Renal Tuberculosis: Diagnosis & Management<br />PuneetArora<br />13/07/2011<br />
TB's History<br />Proof of TB has been found in 4 000 year old mummies.<br />Corpus Hippocraticum<br />Great white plague<...
Indian History<br /><ul><li>Rigveda</li></ul>  Calls the disease : yaksma<br />Atharvaveda<br />    calls it another name:...
Robert Koch discovered in 1882 that <br />	TB was caused by a bacteria. <br />1920 – BCG vaccine<br />1944 –Streptomycin.<...
Etiology    <br />Genus Mycobacterium<br />Weakly gram+ive,Acid fast <br />Non-motile,nonsporing,strictlyaerobic,straight ...
                   Epidemiology<br />1993 – the WHO declared TB a global emergency<br />2 billion people latently infected...
               Renal tuberculosis<br />Disease of young to middle-aged adults.<br />M/F ratio= 5:3(In contrast to other fo...
                Renal tuberculosis<br />Hematogenousspread<br />Observed in two clinical settings: commonly, as a late man...
25% of the patients with genitourinary tuberculosis have a history of diagnosed tuberculosis.<br />In an additional 25% to...
Considerable lapse of time between the onset of pulmonary infection and the diagnosis of active genitourinary tuberculosis...
Pathogenesiscaseation 	fibrosis<br />The small silent renal granulomas resulting from silent hematogenous dissemination ar...
Bacilli in the nephron are trapped at the level of loop of henle,where they multiply and survive well possibly on account ...
Progressive destruction with cavity formation<br />Papillary necrosis<br />tuberculouspyonephrosis (caseocavernous renal t...
Fibrosis accompanies the granulomatous process <br />infundibularstrictures <br />			and renal pelvic kinking<br />       ...
Pathology: Gross<br />Renal tuberculosis. Photograph of a cut gross specimen shows multiple, predominantly peripheral, whi...
Photographs of a cut gross specimen show the early necrosis of the medullary tip (black spot in a). Once devitalized, the ...
Calcification in advanced lesions is common and may be focal or generalized, which produces a putty or cement kidney.<br />
Pathology: Microscopic<br />Caseatinggranuloma<br />Bilateral microscopic renal involvement is the rule.<br />
Necrotizing granulomas<br />fungal infections<br />wegener'sgranulomatosis. <br />Non-caseatinggranulomas<br />sarcoidosis...
Insidious mode of presentation, with approximately 20% of cases diagnosed unexpectedly at operation or autopsy. <br />A hi...
close contact with sputum positive individuals<br />vagrancy,<br />social deprivation,<br />neglect,<br />immunosuppressio...
Approximately 75% of patients present with symptoms suggesting urinary tract inflammation. <br />		-Dysuria<br />		-Mild o...
Proteinuria<br />		Mild Proteinuria (<1gm/day in 50% cases)<br />		>1gm/day in 15% patients<br />		Rarely nephrotic range ...
patients with renal tuberculosis may be subject to dehydration because of a concentrating defect, a tendency to lose salt<...
complete renal function loss owing to parenchymatous infection and destruction <br />Strictures, can result in hydronephro...
Rare presentations:<br />    Tubercular interstitial nephritis<br /><ul><li>In some patients with pulmonary or disseminate...
 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 immunological renal damage is the recove...
Glomerular Diseases<br />Rare association with<br />		-dense deposit disease<br />Hariprasad et al. New york state journal...
Three other major complications of renal tuberculosis: 				<br />				hypertension (RAS axis mediated)<br />				super-infec...
                              Descending infection to bladder                                                 Healingsmall...
DiagnosisUrine analysis<br />Essentially every patient with established urinary tract tuberculosis has an abnormal urinaly...
                     Sterile Pyuria<br />Tuberculosis of the urinary tract <br />Chlamydia trachomatis, Mycoplasma, or Ure...
Early-morning urine specimens are preferred<br />Sterile container<br />three to five daily specimens<br />Preferably imme...
concentrated by centrifugation. <br />Smears prepared from sediment<br />Z-N staining.<br />Problem of E.M.s(MycobacteriaS...
ZN staining<br />Hot 1% carbol-fuchsin for five minutes.<br />3% HCl or 20% sulphuric acid<br />Ethanol<br />counterstaine...
Culture<br /><ul><li>Gold standard
positive in 80% to 90% of cases
Decontamination of sediment.
main problems:</li></ul>-COST<br />			-AVAILABILITY<br />			-DELAYS<br />
newer commercial media (BACTEC..)<br />-faster (about 10 days)<br />-but expensive++, <br />-technical demanding<br />-not...
<ul><li>High dose IVU – traditional gold standard
CT – new standard
Pyelography (ante/retrograde) – limited use
Plain radiographs – important</li></ul>CXR,spine X-Ray,X-Ray KUB<br /><ul><li>US – limited value
Nuclear Perfusion Scan – function
MRI,Arteriography – little application</li></ul>                        Imaging <br />
                         Radiology<br />X-Rays<br />Plain films of the abdomen-<br />		-genitourinary calcifications (pres...
Plain radiograph of the abdomen demonstrates extensive calcification in the left kidney, which was nonfunctional (the putt...
Genitourinary tract tuberculosis. Plain radiograph of the abdomen in a patient with calcified seminal vesicles due to tube...
