Tuberculosis of the Urinary Tract MN Definition Genitourinary

Tuberculosis of the Urinary Tract MN 이 은빈

Definition Genitourinary TB secondary to primary lesion in the lung (symptomatic or asymptomatic) renal involvement - a complication of miliary (septicemic) TB. 5% of active cases in TB(non–HIV-infected population)

Etiology tubercle bacillus non motile non sporing strictly aerobic straight or slightly curved rod-like weakly gram positive acid and alcohol fast lipid shell (“lipid barrier”) -containing mycolic acid -resists proteolysis and uptake into phagolysosomes muramyl dipeptide -stimulates a T-cell response that elicits the characteristic granuloma cell wall glycolipids -inhibit macrophage function. This surrounding coat of lipids and proteins -allows mycobacteria to survive inside phagocytes -remain dormant for years NTM genitourinary TB - M. tuberculosis

Pathogenesis clinical and pathologic manifestations of TB depend on virulence of the organism effectiveness of the host response may lead to complete containment of infection illness of varying severity

calcification Intracellular calcification by the accumulation of calcium and phosphate - from the disintegration of nucleoproteins calcium ions -from cell membrane damage These lesions may harbor live mycobacteria, dystrophic calcification lesions should be considered active disease and not a sign of healing. dystrophic calcification of damaged structures may result in a nonfunctioning kidney called “cement” kidney. strictures and obstruction spread of TB to contiguous structures calyx, pelvis, ureter healing with fibrosis and scarring may result in strictures and obstruction obstructive uropathy

The bladder superficial ulcers and granulomatous change- involving all layers (pancystitis) “golf-hole” ureter healing by fibrosis at the ureteral orifice results in reflux “thimble” bladder extensive fibrosis of the bladder wall results in a thick, small capacity bladder

Thimble bladder - cystogram

Involvement of the genital tract Is common in man but rare in women 70% - 80% of men with TB of the urinary tract have epididymitis, prostatitis, seminal vesiculitis, orchitis, or cold abscesses. 5% of women with TB of the urinary tract have genital tract involvement but if it is present, it usually presents as salpingitis that is often diagnosed during investigation for infertility. Transplanted kidneys may also transmit TB to their recipients.

Clinical Manifestations Urinary tract TB asymptomatic or mimic other disorders. constitutional symptoms related to the lower urinary tract, abdomen, or genitalia. 20 - 40 yrs old rare in children (because active genitourinary TB presents 5 to 15 years after primary infection) male: female =2: 1 risk factors for TB close contact with sputum smear–positive individuals vagrancy, social deprivation, neglect, Immunosuppression HIV infection , AIDS, DM, renal failure

acid-sterile pyuria Urine concentration defect stone, clot

tubular proteinuria long-standing renal TB may result in mild tubular proteinuria (<1 g/24 h) in up to 50% of patients about 15% have proteinuria of more than 1 g/24 h anemia is seen in less than 20% of patients with non miliary disease, but the frequency is higher in those with renal dysfunction. tubulointerstitial injury (d/t obstructive uropathy) nephrogenic diabetes insipidus renal tubular acidosis hyporeninemic hypoaldosteronism renal function is usually normal CKD may develop if both kineys are extensively damaged

Hypertension unusual in renal TB but intimal proliferation of vessels near inflamed areas -segmental ischemia - renin release In nonfunctioning kidney, nephrectomy may improve the hypertension relief of obstruction may lower the blood pressure Nephrolithiasis 7% to 18% of renal TB Secondary infection E. coli may be seen in 20% to 50% of renal TB patients. chest radiograph show evidence of active or healed tuberculous lesions in more than 50% of renal TB.

Pathology Gross appearance Outer surface Yellow white, hard, pine head size nodules On cut section granulomas and ulcers in the renal pyramid or medullary cavities larger cavities filled with caseous material communicating with the collecting system multiple ulcers in the infundibular region of the calyces calyceal stenosis with caliectasis, ulcers or strictures of the ureter Hydronephrosis pyonephrosis subcapsular collections perinephric abscesses

microscopy in early disease neutrophilic infiltration with phagocytosis of the bacilli subsequent histologic features depend on the virulence of the organism and the cell-mediated immunity. effective cell-mediated response, granulomas (macrophages with engulfed bacilli surrounded by epithelioid cells and Langhans giant cells) healing occurs by fibrosis and scarring. less effective immune response, caseating necrosis (amorphous cheese-like eosinophilic material replacing the normal tissue architecture) implies that the lesion is active later, this may calcify dystrophic calcification suggests activity rather than healing.

