Hematuria

By admin On Sep 27, 2023

Ovid: 5-Minute Sports Medicine Consult, The

Hematuria

Charles W. Webb

C. Thayer White

Basics

Exercise-induced hematuria (1):

Occurs with or without trauma in males and females; resolves with rest in 2–3 days
Although a benign condition, it is a diagnosis of exclusion.
Directly correlated with intensity and duration of exertion
Traumatic mechanisms:
- Direct kidney trauma
- Contusion of the mobile bladder wall with the fixed wall in an empty bladder during running
Atraumatic mechanisms:
- Physiologic decreased renal blood flow during exercise causing hypoxic damage to the nephron and leading to increased permeability for RBCs and proteins
- Relatively more marked constriction of the efferent arteriole leads to increased filtration pressure favoring excretion of RBCs and protein.
- Hydration and a partially full bladder during exercise may help to prevent or minimize this condition (2).

Description

Microscopic hematuria or microhematuria: Presence of 3 or more RBCs per high-powered field (RBCs/HPF) on microscopic analysis of at least 2 of 3 properly collected urine samples:
- A urine dipstick of 1+ blood or greater usually corresponds to at least 3–5 RBCs/HPF but also can be caused by free hemoglobin, myoglobin, or other interfering substances in foods or drugs. A dipstick test is not diagnostic of hematuria.
- A clean-void specimen for males and nonmenstruating females
- May require catheterized or carefully collected sample in menstruating or postpartum women
The RBC count drops 5–9% over 5 hr and 11–28% over 24 hr, so immediate microscopic analysis is important.
Gross hematuria: Red to brown discoloration of the urine with numerous RBCs seen on microscopy
Exercise-induced hematuria (EIH): Transient appearance of usually microscopic hematuria following physical exertion with no history of trauma. It typically resolves within 48–72 hr.
Symptomatic hematuria: Either gross or microscopic hematuria in the presence of any lower or upper urinary tract symptoms (eg, flank pain, renal colic, dysuria, urgency, etc.)
Asymptomatic hematuria: Either gross or microscopic hematuria in the absence of any urinary tract symptoms
Note: 1 mL of blood per liter of urine can produce a visible color change.
Persistent recurrent, symptomatic, or traumatic hematuria warrants further evaluation (1,2,3).

Epidemiology

EIH: Unknown
All other causes:
- Age <40 yrs: Usually infection
- Age >40 yrs: Increasing incidence of tumor
- Males >60 yrs: Usually prostatic obstruction, calculi, or tumor
- Females >60 yrs: Usually malignancy (1,2)

Prevalence

Prevalence of hematuria in the general population is 2.5–20% depending on the population studied and the criteria for diagnosis.
Prevalence in the general pediatric population is 0.5–2%.
Prevalence increases to 18–80% following athletic competition and usually resolves in 48 hr (1,3).

Risk Factors

Chronic urinary tract infection
Anticoagulation
Strenuous exercise
History of calculi, prostatitis, trauma, malignancy, coagulopathy, or sexually transmitted disease
Family history of renal failure
Travel to Africa, India, or the Middle East (1,2,3)

General Prevention

There are currently no recommendations to screen any population for hematuria.
There are currently no recommendations to screen any populations using urine dipsticks.