USG<br />	-initial investigation of choice<br />			Cavities<br />			Obstruction<br />Early findings may be missed<br />Son...
Intravenous pyelography & CT urogram findings<br />Intravenous urography  - most useful because of its ability to detect c...
Hicked-up pelvis (Kerr kink sign) <br />Infundibularstrictures <br />Hydrocalyces without dilatation of renal pelvis, or <...
When ureters are involved, usually the upper or lower third (more common) <br />Beading (sawtooth ureter)<br />Corkscrew u...
IVP of 32-year-old woman. A, left renal parenchymal mass (arrows) and left hydroureter due to left distal ureteral strictu...
Genitourinary tract tuberculosis. Lobar calcification in a large destroyed right kidney in a patient with renal tuberculos...
 IVP of 45-year-old woman demonstrates tubercular autonephrectomy and calcifications (white arrowheads) of small right kid...
IVP film-The lower end of the right ureter demonstrates an irregular caliber with an irregular stricture at the right vesi...
Genitourinary tract tuberculosis. Intravenous urography series in a man with renal tuberculosis shows marked irregularity ...
Renal Tuberculosis. Coronal reformatted non-enhanced CT scan of the abdomen and pelvis demonstrates a small, left kidney c...
A, Contrast-enhanced CT scan obtained at level of right renal hilum shows wedge-shaped hypoperfused areas (arrowheads).<br...
53-year-old man with tuberculosis involving collecting system. Contrast-enhanced CT scan of left kidney shows uneven calie...
A, CT urogram shows severe nonuniformcaliectasis and multifocal strictures (arrowheads) involving renal pelvis and ureter....
50-year-old woman with putty kidney. CT scan shows dense calcification replacing right kidney, so-called “putty kidney.”<b...
Limitations-<br />May be normal in patients with early genitourinary tuberculosis. <br />Calcification may occur in patien...
Genitourinary tract tuberculosis. Lateral view of the abdomen in a patient with schistosomiasis shows tubular calcificatio...
Radiograph of the pelvis in a patient with schistosomiasis shows fine linear calcifications of the bladder wall with norma...
Cystoscopy under general anaesthesia with adequate muscle relaxation helps to visualize the mucosal lesions,golf hole uret...
Two goals<br />Clinical Management<br /> conservation of tissue <br />and function<br />antimycobacterial cure. <br />
Antimicrobial cure<br />It is a common practice for clinicians to treat GUTB for periods longer than six months. <br />DOT...
RNTCP- DOTS Therapy<br />Genito-urinary T.B. -- Cat I<br />(HRZE)2 + (HR)4<br />Drug			Daily Dose		Intr. Dose<br />		Isoni...
Longer courses of ATT ranging from 9 months to 2 years are useful in patients:<br />Who do not tolerate Pyrazinamide<br />...
Daily or intermittent?<br />Intermittent regimens have been compared head-to-head with daily treatment in several RCTs and...
Dose modification in renal failure<br />		INH<br />		Rifampicin 			no adjustment <br />		Pyrazinamide<br />	Drug		Cr. Clea...
Important side-effects of first-line anti-tuberculosis drugs<br />
Treatment monitoring<br />RNTCP guidelines- silent.<br />After 2 month of therapy- <br />			3 urine cultures<br />		If neg...
IVP <br />		-at the end of 2 months <br />		-and at the completion of Tt.<br />In case of renal calcification- yearly 3 ur...
Another area of controversy in the treatment of GUTB is the utility of corticosteroids in the prevention of complications ...
Most  ATDs  are safe during pregnancy except Streptomycin<br />No contraindication during breast feeding and not necessary...
The kidney is often involved in the disseminated tuberculosis but only a minority of patients have clinical features<br />...
HIV screening<br />In India, about 5.2% of patients with TB have underlying HIV co-infection<br />Extrapulmonary involveme...
Tuberculosis should always be considered when a renal transplant patient develops fever, especially when the patient is fr...
European Best Practice Guidelines for Renal Transplantation (2002) recommend that all renal transplant candidates and reci...
Surgical Management<br />In the prechemotherapy era, surgical ablation of infected foci was the only therapy available for...
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Seminar on renal tuberculosis

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Seminar prepared by Dr. Puneet Arora, DM resident in Nephrology, IPGMER Kolkata

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  • suffering from tuberculosis was thought to bestow upon the sufferer heightened sensitivity. The slow progress of the disease allowed for a &quot;good death&quot; as sufferers could arrange their affairs.[45] The disease began to represent spiritual purity and temporal wealth, leading many young, upper-class women to purposefully pale their skin to achieve the consumptive appearance. British poet Lord Byron wrote in 1828, &quot;I should like to die from consumption,&quot; helping to popularize the disease as the disease of artists.[46] 
  • The first references to tuberculosis in Asian civilization is found in the Vedas. The oldest of them (Rigveda, 1500 BCE) calls the disease yaksma.[9] The Atharvaveda calls it another name: balasa. It is in the Atharvaveda that the first description of scrofula is given.[10] The SushrutaSamhita, written around 600 BCE, recommends that the disease be treated with breast milk, various meats, alcohol and rest.[11] The Yajurveda advises sufferers to move to higher altitudes.[11]The Manu Smriti, written around 1500 BCE, states that sufferers of yaksma are impure and prohibits Brahmans from marrying any women that has a family history of the disease
  • but caseation may not always be apparent, notably in overwhelming or miliary infections, environmental mycobacteria, BCG-related lesions and in leprosy. Although acid-fast bacilli may often be demonstrated in early active disease and in lesions in the immunosuppressed (Ridley and Ridley 1987) (Fig. 10), they may be difficult or impossible to identify in immunocompetent or treated patients and in old lesionsInimmunosuppressed patients the granulomas may be less well formed and organisms more readily demonstrated. Caseous necrosis, which is the result of cell-mediated hypersensitivity and therefore dependent on an effective immune response, is less frequently seen
  • Circulating calcitriol levels were elevated but those of parathyroid hormone were not. Hypercalcaemia has been described in patients with disseminated tuberculosis who had neither renal failure nor renal involvement. Levels of calcitriol [1,25-(OH)2D3] are elevated in such patients as a result of increased synthesis of this active form of vitamin D by activated macrophages within the granulomas (Rook 1988).
