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UA Interpretation
Hematuria
Proteinuria

I find that for residents often find interpreting the UA a challenge, but understanding the urinalysis can give you amazing insight into what may be wrong with the patient. I will also give some pearls in interpreting commonly requested urine studies. 

We follow the UA with a brief description and workup of hematuria and proteinuria, and describe the more common conditions associated with each, respectively.

Urinalysis Interpretation Guide

Specimen Considerations

  • First-morning urine improves detection of protein, blood, and casts and are necessary for diagnostics, particularly proteinuria. However, if overly concentrated it may cause false positive proteinuria (since its measured in mg/dL) and blood (some cells lyse due to dehydration).

    • Ordering with urine creatinine alleviates some of the problems with proteinuria in a concentrated sample. ALWAYS order a urine creatinine if checking for proteinuria.

    • Similarly, a very dilute sample can overestimate proteinuria (e.g. a UP/C of 2mg/mg but urine creatinine is 17.8mg is unlikely to be significant- another reason to obtain a first morning sample. I prefer a urine creatinine of at least 40mg/dL.

  • Refrigeration slows bacterial growth but promotes crystal precipitation, so urine may appear cloudy.

  • Dilute or alkaline urine promotes RBC/WBC lysis and cast dissolution=false negatives and a missed diagnosis.

  • Exercise can cause both hematuria and proteinuria

 

*Commonly encountered items  are in bold*

 

Color:

Red/pink/brown:  Gross hematuria, hemoglobinuria, myoglobinuria, jaundice, phenytoin, nitrofurantoin (brown), Senna (yellow/brown red), Beetroot (red
White: Chyluria
Pink: uric acid crystalluria
Red to black upon standing: Porphyrinuria, alkaptonuria

Yellow/orange: Rifampin

Darkening upon standing Flagyll, 

 

Specific Gravity:

  • Measurement of particle/solute in the urine and compares urine to water, the closer to 1.0, the more watery. 1.010 is called isosthenuric- identical SG as plasma. This may indicate kidney injury as it demonstrates an inability to concentrate or dilute. However, many times these UAs are being collected in setting of receiving fluids. If <1.010= hyposthenuric, indicating a concentrating defect (e.g. seen in patients with sickle cell anemia/disease and possibly trait, who can also be 1010).

 

pH:

  • Relevant for risk of stone formation (in combination with risk factors), RTA (see "RTA") and in certain clinical scenarios (e.g. clearance of methotrexate).

 

Dipstick Chemistry & Mechanisms

  • Specific gravity: Urine concentration estimate.

  • Blood: Detects heme (hemoglobin, myoglobin, intact RBCs).

  • Protein: Detects primarily albumin (protein error of indicators).

  • Glucose: Glucose oxidase reaction.

  • Ketones: Detects acetoacetate

  • Bilirubin: Detects conjugated bilirubin.

  • Urobilinogen: Intestinal bilirubin metabolite.

  • Nitrite: Bacterial nitrate reduction.

  • Leukocyte esterase: Neutrophil enzyme.

 

False Positives & False Negatives

Blood

  • False Positives:

    • Myoglobin. Myoglobin has a very short half life and may not be there when checking the urine, but one can rely on + heme with nor RBC’s on microscopy in the right context.

    • Free hemoglobin, i.e. hemoglobinuria from intravascular hemolysis, not urinary tract bleeding.

    • Oxidizing agents

    • Bacterial peroxidase (e.g. lactobacillus, MAY be commensal bacteria, enterobacter, staph, strep)

  • False Negatives:

    • Vitamin C

    • High specific gravity

    • RBC lysis in dilute urine

    • See below for more!

 

Protein

  • False Positives:

    • Alkaline urine

    • Highly concentrated urine

    • Semen/vaginal contamination

  • False Negatives:

    • Dilute urine (see “specific gravity” for more details.)