Diagnosis

Hematuria itself is rarely a medical emergency but may be a sign of underlying pathology, such as malignancy or medical renal disease.
Microscopic hematuria is usually transient and benign, but this is a diagnosis of exclusion.
History and exam features will help to guide which patients need further workup.
Confirm the diagnosis as asymptomatic microscopic hematuria with microscopic examination at least 2 separate urine samples before initiating further workup.
>50 RBCs/HPF is generally considered significant hematuria and may warrant immediate further investigation, depending on the situation.
Any symptomatic or gross hematuria warrants further evaluation.
Causes:
- Unexplained/idiopathic: No urologic cause is found in 87% of microhematuria and 72% of gross hematuria seen at a referral clinic.
- Spurious:
  - Menstruation
  - Sexual intercourse
- Pseudohematuria (aka dipstick hematuria)
- Rhabdomyolysis
- Foods (beets, rhubarb, blackberries)
- Drugs (doxorubicin, chloroquine, rifampin)
- UTI: Acute cystitis or pyelonephritis:
  - If UTI is suspected as a cause, send urine for culture to confirm, treat infection, and repeat test in 6 wks before initiating workup.
  - Recurrent UTI could signal pathology.
- Prostatitis or urethritis
- Urinary tract calculi
- Exercise-induced
- Trauma to flank or abdomen (renal fracture)
- Cancer: Renal, bladder, prostate, ureter:
  - Present in 19–25% of gross hematuria but <1.5% of microhematuria in the general population:
    - Exceedingly rare under age 40
    - Transient hematuria and intermittent hematuria are common.
  - Benign prostatic hyperplasia (BPH)
  - Glomerular disease (many causes; consider nephrology referral if suspected); IgA nephropathy and thin basement membrane (TBM) disease most common
  - Sickle-cell disease
Rare causes:
- Polycystic kidney disease
- Schistosoma haematobium infection
- Radiation cystitis
- Urethral strictures
- Tuberculosis
- Medullary sponge kidney
- Cyclophosphamide-induced cystitis
- Arteriovenous malformation
- Renal artery thrombosis
- Papillary necrosis of any cause
- Loin pain hematuria syndrome
EIH (4):
- Diagnosis of exclusion
- Can make the diagnosis without further workup in athletes <40 yrs old who have hematuria within 12 hr of vigorous activity that resolves completely within 48–72 hr.
- Not fully understood; thought to be multifactorial
- More common with increased intensity of exercise
- Epinephrine and norepinephrine release cause renal vasoconstriction and decreased glomerular filtration rate (GFR), which results in increased glomerular filtration and permeability.
- Bladder trauma can occur in runners as the posterior bladder wall repeatedly strikes the base. This can be alleviated by keeping a small amount of urine in the bladder.
- Cyclist can experience direct trauma to the prostate and urethra.
- Hemoglobinuria can be caused by RBC lysis for a number of reasons.
- Dehydration and increased blood viscosity
- Increased body temperature
- Oxidative-damage myoglobinuria
- March, or foot-strike, hematuria is thought to occur from trauma to the foot capillaries.
- Can result from muscle breakdown (3)
Traumatic hematuria:
- More likely to present as gross hematuria
- Children are more likely to have renal injury following trauma owing to lack of perinephric fat and less protection by the ribs.
- There is a lower threshold for imaging of children.
- Serious renal injury is much more likely to occur after a fall, bike, or motor vehicle accident (high-velocity accidents and/or collisions) than with athletic participation.
- A pediatric database of 49,651 trauma cases also includes 813 renal injuries with 28 lost kidneys. There were 85 sports-related renal injuries with no lost kidneys. Football was the most common sport causing traumatic renal injury.
- The presence of any one of the following: (1) gross hematuria, (2) hypotension, or (3) significant mechanism (eg, fall from a height or rapid deceleration) should prompt imaging in an adult. In a large review, no significant injuries were missed with these criteria.
- In children, additional criteria for imaging include >50 RBCs/HPF and abdominal/flank pain or ecchymosis.
- All penetrating trauma needs a surgical consultation.
- The severity of injury is graded I to V on the organ Injury Severity Scale (ISS). Grades I and II are considered minor, and grades III through V are considered major (4).

