DIAGNOSIS AND TREATMENT OF HEMATURIA Rainy Umbas Department of Urology “Cipto Mangunkusumo” Hospital / Faculty of Medicine University of Indonesia

What is hematuria? What causes hematuria? Is hematuria always a bad thing? What tests are needed? What is the treatment? What if no cause is found?

What is hematuria? Hematuria means the appearance of blood in the urine. It could be visible (= macroscopic hematuria) Or microscopic hematuria, it means there were three or more red blood cells per high-power microscopic field in urinary sediment

(McDonald MM et al, Am Fam Physician 2006) What causes hematuria? Macroscopic hematuria : about one in three cases are associated with malignancy somewhere in the urinary tract (www.renux.ed.ac.uk) Microscopic hematuria : maybe associated with urologic malignancy in up to 10% of adults (Khadra MH et al, J Urol 2000; 163: 524-527) Glomerular cause Non-glomerular cause: - renal - extra-renal - other causes (McDonald MM et al, Am Fam Physician 2006)

What causes hematuria? Glomerular cause: Alport’ syndrome Membranoprliverative glomerulonephritis Fabry’s disease Mesangial proliverative glomerulonephritis Goodpasture’s syndrome Nail-patella syndrome Hemolytic uremia Other postinfectious glomerulonephritis Henoch-Schönlein purpura Thin basement nephropathy (benign familial hematuria) Immunoglobulin A nephropathy Wegener’s granulomatosis Lupus nephritis Poststreptococcal glomerulonephritis (McDonald MM et al, Am Fam Physician 2006)

Medications that can cause hematuria: What causes hematuria? Medications that can cause hematuria: Aminoglycosides Cyclophosphamide (Cytoxan) Amitriptyline Diuretics Analgesics Oral contraseptives Anticonvulsants Penicillins (extended spectrum) Aspirin Quinine Busulfan Vincristine (Oncovin) Chlorpromazine Warfarin (Coumadin) (McDonald MM et al, Am Fam Physician 2006)

Non-glomerular cause: What causes hematuria? Non-glomerular cause: Renal (tubulointerstitial) Acute tubular necrosis Familial - hereditary nephritis - medullary cystic disease - multicystic kidney disease - polycystic kidney disease Infection: pyelonephritis, tuberculosis, schistomiasis (McDonald MM et al, Am Fam Physician 2006)

What causes hematuria? Non-glomerular cause Renal (con’t): Interstitial nephritis - drug induced - infection: syphylis, toxoplasmosis, viral - systemic disease: sarcoidosis, lymphoma Loin pain-hematuria syndrome Metabolic - hypercalciuria - hyperuricosuria (McDonald MM et al, Am Fam Physician 2006)

What causes hematuria? Non-glomerular cause Renal (con’t): Renal cell carcinoma Solitary renal cyst Vascular disease - arteriovenous malformation - malignant hypertension - renal artery embolism/thrombosis - renal venous thrombosis - sicle cell disease (McDonald MM et al, Am Fam Physician 2006)

What causes hematuria? BPH Non-glomerular cause Extra-renal: Calculi Coagulopathy related: warfarin, heparin, secondary to systemic disease Congenital abnormalities Endometriosis Factitious Foreign bodies Infection: prostate, epididymis, urethra, bladder (McDonald MM et al, Am Fam Physician 2006)

Hematuria Stone or BPH as a cause for hematuria

What causes hematuria? Non-glomerular cause Extra-renal (con’t): Inflammation: drug or radiation induced Perineal irritation Posterior urethral valves Strictures TCC of ureter, bladder Trauma: catheterization, blunt trauma Tumor (McDonald MM et al, Am Fam Physician 2006)

Hematuria Malignancy of kidney/collecting system, ureter, bladder, prostate, and urethra

What causes hematuria? Non-glomerular cause Other causes: Exercise hematuria Myoglobinuria due to strenuous exercise, associated with muscle pain and tenderness Menstrual contamination Sexual intercourse

Hematuria Strenuous exercise can cause blood in urine ! ! !