  • The most suitable containers are sterile 28 ml glass or plastic screw-capped bottles (Universal Containers). to prevent replication of bacterial and fungal contaminants.
  • As contamination by EM is common, genitourinary tuberculosis should never be diagnosed on the basis of microscopical evidence alone. Tissue biopsies reveal the characteristic histological appearances associated with mycobacterial disease and can be stained for acid-fast bacilli. Failure to detect acid-fast bacilli on microscopic examination does not rule out their presence in the specimen. Tissue must contain 104–105acid-fast bacilli per gram for them to be detected with confidence
  • Egg-based media, such as Löwenstein–Jensen medium have been the mainstay of mycobacterial culture but colonies of M. tuberculosistake 2–8 weeks to appear
  • The use of nucleic acid amplification techniques, such as the PCR and its derivatives have been extensively investigated for the rapid detection of mycobacteria in clinical specimens, notably sputum. Although few studies have specifically evaluated PCR for the diagnosis of genitourinary tuberculosis, the limited information available shows that the technique is sensitive and specific although some urine specimens contain substances that inhibit the PCR A neg test in absence of immunosuppressed state rules out tb infection
  • Antegrade or retrograde pyelography to dileneate upper urinary tract.CT most sensitive to detect calcification and cavitary lesions.
  • GUTB is more amenable to medical treatmentbecoz of the presence of significantly lesser no of organisms in the lesion as compared with lesions in the lungs
  • Seminar on renal tuberculosis

    1. 1. Renal Tuberculosis: Diagnosis & Management<br />PuneetArora<br />13/07/2011<br />
    2. 2. TB's History<br />Proof of TB has been found in 4 000 year old mummies.<br />Corpus Hippocraticum<br />Great white plague<br />Consumption<br />Scrofula (king’s evil)<br />Phtisis<br />Romantic disease<br />
    3. 3. Indian History<br /><ul><li>Rigveda</li></ul> Calls the disease : yaksma<br />Atharvaveda<br /> calls it another name: balasa. <br /> first description of scrofula is given.<br />The SushrutaSamhita, written around 600 BCE, recommends that the disease be treated with breast milk, various meats, alcohol and rest.<br />The Yajurveda advises sufferers to move to higher altitudes.<br />The Manu Smriti, written around 1500 BCE, states that sufferers of yaksma are impure and prohibits Brahmins from marrying any women that has a family history of the disease<br />.<br />
    4. 4. Robert Koch discovered in 1882 that <br /> TB was caused by a bacteria. <br />1920 – BCG vaccine<br />1944 –Streptomycin.<br />1970 – first outbreak of MDR-TB in USA.<br />2005- XDR-TB (KwaZulu-Natal, South Africa)<br />
    5. 5. Etiology <br />Genus Mycobacterium<br />Weakly gram+ive,Acid fast <br />Non-motile,nonsporing,strictlyaerobic,straight or slightly curved rod 2 to 4 µm in length with a diameter of 0.3 to 0.6 µm <br />
    6. 6. Epidemiology<br />1993 – the WHO declared TB a global emergency<br />2 billion people latently infected<br />7-8 million cases of active TB <br />Surge due to HIV Infection<br />
    7. 7. Renal tuberculosis<br />Disease of young to middle-aged adults.<br />M/F ratio= 5:3(In contrast to other forms of non-pulmonary TB)<br />Uncommon in children and seen today almost exclusively in the rare child with miliary disease.<br />Approximately 20-30% of extra-pulmonary infection(second most frequent form of non pulmonary TB)<br />Seen in approximately 4% to 8% of non-HIV infected individuals with pulmonary tuberculosis.<br />
    8. 8. Renal tuberculosis<br />Hematogenousspread<br />Observed in two clinical settings: commonly, as a late manifestation of earlier clinical or subclinical pulmonary infection and rarely, as part of the multiorgan infection (miliary tuberculosis)<br />Rarely primary one—<br /> BCG Tt for Ca bladder<br /> Transplant recipient<br />
    9. 9. 25% of the patients with genitourinary tuberculosis have a history of diagnosed tuberculosis.<br />In an additional 25% to 50% of patients, changes compatible with old pulmonary tuberculosis can be found on chest x-ray films.<br />
    10. 10. Considerable lapse of time between the onset of pulmonary infection and the diagnosis of active genitourinary tuberculosis.<br />Time lapse of 16 to 25 years from primary tuberculous infection (i.e., erythema nodosum, pleurisy, or hilar adenopathy)<br />If one looks at patients with reactivation pulmonary tuberculosis, then the time lapse is usually about 4 to 8 years<br />It may be as long as several decades.<br />
