02. Approach to the abnormal UA

Meghan Jobson, MD PhD

Lowell Lo, M.D.

Initial Approach

  • Although H&P is helpful, urinalysis and examination of urine sediment are crucial in evaluating renal pathology & providing a window into systemic disease
  • UA is the primary noninvasive diagnostic tool, but there is not always correlation between severity of disease & UA findings
  • How to collect a UA: examine urine within 30-60 minutes of voiding, mid-stream urine specimen (except first-void for urine STD screening) and check dipstick. For microscopy, pour 10mL urine into graduated centrifuge tube and centrifuge at 3000 rpm for 3-5 mins. Decant 9mL supernatant and resuspend remaining 1mL urine with pipet. Place one drop of this resuspended urine on slide with coverslip. Examine under microscope.

Components of the Routine Urinalysis & Microscopy
Color

  • Clear to dark yellow based on concentration
  • Red (see Hematuria) – blood, beeturia, achlorhydria due to pernicious anemia, or coingestion of oxalate-containing foods (e.g., spinach & rhubarb)
    • If lots of “blood” but no RBCs & heme-positive consider hemoglobinuria or myoglobinuria
    • For true hematuria, initially check if transient or persistent, microscopic or gross
  • Black: alkaptonuria/ochronosis, sometimes hemoglobinuria, myoglobinuria
  • Purple: purple urine bag syndrome, porphyria
  • Green: bilirubinuria, propofol, amitriptyline, methylene blue
  • Orange/Brown: jaundice, rhabdomyolysis, Gilbert’s, porphyria, rifampin, pyridium
  • Blue: methylene blue
  • Pink (see Hematuria): uric acid crystals with high dose propofol
  • White: pyuria, phosphate crystals, chyluria, propofol

Urine pH

  • Usually between 4.6 – 6
  • High urine pH suggests an alkali load or inability to acidify urine appropriately
  • High urine pH seen with Proteus UTI, systemic alkalosis, proximal or distal RTA, carbonic anhydrase inhibitors

 

Protein (see chapter on Proteinuria for further details)

  • Dipstick detects albumin (e.g., not light chains) – specific but insensitive, so you have to order urine microalbumin : creatinine ratio  specifically to assess for early albuminuria and quantification
  • If proteinuria seen on dipstick, check spot protein: creatinine  ratio
  • Mild transient proteinuria can be seen with infection, fever, heavy exercise and benign orthostatic proteinuria
  • Nephrotic range proteinuria > 3.5 g/day
  • Iodinated contrast gives a false positive for urine protein for at least 24 hours

Urine osmolality

  • Unlike serum osmolality, vast variation, and you have to correlate with volume status – useful to check if patients with hypo/hypernatremia, AKI, polyuria
    • UOsm < 100 mosm/kg in a hyponatremic patient often indicates appropriate ADH suppression and can indicate primary polydipsia
    • UOsm > 300mosm/kg in hyponatremic patient often indicates low effective circulating volume (e.g., hypovolemia, cirrhosis, CHF) or SIADH
    • In AKI, the tubule loses its ability to concentrate so UOsm is often < 350mosm/kg whereas UOsm > 500 suggests pre-renal state if patient is oliguric

Specific gravity

  • Specific gravity determined by number & size of particles in the urine (water = 1.0 as a reference)
  • Urine s.g. < 1.003 shows maximally dilute urine whereas > 1.035 is very concentrated
  • Repeated urine s.g. = 1.010 represents isosthenuria which suggests loss of tubular concentrating and diluting capacity – seen clinically with significant renal diseases

Glucose/Ketones

  • Usually glucosuria occurs if plasma glucose > 180mg/dL, not sensitive/specific
  • Think of Fanconi’s syndrome (associated w/ multiple myeloma, tenofovir or ifosfamide use, heavy metal exposure) if glucosuria seen with hypophosphatemia, hypouricemia, RTA (i.e. proximal tubule dysfunction)
  • Ketonuria seen with DKA, fasting, starvation, alcoholic ketoacidosis, isopropyl alcohol intoxication (with osmolar gap)

Crystals

  • Uric acid, calcium phosphate, calcium oxalate (stones, various)
  • Magnesium ammonium phosphate crystals (struvite stones)
  • Calcium oxalate crystals (ethylene glycol ingestion)
  • Uric acid crystals (nonspecific finding – can be seen in hypovolemia or severe problem like tumor lysis syndrome)
  • Healthy people with concentrated urine from decreased fluid intake can have crystals in urine

Bacteria

  • Leukocyte esterase represents pyuria (detects lysed WBCs)
  • Nitrite represents Enterobacteraciae species
  • Combination of +LE/+nitrite has PPV of 74% for UTI if both are positive, NPV of >97% if both are negative

Pyuria

  • Infection is most common cause, but sterile pyuria can be seen in urinary TB, prostatitis, analgesic nephropathy, and interstitial nephritis
  • Urine eosinophilia suggestive of AIN
  • Correlate pyuria with number of epithelial cells seen to assess for contamination

Casts

  • Hyaline casts - hypovolemia or diuretic use, not pathogenic
  • RBC casts -specific for glomerulonephritis
  • WBC casts -non-specific, pyelonephritis, tubulointerstitial disease, glomerular disorders
  • Fatty casts -nephrotic syndrome, “Maltese cross” appearance
  • Muddy brown and granular casts –ATN-

Suspicious Constellations on UA and Disease Associations

  • Hematuria, RBC casts, dysmorphic RBCs, proteinuria - Glomerular disease
  • Pyuria with WBC and granular or waxy casts but no proteinuria - Suggests tubular or interstitial disease or urinary tract obstruction
  • Hematuria and pyuria but no casts - Seen in AIN, glomerular disease, vasculitis, obstruction, renal infarction
  • Relatively “normal” UA does not rule out AKI. Cannot exclude pre-renal, obstructive or intrinsic renal diseases

References

Lin J, Denker BM. Azotemia and Urinary Abnormalities. Harrison’s Online.

Wald.. Urinalysis in the diagnosis of kidney disease. UptoDate, 2016.