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Hematuria: Causes, Diagnosis, and Management

Introduction

Hematuria, the presence of blood in urine, is one of the most common clinical presentations encountered in medical practice. It can be a benign, transient finding or a harbinger of serious underlying disease, including urinary tract infections (UTIs), nephrolithiasis, glomerular diseases, or malignancies of the urinary tract. Hematuria may present as gross hematuria, in which blood is visible to the naked eye, or microscopic hematuria, in which red blood cells (RBCs) are identified only on urine microscopy.

Understanding hematuria requires knowledge of urinary tract anatomy, potential etiologies, diagnostic pathways, and management strategies. The challenge for clinicians lies in distinguishing benign and self-limiting causes from those requiring urgent intervention. This article provides a comprehensive review of hematuria, covering definitions, epidemiology, pathophysiology, causes, diagnostic evaluation, and management approaches.

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Definition and Classification

Definition

Hematuria is defined as the presence of red blood cells in urine, with or without visible discoloration. It is classified based on visibility and timing within the urinary stream.

Types of Hematuria

1. Gross Hematuria

   • Urine visibly red, pink, or cola-colored.
   • Indicates significant bleeding and often raises concern for malignancy or major urinary tract pathology.

2. Microscopic Hematuria

   • Detected on urinalysis, usually defined as ≥3 red blood cells per high-power field (RBCs/HPF) in a properly collected urine specimen.
   • May be asymptomatic and discovered incidentally.

Classification by Timing

• Initial hematuria – blood present at the start of urination; suggests urethral source.
• Terminal hematuria – blood appears at the end of micturition; often related to bladder neck or prostatic urethra.
• Total hematuria – blood throughout the stream; usually due to bladder, ureter, or kidney pathology.

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Epidemiology

Hematuria is a relatively common clinical finding across all age groups. Its prevalence depends on the definition and population studied.

• Microscopic hematuria is found in 2–31% of adults in screening studies.
• Gross hematuria occurs less frequently but is more alarming due to its association with serious diseases.
• Age and gender influence prevalence and etiology:
  • In young adults, hematuria is often due to infections, exercise, or glomerular disease.
  • In older adults, malignancy (e.g., bladder cancer, renal cell carcinoma) becomes a significant concern.
  • Men are more likely to present with hematuria due to prostate disease, while women often present with UTI-related hematuria.

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Pathophysiology

Blood in urine can arise from any site in the urinary tract: kidneys, ureters, bladder, prostate, or urethra. The underlying mechanisms include:

1. Glomerular causes

   • Damage to glomerular basement membrane allows RBCs to leak into urine.
   • Common in glomerulonephritis, IgA nephropathy, or hereditary nephropathies.
   • Often associated with dysmorphic RBCs and red blood cell casts.

2. Non-glomerular renal causes

   • Bleeding from renal tubules, interstitium, or vascular abnormalities.
   • Seen in renal cysts, papillary necrosis, trauma, or tumors.

3. Post-renal causes

   • Originating from collecting system, ureters, bladder, or urethra.
   • Most common causes include infections, stones, trauma, and malignancy.

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Causes of Hematuria

1. Renal (Kidney-related) Causes

• Glomerular disease (IgA nephropathy, post-streptococcal glomerulonephritis, lupus nephritis, Alport syndrome).
• Hereditary nephropathies (thin basement membrane disease).
• Polycystic kidney disease (ruptured cysts can bleed).
• Papillary necrosis (diabetes, analgesic nephropathy, sickle cell disease).
• Renal tumors (renal cell carcinoma).

2. Ureteral Causes

• Ureteric stones (urolithiasis).
• Ureteral trauma or strictures.
• Urothelial carcinoma.

3. Bladder Causes

• Infections: cystitis, schistosomiasis (in endemic areas).
• Bladder cancer (transitional cell carcinoma).
• Radiation or chemotherapy-induced cystitis (e.g., cyclophosphamide).
• Bladder stones.

4. Prostate and Urethral Causes

• Benign prostatic hyperplasia (BPH).
• Prostate cancer.
• Urethritis (sexually transmitted infections).
• Urethral trauma (catheterization, instrumentation).

5. Systemic Causes

• Coagulopathies (hemophilia, thrombocytopenia, anticoagulant therapy).
• Sickle cell disease.
• Vasculitis (Henoch–Schönlein purpura).

6. Benign and Transient Causes

• Vigorous exercise (“exercise-induced hematuria”).
• Menstrual contamination.
• Medications (anticoagulants, cyclophosphamide, phenazopyridine).
• Foods (beets, rhubarb) that mimic hematuria (“pseudohematuria”).

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Clinical Presentation

The presentation of hematuria varies depending on the underlying cause.