    11. 11. Pathogenesiscaseation fibrosis<br />The small silent renal granulomas resulting from silent hematogenous dissemination are typically found bilaterally in the renal cortex<br />Arise from capillaries within and adjacent to glomeruli<br />These cortical granulomas remain dormant until unknown factors permit the bacilli to proliferate.<br />If enlarging granuloma rupture, delivers organisms into the proximal tubule. <br />
    12. 12. Bacilli in the nephron are trapped at the level of loop of henle,where they multiply and survive well possibly on account of impaired phagocytosis in the hypertonic environment.<br /> Clinically important renal tuberculosis, therefore, is usually initially localized to the medulla and is usually unilateral.<br />
    13. 13. Progressive destruction with cavity formation<br />Papillary necrosis<br />tuberculouspyonephrosis (caseocavernous renal tuberculosis) are common in advanced disease.<br /> Communication with the collecting system usually is responsible for the spread of bacilli to the renal pelvis, ureters & bladder <br />Lymphatic spread to contiguous structures also occurs.<br />Direct hematogenous seeding of pelvic genital organs with clinical sparing of the kidney can occur occasionally.<br />
    14. 14. Fibrosis accompanies the granulomatous process <br />infundibularstrictures <br /> and renal pelvic kinking<br /> obstructive uropathy<br />The end-stage kidney is nonfunctional (autonephrectomy) and destroyed by the combined necrotizing and obstructive processes<br />
    15. 15. Pathology: Gross<br />Renal tuberculosis. Photograph of a cut gross specimen shows multiple, predominantly peripheral, white tuberculous granulomas throughout the kidney.<br />
    16. 16. Photographs of a cut gross specimen show the early necrosis of the medullary tip (black spot in a). Once devitalized, the papilla sloughs off, leaving a defect (cavity in b)<br />
    17. 17. Calcification in advanced lesions is common and may be focal or generalized, which produces a putty or cement kidney.<br />
    18. 18. Pathology: Microscopic<br />Caseatinggranuloma<br />Bilateral microscopic renal involvement is the rule.<br />
    19. 19. Necrotizing granulomas<br />fungal infections<br />wegener'sgranulomatosis. <br />Non-caseatinggranulomas<br />sarcoidosis<br />leprosy, and <br />brucellosis. <br />Foreign body type granulomas<br />amyloid<br />ruptured tubules<br />myeloma protein, and <br />therapeutic embolization<br />Differential diagnosis<br />
    20. 20. Insidious mode of presentation, with approximately 20% of cases diagnosed unexpectedly at operation or autopsy. <br />A high index of suspicion enables early diagnosis<br />One measure of the frequently occult nature of urinary tract tuberculosis comes from Lattimer'sreport in which 18 of 25 physicians with renal tuberculosis being diagnosed only after far-advanced cavitary disease had developed.<br />Lattimer JK. Renal tuberculosis. N Engl J Med 1965;273:208. <br />Clinical Features<br />
    21. 21. close contact with sputum positive individuals<br />vagrancy,<br />social deprivation,<br />neglect,<br />immunosuppression,<br />HIV infection,<br />diabetes mellitus<br />renal failure<br />elderly<br />patients with TB elsewhere<br /> Risk factors<br />
    22. 22. Approximately 75% of patients present with symptoms suggesting urinary tract inflammation. <br /> -Dysuria<br /> -Mild or moderately severe back or flank pain<br /> -Recurrent bouts of painless gross hematuria<br />-Nocturia(due to conc. Defect)<br /> -Pyuria(esp. episodic)<br /> -Renal colic– up to 10% cases<br />
    23. 23. Proteinuria<br /> Mild Proteinuria (<1gm/day in 50% cases)<br /> >1gm/day in 15% patients<br /> Rarely nephrotic range proteinuria<br />Bladder symptoms in advanced cases (urgency, frequency)<br />Paucity of constitutional symptoms usually associated with tuberculosis such as fever, weight loss, night sweats, and anorexia.<br />Constitutional symptoms should lead to a search for other foci of tuberculosis<br />
    24. 24. patients with renal tuberculosis may be subject to dehydration because of a concentrating defect, a tendency to lose salt<br /> Rarely NDI<br />Always think of concomitant tuberculous adrenal disease (Addison's disease)<br />
