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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 79-83

The effect of treatment timing and urinary drainage on the outcome of urinary tuberculosis


1 Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan
2 Department of Urology, Mackay Memorial Hospital; Department of Medicine, Mackay Medical College; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
3 Department of Urology, Mackay Memorial Hospital; Department of Medicine, Mackay Medical College; Mackay Junior College of Medicine, Nursing, and Management; School of Medicine, National Yang-Ming University, Taipei, Taiwan

Date of Submission09-Nov-2018
Date of Decision12-Aug-2018
Date of Acceptance12-Dec-2018
Date of Web Publication28-Mar-2019

Correspondence Address:
Allen W Chiu
Department of Urology, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan North Road, Zhongshan District, Taipei 104
Taiwan
Stone Yang
Department of Urology, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan North Road, Zhongshan District, Taipei 104
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_119_18

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  Abstract 


Background: Urinary tuberculosis (TB) has a variety of clinical manifestations and is a diagnostic challenge for urologists. Delayed treatment can lead to loss of renal function and structural destruction. In this study, we analyzed the relationship between the timing of treatment and outcomes in patients with urinary TB. Methods: We performed a retrospective chart review of all patients with urinary TB from 1978 to 2016 at our hospital and analyzed the patients' symptoms, diagnostic methods, imaging studies, time to diagnosis, treatment methods, and follow-up. Results: Twenty-one patients (median age: 49 years) had urinary TB, of whom 18 had hydronephrosis and hydroureter. No bilateral renal involvement was noted. The median duration from symptom onset to anti-TB treatment was 78.5 days. There was no significant relationship between symptom-to-treatment time and posttreatment changes in renal function (Pearson's r = 0.103, P > 0.05); however, the symptom-to-treatment time was linearly associated with pre- and posttreatment hydronephrosis grade (Pearson's r = 0.667, P= 0.03, and r = 0.710, P= 0.007, respectively). In multivariate analysis, the symptom-to-treatment time was found to be an independent predictor of improvements in hydronephrosis but was not associated with renal function change. Of nine patients with upper urinary tract drainage, hydronephrosis improved in three and was stable in five patients. Of 12 patients without drainage, four experienced renal loss. Conclusion: Urinary TB has vague clinical manifestations and is prone to a delayed diagnosis. Early diagnosis and prompt internal ureteral stenting may prevent renal loss in certain patients.

Keywords: Early urinary drainage, hydronephrosis, ureteral stenting, urinary stricture, urinary tuberculosis


How to cite this article:
Lin TF, Lin WR, Chen M, Chang HK, Lin WC, Tsai WK, Yang S, Chiu AW. The effect of treatment timing and urinary drainage on the outcome of urinary tuberculosis. Urol Sci 2019;30:79-83

How to cite this URL:
Lin TF, Lin WR, Chen M, Chang HK, Lin WC, Tsai WK, Yang S, Chiu AW. The effect of treatment timing and urinary drainage on the outcome of urinary tuberculosis. Urol Sci [serial online] 2019 [cited 2019 Aug 19];30:79-83. Available from: http://www.e-urol-sci.com/text.asp?2019/30/2/79/255159




  Introduction Top


Mycobacterium tuberculosis typically affects the lungs and is most prevalent in Southeast Asia. In 2016, there were an estimated 10.4 million new cases of tuberculosis (TB) worldwide, of whom approximately 15% were diagnosed with extrapulmonary TB.[1] Urinary TB accounts for 30%–40% of all extrapulmonary cases of TB[2],[3] and can cause severe consequences such as loss of renal function. Approximately 13,000 people are diagnosed with pulmonary TB every year in Taiwan.[4] The re-emergence of TB infection due to an increasing prevalence of HIV has been reported.[1],[2] Taiwan was an endemic area of TB in the early 1950s; however, the Bacillus Calmette–Guerin (BCG) vaccination has effectively controlled the disease since then. Nevertheless, 50 new cases of urinary TB are still reported every year in Taiwan.[4] The wide spectrum of symptoms makes it difficult to diagnose urinary TB in a timely manner.[2],[5] In this study, we report our experience with the clinical manifestations and treatment modality of urinary TB and analyze the relationship between the timing of treatment and therapeutic outcomes in the post-BCG vaccination era in Taiwan.


  Methods Top


After institutional review board approval, the charts of all patients with urinary TB with relevant ICD-9 codes were reviewed retrospectively from 1978 to 2016 at our 2500-bed hospital located in the center of Taipei City. We collected data on the patients' background, initial symptoms, imaging (intravenous urography [IVU], renal ultrasound, and abdominal computed tomography [CT]), diagnostic methods, duration of symptoms, duration of first medical consultation for anti-TB treatment, treatment duration, accessory treatment (ureterorenoscopy, ureteral stent insertion, percutaneous nephrostomy [PCN], or nephrectomy), and outcomes.