    • Non-albumin proteins (light chains, tubular proteins)

    • Protein is reported as 1+, 2+ etc, that supposedly can be quantified (see chart below), but oftentimes inaccurate.

    • See below for more !

 

Glucose

  • False Positives:

    • Oxidizing contaminants

  • False Negatives:

    • Vitamin C

    • Bacterial consumption

    • Improper storage

 

Ketones: Seen in fasting, vomiting, exercise as well  as DKA. Ketones are freely filtered and is present in low glucose states.

  • False Positives:

    • Pigmented medications

  • False Negatives:

    • β-hydroxybutyrate predominance. (not measured on UA), therefore early DKA may be underestimated. 

    • Delayed analysis of UA.

 

Bilirubin: detected as a result of liver disease/cholestasis. Occasionally due to fasting. Urine is dark.

  • False Positives:

    • Pigmented drugs

  • False Negatives:

    • Light exposure

    • Oxidation

    • Vitamin C

 

Urobilinogen: detected as a result of RBC breakdown (Hb->biliverdin->bilirubin->conjugated bilirubin (liver)-> urobilinogen (duodenum)->30-50% absorbed in colon back to liver into bile, some into circulation->kidney. Urobilin gives urine its yellow  color. May be detected in hepatocellular disease, but NOT in obstruction

  • False Positives:

    • Drug cross-reactivity

  • False Negatives:

    • Standing urine oxidation

    • Antibiotics

    • Biliary obstruction

 

Nitrites. SPECIFIC  for UTI but not sensitive, as may be falsely negative, see below.

  • False Positives:

    • Standing urine

    • Contamination

  • False Negatives:

    • Frequent voiding (needs to be present ~ 4+ hours for bacteria to convert nitrate-> nitrite

    • Non–nitrate reducers (e.g. Enterococcus, Pseudomonas, Staph)

    • Vitamin C

 

Leukocyte Esterase. SENSITIVE for UTI, but not specific since it is elevated in systemic infection/inflammation and contamination. (e.g. sterile pyuria in Kawasaki disease). Cells may also lyse in alkaline urine, yielding neg microscopy

  • False Positives:

    • Vaginal contamination

    • Oxidizing contaminants

  • False Negatives:

    • High glucose/protein

    • High specific gravity

    • Vitamin C

 

Specific Gravity

  • False Positives:

    • Radiocontrast dye

    • High glucose/protein

  • False Negatives:

    • Alkaline urine

    • Temperature variation

Microscopy

  • RBCs

    • Glomerular injury (dysmorphic) , lower tract bleeding or trauma (isomorphic). RBC casts indicate GN. 

  • WBCs
    • Neutrophils in sediment via migration. WBC indicate infection or inflammation, casts indicate intrarenal location (AIN, Pyelo)

  • Tubular epithelial cells- tubular injury- ATN/ischemia/Nephrotoxins

  • Casts= Tamm-Horsfall proteins  (uromodulin) produced by tubular in the thick AL, plus one of the contents below
    • Hyaline: non specific- dehydration, fever, exercise, normal.
    • RBC: GN, vasculitis
    • WBC: AIN, pyelo
    • Granular (muddy brown): ATN
    • Epithelial: tubular damage
    • Waxy: CKD
    • Fatty: nephrotic syndrome

  • Crystals: Supersaturation + pH dependent precipitation. like a precursor for a stone
    •  Can U Order a Stone Panel is a mnemonic for stones and pH environment conducive to their formation listed from acidic->basic with oxalate at neutral pH (7) :
    • Cystine, Uric acid, Ca Oxalate, Struvite, Phosphate

Dipstick findings                                                                                           
Microscopy findings                                                                                           

Proteinuria

Dipstick:~urine protein concentration (we "notice, i.e. perk up" ~ 2+ range/>100mg/dL). Note UP/C ratio cutoffs and use below.

First Morning Urine & Role of Creatinine

  • Urine creatinine corrects for concentration (U/PC ratio, see "UA").

