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Proteinuria

Proteinuria

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Proteinuria

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  1. Proteinuria Anh Nguyen, MD, MPH

  2. Objectives • Define normal range of proteinuria • Define abnormal range of proteinuria • Learn to work-up for proteinuria

  3. Normal urinary protein excretion • In normal adult, normal urinary protein excretion should be < 150 mg/day • Normal rate of albumin excretion is < 20 mg/day (15 mcg/min), increases with age and higher body weight

  4. Abnormal proteinuria • Previously, abnormal proteinuria was defined as excretion of protein > 150 mg/day • However, early renal disease is reflected by lesser degrees of proteinuria • 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)

  5. Nephrotic Syndrome • 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

  6. Isolated proteinuria (benign) • 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 (non-nephrotic) • Serologic markers of systemic disease are absent

  7. Types of proteinuria • Glomerular proteinuria: increased filtration of macromolecules (such as albumin) across the glomerular capillary wall. • Tubular proteinuria: excretion of low-molecular-weight proteins, such as beta2-microglobulin, immunoglobin light chains, retinol-binding protein and polypeptides derived from breakdown of albumin • 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 • Post-renal proteinuria: inflammation in the urinary tract (UTI), excreted proteins are generally non-albumin (IgA or IgG)

  8. Approach to the patient with proteinuria • 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

  9. Case 1 • 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

  10. Work-ups for proteinuria • 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)

  11. Case 1 (cont.) • Repeat UA in the morning before physical activites: negative

  12. Case 2 • 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

  13. Case 2 • 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

  14. Case 2 • Lab Studies: • 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

  15. Work-ups for proteinuria • 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

  16. Case 2 (cont.) • Work-ups for nephrotic-range proteinuria showed: • ANA Positive 1:320 • Anti-dsDNA1:640 • 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)

  17. Take Home Messages • 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

  18. Take Home Messages (cont.) • Work-ups for isolated proteinuria: repeat UA in the morning or split urine collection • Work-ups for proteinuria with systemic disease symptoms: 24-hour urine Pro/Cr, rule out secondary causes, renal biopsy

  19. References • 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 non-nephrotic proteinuria in adults. UpToDate