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PROTEINURIA

  • Definition:

    • - Urine protein to creatinine ratio (UPCR) >150 mg/g or 24-hr protein >150 mg

      • Greater than 3 g/24 hr is nephrotic-range proteinuria

    • - Urine albumin to creatinine ratio (UACR) >30 mg/g or 24-hr albumin excretion >30 mg

      • 30–300 mg/g is termed microalbuminuria

      • >300 mg/g is termed macroalbuminuria

  • Etiology:

    • - Glomerular proteinuria: Increased glomerular permeability; due to primary glomerulonephritis (GN) or GN secondary to systemic illness (e.g., diabetes)

    • - Tubular proteinuria: Impaired tubular reabsorption due to tubular dysfunction; seen in tubular interstitial injury from systemic illness, congenital disease, endogenous toxins or exogenous toxins (e.g., beta-lactam antibiotics)

    • - Overflow proteinuria: Impaired resorptive ability of the proximal tubule; due to excess filtration and/or production of proteins (e.g., hemolysis, rhabdomyolysis, Bence-Jones protein in multiple myeloma, amyloidosis)

    • - Other: Fever, exercise, orthostatic proteinuria (i.e., proteinuria only when standing; benign/self-limited, typically occurs in young people)

  • Diagnosis:

    • - Spot tests: UPCR, UACR, or dipstick; dipstick detects albumin ranges from 1+ (30–100 mg/dL) to 4+ (>1000 mg/dL)

    • - 24-hour urine is rarely needed, but may be useful in establishing the accuracy of spot tests and quantifying a baseline level of proteinuria in a patient with persistent proteinuria; however, it is cumbersome and susceptible to collection error

  • Pearls:

    • - Multiple myeloma and other light-chain diseases will produce proteinuria without significant albuminuria; therefore, UACR or dipstick will be “falsely” negative (or unexpectedly mild)

    • - Dilution and high pH may also yield false-negative dipstick results. Specific gravity should be greater than >1.005 and pH <8 for accurate results.

    • - Persistent proteinuria is associated with progression of kidney disease, and thus is often a treatment target and a surrogate outcome in the treatment of kidney disease. One needs to identify the underlying cause and treat. ACEi/ARBs are often used to improve proteinuria.

HEMATURIA

  • Types:

    • - Microscopic hematuria: Normal appearing urine with ≥ 2 RBCs/HPF detected in the UA → Consider glomerular disease

    • - Gross hematuria: Visibly abnormal appearing urine with RBCs on microscopy → More likely urologic disease (e.g., trauma, infection, stones, malignancy, PKD)

    • - Mimics of gross hematuria: Menstruation or other uterine sources of bleeding, medications (e.g., pyridium, phenytoin, rifampin), foods (e.g., beets), metabolites (e.g., bile, porphyrin, methemoglobin)

    • - Causes of UA positive for blood without hematuria on microscopy: Hemolysis, rhabdomyolysis

  • History: The following clues may inform the differential diagnosis:

    • - Gross hematuria (e.g., visible blood in the urine) → More likely urologic but may also be caused by IgA nephropathy or renal vasculitis

    • - Concurrent dysuria → UTI, malignancy, stone

    • - Recent URI → IgA nephropathy if SYNpharyngitic (i.e., at the same time as the infection) vs. post-infectious GN (usually occurs 2-3 weeks after)

    • - Family history (polycystic kidney disease, Alport’s syndrome, benign familial hematuria)

    • - Flank pain → Stones

    • - Recent vigorous exercise → Exercise-induced hematuria

    • - Travel → Urinary schistosomiasis, renal tuberculosis

    • - Timing:

      • Beginning of urination → Urethra

      • End ...

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