Tuberculosis of kidney
Tuberculosis of the kidney and urinary tract is, like other forms of the disease, caused by members of the mycobacterium tuberculosis complex. By far the most common causative organism is the human tubercle bacillus, M.tuberculosis, but the bovine tubercle bacillus, M.bovis, occasionally can be responsible.
Globally, tuberculosis is a common disease, with 8 to 10 million new cases annually and a rising incidence, particularly in regions with a high incidence of HIV infection. Most often the lung is affected, but, after lymphadenopathy, the most common form of non pulmonary tuberculosis is genitourinary disease, accounting for 27%.
Classical renal tuberculosis: Tuberculosis of the urinary tract is easily overlooked. Many patients present with lower urinary symptoms typical of ” conventional ” bacterial cystitis and suspicions of tuberculosis are aroused only when there is no response to the usual antibacterial agents or when urine examination reveals pyuria in the absence of a positive culture on routine media. Other symptoms that sometimes occur include back, flank, and supra public pain; haematuria; frequency; and nocturia; these might also suggest conventional bacterial urinary tract infection. Renal colic is uncommon, occurring in fewer than 10% of patients, and constitutional symptoms such as fever, weight loss, and night sweats also are unusual. Only one third of patients have an abnormal chest x- ray.
The diagnosis of tuberculosis of the urinary tract is based on the finding of pyuria in the absence of infection as judged by culture on routine media. In early disease, it often is possible on intravenous urography to detect changes in a single calyx with evidence of parenchymal necrosis, and typically there is calcification on the plain film. In more advanced disease, urography will show calyceal distortion, ureteric strictures and bladder fibrosis. Ultrasound examination of the urinary tract may reveal renal calyceal dilation and more overt evidence of obstruction.
Ultimately, a tuberculosis kidney may become calcified and non functioning. Not surprising, if the gross anatomic distortion is advanced and bilateral, the GFR will fall and, in some patients, there is progression to end- stage renal failure.
Tuberculous interstitial nephritis:
It now is clear that tuberculosis can affect the kidney more insidiously. There may be advanced renal failure. Renal histology may reveal chronic tubulointerstial nephritis with granuloma formation and occasional caseation. Sometimes, acid- fast bacilli can be identified with appropriate stains. Some of these patients may show evidence of tuberculosis on chest x- ray and may have tubercular peritonitis.
When the diagnosis has been made while useful renal function remains, it sometimes has been possible to arrest the fall in GFR or even produce improvement. In some of these patients, there is pyuria, but in others there is not.
Tuberculosis and Glomerular Disease:
Chronic tuberculosis sometimes is complicated by amyloidosis.
End- stage Renal Disease:
Tuberculosis, although an uncommon cause of progressive renal failure, is an important one because, unlike many renal conditions, it is potentially preventable and easily tolerable. Whereas most of the world’s tuberculosis is in developing countries, registries of patients with end- stage renal failure are mainly in the developed world.
In men, the site most commonly involved is the epididymis, followed by the prostate. Testicular involvement is less common and usually is the result of direct invasion from the epididymis.
It is generally believed that tuberculous prostatitis results from antegrade infection within the urinary tract; epididymis, however, probably is the result of blood- borne infection because it often is an isolated finding without urinary tract involvement.
It is important to be aware that a high proportion, perhaps 50 to 75% of men with genital tuberculosis have radiological abnormalities in the urinary tract, so the urinary tract of all such patients should be investigated. In women there is no close correlation between urinary tract and genital tuberculosis; indeed, renal tract tuberculosis accompanies lesions of the reproductive tract in fewer than 5% of cases.
A microbiologic diagnosis of tuberculosis usually is made by isolation of the causative organism from urine or biopsy material on conventional solid media or by an automated system such as radiometry. Acid- fast bacilli may be seen on microscopy of centrifuged urine, but care must be taken when very few bacilli are seen, “because there may be environmental mycobacteria that contaminate the lower urethra.
In recent years, nucleic- acid amplification techniques, such as PCR, have been investigated extensively for the detection of M. Tuberculosis and other mycobacteria in clinical specimens, notably sputum. Relatively few studies have specifically evaluated PCR for detection of genitourinary tuberculosis, and these show the technique to be sensitive and specific, although some urine specimens contain inhibitory substances. In addition, PCR has been used to detect mycobacterial DNA in urine in cases of HIV- related disseminated tuberculosis.
