Proteinuria
Anh Nguyen, MD, MPH
Objectives
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Define normal range of proteinuria
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Define abnormal range of proteinuria
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Learn to work-up for proteinuria
Normal urinary protein excretion
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In normal adult, normal urinary protein
excretion should be < 150 mg/day
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Normal rate of albumin excretion is < 20
mg/day (15 mcg/min), increases with age and
higher body weight
Abnormal proteinuria
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Previously, abnormal proteinuria was defined as excretion of
protein > 150 mg/day
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However, early renal disease is reflected by lesser degrees of
proteinuria
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Persistent albumin excretion between 30 and 300 mg/day (20 to
200 mcg/min): high albuminemia (formerly called
microalbuminuria)
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Albumin excretion > 300 mg/day (200 mcg/min): overt proteinuria
or very high albuminuria (formerly called macroalbuminuria)
Nephrotic Syndrome
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Massive proteinuria—at least 3.5 g/day
Hypoalbuminemia (albumin < 3.5 mg/dL)
Generalized edema
Hyperlipidemia, hyperlipiduria
Dysmorphic and red cell casts in urine
Isolated proteinuria (benign)
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Defined as proteinuria without hematuria or
reduction in glomerular filtration rate (GRF)
In most cases, patient is asymptomatic
Urine sediment is unremarkable: few than 3
erythrocytes/hpf and no casts)
Protein excretion is less than 3 g/day (nonnephrotic)
Serologic markers of systemic disease are
absent
Types of proteinuria
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Glomerular proteinuria: increased filtration of macromolecules
(such as albumin) across the glomerular capillary wall.
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Tubular proteinuria: excretion of low-molecular-weight proteins,
such as beta2-microglobulin, immunoglobin light chains, retinolbinding protein and polypeptides derived from breakdown of albumin
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Overflow proteinuria: increased excretion of low-molecular-weight
proteins; almost always due to immunoglobin light chains in multiple
myeloma, lysozymes in AML, or myoglobin in rhabdomyolysis
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Post-renal proteinuria: inflammation in the urinary tract (UTI),
excreted proteins are generally non-albumin (IgA or IgG)
Approach to the patient with proteinuria
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Careful medical history and physical exam
Examine urine sediments
A patient with isolated proteinuria (normal
urine sediment, normal kidney function),
should rule out transient and orthostatic
proteinuria
Case 1
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20 year-old man with no significant PMH who
came to clinic for a physical for college
football. No physical complaints. Vital signs,
BP WNL. Physical exams WNL.
UA: no casts, +2 protein
Work-ups for proteinuria
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UA and microscopic examination for at least
3 separate occasions
Spot Alb/Cr or Pro/Cr ratio
UA on early morning sample before patient is
involved in physical activities or
Split urine collection: daytime (7 AM to 11
PM) and nighttime (11 PM to 7 AM)
Case 1 (cont.)
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Repeat UA in the morning before physical
activites: negative
Case 2
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43 year-old woman with h/o HTN and anemia since age 12 presents
progressive shortness of breath, hematuria, abdominal pain, and
recurrent epistaxis.
Constitutional symptoms: subjective fever with night sweat, 30 lb weight
loss, extreme fatigue and weakness, dry mouth and dry eyes
Pleuritic chest pain, shortness of breath with walking 5 steps
Arthritis with morning stiffness
Abdominal pain with loose stool, more recently becoming black
Large lymph nodes in the neck
Epitaxis for one week
Fingers and toes are cold with tingling and had non-blanching petechiae
Excessive hair loss every morning on pillows over the past 6 months
Violaceous rash on from thighs to ankles, neck and chest
Case 2
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43 year-old woman with h/o HTN and anemia since age 12 presents
progressive shortness of breath, hematuria, abdominal pain, and
recurrent epistaxis.
Constitutional symptoms: subjective fever with night sweat, 30 lb weight
loss, extreme fatigue and weakness, dry mouth and dry eyes
Pleuritic chest pain, shortness of breath with walking 5 steps
Arthritis with morning stiffness
Abdominal pain with loose stool, more recently becoming black
Large lymph nodes in the neck
Epitaxis for one week
Fingers and toes are cold with tingling and had non-blanching petechiae
Excessive hair loss every morning on pillows over the past 6 months
Violaceous rash on from thighs to ankles, neck and chest
Case 2
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Lab Studies:
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BMP: electrolytes WNL, BUN 10 Cr 0.8, Glu 97, Ca 7.8
CBC: WBC 3.3 Hgb 8.6 Hct 25.6 PLT 42 MCV 84.9
AST: 56 ALT: 13
Iron Panel: Iron plasma 32, TIBC 217, FeSat 50%, Ferritin
213
UA: 200 protein spot, RBC 182
24 hour urine protein: 5.7 g
CRP 2.6 ESR 109
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Work-ups for proteinuria
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24-hour urine Pro/Cr
Rule out secondary causes: HA1C, ANA,
ANCA, anti-dsDNA, C3, C4, SPEP/UPEP,
HBV, HCV, HIV, RPR, phospholipase A2
receptor Ab
Renal biopsy
Case 2 (cont.)
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Work-ups for nephrotic-range proteinuria
showed:
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ANA Positive 1:320
Anti-dsDNA 1:640
Decreased C3 of 13.8
Decreased C4 of 2.0
Renal biopsy: Lupus Nephritis Class IV (capillary proliferation,
wire loop thickening and sub-endothelial deposits)
Take Home Messages
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In normal adult, normal urinary protein excretion should be < 150
mg/day

Persistent albumin excretion between 30 and 300 mg/day (20 to
200 mcg/min): high albuminemia (formerly called
microalbuminuria)

Albumin excretion > 300 mg/day (200 mcg/min): overt proteinuria or
very high albuminuria (formerly called macroalbuminuria)

Nephrotic syndrome: massive proteinuria—at least 3.5 g/day,
hypoalbuminemia (albumin < 3.5 mg/dL), generalized edema,
hyperlipidemia, hyperlipiduria
Take Home Messages (cont.)
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Work-ups for isolated proteinuria: repeat UA
in the morning or split urine collection
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Work-ups for proteinuria with systemic
disease symptoms: 24-hour urine Pro/Cr,
rule out secondary causes, renal biopsy
References
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Rennke HG, Denker BM. Renal
Pathophysiology: The Essentials 2nd edition.
Lippincott Williams & Wilkins, 2007.
Sabatine MS. Pocket Medicine, 4th edition.
Wolters Kluwer Health/Lippincott Williams &
Wilkins, 2011.
Rovin BH. The assessment of urinary protein
excretion and evaluation of isolated nonnephrotic proteinuria in adults. UpToDate