    25. 25. complete renal function loss owing to parenchymatous infection and destruction <br />Strictures, can result in hydronephrosis and loss of renal function. <br />Obstruction and hydronephrosis can develop during therapy because such sclerotic strictures are frequently part of the healing process. <br />
    26. 26. Rare presentations:<br /> Tubercular interstitial nephritis<br /><ul><li>In some patients with pulmonary or disseminated tuberculosis there is evidence of renal failure without typical miliary involvement or localized genitourinary lesions
    27. 27. In these cases biopsy has shown interstitial nephritis, usually, but not in all cases, with granulomata
    28. 28. The evidence that the renal malfunction is due to a combination of infection and immunological renal damage is the recovery of function with a combination of antituberculosis treatment and corticosteroids </li></li></ul><li>The incidence of urinary tract tuberculosis as a cause of endstage renal disease is probably being underestimated as, although many individuals with classical urinary tract tuberculosis are identified, the interstitial form is easily overlooked.<br /> Hence, it is important that the diagnosis is considered in all patients with equal-sized smooth kidneys without a clear-cut renal diagnosis, especially in high-risk groups <br />In such patients renal biopsy should always be considered.<br />Mallinson et al. Quarterly Journal of Medicine 1981<br />Tubercular interstitial nephritis<br />
    29. 29. Glomerular Diseases<br />Rare association with<br /> -dense deposit disease<br />Hariprasad et al. New york state journal of medicine, 1979<br /> -Mesangio-capillary glomerulonephritis<br />Amyloidosis<br /> Chronic tuberculosis sometimes leads to amyloidosis and in India is a not uncommon cause of renal amyloid and renal failure <br />Chugh et al. 1981<br />Hypercalcemia in Tuberculosis<br />Due to increased synthesis of calcitriol by granulomas.<br />Paces R et al. Nephron 1987<br />
    30. 30. Three other major complications of renal tuberculosis: <br /> hypertension (RAS axis mediated)<br /> super-infection (12 to 50%)<br /> nephrolithiasis (7 to 18%)<br />In 1940, Nesbit and Ratliff reported that hypertension could be cured by the removal of a tuberculous kidney, <br />More recent data, however, suggest that this is an uncommon event. <br />Nesbit RM, Ratliff RK. Hypertension associated with unilateral nephropathy. J Urol 1940;43:427. <br />
    31. 31. Descending infection to bladder Healingsmall, contracted bladder with greatly thickened walls (thimble bladder) three functional consequences-small bladder capacity -incomplete emptying with sec. bacterial infection -vesicoureteral reflux<br />
    32. 32. DiagnosisUrine analysis<br />Essentially every patient with established urinary tract tuberculosis has an abnormal urinalysis with pyuria, hematuria, or both. <br />Acid-Sterile pyuria—<br />the old clinical teaching that the asymptomatic patient with pyuria, particularly with an acid urine and a urine culture that fails to reveal conventional bacterial pathogens, must be considered as having tuberculosis until proved otherwise remains true today<br />Another indicator is failure of the patient's symptoms to respond to conventional antibacterial treatment<br />
    33. 33. Sterile Pyuria<br />Tuberculosis of the urinary tract <br />Chlamydia trachomatis, Mycoplasma, or Ureaplasma infection<br />Chemically induced cystitis<br /> Renal calculi, <br />prostatitis<br />Coliform (or other pathogen) urinary tract infection but antibiotic inhibiting growth<br />WBC from outside urinary tract, e.g. from foreskin or vulva <br />Renal parenchymal causes as acute tubulointerstitial nephritis, glomerular disease<br />
    34. 34. Early-morning urine specimens are preferred<br />Sterile container<br />three to five daily specimens<br />Preferably immediate examination, if delay unavoidable sample must be refrigerated, not freezed. <br />
    35. 35. concentrated by centrifugation. <br />Smears prepared from sediment<br />Z-N staining.<br />Problem of E.M.s(MycobacteriaSmegmatis)<br />G.U.T.B. should never be diagnosed solely on the basis of microscopy<br />
    36. 36. ZN staining<br />Hot 1% carbol-fuchsin for five minutes.<br />3% HCl or 20% sulphuric acid<br />Ethanol<br />counterstained with 0.1% methylene blue for 30 sec.<br />Fluorescence methods: Auramine O- Bright yellow<br />Auramine O-Rhodamine B- Yellow orange.<br />
    37. 37. Culture<br /><ul><li>Gold standard
    38. 38. positive in 80% to 90% of cases
    39. 39. Decontamination of sediment.