Tuberculosis may involve the kidney as part of generalized disseminated infection or as localized genitourinary disease. The morphology of the lesions depends on the site of infection, the virulence of the organism, and the immune status of the patient.
Renal involvement as part of disseminated infection:
The kidney frequently is involved in miliary ( ” septicemic ” ) tuberculosis where blood borne miliary tubercles are seen throughout the renal substance, most noticeably in the cortex.
The lesions measure up to 3 mm in diameter and usually are pale or white. Histologically, they consist of epitheloid granulomata, with or without caseation , and often contain Langhan’s- type giant cells. Organisms usually can be demonstrated microscopically within these lesions but sometimes are difficult to find. Renal function usually is not compromised in these patients.
When the patient is immunosuppressed, the granulomas may be less well formed and organisms may be more readily demonstrated. Caseous necrosis is seen less frequently. When immunosuppression is severe and in cases in which the infective organism is one of the environmental mycobacteria, such as M. Avium- intracellulare, the lesions may be more diffuse and poorly formed than the usual miliary lesions; the granulomatous response consists of histiocytic cells with abundant pale cytoplasm packed with organisms ( “multibacillary histiocytosis”). Caseous necrosis is not a feature.
In some patients with pulmonary or disseminated tuberculosis, there is evidence of renal failure without typical miliary involvement or localized genitourinary lesions. In these cases, biopsy has shown interstitial nephritis, usually but not in all cases with granulomata. The evidence that the renal malfunction is due to a combination of infection and immunologic renal damage. Arrest of decline or even improvement in function occurs with a combination of anti tuberculosis treatment and corticosteroids.
Localized urinary tract tuberculosis:
The kidney usually is infected by haematogenous spread of bacilli from a focus of infection in the lung. In most cases, at the time of presentation there is no evidence of active pulmonary disease, although there may be clinical or radiologic evidence of past infection, suggesting that renal involvement occurs as a result of reactivation after a period of dormancy. Clinically, renal tuberculosis usually presents unilaterally, but postmortem studies undertaken in the first half of the 20th century indicate that the disease frequently is bilateral.
In a tuberculous lesion in the lung gains access to the vascular system by erosion of the wall of a vessel, usually a vein, then emboli containing organisms may be disseminated throughout the body. However, the bacilli have stringent growth requirements and generally tend to proliferate only in a small number of sites, including the kidney, epididymis, Fallopian tube, bone marrow, and brain, particularly the hindbrain. In the kidney, the site of preference is the renal medulla, where the lesions produced are con fluent epitheloid granulomata with caseous necrosis, leading to local tissue destruction. The infection may cause vascular insufficiency of the papillae by damaging vessels, and papillary necrosis may ensue. Spread to the renal pelvis produces a tuberculous pyelonephritis that may even progress to a pyelonephritis- like lesion, also known as a ” cement ” or ” putty ” kidney. Scarring develops within the renal pelvis with calcification in 24% of cases, identifiable as renal or ureteric stones in up to 19% of cases. Infection frequently spreads down the ureters into the bladder, producing mucosal and mural granulomatous lesions associated with scarring. The clinical consequences of an extensive renal lesion include autonephrectomy. The destructive renal lesions may spread outside the renal capsule and produce a mass lesion, which can mimic a neoplasm. Ureteric involvement also may produce irregular ureteric strictures and segmental dilation, leading to obstruction and /or reflux. Recognition that ureteric obstruction and reflux sometimes may be due to tuberculosis may prevent an unnecessary Nephrectomy if active treatment, including relief of obstruction, can be instituted early. Secondary bacterial infection of the urinary tract is common. Keratinizing squamous neoplasia may develop as a late complication of chronic inflammation and infection of renal pelvis and may persist even after treatment of the active tuberculous lesion. This is a potential risk factor for the development of squamous carcinoma in chronic cases.
Up to three quarters of instances of tubercular bladder infection are associated with renal infection, although in some cases tuberculous cystitis is believed to be due to spread from the epididymis.