  • First morning sample that is normal (<0.2mg/mg) can rule out orthostatic proteinuria.

  • Low urine creatinine may reflect dilute urine or low muscle mass. I use a cutoff of at least 40mg/dL for a UP/C ratio

  • UP/C ratios ranges below are in mg/mg- take note of your lab's units!

 

Physiologic vs Pathologic Proteinuria

  • Fever: Mild (UP/C ratio<1mg/mg).

  • Exercise: Mild (UP/C ratio<1mg/mg ).

  • Orthostatic: Elevated daytime; normal first morning.

  • Disease: Persistent; often UP/CR >0.5–2mg/mg 

  • Nephrotic range: UPC/R ≥2mg/mg .

Due to the frequency for which it is encountered, we will discuss nephrotic syndrome below. Of note, while we often admit these patients for the first diagnosis, oftentimes it's more for the education as well as stabilization. With relapses (see below) they are often treated outpatient as tolerated/clinical signs/symptoms dictate. Also remember that lasix treats the fluid overload, but not the underlying conditon. In Minimal Change Disease, the steroids are (hopefully) treating the proteinuria/condition

 

Nephrotic syndrome is a clinical description of physical and chemical findings characterized by:

  • Heavy proteinuria (UP/C ratio of  ≥2mg/mg).

  • Hypoalbuminemia (<2.5-3mg/dL).

  • Edema (periorbital early).

  • Hyperlipidemia due to increased liver production and decreased lipid removal.

It is NOT a diagnosis. Depending on age of onset of these findings, we can make a presumptive diagnosis:

  • Etiology by Age of Onset

    • <3 months: Congenital nephrotic syndrome (genetic).

    • 3–12 months: Genetic causes vs  Infantile vs minimal change disease.

    • ~1–10 years: Minimal change disease most common (80-90%).

    • >10–12 years: Minimal change still common (50-70%), but increased proportion of FSGS and membranous nephropathy- consider biopsy/genetic testing.

 

  •  Minimal Change has some specific features.

    • If a child in the ~1-10 year age group presents with nephrotic syndrome, we do NOT get a biopsy. Why? 

      • Diagnosis is most likely MCD, so no new information is gathered

      • It usually responds to steroids (80-90%) so a biopsy won't change management

    • Initial therapy: Prednisone 2mg/kg/day max (60mg) for 4–6 weeks followed by an alternate-day taper.

      • 85–90% achieve remission within 4 weeks.

      • 70–80% relapse at least once.

      • ~50% of relapsers develop FRNS or SDNS.

    • Indications for biopsy: Steroid resistance, atypical age, persistent hematuria, low complement, hypertension, AKI.

 

Albumin vs Tubular Protein Assessment

  • While the UA measures albumin, the UP/C measure total protein (including tubular proteins, such as in CKD and certain genetic conditions, toxic injuries etc.). If a patient has elevated urine albumin and an elevated UP/C, you can "ballpark" if the proteinuria is mostly glomerular (albumin) or tubular (B2 microglobulin, retinol binding protein etc.)

  • An aside, microalbumin, which is drawn in those with diabetes and sickle cell disease/anemia, for example, just means measuring albumin in low concentrations, not small albumin.

  • APR (Albumin-to-Protein Ratio) = UACR ÷ UPCR, which estimates the fraction of total protein that is albumin. remember to convert your units!

  • APR ≥ 0.4 suggests albumin-predominant (glomerular) proteinuria.

  • APR ≤ 0.4 suggests non-albumin predominant (tubular) proteinuria.