Diagnosis and Differential Diagnosis suspicion may also occur sterile pyuria tuberculin test (Mantoux test) useful for proving infection (or prior immunization with BCG) positive test-prior exposure to the antigen and does not indicate active infection. negative test- rule out tuberculous infection (in the absence of an immunosuppressed state) isolation of M. tuberculosis by urine culture definitive diagnostic test fully voided early morning urine samples for 3 to 5 consecutive days on two standard solid media egg-based Lowenstein-Jensen medium agar-based Middlebrook 7 H 10 medium transparent media - earlier visualization of microcolonies grow by 6 to 12 weeks sensitivity tests to choose the optimum chemotherapeutic agents take an additional 6 to 12 weeks

Rapid methods radiometric broth method for AFB positive growth-in 9 days serologic tests polymerase chain reaction Enzyme linked immunospot assays in-vitro diagnostic tests measure T cell specific M. tuberculosis antigens test results -unaffected by prior tuberculin testing or low CD 4 counts Quantiferon test qutifying the interferon-γ released from the WBC (exposed to the mycobacterial antigens) result in 24 hours(main advantage) fine-needle aspiration cytology useful in defining the granulomatous nature in patients with urine AFB culture(+) pathologic triad : caseating necrosis loose aggregates of epithelioid histiocytes Langhans giant cells

Imaging studies once a diagnosis of genitourinary TB is made the extent and severity of involvement plain radiographs extensive dystrophic calcification in advanced renal TB “cumulus cloud” calcification plain radiographs of chest and spine s active or healed tuberculous lesions in 60% to 70% of patients excretory urogram abnormalities may be seen in 70% to 90% of patients. minimal erosion of the tip of the calyx with spasticity, incomplete filling, distortion, infundibular stenosis, hydrocalicosis, multiple ureteral strictures, hydronephrosis, hydroureter nonvisualization of the kidney renal pelvis-dilated ->obliterated and distorted ureter -irregularities or multiple strictures -> beaded or corkscrew appearance of the or hydronephrosis -> thickening and straightening of the whole ureter(“pipe-stem” ureter).

High-resolution ultrasound rule out obstruction identify granulomas, small abscesses, bladder mucosal thickening, or calcification earliest finding - mucosal thickening and calyceal irregularity

Computed tomography (CT) most sensitive method for identifying renal parenchymal scarring, calcification, and cavitary lesions cortical thinning - m/c CT finding helpful in the follow-up of patients with cavities or mass lesions in the kidney

Cystoscopy visualize the mucosal lesions the golf-hole ureteral orifice the efflux of toothpaste-like caseous material Biopsy during the acute stage is avoided for fear of dissemination of TB.

Treatment usually amenable to medical treatment antituberculous drugs reach in high concentration the kidneys, urinary tract, urine, cavitary lesions fewer organisms in the lesions compared with cavitary lung lesions short-course regimen is recommended started with daily rifampin (600 mg), isoniazid (300 mg), and pyrazinamide (1500 mg) in the morning. pyrazinamide: DC after 2 months isoniazid , rifampin : continued for another 4 months streptomycin in daily doses of 1 g may be added during the first 2 months -very sick with irritative bladder symptoms older than 40 yrs daily dose- 0. 75 g + monitoring for ototoxicity and vestibular toxicity. ethambutol probability of drug resistance is high 800 -1200 mg/day in the first 2 months

treatment and healing by fibrosis obstruction of ureter hydronephrosis parenchymal damage renal failure allergic interstitial nephritis receiving intermittent rifampin therapy oliguric acute renal failure

Surgical Treatment The role of surgical treatment in urinary TB is limited. reconstructive surgery correction of ureter obstruction by pyeloplasty Ureteroureterostomy ureteral reimplantation(correction of reflux ) augmentation cystoplasty(increasing the bladder capacity) timely introduction of stents across the narrow segment -avoid the major surgical procedures ablative surgery (nephrectomy) secondary sepsis pain bleeding uncontrollable hypertension continued positive urinary cultures Tuberculous abscesses aspiration under ultrasound or CT guidance direct instillation of antituberculous drugs into the cavity

Treatment of Patients with Renal Failure isoniazid, rifampin, pyrazinamide eliminated by biliary route normal dosages isoniazid -pyridoxine (50 mg/day) to prevent peripheral neuropathy Streptomycin, ethambutol-excreted by the kidney Streptomycin -(15 mg/kg) 24 - 72 hrs 10 <GFR < 50 ml/m 72 - 96 hrs GFR<10 ml/min 50 -75% supply after HD maintain a therapeutic peak level of 20 - 30 µg/ml monitoring for high-pitched tinnitus sense of fullness in the ears audiography Ethambutol 800 -1200 mg 24 - 36 hrs 10<GFR< 50 ml/min 48 hrs GFR< 10 ml/min no supply after HD alterations in visual fields, acuity, and blue-green color vision