Proteinuria & Hematuria!

RESOURCES & REFERENCES!

Choosing Wisely campaign recommendations via the AAP section on nephrology: 

Other resources:


TESTING PEARLS!

The gold standard for measuring protein excretion is a 24-hour urine collection, which is a challenging test to perform correctly. A good substitute is a spot urine protein-to-creatinine ratio (UPCR). 

  • Proteinuria in adults: >150 mg/day or UPCR >0.2 mg/mg (>200 mg/g)
  • Proteinuria in kids >2yo: >100 mg/m2/day or UPCR >0.2 mg/mg (>200 mg/g)

Urine albumin-to-creatinine ratio (UACR) is the preferred screening test for diabetic nephropathy. (Urine dipstick and UA are insensitive for albuminuria.)

  • Epic tip: Ordering “random urine microalbumin” automatically includes a random urine creatinine

Urine dipstick grading for proteinuria (e.g. 2+) is highly dependent upon urine concentration and pH (i.e. false-positive proteinuria can occur in the presence of high specific gravity or alkaline pH). Also, albumin is the only protein detected by urine dipstick testing. 

  • Generally, dipstick grading correlates with protein concentration (mg/dL): 
    • 1+ = 30-100
    • 2+ = 100-300
    • 3+ = 300-1000
    • 4+ = ≥1000 (nephrotic range ≥3500)

Hematuria is generally accepted to be >5 erythrocytes/hpf

  • Urine dipstick tests for heme pigment. Thus, unlike proteinuria, there is no clear correlation between dipstick grading of hematuria and the number of urine sediment RBCs

DISEASE PEARLS!

Both proteinuria and hematuria have several transient causes:

  • Transient proteinuria: fever, exercise, stress, seizure, dehydration, etc
  • Transient hematuria: fever, exercise, UTI, trauma, urethritis, stones, schistosomiasis, hemorrhagic cystitis, etc

Persistent proteinuria suggests underlying renal or systemic disease, and is a well-known risk factor for progression to CKD in both adults and children. The type of protein excreted depends on the type of kidney disease–albuminuria is more strongly associated with glomerular disease from HTN/DM, whereas excretion of low molecular weight proteins (e.g. immunoglobulin) suggests tubulointerstitial disease

  • Key point: the absence of proteinuria essentially rules out glomerulonephritis. 

Moderately increased albuminuria (previously known as microalbuminuria) is persistent albumin excretion of 30-300 mg/day. Albuminuria is an independent risk factor for CV mortality

Hematuria of lower urinary tract etiology is typically gross hematuria with eumorphic RBCs. Glomerular hematuria is typically tea/cola-colored with acanthocytes (RBCs of variable size/shape) and/or RBC casts. 


QUESTIONS TO PONDER!

  • Should we ever order a screening UA on an asymptomatic child? 
    • Yes! Consider performing this test regularly in kids at risk for CKD: 
      • h/o prematurity (<32wk GA), VLBW, other neonatal complications requiring intensive care, umbilical artery line;
      • congenital heart disease (repaired or unrepaired);
      • recurrent UTIs, hematuria, or proteinuria;
      • known kidney disease or urologic malformations;
      • solid organ transplant;
      • malignancy or bone marrow transplant;
      • h/o or prolonged treatment with drugs known to be nephrotoxic;
      • h/o recurrent episodes of AKI;
      • FHx of inherited kidney disease 
  • What’s the difference between urine dipstick testing and urinalysis with microscopy?
  • What’s the difference between albuminuria and proteinuria? Is it ok to order a UPCR instead of UACR when screening a pt for diabetic nephropathy?
  • What medications help control proteinuria in adult pts with HTN or DM? 
    • ACEI/ARB and non-dihydropyridine CCBs (i.e. verapamil, diltiazem) can reduce proteinuria and progression of CKD. 
  • What’s the difference between hematuria and hemoglobinuria?
  • How does the work-up of persistent proteinuria differ in children vs adults?
  • How does the work-up of persistent hematuria differ in children vs adults?