The patients' clinical and demographic data including age, sex, underlying diseases, pre- and posttreatment renal function, pulmonary TB history, infection site, history of BCG instillation therapy, and concomitant TB infection outside the urinary tract were recorded. The diagnostic methods included acid-fast stain, TB polymerase chain reaction (PCR), TB culture, and pathology. The severity of urinary tract obstruction was graded according to the Fetal Urology grading system. Cases of drug-resistant M. tuberculosis were also recorded.

Descriptive and analytic statistics of the data were calculated using SPSS (version 21.0; IBM SPSS Statistics, IBM Corporation, Chicago, IL, USA) for Windows. All tests were two-tailed, and the level of significance was set at P < 0.05. The t-test was used for comparisons of pre and posttreatment hydronephrosis grade and renal function. Relationships between the time to diagnosis, symptom to treatment, obstruction severity, and renal function were analyzed using Pearson's correlation analysis. Multivariate logistic regression analyses were performed to determine the B value and 95% confidence intervals of variables affecting renal function and hydronephrosis grade.


  Results Top


A total of 26 cases of urinary TB were identified, of whom five (before 2000) were excluded due to incomplete medical records or missing data. The remaining 21 patients (9 men and 12 women; median age: 49 years, range: 19–83 years) were enrolled into the analysis. Five patients had renal function impairment (estimated glomerular filtration rate [eGFR] <60 mL/min), two patients had a history of pulmonary TB, and one patient had bladder cancer with BCG bladder instillation. Nineteen patients (90%) had upper urinary tract TB and two had lower urinary tract TB. Nine patients had concomitant extra urinary site TB and seven patients had concomitant pulmonary TB found after urinary TB had been diagnosed [Table 1]. Sixteen patients (76%) had urinary symptoms, including lower urinary tract symptoms (48%), hematuria (24%), persistent urinary tract infection (19%), and flank pain (14%). The lower urinary tract symptoms included dysuria, frequency, urgency of urination, and difficulty in voiding. Five patients (24%) had nonurinary symptoms, including three with fever, one with abdominal pain, and one with shortness of breath. One patient had concomitant arthritis and pulmonary TB, and another patient had concomitant osteomyelitis of the upper sternum with abscess formation. She received sequestrectomy and debridement, and the pathology showed chronic granulomatous inflammation with caseous necrosis, consistent with tuberculous osteomyelitis. One patient had neck lymph node enlargement during anti-TB treatment, and an excision biopsy of the lymph node showed granulomatous inflammation with caseous necrosis. None of the patients had concomitant HIV infection.
Table 1: Background of the reported urinary tuberculosis patients

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Nineteen cases had pretreatment radiographic imaging of the urinary tract, including renal ultrasound, IVU, and CT. Hydronephrosis and hydroureter were found in 18 patients (95%) [Table 2], 11 of whom (58%) had Grade III hydronephrosis, four had (21%) Grade II, and two (11%) had Grade IV. Two patients were diagnosed with lower urinary tract TB, in whom fibrocystoscopy revealed severe cystitis with easy contact bleeding. The posttreatment radiological images showed unchanged renal calcification, stones, or ureteral stones in six patients (32%), and three patients were initially mistreated with extracorporeal shock wave lithotripsy or ureteroscopic lithotripsy for urinary stones. Tissue necrosis was found during ureteroscopy in these patients, and urine TB cultures were performed. Seven patients with high-grade obstruction (Grade III or IV) had persistent pelvis dilatation with no deterioration in renal function. In four patients with nonfunctioning kidneys (which were not enhanced in contrast abdominal CT), two received nephrectomy due to uncontrolled infections. One patient received ileal calyceoureteral reconstruction due to complete obliteration of the renal pelvis and whole segmentation of the ureter.
Table 2: Radiographic findings in the urinary tuberculosis patients

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Of the nine patients who received upper urinary tract drainage (eight with ureteral stent [double-J] insertion and one with PCN), three had improved obstruction and five had unchanged obstruction with the same hydronephrosis grade [Table 3]. The double-J stent was removed after at least 6 months of oral anti-TB treatment. The patient with PCN received ileal calyceoureteral reconstruction. Of the patients with no upper urinary tract drainage, only one had improved obstruction, three had stable obstruction, and four had renal loss as confirmed by contrast CT and nephrectomy.
Table 3: Relationships between obstruction condition and ureteral stenting

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The mean duration of symptoms was 52.5 days (range, 7–300 days), and the mean time to the first medical consultation for anti-TB treatment was 46.7 days (range, 2–146 days). The mean symptom-to-treatment time was 78.5 days (range, 3–342 days).