History

Recent physical activity: Type, intensity, and duration; EIH can occur up to 12 hr after activity.
Trauma
Urinary tract symptoms: Flank pain, renal colic, dysuria, weak stream, etc.
Medication use, including herbals and over-the-counter drugs: Anticoagulants do not increase the risk of hematuria and should not influence the workup.
Family history of sickle cell disease/trait or hematuria. PCKD and TBM can have autosomal dominant inheritance.
Red flags for malignancy or tuberculosis such as fevers, night sweats, and weight loss
Assess risk factors for significant urologic disease.
- Abuse of analgesic drugs (NSAIDs)
- Age >40 yrs increases likelihood of cancer.
- Cyclophosphamide use
- Exposure to pelvic radiation
- History of urinary tract infections
- Irritative voiding symptoms
- Occupation exposure to chemicals or dyes
- Smoking
- Personal urologic history
- Recent sore throat could suggest poststreptococcal glomerulonephritis or immunoglobulin A nephropathy
- Travel to developing nations increases risk of urinary schistosomiasis.
- Unilateral flank pain suggests calculi or pyelonephritis.

Physical Exam

Many patients will not have any signs or symptoms. Nearly all patients with EIH will have no symptoms whatsoever. The symptoms listed below suggest something other than benign EIH.
- Fever
- Urethral discharge
- Flank ecchymosis
- Painless red or brown urine
- Dysuria
- Frequency
- Hesitancy
- Flank pain
- Suprapubic pain
Physical examination:
- Vitals (ie, fever, hypotension, hypertension, tachycardia)
- Thorough abdominal and flak exam including auscultation for bruits
- Genital and prostate exam in males
- Pelvic exam in females
- Additional exam as indicated by history
- Inspection of urethral meatus, flank, and abdomen for signs of trauma
Stepwise approach to the patient:
- Step 1: History and physical examination (HPE) as above:
  - If HPE reveals only a history of exercise in a patient <40 yrs of age, observe and repeat urinalysis after 48–72 hr.
  - If urinalysis is normal, no further studies are warranted. Observe the patient for recurrence.
  - If hematuria persists or HPE suggest cause other than EIH, proceed to step 2.
- Step 2: Obtain the following laboratory tests:
  - Urine culture and serum creatinine, BUN, CBC, prothrombin time (PT), partial thromboplastin time (PTT), sickle-cell preparation
  - Consider serum creatine kinase to rule out rhabdomyolysis.
  - If serum creatinine is normal, obtain intravenous pyelogram (IVP) to evaluate for obstruction, mass, and kidney function.
  - If results of these tests are normal, proceed to step 3.
- Step 3: Cystoscopy. If normal, proceed to step 4.
- Step 4: US or CT scan:
  - Include bladder, especially if patient >40 yrs of age
  - CT scan can detect early bladder tumors missed on cystoscopy.
  - If normal, proceed to step 5.
- Step 5: Consider renal arteriogram.
  - Evaluate for vasculitis, atrioventricular (AV) malformation, and renal infarction/thrombosis
  - If normal, proceed to step 6.
- Step 6: Consider renal biopsy.
  - Evaluate for interstitial kidney disease.
  - If at any time concurrent proteinuria, dysmorphic RBCs, or casts are present, obtain 24-hr urine for protein, creatinine, calcium, citrate, and uric acid.
  - Consider serum antistreptolysin O titer, Venereal Disease Research Lab (VDRL), antineutrophil cytoplasmic antibody complement levels, antiglomerular basement membrane antibody levels, hepatitis B serology.
- Consider renal biopsy if results of all preceding tests are negative.

