UTI
Bacteria in a SPUN urine are NOT diagnostic and most of the time represent contaminationthe time represent contamination
GlomerularGlomerular TubularTubular InterstitialInterstitial VascularVascular
Heme positiveHeme positive ++++++ ++++ --/+/+ ++++
Protein 2+Protein 2+ ++++++ -- --/++/++ --/+/+Protein 2+Protein 2+ ++++++ /++/++ /+/+
Dysmorphic Dysmorphic RBCRBC
++++++ -- --/+/+ ++++
Renal cells Renal cells 1515--2020
--/+/+ ++++++ ++ ++
RBC castsRBC casts ++++ -- -- ++
Granular castsGranular casts ++ ++++ ++ ++
Heme/granularHeme/granular ++ ++++++ ++++++Heme/granular Heme/granular castscasts
++ -- ++++++ ++++++
Herrin, JT.