Mark R. Anderson, MD, MSc
Judd W. Moul, MD, FACS
BASICS
DESCRIPTION
• Genitourinary tuberculosis (TB) refers to urinary and GU infection with Mycobacterium tuberculosis. Common GU sites include the kidney, ureter, bladder, prostate, and testis/epididymis.
• GU tract is 2nd most common site after lungs for tuberculous infection. Urogenital TB represents 27% of extrapulmonary cases (1).
• Tubercle bacilli found in 7–29% of urine in patients with extrarenal TB.
• In 1882, the bacillus causing TB, M. tuberculosis, was 1st identified and described by Robert Koch.
• 10% of TB is extrapulmonary with GU locations accounting for 33% of these sites and these rates double in developing countries.
• TB is 2nd only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent.
• In 2010, there were about 10 million orphan children as a result of TB deaths among parents.
• TB is a leading killer of people living with HIV causing one-quarter of all deaths.
• Although declining, multidrug-resistant TB (MDR-TB) is present in virtually all countries surveyed.
• The world is on track to achieve the Millennium Development Goal to reverse the spread of TB by 2015.
• The TB death rate dropped 41% between 1990 and 2011.
EPIDEMIOLOGY
Incidence
• 1/3 of the world’s population are infected with TB.
• In 2011, 8.7 million people fell ill with TB and 1.4 million died from TB.
• Over 95% of TB deaths occur in low- and middle-income countries, and it is among the top 3 causes of death for women aged 15–44.
• About 1/3 of the world’s population has latent TB and can transmit infection.
Prevalence
In US, the peak surge in 1992 of reported TB cases has steadily declined to about half its peak value.
RISK FACTORS
• Health care providers
• Immunosuppression (eg, HIV)
• TB is spread from person to person through the air.
• Smoking
PATHOPHYSIOLOGY
• Hematogenous spread to kidneys from pulmonary disease proved by Medlar, et al. in 1949
• 2–12 wk often ensue before mycobacterial numbers are sufficient to mount a clinically detectable cellular immune response.
• M. tuberculosis infections acquired by inhalation of aerosolized droplet nuclei (1–5 μm), which reach pulmonary alveoli
• Invasion of GU organs by ascent (prostate to bladder) or descent (kidney to bladder, prostate to epididymis)
• Kidney and epididymis are primary sites of TB infection in the GU tract in men, and fallopian tubes in women.
• Tuberculomas develop in glomerular capillaries as a result of hematogenous seeding from lungs.
• Renal TB may take years to develop in patients with normal immune system.
• Normal renal parenchyma is slowly replaced by caseous material; calcium is laid down as part of the reparative process.
• Adrenal TB is seen in <6% of active TB cases (up to 56% of patients with adrenal TB will have a subnormal cortisol response to corticotrophin stimulation).
ASSOCIATED CONDITIONS
• Chronic TB infection
• Immunocompromised states (eg, AIDS)
• Malnutrition
• Poor living conditions/poverty/drug use
GENERAL PREVENTION
• Diagnose and treat patients with TB before development of active disease.
• Take careful precautions with patients hospitalized with TB (N95 mask, negative pressure room flow)
• Test annually with PPD if at high risk for exposure.
• Females of the childbearing age should be advised to avoid pregnancy while on antituberculous treatment.
DIAGNOSIS
HISTORY
• Initial symptoms may be minimal, even in presence of extensive disease. No classical clinical picture, most symptoms are of bladder/lower urinary origin.
• History or exposure to TB; determine last PPD testing 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 UTIs with Escherichia coli
• Dysuria from seeding of the bladder with TB
• Chronic cystitis unresponsive to therapy
• Urinary tract involvement occurs in up to 50% of transplant recipient cases. PPD skin testing may be falsely negative in 70% of cases due to anergy.
PHYSICAL EXAM
• Physical exam is often of limited value in the diagnostic process, because physical signs develop late in the disease. The most common physical finding is an abnormal scrotal exam in about half the patients.
• Suprapubic pain when disease is extensive
• Painful swollen testis
• Chronic draining scrotal sinuses should be considered TB until proven otherwise.
• Nontender, enlarged epididymis with beaded or thickened vas deferens
• Nodular, indurated prostate and thickened seminal vesicles on rectal exam mimic neoplasm.