Diagnostic Tests & Interpretation

Lab

Initial testing: Urinalysis: To observe for clearing of the hematuria within 48–72 hr. Further testing is indicated if it does not clear.
Follow-up testing: To be done if urinalysis does not clear in 48–72 hr.
Analyze within 30 min or refrigerate immediately to prevent change in bacterial count and hemolysis.
- Must include cell count to rule out pseudohematuria
- RBCs alone suggest prostatic disease, pelvic or ureteral calculi, trauma, heavy exercise, or malignancy. Dysmorphic RBCs can be seen in EIH as well as intrinsic renal disease.
- WBCs + RBCs suggests infection.
- RBCs + protein/casts/dysmorphic RBCs or absence of clots suggests glomerular disease.
- RBC casts are virtually diagnostic of glomerulonephritis or vasculitis.
- RBC clots usually indicate extraglomerular bleeding (urokinase in the glomeruli prevents clotting).
- Proteinuria suggests medical renal disease.
Urine culture (consider acid-fast bacilli culture if suspect tuberculosis)
24-hr urine for protein (consider electrophoresis for Bence-Jones protein/multiple myeloma), creatinine, calcium, uric acid, and citrate
Protein excretion can be quantified accurately with a spot protein:creatinine ratio instead of a full 24-hr urine collection.
CBC, PT, and PTT to evaluate for coagulopathy, anemia, and leukocytosis
Serum creatinine/BUN/electrolytes to evaluate renal function
3-tube test may help to isolate the specific origin of bleeding in isolated hematuria.
- Collection and comparative evaluation of the number of RBCs in 3 urine specimens of roughly equal volume
- 1st few milliliters (indicates a urethral lesion), a midstream sample, and the last few milliliters (possible lesion at the trigone region of the bladder if this sample alone has most RBCs)
- If all 3 samples have similar levels of RBCs, the lesion more likely is renal, ureteric, or diffuse bladder disease.
Urine cytology is rarely helpful.

Imaging

Imaging is needed only for further workup should the hematuria not clear after 48–72 hr of rest on urinalysis and the 2nd-line testing is also negative (ie, urine culture).
Imaging is rarely needed unless there is a traumatic incident or suspected nephrolithiasis or tumor.
Non-contrast-enhanced CT scan is the preferred modality for evaluating calculi with a sensitivity of 98–100% and a specificity of 92–100%. Many institutions have a renal stone CT scan protocol to minimize radiation exposure.
CT urography is the preferred test to evaluate urologic pathology such as malignancy or obstruction. Images are collected in 3 phases:
- Unenhanced
- Nephrographic phase done shortly after administration of contrast material
- Pyelographic phase done several minutes later to visualize the collecting system
Direct visualization with cystoscopy is necessary to rule out bladder cancer.
The combination of CT urography and cystoscopy generally is considered sufficient to rule out serious urinary tract pathology.
Plain radiographs have the benefit of being inexpensive and easily available but have only a 60% sensitivity for calculi and a limited utility for diagnosing malignancy.
US has the benefit of no radiation exposure, so it can be used safely in children and pregnant women. It has a low sensitivity for detection of calculi or tumors, especially tumors <3 cm in size.
IV urography is used to visualize the collecting system but is being rapidly replaced by CT urography owing to much higher sensitivity.
Retrograde pyelography also can be used to visualize the bladder and collecting system.
Voiding cystourethrogram (VCUG) is used to detect vesicoureteral reflux.
MR urography can be used in place of CT scan to minimize radiation or contrast material exposure but is more expensive and time-consuming.
Arteriography detects renovascular hypertension, polyarteritis nodosa, thromboemboli, mass, and aneurysm (4,5).

Differential Diagnosis

Painless:
- EIH
- Malignancies
- Glomerulonephropathy, especially in children
- PCKD
- Sickle-cell trait or disease
- Coagulation defect (clotting factor deficiency, thrombocytopenia, polycythemia)
- Vasculitis (lupus, Goodpasture syndrome)
- Infection (endocarditis, tuberculosis, syphilis)
- Iatrogenic: Anticoagulation, catheterization, NSAID) nephritis: Decrease in vasodilating prostaglandin causes decreased renal blood flow leading to nephron damage and hyperfiltration
- Early calculi formation (cause of microscopic damage): Hypercalciuria (>4 mg Ca/kg/day in a 24-hr urine specimen); hyperuricosuria (>750 mg uric acid/day); hypocitruria (<450 mg citrate/day for men, <650 mg/day for women; citrate helps to prevent stone formation)
Painful:
- Pyelonephritis
- Prostatitis
- Cystitis
- Urethritis
- Calculi
- Trauma
- Bladder tumor
- Renal tumor
- Renal artery aneurysm
- Renal vein thrombosis
- Pseudohematuria
- Myoglobinuria owing to rhabdomyolysis (no RBCs in HPF)
- Hemolysis and/or “march hematuria” (no RBCs in HPF; RBCs are hemolyzed in foot capillaries during marching)
- Medications: Phenothiazine, phenolphthalein laxatives, rifampin, phenazopyridine (Pyridium), phenytoin, quinine
- Porphyria
- Vegetable dyes (beets, rhubarb)
- Vaginal blood contamination

