13. Hematuria

Definition

  • Five or more RBCs per high power field in at least 3 of 3 consecutive centrifuged specimens at least 7 days apart.
  • Macroscopic hematuria is grossly visible whereas microscopic hematuria is not.
    • Gross hematuria is visible with as little as 1 mL of blood per liter of urine.

Etiology

It is important to find out if gross or microscopic, symptomatic or asymptomatic, and transient or persistent. One key is to differentiate between glomerular vs. non-glomerular. Presence of proteinuria can be suggestive of glomerular etiology.

  • SHIITTE: stones, hematopoietic pathology, infection, inflammation, tumor, trauma, exercise.
  • Glomerular: glomerulonephritis, thin basement membrane disease, Alport syndrome, HUS. Usually see dysmorphic RBCs.
  • Non-glomerular: nephrolithiasis, UTI or other lower urinary tract infection including urethritis or prostatitis, trauma (Foley catheter), cancer (kidney, urothelial, prostate), BPH, polycystic kidney disease, sickle cell disease or trait, AVM, “loin pain hematuria” syndrome.
  • Gross hematuria: lower urinary tract source or intrarenal bleeding (e.g. renal carcinoma).
  • Contamination: GI or gynecologic bleeding. 
  • Other causes of dark urine (e.g., positive dipstick but without presence of ≥3RBCs/HPF): hemoglobinuria (seen in hemolysis, PNH, G6PD), myoglobinuria (seen in rhabdomyolysis), medications (rifampin, laxatives, propofol), presence of semen in men. Therapeutic anticoagulation can cause hematuria but other causes should still be excluded. 

Evaluation

  • History:
    • Previous episodes, symptoms of UTI, acute onset unilateral flank pain with or without radiation to the groin area (suggestive of nephrolithiasis), personal history of renal stones, known recent trauma (e.g. recent instrumentation/Foley), passage of clots (suggests extraglomerular source), recent menses.
      • Glomerular causes: bleeding often painless, periorbital puffiness, weight gain, oliguria, dark-colored urine, edema, hypertension.
      • Collagen vascular disease: joint pain, rashes, persistent fever.
    • FHx of GU disease (e.g. ADPKD, Alport syndrome), collagen vascular diseases, urolithiasis.
    • Risk factors for GU cancer: smoking, cyclophosphamide, ifosfamide, chronic inflammation, age >35y, environmental exposures (e.g. benzenes, aromatic amines), history of chronic or recurrent UTIs, history of pelvic radiation, prior use of aristolochic acid.
  • Physical:
    • Abdominal (tenderness or masses), MSK (CVA tenderness), GU exam, assess for edema, measure BP to evaluate for HTN, skin exam for rash (particularly palpable purpura or petechiae).
  • Labs:
    • CBC, coags, chem 10, urinalysis with sediment/microscopy, urine culture, urine protein (e.g., spot urine protein:creatinine ratio).
      • As history and physical suggest, may also consider other serologic testing (e.g. C3/C4, ASO, anti-DNase B, ANA, dsDNA, ANCA).
      • Glomerular hematuria: brown-colored urine, RBC casts, WBC casts, dysmorphic RBCs, proteinuria, albuminuria, elevated Cr, hypoalbuminemia.
      • Non-glomerular hematuria: reddish/pink urine, clots, normal appearing RBCs.
    • In menstruating women in whom there is concern that bleeding may be from GYN source, a tampon can be inserted and UA re-obtained.
    • Centrifugation of the urine and delineation of whether the red color is due to cells or other substances helps to discern whether there are RBCs in the urine (in the sediment) vs. myoglobin/hemoglobin (in the supernatant).
    • Can do urine cytology for patients with gross hematuria and risk factors for urinary tract cancer. Only 48% sensitive, though 94% specific.
  • Imaging: 
    • Consider renal/bladder US to assess for stones or evidence of hydronephrosis.
    • CT “stone protocol” (non-contrast, 3-5 mm cuts) for patients with renal colic.
    • Consider CT urogram (or CT with/without contrast), especially if blood clots are present in the urine. 
    • If evidence of ureteral obstruction, magnetic resonance urography w/o contrast can pinpoint location of obstruction.

Management

  • IV access and IVF/pRBCs, if needed.
  • Microscopic hematuria in the setting of UTI that clears with treatment of the UTI does not need further workup.
    • Depending on the clinical scenario, repeat UA may be warranted six weeks after treatment for UTI.
  • Hematuria in the setting of a catheter:
    • In patients with an obstructed catheter, get a CT urogram, urine cytology once the hematuria has improved, and an outpatient cystoscopy.
    • If the catheter is not draining due to clot or blood build up, flush and remove clots if possible. Continuous bladder irrigation may be needed with urology involvement for significant catheter obstruction to keep urine cranberry color or lighter. 
  • Relative indications for kidney biopsy: 
    • Significant proteinuria (e.g. UPCr >300mg/g or 30mg/day in those with evidence of glomerular hematuria), abnormal renal function (progressive rise in Cr), recurrent or persistent hematuria, serologic abnormalities, suggestive family history.
  • Asymptomatic (isolated) hematuria generally does not require treatment, however, persistent microscopic hematuria over the course of 6-12 months may necessitate further work-up to evaluate for underlying cause.

Key Points

  • When to consult/refer to urology: one or more episode of hematuria, presence of clots (which can cause obstruction and bladder distension or hydronephrosis), isolated hematuria (without proteinuria), abnormal GU anatomy, mass found on imaging. 
  • Consult renal if: dysmorphic RBCs, RBC casts, WBC casts, proteinuria with hematuria, hypoalbuminemia, CKD, new or worsening HTN, AKI, new or worsening edema, extra-renal manifestations suggestive of systemic processes like ANCA or SLE diseases.
  • 9-18% of asymptomatic patients have RBCs in their urine, so the USPSTF and AUA don’t recommend screening for bladder cancer in asymptomatic patients. 

 

Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med 2003; 348: 2330-2338.

Grossfeld et al. Asymptomatic Microscopic Hematuria in Adults: Summary of the AUA Best Practice Policy Recommendations. Am Fam Physician. 2001 Mar 15;63(6):1145-1155.

Gulati, S. Hematuria. Medscape. Updated 5/10/2020. Accessed at https://emedicine.medscape.com/article/981898-overview

Perazella MA, O’Leary MP. Etiology and evaluation of hematuria in adults. UpToDate.. Accessed at https://www.uptodate.com/contents/etiology-and-evaluation-of-hematuria-in-adults?search=Etiology%20and%20evaluation%20of%20hematuria%20in%20adults&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Rao, P., Jones, J.S. How to evaluate ‘dipstick hematuria’: What to do before you refer. Cleveland Clinic Journal of Medicine March 2008 vol. 75 3 227-233.