• Upper abdominal bruit may be indication of advanced renal disease.
• Up to 25% of patients will present only with sterile pyuria and 13% might have gross or microscopic hematuria as their only presentation
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Routine urine analysis (13% might have gross or microscopic hematuria as their only presentation), plus standard culture
• Sterile pyuria classic finding (25%); typically >20 WBC/HPF.
• 20% of patients will also have bacterial cystitis or urinary tract infection with E. coli.
• Specific staining of urine for acid-fast bacteria and mycobacterial culture is gold standard:
– Ziehl–Neelsen or Kinyoun acid-fast stain; more rapid fluorochrome (fluorescence microscopy) procedure 1st morning 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.
• Acid-fast stains from 24-hr urine specimen are positive in 60% of cases.
• High index of suspicion for persistent pyuria without bacteria on repeated cultures (stain with methylene blue)
• PCR assay may identify organisms
• CBC, electrolytes, ESR: Measure monthly as indicator of response to therapy
• 88% have positive skin tests of PPD
• Heavy proteinuria in a patient with TB suggests secondary involvement of the kidney with amyloid.
Imaging
• Chest x-ray: Abnormal in 75%
• KUB: Enlargement of 1 kidney
• Punctuate calcifications in renal parenchyma
• Large calcified structures in prostate
• Renal stones in 10%
• Obliteration of psoas shadow due to perinephric abscess
• Excretory urogram: Considered a mandatory study; moth-eaten appearance in ulcerated calyces; dilation of upper tract secondary to ureteral stricture; obliteration of calyces
• Loss of kidney function due to complete occlusion or renal destruction
• Retrograde pyelography with selective culture for TB; assessment of ureteral stricture
• CT is an option if IVP contraindicated: Useful in delineating disease in seminal vesicles; limited value in early management
Diagnostic Procedures/Surgery
• Tuberculin skin test: Induration >10 mm in diameter is considered positive reaction; >5 mm in high-risk 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.
• Must not have had BCG vaccine or therapy in the past due to false-positive effect
• Cystoscopy: TB appears as a patchy erythematous ulceration with exudate.
• TB may mimic urothelial carcinoma including carcinoma in situ (CIS).
Pathologic Findings
• Microscopically, the inflammation produced with TB infection is granulomatous, with epithelioid macrophages and Langhans giant cells along with lymphocytes, plasma cells, maybe a few PMN’s, fibroblasts with collagen, and characteristic caseous necrosis in the center.
• The inflammatory response is mediated by a type IV hypersensitivity reaction which can be utilized as a basis for diagnosis by a TB skin test.
• An acid-fast stain (Ziehl–Neelsen or Kinyoun acid-fast stains) will show the organisms as slender red rods.
• An auramine stain of the organisms as viewed under fluorescence microscopy will be easier to screen and more organisms will be apparent.
DIFFERENTIAL DIAGNOSIS
• Amicrobic cystitis
• BCG sepsis/BCGosis
• Chronic nonspecific cystitis or pyelonephritis
• Disseminated coccidioidomycosis
• Granulomatous prostatitis; prostate cancer
• Medullary sponge kidney
• Necrotizing papillitis
• Nonspecific epididymitis
• Renal stones or nephrocalcinosis
• Urinary bilharziasis (schistosomiasis)
TREATMENT
GENERAL MEASURES
• Quarantine until on appropriate medications
• Screen close contacts
MEDICATION
First Line (2)
• Antituberculous drugs are 1st choice: Isoniazide, rifampicin, pirazinamide, ethambutol, and streptomycin.
• Patient with uncomplicated TB infection: Isoniazid (300 mg/d), rifampin (450–600 mg/d), and pyrazinamide (25 mg/kg/d) once a day in the morning, 3 times a week, for 2–4 mo, followed by isoniazid and rifampin once a day, 3 times a week, for an additional 2–4 mo. (add 1 g of vitamin C, 3 times a week, for 4 mo with above regimen).
Second Line
• Patient with complicated TB infection: Add streptomycin to the above for severe infection or severe bladder symptoms.
• Drug resistance is increasing and necessitates tight therapy control, expanded antibiotic regimen of 4 of the following: Ethionamide, prothionamide, quinolones, clarithromycin, cycloserine, kanamycin, viomycin, capreomycin, thiacetazone, and para-aminosalicylate.
