Mohamed S. Ismail, MBChB, MRCS, PhD
Jayram Krishnan, DO, MBA
BASICS
DESCRIPTION
• Mycobacterium tuberculosis (TB) may affect the urinary system including the kidney and ureter
• Most TB occurs in the lung but 15% occurs in extrapulmonary sites
– GU system is the most common extrapulmonary site
Kidneys are the most common GU site
EPIDEMIOLOGY
Incidence
• Worldwide—9.27 million worldwide (140 per 100,000) (2007)
• US—12,904 cases (4.2 per 100,000) (2008)
Prevalence
• GU TB:
– Developed countries—2–10%
– Developing countries—15–20%
• Male > female (2:1) (1)[C]
• Mean age 40.7 yr (1)[C]
RISK FACTORS
• Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)
• Chronic dialysis patients
• Immunocompromised states (renal transplants)
• Foreign travel
PATHOPHYSIOLOGY
• M. tuberculosis infections are acquired by inhalation of aerosolized droplet nuclei which reach the pulmonary alveoli
• Hematogenous spread to kidneys from pulmonary disease
– Tuberculomas develop in glomerular capillaries as a result of hematogenous seeding
– Normal renal parenchyma is slowly replaced by caseous material and calcium is laid down as part of the reparative process
– Renal papilla involvement results in sloughing and caseous material gaining access to the collecting system by calyceal ulceration
– Extensive fibrosis with healing tubercles results in disfiguration and hydronephrosis with obstruction
• Ureteral involvement is almost always from direct extension from the kidney
– Mycobacteria caseous material leads to tubercle formation within the ureteric mucosa
– This usually affects the lower ureter and the ureterovesical junction with the middle and upper ureter less commonly affected (2)[C]
– Dense fibrosis on the ureteric serosa leads to stricture formation and/or shortening in 50% of patients with renal involvement
• Secondary amyloidosis can be found; often resulting in proteinuria and nephrotic syndrome
ASSOCIATED CONDITIONS
• Chronic TB infection
• Immunocompromised states (HIV/AIDS)
• Malnutrition
• Poor living conditions/poverty
GENERAL PREVENTION
• Diagnose and treat patients with TB before development of active disease
• Take careful precautions with patients hospitalized with TB
• Test annually with the purified protein derivative (PPD) skin test if at high risk for exposure
DIAGNOSIS
HISTORY
• Often mimics a wide range of nonspecific urologic symptoms and are often minimal even with extensive disease
• History or exposure to TB; determine last PPD test results; latency can be >20 yr after primary TB
• Vague, intermittent, nonspecific complaints such as malaise, lethargy, weight loss, and low-grade fevers common
• Men commonly present with epididymitis
• Bacterial cystitis may be superimposed on bladder TB. Common to see recurrent urinary tract infections with Escherichia coli
• Dysuria from seeding of the bladder with TB
• Chronic cystitis unresponsive to therapy
PHYSICAL EXAM
• Significant physical signs develop late and with extensive disease
• Storage symptoms are the most common overall presentation (50.5%) (1)[C]
– Hematuria (35.6%) (1)[C]
– Lumbar pain (34.4%) (1)[C])
– Most common physical finding in men is an abnormal scrotal exam (49.8%) (1)[C]
Scrotal lumps, epididymal hardening, or draining scrotal fistulas
• Upper abdominal bruits may indicate advanced renal disease
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis and culture:
– Classic finding: Sterile pyuria (>20 white blood cells/high power field)
– 20% of patients will also have bacterial cystitis or urinary tract infection with E. coli
– 13% of patients will present with gross or microscopic hematuria (3)[C]
• GOLD STANDARD: Specific staining of urine for acid-fast bacteria and mycobacterial culture
– Nonpathogenic mycobacteria can also stain positive, so culture more useful