CLINICAL PICTURE OF HEMATURIA Initial hematuria Entirely hematuria (total) Terminal hematuria (Courtesy of Prof. Dr. Djoko Rahardjo)

THE SOURCE OF THE BLEEDING Initial hematuria possible source of bleeding : Penile or bulbous urethra The flow of urine initials bleed and afterwards “wash clear” Pathology : inflammation, stone, malignancy (Courtesy of Prof. Dr. Djoko Rahardjo)

THE SOURCE OF BLEEDING Entirely Hematuria Source : higher than bladder neck The blood mixed with urine, due to: © Malignancy © Stone © Infection including TB (Courtesy of Prof. Dr. Djoko Rahardjo)

Bladder neck due to “snapping shut” THE SOURCE OF BLEEDING Terminal Hematuria Prostatic urethra Bladder neck due to “snapping shut” (Courtesy of Prof. Dr. Djoko Rahardjo)

Is hematuria always a bad thing? It may not be important if any of the following can explain it : Hematuria during a menstrual period When it occurs only during a urinary infection Some medicines or foods can coor the urine red. This is not the same as passing blood When it only occurs following strenuous exercise

What test are needed? First of all is to prove that the red urine is hematuria: urine sediment or strip test

What tests are needed? Physical exam incl. blood pressure Confirm with urine microscopic exam if striptest / dipstick was positive. Strip test / dipstick cannot distinguish among myoglobin, hemoglobin, and red blood cells Urine test: - presence of infection - proteinuria, red cell casts or dysmorphic red blood cells (together with increased creatinine) suggestive of glomerular cause referred to nephrologist

What tests are needed? Urine cytology The sensitivity of urine cytology is highest for detection of high-grade lesions in the bladder and carcinoma in situ Urine cytology studies alone may provide sufficient evaluation of the lower urinary tract in certain low-risk patients Urine PCR for TB / acid-fast bacilli staining Consider for referral to urologist for further evaluation

What tests are needed? Imaging: - Ultrasonography - KUB & IVU or CT Scan

Should have their lower tract assessed by cystoscopy What tests are needed? Patients > 40 years old, those with posotive or atypical cytology, or any patient with the presence of any of the following risk factors: - smoking history - occupational exposure to chemicals or dyes - history of irritative voiding symptoms - analgesic abuse with phenacetin - history of pelvic irradiation, or cyclophosphamide exposure Should have their lower tract assessed by cystoscopy

What tests are needed? Cystoscopy or Uretero-renoscopy

What is the treatment? Hematuria has no specific treatment. One should focus on the underlying condition ! ! ! Underlying cause Treatment Urinary tract infection Antibiotics Kidney disease Relieve inflamation and limit further damage Inherited disorders Vary greatly depend on the disorders Stone disease Stone removal BPH Relieve obstruction & irritation Malignancy Depend on tumor stage

What if no cause is found? If there are no signs of serious disease, follow-up every 6 months, up to 36 months, of the urinalysis, urine cytology, blood test and blood pressure. This is especially important for persons > 40 years old who have risk factors for urothelial cancers: - smoking history - occupational exposure to benzenes or aromatic amines (e.g. Leather dye, rubber, tire industries) - or history of urologic neoplasm This group of patients merit referral to a urologist for cystoscopy

What if no cause is found? Immediate urologic re-evaluation with consideration of cystoscopy, cytology or repeat imaging should be performed in case of: - gross hematuria - abnormal urinary cytology - irritative voiding symptoms without infection If none of these occurs within three years, the patient does not require further urologic monitoring

Conclusions Hematuria, especially microscopic, present a challenging clinical scenario for family physicians / general practioners All patients should be investigated by urine cytology and urinary tract imaging after excluding non-important causes (menses, infection, exersice ect) Referral to urologist for further evaluation and cystoscopy is indicated in patients with positive or atypical cytology, patients > 40 years old, and any patients risk factors Patients with suspicious cause of glomerular cause should be referred to nephrologist Patients shoulod be followed up to 3 years

References Mayo Clinic.com (www.mayoclinic.com) Renal unit, Royal Infirmary of Edinburg (www.renux.ed.ac.uk) Grossfeld GD et al, Am Fam Physician 2001; 63: 1145-54 Khadra MH et al, J Urol 2000; 163: 524-527 McDonald MM et al, Am Fam Physician 2006; 73: 1748-54 Wollin T et al, Can Urol Assoc J 2009; 3: 77-80

Acknowledgements Prof. Djoko Rahardjo, MD Chaidir A. Mochtar, MD, PhD Rizal Hamid, MD Mr. Ruhyat Yamani Ms. Leslie Dolfo Nugroho Ms. Tri Darani Department of Urology “Cipto Mangunkusumo” Hospital / Faculty of Medicine, University of Indonesia