• Steroids: No role in initial therapy but can be used for acute TB cystitis or stricture at distal ureter (prednisone 20 mg PO TID)
SURGERY/OTHER PROCEDURES
• Nephrectomy for symptomatic (HTN, obstruction, pyelonephritis) nonfunctioning kidney with extensive disease or coexistent renal cell carcinoma.
• Perform 4–6 wk after start of antituberculous drugs
• Epididymectomy: Indicated for caseating abscess unresponsive to chemotherapy
• Ureteral strictures: Stenting vs. reconstruction
• Bladder augmentation: Small capacity, fibrotic bladder.
• Surgery not necessary for TB abscesses: Treat medically
ONGOING CARE
PROGNOSIS
• Awareness of renal TB is urgently needed by physicians to suspect this disease in patients with unexplained urinary tract abnormalities, mainly in those with any immunosuppression and those coming from TB-endemic areas (1).
• No specific statistics, but overall patients can do well with appropriate, early antituberculosis medications and surgical interventions.
COMPLICATIONS
• Ureteral TB: Stricture formation, hydronephrosis
• Complete nonfunctioning of an affected kidney (“autonephrectomy”) described
• Renal TB: Obliteration of the renal and psoas shadow on plain radiographs, perinephric abscess may cause an enlarging mass in the flank.
• Genital TB: Sterility a consequence
• An abscess of the epididymis may erode through the scrotal wall or testis, creating a sinus tract and drainage.
• Bladder TB: Stenosis of ureterovesical junction, fibrosis, and contraction of bladder
• Nephrotoxicity induced by antimicrobial agents (especially rifampin)
FOLLOW-UP
• Completion of TB regimens long term is essential.
• Strictures can evolve after organism is eradicated.
• Follow regularly after completion of therapy as stricturing can continue: 3, 6, 9, 12 mo with urine culture and TB staining and excretory urography.
• Need long-term imaging follow-up of calcifications if present.
REFERENCES
1. Daher Ede F, da Silva GB Jr, Barros EJ. Renal tuberculosis in the modern era. Am J Trop Med Hyg. 2013;88(1):54–64.
2. The Medical Letter: Drugs for tuberculosis. Treat Guidel Med Lett. 2004;2(28):83–88.
ADDITIONAL READING
• de Figueiredo AA, Lucon AM, Srougi M. Bladder augmentation for the treatment of chronic tuberculous cystitis. Clinical and urodynamic evaluation of 25 patients after long term follow-up. Neurourol Urodyn. 2006;25(5):433–440.
• Fischer M, Flamm J: The value of surgical therapy in the treatment of urogenital tuberculosis. Urologe A. 1990;29(5):261–264.
• Gow JG, Barbosa S. Genitourinary tuberculosis. A study of 1117 cases over a period of 34 years. Br J Urol. 1984;56(5):449–455.
• Wise GJ, Marella VK. Genitourinary manifestations of tuberculosis. Urol Clin North Am. 2003;30:111–121.
See Also (Topic, Algorithm, Media)
• Bacteruria and Pyuria
• BCG Sepsis/BCGosis
• Prostatitis, Granulomatous
• Prostatitis, Tuberculous
• Tuberculosis, Bladder, and Urethra
• Tuberculosis, Genitourinary, General Considerations Image 
• Tuberculosis, Kidney, and Ureter
• Tuberculosis, Male External Genitalia
CODES
ICD9
• 016.00 Tuberculosis of kidney, unspecified
• 016.10 Tuberculosis of bladder, unspecified
• 016.90 Genitourinary tuberculosis, unspecified, unspecified
ICD10
• A18.10 Tuberculosis of genitourinary system, unspecified
• A18.11 Tuberculosis of kidney and ureter
• A18.12 Tuberculosis of bladder
CLINICAL/SURGICAL PEARLS
• Chronic draining scrotal sinuses should be considered TB until proven otherwise.
• Sterile pyuria is the classic finding, typically >20 WBC/HPF.
• Renal involvement by TB infection is underdiagnosed in most health care centers.
• Posttreatment follow-up is essential as strictures can evolve after organism is eradicated.