    40. 40. main problems:</li></ul>-COST<br /> -AVAILABILITY<br /> -DELAYS<br />
    41. 41. newer commercial media (BACTEC..)<br />-faster (about 10 days)<br />-but expensive++, <br />-technical demanding<br />-not useful for control in high prevalence<br />.Role of PCR<br />.PPD Any role in India???????<br /> False negative results in uraemia<br />
    42. 42. <ul><li>High dose IVU – traditional gold standard
    43. 43. CT – new standard
    44. 44. Pyelography (ante/retrograde) – limited use
    45. 45. Plain radiographs – important</li></ul>CXR,spine X-Ray,X-Ray KUB<br /><ul><li>US – limited value
    46. 46. Nuclear Perfusion Scan – function
    47. 47. MRI,Arteriography – little application</li></ul> Imaging <br />
    48. 48. Radiology<br />X-Rays<br />Plain films of the abdomen-<br /> -genitourinary calcifications (present in up to 50%) as well as other extrapulmonary foci of mycobacterial disease (vertebral, mesenteric lymph node, adrenal glands) may be present (approximately 10%) <br />Chest radiographs show evidence of tuberculosis in 50% to 75% of patients with active renal disease <br />
    49. 49. Plain radiograph of the abdomen demonstrates extensive calcification in the left kidney, which was nonfunctional (the putty kidney), consistent with autonephrectomy from tuberculosis.<br />
    50. 50. Genitourinary tract tuberculosis. Plain radiograph of the abdomen in a patient with calcified seminal vesicles due to tuberculosis. Note the amorphous and speckled calcification in the right kidney.<br />
    51. 51. USG<br /> -initial investigation of choice<br /> Cavities<br /> Obstruction<br />Early findings may be missed<br />Sonogram of left kidney shows 1.5-cm hypoechoic nodule (arrowhead) in cortex<br />
    52. 52. Intravenous pyelography & CT urogram findings<br />Intravenous urography - most useful because of its ability to detect calcification, to provide images of detailed anatomy and to show the commonly occurring multiple lesions<br />Affected kidney may contrast-enhance on CT <br />Renal calcification is common (24-44%) <br />Stones, focal or extensive globular calcification, ring-like calcifications of papillary necrosis <br />Cortical scarring <br />"Smudged" papillae (moth-eaten) –irregular due to inflammation and  necrosis <br />Several cysts surrounding a calyx with cortical thinning <br />
    53. 53. Hicked-up pelvis (Kerr kink sign) <br />Infundibularstrictures <br />Hydrocalyces without dilatation of renal pelvis, or <br />Hydronephrosis<br />"Putty kidney" – sacs of casseous, necrotic material <br />Autonephrectomy – small, shrunken kidney with dystrophic calcification <br />Bilateral, but frequently asymmetric <br /> About 75% unilateral radiologically<br />
    54. 54. When ureters are involved, usually the upper or lower third (more common) <br />Beading (sawtooth ureter)<br />Corkscrew ureter<br />Pipe stem ureter <br />Bladder involvement rarely leads to calcification of wall (think schistosomiasis) <br />Reflux, thickening of bladder wall (thimble bladder), fistula formation <br />
    55. 55. IVP of 32-year-old woman. A, left renal parenchymal mass (arrows) and left hydroureter due to left distal ureteral stricture (arrowheads). B, magnification of left kidney shows irregular caliceal contour as moth-eaten appearance (arrows) of upper calix and multiple cavities (arrowheads) of lower pole.<br />
    56. 56. Genitourinary tract tuberculosis. Lobar calcification in a large destroyed right kidney in a patient with renal tuberculosis. Note the involvement of the right ureter.<br />
    57. 57. IVP of 45-year-old woman demonstrates tubercular autonephrectomy and calcifications (white arrowheads) of small right kidney (white arrows). Amputated infundibulum (black arrowhead) of left kidney and left distal ureteral stricture (black arrow) are also visible.<br />
    58. 58. IVP film-The lower end of the right ureter demonstrates an irregular caliber with an irregular stricture at the right vesico-ureteric junction. Note the asymmetric contraction of the urinary bladder, with marked irregularity due to edema and ulceration.<br />
    59. 59. Genitourinary tract tuberculosis. Intravenous urography series in a man with renal tuberculosis shows marked irregularity of the bladder lumen due to mucosal edema and ulceration<br />
    60. 60.
    61. 61. Renal Tuberculosis. Coronal reformatted non-enhanced CT scan of the abdomen and pelvis demonstrates a small, left kidney containing globular calcifications (white circle) pathognomonic for renal tuberculosis. <br />
    62. 62. A, Contrast-enhanced CT scan obtained at level of right renal hilum shows wedge-shaped hypoperfused areas (arrowheads).<br />B, CT scan obtained at level 2.5 cm caudad to A shows hypoperfused areas (arrowheads) and focal caliectasis (arrows)<br />
    63. 63. 53-year-old man with tuberculosis involving collecting system. Contrast-enhanced CT scan of left kidney shows uneven caliectasis caused by varying degrees of stricture at various sites.<br />
    64. 64. A, CT urogram shows severe nonuniformcaliectasis and multifocal strictures (arrowheads) involving renal pelvis and ureter.Calcification (arrow) is noted in left distal ureter.<br />B, Contrast-enhanced CT scan shows wall thickening and enhancement of left ureter (arrowhead).<br />
    65. 65. 50-year-old woman with putty kidney. CT scan shows dense calcification replacing right kidney, so-called “putty kidney.”<br />
    66. 66. Limitations-<br />May be normal in patients with early genitourinary tuberculosis. <br />Calcification may occur in patients with Diabetes mellitus and schistosomiasis. Brucellosis also may mimic tuberculosis.<br />A congenital megacalyx and focal papillary necrosis may mimic renal tuberculosis radiologically.<br />
    67. 67. Genitourinary tract tuberculosis. Lateral view of the abdomen in a patient with schistosomiasis shows tubular calcification of the ureters in contrast to the speckled calcification in tuberculosis.<br />
