DIAGNOSIS AND TREATMENT OF HEMATURIA

Rainy UmbasDepartment of Urology

“Cipto Mangunkusumo” Hospital / Faculty of MedicineUniversity 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

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)

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)

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?

Non-glomerular cause

Extra-renal:

BPH

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 hematuriaEntirely hematuria (total)Terminal hematuria

(Courtesy of Prof. Dr. Djoko Rahardjo)

THE SOURCE OF THE BLEEDING

Penile or bulbous urethraThe flow of urine initials bleed and

afterwards “wash clear”Pathology : inflammation, stone,

malignancy

Initial hematuria possible source of bleeding :

(Courtesy of Prof. Dr. Djoko Rahardjo)

THE SOURCE OF BLEEDING

Source : higher than bladder neck

The blood mixed with urine, due to:

© Malignancy© Stone© Infection including TB

Entirely Hematuria

(Courtesy of Prof. Dr. Djoko Rahardjo)

THE SOURCE OF BLEEDING

• Prostatic urethra

• Bladder neck due to “snapping shut”

Terminal Hematuria

(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

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