– Ziehl–Neelsen or Kinyoun acid-fast stain; more rapid fluorochrome (fluorescence microscopy) procedure
– 1st morning urine specimen has highest yield of tubercle bacilli
– Minimum 3 and up to 6 early-morning urine specimens are recommended, as TB organisms shed into urine intermittently
– 64.2% of patients had M. tuberculosis in their urine (1)[C]
– High index of suspicion for persistent pyuria without bacteria on repeated cultures (stain with methylene blue)
• Polymerase chain reaction (PCR) assay may identify organisms
• Complete blood count and electrolytes
– Renal failure is present in 7.4% of cases (creatinine >1.5) (1)[C]
Functional loss of the affected kidney can be present in up to 25% of cases (1)[C]
• Erythrocyte sedimentation rate (ESR):
– Measure monthly as indicator of response to therapy
• Heavy proteinuria may suggest secondary involvement of the kidney with amyloid
Imaging
• Chest radiograph: Abnormal in 75%
• Abdominal radiograph:
– Enlargement of 1 kidney
– Renal stones in 10%
– Focal punctate calcifications occur within the caseating lesions in renal parenchyma
– Obliteration of psoas shadow due to perinephric abscess
– Characteristic diffuse, uniform, extensive parenchymal calcifications are present with lobar cast of the kidney (autonephrectomy)
• Excretory urogram:
– Moth-eaten appearance in ulcerated calyces (4)[C]
– Dilation of upper tract secondary to ureteral stricture (4)[C]
– Obliteration of calyces
– Loss of kidney function due to complete occlusion or renal destruction
• Computed tomography (4)[C]:
– Most common finding: Renal parenchymal scarring (76%)
– Hydrocalycosis, hydronephrosis, or hydroureter due to stricture (67%)
– Thick walls of the renal pelvis, ureters, or bladder (61%)
Diagnostic Procedures/Surgery
• Tuberculin skin test (PPD):
– 88% patients have positive skin tests
– 5 mm or more of induration is considered positive in persons with the highest likelihood of developing active disease
HIV, immunosuppression, organ transplants
– 10 mm or more of induration is considered positive in those who are at high risk for TB
Drug abuse, health care workers, family members
– 15 mm or more of induration is considered positive in any patient
– Positive reaction indicates exposure, not necessarily active disease
– May be negative in a patient with miliary TB, AIDS, or advanced age
– Negative tuberculin skin test makes diagnosis of TB unlikely
– Not used in patients with history of Bacille Calmette–Guérin (BCG) vaccine or therapy
• Retrograde pyelography
– Obtain selective cultures for TB
– Assessment of ureteral stricture
• Cystoscopy and ureteroscopy play a limited role
Pathologic Findings
Tubercles replaced by caseating necrosis
DIFFERENTIAL DIAGNOSIS
• Amicrobic cystitis
• Systemic BCG infection
• Chronic nonspecific cystitis or pyelonephritis
• Disseminated coccidioidomycosis
• Medullary sponge kidney
• Necrotizing papillitis
• Nonspecific epididymitis
• Renal stones or nephrocalcinosis
• Urinary bilharziasis (schistosomiasis)
TREATMENT
GENERAL MEASURES
• Early diagnosis of active disease is imperative and requires prompt initiation of adequate drug regimens
– Surgical treatment is reserved for advanced cases and with the goal of renal preservation
– Correct the obstructive effects of fibrosis and scarring rather than removal of infected tissues
– Drainage of abscesses
• Balanced approach is required between medications and surgery to preserve function and eradicate mycobacteria
• Supervision of therapy is required to ensure compliance and to monitor for complications
MEDICATION
First Line
• Initial treatment requires 6 mo of anti-TB medications
• 1st 2 mo: Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB)
• Following 4 mo: INH and RIF