    68. 68. Radiograph of the pelvis in a patient with schistosomiasis shows fine linear calcifications of the bladder wall with normal volume. In tuberculosis, the bladder is contracted and demonstrates speckled calcification<br />
    69. 69. Cystoscopy under general anaesthesia with adequate muscle relaxation helps to visualize the mucosal lesions,golf hole uretericorifice.or the reflux of toothpaste like caseous material<br />Biopsy during acute stage is avoided for fear of dissemination of T.B<br />Aspirated pus and caseous material generally contain few viable mycobacteria so it is more rewarding to examine biopsies of the surrounding tissue.<br /> Cystoscopy <br />
    70. 70. Two goals<br />Clinical Management<br /> conservation of tissue <br />and function<br />antimycobacterial cure. <br />
    71. 71. Antimicrobial cure<br />It is a common practice for clinicians to treat GUTB for periods longer than six months. <br />DOTS is the most effective way <br />Standard Category I regimen is effective for the treatment of patients with GUTB <br />
    72. 72. RNTCP- DOTS Therapy<br />Genito-urinary T.B. -- Cat I<br />(HRZE)2 + (HR)4<br />Drug Daily Dose Intr. Dose<br /> Isoniazid 5mg/kg 10mg/kg<br /> Rifampicin 10mg/kg 10mg/kg<br /> Pyrizinamide 25mg/kg 35mg/kg<br /> Ethambutol 15mg/kg 25mg/kg<br /> Streptomycin 15mg/kg 15mg/kg daily<br />Streptomycin- max. dose 750 mg in pts. <40 yrs age<br />
    73. 73. Longer courses of ATT ranging from 9 months to 2 years are useful in patients:<br />Who do not tolerate Pyrazinamide<br />Those responding slowly to standard regimen<br />Those with miliary and CNS disease<br />Children with multiple site involvement<br /> Longer courses of ATT<br />
    74. 74. Daily or intermittent?<br />Intermittent regimens have been compared head-to-head with daily treatment in several RCTs and have been shown to be as effective as the latter.<br />Evidence from animal models suggests that intermittent treatment is in fact more efficacious that daily treatment.<br />The reason for this might lie in post-antibiotic effect (PAE). PAE is the continued suppression of bacterial multiplication even after the level of the drug has fallen below the therapeutic concentration.<br />drug-induced hepatotoxicity occurs less commonly in patients treated with intermittent regimens. <br />
    75. 75. Dose modification in renal failure<br /> INH<br /> Rifampicin no adjustment <br /> Pyrazinamide<br /> Drug Cr. Clearance Dose interval <br /> Ethambutol 10-50 ml/min 24-36 hrs<br /> <10 ml/min 48 hrs <br /> Streptomycin 10-50 ml/min 24-72 hrs<br /> <10 ml/min 72-96 hrs or avoid<br />
    76. 76. Important side-effects of first-line anti-tuberculosis drugs<br />
    77. 77.
    78. 78. Treatment monitoring<br />RNTCP guidelines- silent.<br />After 2 month of therapy- <br /> 3 urine cultures<br /> If negative- continue therapy<br /> At the end of therapy<br /> 3 consecutive negative samples<br /> Repeated after 3 months and at 1 year.<br />
    79. 79. IVP <br /> -at the end of 2 months <br /> -and at the completion of Tt.<br />In case of renal calcification- yearly 3 urine examinations up to 10 years.<br />Treatment monitoring<br />
    80. 80. Another area of controversy in the treatment of GUTB is the utility of corticosteroids in the prevention of complications such as ureteric stricture/fibrosis<br />Lack of RCTs on this issue<br />it seems unlikely that corticosteroids would be able to reduce the development of complications such as ureteric obstruction in patients with GUTB. This issue is worth investigating<br />What is the role of corticosteroids?<br />
    81. 81. Most ATDs are safe during pregnancy except Streptomycin<br />No contraindication during breast feeding and not necessary to isolate the baby from mother<br />Baby should receive BCG immunization and Isoniazide prophylaxis<br />Women taking OCPs should be advised to take higher doses or use alternative methods.<br />Women during Pregnancy and Lactation<br />
    82. 82. The kidney is often involved in the disseminated tuberculosis but only a minority of patients have clinical features<br /> Marques et al. 1996 <br />In a study in India, 17 of 35 patients dying of AIDS were found to have tuberculous lesions in their kidneys, with this disease being more common than fungal infections (five cases) and CMV (two cases) <br />Lanjewar et al. 1999<br />Tuberculosis and HIV positivity<br />
    83. 83. HIV screening<br />In India, about 5.2% of patients with TB have underlying HIV co-infection<br />Extrapulmonary involvement occurs more commonly among HIV co-infected patients.<br />All patients should therefore be offered voluntary counseling and testing services for detecting HIV co-infection. (NACO guidelines)<br />
    84. 84. Tuberculosis should always be considered when a renal transplant patient develops fever, especially when the patient is from a high-risk group<br />One of the patients acquired tuberculosis from the transplanted kidney (Peters et al. 1984).<br />Tuberculosis preventive therapy-no consensus<br />Transplant patients<br />
    85. 85. European Best Practice Guidelines for Renal Transplantation (2002) recommend that all renal transplant candidates and recipients considered to have latent tuberculosis be treated with isoniazid 300 mg daily for 9 months.<br /> Such patients are defined as those with one or more of the following: <br />induration after Mantoux testing of 5 mm (transplant recipients) or 10 mm (transplant candidates on dialysis);<br /> a history of inadequately treated tuberculosis; <br />a chest X-ray suggestive of old tuberculosis; and <br />close contact with a person with tuberculosis. <br />tuberculin-negative patients who receive a kidney from a tuberculin-positive donor<br />Transplant patients-Prophylaxis<br />
