Definition

Tuberculosis (TB), caused mostly by Mycobacterium tuberculosis, is a major global health problem. According to a recent report by the World Health Organization (WHO), there were almost 9 million new cases in 2011 and 1.4 million deaths attributed to TB.¹ From 1999 to 2020, there will be an estimated 1 billion new cases of TB if control measures are not improved. In developed countries, TB usually affects older individuals and immigrants from countries with high prevalence. The incidence of TB is 100 times greater in patients with human immunodeficiency virus (HIV), and TB is the most common opportunistic infection in HIV-infected patients.² TB also is more common in patients with chronic kidney disease (CKD), especially when associated with anatomic abnormalities or immunosuppression. In some endemic areas, TB has been reported to occur in up to 9% of patients receiving hemodialysis, 9% of renal allograft recipients, and 12% of children with nephrotic syndrome.³

Genitourinary TB occurs in about 5% of active TB cases in the non–HIV-infected population.⁴ It is almost always secondary to a symptomatic or asymptomatic primary lesion in the lung. Renal involvement may also occur as a complication of miliary (septicemic) TB.

In recent years, the incidence of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB has increased. According to WHO estimates, there were 630,000 cases of MDR TB in 2001.¹ This scenario has compromised programs to eradicate TB.

Etiology

The tubercle bacillus is a nonmotile, nonsporing, strictly aerobic straight or slightly curved rod-like bacillus that is weakly gram positive and acid and alcohol fast. Mycobacteria have a lipid shell (“lipid barrier”) containing mycolic acid that resists proteolysis and uptake into phagolysosomes; muramyl dipeptide, which stimulates a T cell response that elicits the characteristic granuloma; and cell wall glycolipids that inhibit macrophage function. This surrounding coat of inert lipids and surface proteins allows mycobacteria to survive inside phagocytes, where they may remain dormant for years.⁵

Whereas most TB including genitourinary TB is caused by M. tuberculosis,⁵ other mycobacteria may rarely cause clinical disease, especially in immunocompromised hosts. These include M. avium-intracellulare, M. kansasii, M. bovis, M. fortuitum, and M. szulgai.

Pathogenesis

The clinical and pathologic manifestations of TB depend on the virulence of the organism and the effectiveness of the host response. The host response may lead to complete containment of infection or result in an illness of varying severity. Strain differences may also determine whether an infected person develops primary TB, reactivation TB, or a chronic asymptomatic infection. A low serum level of 25-hydroxyvitamin D may also compromise cell-mediated immunity and increase the risk for activation of latent TB.

When an infected droplet with the size of 1 to 5 µm is deposited in the respiratory tract, tonsillar fossa, or gastrointestinal tract, a primary focus develops with the formation of a nonspecific, asymptomatic granuloma. The organisms from the primary focus drain to the regional lymph gland, causing its enlargement, resulting in the primary complex. This is often asymptomatic and self-limited.

Bacilli from the regional lymph node may also enter through the thoracic duct into the blood, resulting in silent dissemination to various sites, including the cortex of the kidneys (Fig. 54-1). Here the bacilli elicit an inflammatory response, resulting in granuloma formation that may heal and form a scar, remain dormant for many years, or rupture into the proximal tubule of the nephron. The bacilli in the nephron are trapped at the level of the loop of Henle, where they multiply. The relatively poor blood flow, hypertonicity, and high ammonia concentration in the renal medulla impair the immune responses and favor the formation of medullary granulomas. These granulomas (tuberculomas), which contain macrophages, may undergo coagulative necrosis, forming cheese-like caseous material (Fig. 54-2), and occasionally rupture into the calyx.⁶

The renal medulla is the most common site of involvement of clinical renal TB and is usually unilateral.⁷ When this caseous focus ruptures into the collecting system, cavities and ulcers are formed, and involvement of renal papillae may lead to sloughing and papillary necrosis. Healing in the kidney occurs by fibrosis and scarring, resulting in strictures and obstruction. Calcification commences intracellularly by the accumulation of phosphate ions from the disintegration of nucleoproteins and calcium ions from cell membrane damage. These lesions may harbor live mycobacteria, and such dystrophic lesions should be considered active disease and not a sign of healing. Dystrophic calcification of damaged structures may result in a nonfunctioning kidney called “putty” or “cement” kidney. Spread of TB to contiguous structures may occur; ureteritis is common and may result in strictures and obstructive uropathy (Fig. 54-3).

The bladder may develop hyperemia near the ureteral orifice, followed by superficial ulcers and granulomatous changes involving all layers (pancystitis). Healing by fibrosis at the ureteral orifice results in a refluxing “golf-hole” ureter. Extensive fibrosis of the bladder wall results in a thick, small-capacity bladder called “thimble” bladder (Fig. 54-4). Bladder infection may also rarely result from instillation of bacille Calmette-Guérin (BCG) in the bladder as part of treatment of superficial bladder carcinomas.

Transplanted kidneys may transmit TB to their recipients.⁸