Suggested reading:
- Cavanaugh C, Perazella MA. Urine Sediment Examination in the Diagnosis and Management of Kidney Disease: Core Curriculum 2019. Am J Kidney Dis. 2019;73(2):258-272. doi:10.1053/j.ajkd.2018.07.012
- Viteri B, Reid-Adam J. Hematuria and Proteinuria in Children. Pediatr Rev. 2018;39(12):573-587. doi:10.1542/pir.2017-0300

 

Hematuria

Definition: 3-5 RBCcs per HPF

 

Can be Gross or Microscopic

  • Only 1ml of blood can turn 1000ml red

  • Hematuria does not cause anemia

  • GN is not painful; if painful think trauma, UTI, stones

Likelihood of Identifying a Cause

  • Transient microscopic hematuria: Often benign and self-limited.

  • Persistent microscopic hematuria: Commonly hypercalciuria, AD Alport (formerly TBMN/BFH), IgA nephropathy .

  • Gross hematuria: Higher likelihood of structural, infectious, or glomerular pathology and of getting a diagnosis.

 

Timing During the Urinary Stream

  • Initial: Urethral source (trauma, urethritis).

  • Terminal: Bladder neck or cystitis, possibly kidney.

  • Throughout stream: Kidney or bladder source (GN, stones, UTI).

  • Clots suggest lower urinary tract source.

 

Differential

Nonglomerular Causes:

  • UTI

  • Nephrolithiasis / Hypercalciuria

  • Trauma (blunt abdominal, straddle injury, instrumentation)

  • Structural anomalies (UPJ obstruction, duplex system, PUV, cysts)

  • Sickle cell disease/trait (papillary necrosis, medullary ischemia)

Glomerular Causes:

  • Postinfectious GN (PSGN/PIGN)

  • IgA nephropathy / IgA vasculitis

  • Alport syndrome

  • Thin basement membrane nephropathy

  • ANCA-associated vasculitis

  • Systemic lupus erythematosus

  • HUS

 

Workup

​​

We will now discuss PIGN/PSGN as we see it fairly regularly. In the USA, PSGN is the most common cause of PIGN.  We typically make the diagnosis clinically (GN: hematuria, proteinuria (can be nephrotic) edema, HTN, AKI). Similar to nephrotic syndrome, and RPGN, GN is a clinical presentation, the diseases are varied, as seen above.

PSGN/PIGN

  • Causes:

    • Group A streptococcus (pharyngitis 1–2 weeks prior; skin 3–6 weeks prior).

    • Less commonly staph, gram-negative, viral.

  • Presentation:

    • Cola-colored urine

    • Edema

    • Hypertension

    • Subnephrotic proteinuria, but could be nephrotic

    • Low C3, usually normal C4, but could be slightly low. C3 very important for the differential (see chart below).

  • Workup:

    • UA: RBC casts

    • UP/C mg/mg (usually subnephrotic)

    • C3 (typically low; normalizes in 6–8 weeks)

    • ASO / Anti–DNase B

      • ASO: Best for pharyngitis; peaks 3–5 weeks.

      • Anti–DNase B: More sensitive for skin infections; peaks 6–8 weeks.

      • Both are often ordered in suspected PSGN.

    • Chemistry

    • Renal ultrasound if indicated

  • Treatment:

    • Supportive care

    • Salt restriction

    • Diuretics for edema

    • BP control

    • Treat active infection if present

    • Dialysis if RPGN (unclear incidence, but appears to be ~3-5%)

  • Monitoring & Natural History:

    • Edema/HTN improves within 1–2 weeks.

    • Creatinine normalizes in weeks.

    • C3 normal by 6–8 weeks.

      • If low C3 persists ~8-12 weeks, consider alternative dx, eg. C3G

    • Microscopic hematuria may persist 6–12 months.

    • Proteinuria resolves over weeks–months.

    • Recurrence is rare.

PSGN vs IgA:

  • PSGN: Delayed after infection; low C3; typically resolves.

  • IgA: Occurs during infection; normal complement; recurrent.

Let us know how we are doing and any suggestions for future entries!

This website provides educational materials and clinical calculators for healthcare professionals only. Content is not medical advice and should not replace clinical judgment or institutional guidelines. Users are responsible for verifying all calculations and patient care decisions.

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