Genitourinary tuberculosis and Immunodeficiency:
HIV- positive individuals:
In those who are only mildly immunosuppressed, the disease resembles that in HIV- negative individuals. In the more profoundly immunosuppressed, particularly those with CD4+T- cell counts of 50/cu.mm or lower, a high viral load, and a negative tuberculin test, the disease often is disseminated and the kidney is involved incidentally with various pathologic manifestations, including granulomatous interstitial nephritis. The incidence of renal involvement may be higher than currently believed.
Tuberculosis and vitamin-D deficiency:
There is good evidence that a fall in serum 25-OH-vitamin D levels compromises cell-mediated immune defenses and leads to the activation of latent tuberculosis .
Treatment of Tuberculosis:
Modern short- course anti tuberculosis drug regimens are effective in all forms of tuberculosis. They are based on an initial 2-month intensive phase of treatment in which, usually, four drugs- rifampicin, isoniazid, pyrizinamide, and ethambutol ( streptomycin ) are given, and these destroy almost all tubercle bacilli. This is followed by a 4- month continuation phase in which only rifampicin and isoniazid are given, with the aim of eliminating the few remaining near- dormant, persisting bacilli. For success, all doses must be taken, and because a failure to comply with therapy is the major cause for treatment failure, the World Health Organization has stressed the importance of direct supervision of therapy. To render such observation easier for both patient and supervisor, the drugs may be given twice or thrice weekly during the continuation phase.In recent years, there has been a worrying increase in the incidence of multidrug- resistant tuberculosis, which, by definition, is caused by bacilli resistant to rifampicin and isoniazid, with or without resistance to other drugs. Therapy requires the use of at least four drugs that are selected, on the basis of drug susceptibility tests from ethionamide, prothionamide, quinolones ( e.g., clarithromycin ), cycloserine, kanamycin, viomycin, capreomycin, thiocetazone, and para- amino- salicylic acid. These are less effective and often more toxic and/or costly than the first- line drugs. Duration of therapy is based on bacteriological response but may be 18 months or longer.
Special considerations apply to the treatment of tuberculosis in patients with impaired renal function. Rifampicin, isoniazid, pyrizinamide, ethionamide, and prothionamide may be given in normal doses because they are either eliminated in the bile or broken down to metabolites that are not excreted by the kidney. By contrast, care is required in the use of streptomycin, other amino glycosides and ethambutol because they are wholly excreted via the kidney. Ethambutol causes optic neuritis, which may be irreversible, and reduced doses should be given according to the GFR; 25 mg three times weekly if the GFR is between 50 and 100 ml/ min and twice weekly if it is between 30 and 50 ml/ min. Streptomycin and other amino glycosides are ototoxic and nephrotoxic and should be avoided if possible in patients with impairment of renal function, especially those on cyclosporin , because they have a high risk of nephrotoxicity.
Encephalopathy is an uncommon complication of isoniazid therapy and usually is preventable by the prescription of pyridoxine ( 25 to 50 mg/d ). A few patients on hemodialysis have developed isoniazid- induced encephalopathy that did not respond to pyridoxine, but the condition resolved when isoniazid was withdrawn. Rifampicin increases the rate of metabolism of a wide range of drugs, including corticosteroids, cyclosporin, and tacrolimus, which often are given to transplant patients. Regular measurement of blood concentrations of cyclosporin and tacrolimus in such patients is recommended.
An additional complication is encountered in HIV- positive patients who are receiving highly active antiretroviral therapy because these drugs interact adversely with rifampicin. At present, it is recommended that rifabutin be given instead of rifampicin and that the duration of therapy be extended to 9 month.
Surgical intervention is indicated in cases of advanced unilateral disease complicated by pain or haemorrhage and for bladder augmentation. Surgical excision of non functioning kidneys or extensive lesions in partly functioning kidneys is controversial. Relief of ureteric obstruction by stenting or per cutaneous nephrostomy may aid functional recovery, especially in patients with good renal cortical thickness, limited renal involvement, and a GFR of more than 15 ml/min.
Tuberculosis is a common disease worldwide. In developed nations, tuberculosis is relatively uncommon, but the risk of acquiring the disease is increased in immunosuppressed individuals, including patients on dialysis and recipients of kidney transplants. The signs and symptoms of renal tuberculosis mimic those of other infections of the kidney, so diagnostic awareness may prevent unnecessary morbidity. Diagnosis is not easy, but developments in nucleic acid- based bacteriological tests are very promising.
Dr. A. K. M. Aminul Hoque
Prof. of Medicine