• Ascorbic acid given with treatment
– INH – 5 mg/kg (300 mg/d)
Pyridoxine supplementation required (peripheral neuropathy)
Hepatic toxicity
– RIF – 10 mg/kg (450–600 mg/d)
Hepatic toxicity, flu-like syndrome, pruritics
– PZA – 25 mg/kg/d
Hepatic toxicity, arthralgias, rash, gastrointestinal upset
– EMB – 15–25 mg/kg/d
Irreversible optic neuritis, visual changes
Renal excretion (caution in renal failure)
Second Line
• Complicated/resistant TB infections requiring the use of streptomycin, ethionamide, quinolones, and aminoglycosides
– Streptomycin 15 mg/kg (max 1 g)
Vestibular and auditory toxicity, renal damage
– Ethionamide 15–20 mg/kg (max 500 mg/BID)
Gastrointestinal and hepatic toxicity, hypothyroidism
• Multidrug-resistant TB (MDR-TB)
– Resistant to at least isoniazid and rifampin, and possibly additional agents
• Extensively drug-resistant TB (XDR-TB)
– Resistant to at least isoniazid and rifampin, and additionally resistant to fluoroquinolones and either aminoglycosides or both
SURGERY/OTHER PROCEDURES
• 55% of patients with GU TB will require surgical intervention
– Ureteral obstruction
Early stent or nephrostomy may decrease loss of renal function and increase opportunity for later reconstruction (2)[C]
Some strictures may resolve after medical therapy
– Nephrectomy
Symptomatic (hypertension, obstruction, pyelonephritis)
Removal of nonfunctional unit
Indicated for coexistent renal malignancies
Best delayed 4–6 wk after medical treatment
ADDITIONAL TREATMENT
Additional Therapies
• Steroids
– Used for treatment of TB-induced ureteral strictures or cystitis
Prednisone 20 mg 3 times daily orally
– Not recommended for routine use
• Latent TB
– Consider treatment to avoid conversion to active disease
ONGOING CARE
PROGNOSIS
• Prognosis is good in patients who are compliant in therapy
• Better prognosis with early diagnosis of disease
COMPLICATIONS
• Renal TB:
– Autonephrectomy: Complete nonfunctioning of an affected kidney
– Perinephric abscess may cause an enlarging flank mass
• Ureteral TB:
– Stricture formation
– Hydronephrosis
– Loss of renal function
FOLLOW-UP
Patient Monitoring
• All TB patients should be screened for HIV/AIDS
• Strictures can evolve after mycobacteria is eradicated
– Imaging (excretory urography/contrast computed tomography) and urine culture every 3 mo for 1st yr then annual abdominal radiographs
– Continue long-term imaging if calcifications present
REFERENCES
1. Figueiredo AA, Lucon AM, Junior RF, et al. Epidemiology of urogenital tuberculosis worldwide. Int J Urol. 2008;15:827–832.
2. Shin KY, Park HJ, Lee JJ, et al. Role of early endourologic management of tuberculous ureteral strictures. J Endourol. 2002;16:755–758.
3. Wise GJ, Shteynshlyuger A. An update on lower urinary tract tuberculosis. Curr Urol Rep. 2008;9:305–313.
4. Wang LJ, Wu CF, Wong YC, et al. Imaging findings of urinary tuberculosis on excretory urography and computerized tomography. J Urol. 2003;169:524–528.
ADDITIONAL READING
• Blumberg HM, Leonard MK Jr, Jasmer RM. Update on the treatment of tuberculosis and latent tuberculosis infection. JAMA. 2005;293:2776–2284.
• Cek M, Lenk S, Naber KG, et al. EAU guidelines for the management of genitourinary tuberculosis. Eur Urol. 2005;48:353–362.
See Also (Topic, Algorithm, Media)
• BCG Sepsis/BCGosis
• Prostatitis, Granulomatous
• Tuberculosis, Bladder and Urethra
• Tuberculosis, Genitourinary, General Considerations
• Tuberculosis, Kidney and Ureter Images 
• Tuberculosis, Male External Genitalia
CODES
ICD9
• 016.00 Tuberculosis of kidney, unspecified
• 016.20 Tuberculosis of ureter, unspecified
ICD10
A18.11 Tuberculosis of kidney and ureter
CLINICAL/SURGICAL PEARLS
Compliance to treatment regimen is essential for adequate disease response.