    86. 86. Surgical Management<br />In the prechemotherapy era, surgical ablation of infected foci was the only therapy available for renal tuberculosis<br />Today the primary form of surgical intervention is in the relief of strictures, particularly those of the ureters, which can result from the scarring process.<br />Thus, ureteral dilatations, ureteral reimplantations, and in some cases, relief of intrarenal obstruction to urine flow are important aspects of the modern function-conserving approach to urinary tract tuberculosis <br />
    87. 87. Less commonly, patients whose bladders have been badly scarred by the tuberculosis process have such poor bladder function that bladder augmentation or even urinary diversion may be necessary to deal with unbearable urinary frequency, inadequate emptying, or both.<br />
    88. 88. nephrectomy<br />Rare event now a days<br />End-stage tuberculous kidneys with complications<br /> -conventional bacterial sepsis<br /> -Hemorrhage<br /> -Intractable pain<br /> -Newly developed severe hypertension<br /> -Inability to sterilize the urine because of patient unreliability<br /> -Drug resistance<br />
    89. 89. Not so rare, as thought….<br />Long latent period<br />Clinical symptoms not very prominent<br />The Great Pretender<br />Urine analysis still most time-trusted investigation<br />DOTS best regimen<br /> Take Home Message<br />
    90. 90. Thank you<br />
    91. 91. Tuberculosis can be a difficult therapeutic problem in patients with renal failure. Rifampicin (Fabre et al. 1983) and isoniazid (Gold et al. 1976) can be given in the usual dosage. Neither is cleared significantly by dialysis. Pyridoxine should be given with isoniazid to prevent peripheral neuropathy (Cuss et al. 1986). The plasma half-life of ethambutol is, however, prolonged in renal impairment (Andrew 1980; Lee et al. 1980). If the GFR is less than 30 ml/min, the dose should be 10–15 mg/kg per day with a further reduction to 4 mg/kg daily if the GFR is less than 10 ml/min. Although 10 mg/kg daily has been used at these levels of GFR, cases of optic atrophy have been reported (Andrew 1980). Ethambutol is not dialysed to any significant extent. Pyrazinamide should be given at reduced dose (10–15 mg/kg) (Cuss et al. 1986). Capreomycin (Lehmann et al. 1988), a second-line drug, can be used in isoniazid or streptomycin resistance but is itself nephrotoxic and ototoxic but can be given in a single dose of 500 mg. With repeated transplant patients on cyclosporin, rifampicin cannot be used as it reduces the concentration of cyclosporin very substantially as a result of hepatic enzyme induction (Allen et al. 1985).<br />The necessity to use more than three agents will be dictated by the nature and severity of the infection. Treatment may need to be prolonged to between 9 and 12 months in uraemic or immunosuppressed patients, in contrast to the shorter courses that are preferred in patients with normal renal function.<br />
    92. 92. 75% of male patients with tuberculous epididymoorchitis already have evidence of urinary tract involvement.<br />Epididymitis can present decades after apparently adequate therapy for renal tuberculosis<br />While the incidence of renal disease in women with genital tuberculosis is less than 5%, <br />
    93. 93. In the male, genital tuberculosis is acquired by seeding from infected urine or via the bloodstream. The most common manifestation is epididymo-orchitis; less common is tuberculousprostatitis. Tuberculosis of the urethra and penis are much less common but, like tuberculousprostatitis (O'Flynn 1970; Symes and Blandy 1973), can present with papulonecrotic skin lesions, fistulae, and genital ulceration. Although infection usually results from direct seeding from infected urine, penile tuberculosis can be acquired by direct inoculation from contaminated surgical instruments or clothing following ritual circumcision (Annobil et al. 1990). The urinary tract should be fully investigated in any patient found to have genital tuberculosis since 75 per cent of patients with epididymo-orchitis or prostatitis have evidence of urinary tract involvement (Ferric and Rundle 1983).<br />Tuberculosis of the female genital tract is accompanied by urinary tract tuberculosis in less than 5 per cent of cases—far less commonly than in the male. Presumably, this is because the genital and urinary tracts in the female are separate so avoiding the possibility of direct infection of the genital tract from the urine. Thus tuberculosis of the female genital tract is probably almost always the result of haematogenous spread (Pasternack and Rubin 1993).<br />Tuberculosis of the genital tract<br />
    94. 94. As urine contains contaminating microorganisms which may overgrow the culture medium, deposits for culture must first be ‘decontaminated’, usually by treating the deposits with dilute sulfuric or oxalic acid, neutralizing and recentrifuging before inoculating the medium. Alternatively, a ‘cocktail’ of antibiotics that kill virtually all microorganisms other than mycobacteria can be added to the medium. Aspirated pus and caseous material generally contain few viable mycobacteria so it is more rewarding to examine biopsies of the surrounding tissue.<br />
    95. 95. In cases of multidrug resistance, other agents including ethionamide, prothionamide, thiacetazone, cycloserine, capreomycin, p-amino salicylic acid, fluoroquinolones, such as ofloxacin and sparfloxacin, and the newer macrolides including clarithromycin and azithromycin are used.<br />Limited evidence indicates that the antileprosy drug clofazimine and combinations of aminopenicillins and β-lactamase inhibitors, such as amoxycillin with sulbactam, are also of use. These drugs are generally more toxic, more expensive and less active than the first-line drugs and treatment is often prolonged and costly. Such therapy should, whenever possible, be guided by rigorously controlled drug susceptibility testing and single drugs should never be added blindly to failing treatment regimens<br />
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