• Gross hematuria: visible red or brown urine.
• Microscopic hematuria: often asymptomatic, discovered on screening.
• Associated symptoms:
  • Dysuria, frequency, urgency → infection.
  • Flank pain → renal stones or pyelonephritis.
  • Painless gross hematuria → bladder cancer suspicion.
  • Systemic symptoms (rash, joint pain, edema) → glomerular disease.

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Diagnostic Evaluation

1. History Taking

• Onset, duration, and pattern of hematuria.
• Timing in urinary stream.
• Associated urinary symptoms (pain, burning, frequency).
• History of trauma, recent exercise, or medications.
• Family history of renal disease or hematuria.
• Smoking history (major risk factor for bladder cancer).

2. Physical Examination

• Vital signs (fever, hypertension).
• Abdominal exam (masses, tenderness).
• Genitourinary exam (prostate in men, pelvic exam in women).
• Skin/joint exam (systemic disease signs).

3. Laboratory Investigations

• Urinalysis: RBC morphology, casts, proteinuria, infection indicators.
• Urine culture: rule out infection.
• Urine cytology: detect malignant cells.
• Blood tests: renal function, complete blood count, coagulation profile, autoimmune markers.

4. Imaging Studies

• Ultrasound: non-invasive, good for kidneys and bladder.
• CT urography: gold standard for hematuria evaluation.
• MRI: alternative in patients allergic to contrast.

5. Endoscopic Evaluation

• Cystoscopy: direct visualization of bladder and urethra. Essential in patients >35–40 years with unexplained hematuria.

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Differential Diagnosis

When hematuria is confirmed, differential diagnoses include:

• Glomerular disease (glomerulonephritis, IgA nephropathy).
• Urinary tract infection.
• Urolithiasis.
• Malignancy (bladder, kidney, ureter, prostate).
• Trauma.
• Systemic conditions (coagulopathy, vasculitis).

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Management

1. General Principles

• Management depends on underlying cause.
• Treat life-threatening causes urgently (e.g., clot retention, massive hematuria).
• Address reversible factors (anticoagulants, trauma, infection).

2. Specific Treatments

• Urinary tract infection → antibiotics.
• Stones → analgesia, hydration, lithotripsy, or surgery.
• Glomerular disease → immunosuppressive therapy, ACE inhibitors.
• Bladder or kidney cancer → surgical resection, chemotherapy, immunotherapy.
• BPH → alpha-blockers, 5-alpha-reductase inhibitors, surgery if needed.

3. Supportive Care

• Maintain hydration.
• Blood transfusion if severe anemia.
• Bladder irrigation in clot retention.

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Prognosis

Prognosis varies widely:

• Benign causes (exercise, minor infection) resolve spontaneously.
• Malignancy-related hematuria may indicate advanced disease.
• Early detection and treatment improve outcomes significantly.

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Complications

• Urinary retention due to blood clots.
• Anemia.
• Progressive renal impairment (glomerular disease).
• Missed diagnosis of malignancy if hematuria is ignored.

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Prevention

• Avoid excessive use of nephrotoxic drugs.
• Stay hydrated to reduce risk of stones.
• Smoking cessation (reduces risk of bladder and kidney cancer).
• Regular screening in high-risk populations.

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Case Scenarios

Case 1: Young Adult with Microscopic Hematuria

A 22-year-old male undergoes a routine medical exam for military service. Urinalysis reveals 5 RBCs/HPF. No symptoms. Further evaluation excludes infection and stones. Diagnosis: thin basement membrane nephropathy, benign course.

Case 2: Elderly Patient with Gross Hematuria

A 67-year-old smoker presents with painless gross hematuria. Cystoscopy reveals bladder carcinoma. Early diagnosis leads to curative surgery.

Case 3: Hematuria in a Patient on Anticoagulation

A 55-year-old with atrial fibrillation on warfarin presents with gross hematuria. INR elevated at 4.5. Managed by reversal of anticoagulation and investigation for underlying pathology.

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Recent Advances

• Urine biomarkers (e.g., NMP22, BTA tests) for bladder cancer detection.
• Genomic studies to identify hereditary nephropathies.
• Minimally invasive urologic procedures for diagnosis and treatment.
• Artificial intelligence in imaging for early cancer detection.

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Conclusion

Hematuria is a common but clinically significant symptom that requires careful evaluation. While many cases are benign and transient, hematuria may indicate serious conditions such as malignancy or glomerular disease. A systematic approach—starting with history, examination, urinalysis, imaging, and cystoscopy when appropriate—is essential for accurate diagnosis. Management depends on the underlying cause, ranging from antibiotics for infection to surgery for malignancy. Timely recognition and intervention are critical to prevent complications and improve outcomes.

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