P.301

Treatment

General:
- Treatment is targeted to the underlying condition.
- Antibiotics for infection
- Pain control, if applicable; avoid NSAIDs until renal injury and nephritis are ruled out.
- Pyridium can be given for cystitis.
EIH:
- Reassurance that this is a benign condition
- Proper hydration can ensure adequate renal blood flow and minimize bladder trauma.
Traumatic hematuria:
- Be sure to perform a full primary and secondary survey to assess life-threatening and coexisting injuries.
- Immediate surgical consultation for signs of shock or severe trauma
- Evaluate need for imaging.
- All grades of traumatic kidney injury can be managed conservatively initially with the assistance of a urologist.
Management of asymptomatic microscopic hematuria (AMH):
- Confirm in 2–3 properly collected specimens.
- No further workup needed if present in only one sample or no RBCs seen on microscopic analysis (dipstick hematuria)
- Consider further workup if >50 RBCs/HPF in single sample, unless clear diagnosis of EIH.
- Rule out transient (urinary tract infection or calculi) or spurious causes; treat if present.
- If age ≥40 yrs, refer for urologic evaluation with imaging and cystoscopy.
- If age <40 yrs, assess for:
  - GFR <60 mL/min
  - Proteinuria (albumin:creatinine ratio ≥30 or protein:creatine ratio ≥50)
  - Hypertension (BP ≥140/90 mm Hg)
- If any of the above are abnormal, refer to nephrology.
- If no diagnosis is found, monitor GFR, proteinuria, and hypertension yearly.
Management of symptomatic microscopic hematuria (SMH):
- Less well defined than for AMH
- Rule out transient and spurious causes; treat if present.
- Consider immediate referral to urology. One small study showed a nonstatistically significant increase in cancer diagnosis with SMH vs AMH.
- Alternatively, you may follow the same algorithm as for AMH.
Management of gross hematuria:
- All patients should be considered for urologic evaluation.
- Evaluate and treat transient causes.
- Assess renal function, and consider imaging before referral (1,4).

Additional Treatment

Additional Therapies

Signs of shock (ie, tachycardia, hypotension), expanding flank mass, or oliguria require emergent urologic referral.
Prescribe rest until hematuria resolves if EIH is suspected.
Emphasize hydration during exercise and avoidance of urination within 15–20 min of onset of exercise.

Ongoing Care

Referral to urology or nephrology is rarely needed to assist with diagnosis.
It is useful when other etiologies cannot be found and the hematuria persists.

Follow-Up Recommendations

Referral to a urologist or nephrologist where appropriate

Prognosis

Based on underlying diagnosis, if known.
Unexplained hematuria is relatively common in the general population and does not carry a negative prognosis as long as an appropriate diagnostic workup has been done (2,4).

References

1. Rao PK, Jones JS. How to evaluate dipstick hematuria: what to do before you refer. Clev Clin J Med. 2008;75:227.

2. Kelly JD, Fawcett DP, Goldberg LC. Assessment and management of non-visible haematuria in primary care. BMJ. 2009;338:a3021.

3. Mercieri A. Exercise-induced hematuria. Up To Date. 21 Aug 2009 www.uptodate.com.

4. Bernard JJ. Renal trauma: evaluation, management, and return to play. Curr Sports Med Rep. 2009;8:98–103.

5. O'Connor OJ, McSweeney SE, Maher MM. Imaging of hematuria. Radiol Clin N Am. 2008;46:113–132.

Codes

ICD9

599.70 Hematuria, unspecified
599.71 Gross hematuria
599.72 Microscopic hematuria