Seventeen patients were diagnosed by TB PCR and TB cultures and four by pathology after nephrectomy or ureteral or bladder biopsy. Urine bacterial cultures were negative in 12 of 14 (86%) patients, and their urine analysis showed persistent pyuria. Of the 17 patients with positive TB cultures, one was resistant to trimethoprim. No cases of multidrug-resistant TB were noted. All of the patients received three combined anti-TB drug therapies for an average of 6 months (range, 3–15 months). After treatment, 20 patients had an acceptable recovery, defined as a negative urine culture and persistent hydronephrosis without the need for additional treatment, including antibiotics. One patient became bedridden and died of recurrent pneumonia and sepsis. The median follow-up time of this study was 5.5 years.

There was a significant difference between pre- and posttreatment obstruction grade (paired t-test, P = 0.028); however, there was no significant difference in changes in eGFR after anti-TB treatment (paired t-test, P = 0.609). Pearson's correlation analysis was used to determine the associations among eGFR, hydronephrosis grade, and symptom-to-treatment time. The symptom-to-treatment time was linearly associated with pretreatment hydronephrosis grade (Pearson's r = 0.667, P = 0.03) and posttreatment hydronephrosis (Pearson's r = 0.710, P = 0.007). However, there was no significant association between symptom-to-treatment time and changes in eGFR (P > 0.05). In multivariate analysis, the symptom-to-treatment time was found to be an independent predictor of improvements in hydronephrosis [Table 4]. Gender and treatment time were not associated with changes in renal function.
Table 4: Multivariate associations between renal function and hydronephrosis grade

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  Discussion Top


The symptoms of urinary TB vary widely, making it difficult to make a prompt diagnosis.[2],[5],[6],[7] In this study, most of the patients (16/21, 76%) had nonspecific urinary symptoms such as urgency, frequency, hematuria, and flank pain. Nineteen of the 21 patients (90%) had upper urinary TB, and 16 (76%) had lower urinary tract symptoms. Nakane et al. reported that most of their patients with urinary TB had symptoms including pollakisuria, scrotal mass, and fever, but that 12% had no obvious symptoms.[6] TB contact and infectious history are very important when making a differential diagnosis.[5] Lenk and Schroeder reported that sterile pyuria was the most common urinary finding in routine urinalysis and cultures.[7] In the current study, 86% of the patients had sterile pyuria, as indicated by a persistently positive white blood cell count in urine analysis, and negative findings in urine bacterial cultures. Therefore, the differential diagnosis of urinary TB should be kept in mind if patients present with sterile pyuria with irritating urinary symptoms that do not respond to antibacterial drugs. A high index of suspicion is required to make a prompt diagnosis of upper tract TB.

Radiography may provide some hints for the diagnosis of urinary TB, such as punctate calcifications, “putty-like calcification” in the renal parenchyma on plain X-ray; evidence of parenchymal necrosis, “phantom calyx,” and infundibular narrowing on IVU; calyceal distortion, ureteric stricture, bladder fibrosis, and parenchymal scarring on CT.[2],[5],[6],[8],[9],[10],[11] The most common radiologic findings are hydronephrosis and hydroureter on IVU and renal parenchymal scarring on CT.[6],[9],[10] In the current study, 95% of the patients had urinary obstruction of various grades due to ureteral or infundibular stricture. In addition, 32% of the patients had unchanged urinary tract calcification. We therefore recommend performing a complete survey with different imaging studies including renal ultrasound, plain X-ray, IVU, or CT in patients with upper urinary TB with calcification.

In a nationwide questionnaire report from Japan, the median symptom-to-medical consultation time was 4 months, and the median diagnosis time was 7.5 months.[6] In the current study, the mean symptom-to-treatment time was 78.5 days. Nakane et al. reported that the outcome was not significantly different if treatment was delayed for 3 months or more. However, because it was a questionnaire survey and because they lacked detailed information of these patients, they could not conclude whether a delay in treatment influenced the patients' outcomes. In the current study, we found a significant association between symptom-to-treatment time and obstruction grade, and the timing of treatment was important for the prognosis. Early interventions with medical treatment and upper urinary tract drainage including ureteral stenting or PCN drainage have been reported to help prevent renal loss.[12] This may be because early TB treatment reduces inflammation and fibrotic changes in the urinary tract. As in our series, TB in the kidney and ureter has been reported to usually occur on one side,[5] so total renal function in patients with urinary TB remains normal.

Shin et al. analyzed patients with tuberculous ureteral strictures treated with medical treatment alone or with early ureteral stenting/PCN.[12] In their series, the nephrectomy rate was lower and the ureteral stricture reconstruction rate was higher in those receiving early ureteral stenting and PCN. The authors suggested that early ureteral stenting or PCN in patients with tuberculous ureteral strictures may increase the opportunity for later reconstructive surgery and decrease the likelihood of renal loss. In the current study, nine patients received a double-J stent or PCN drainage, of whom three had improved obstruction and five were stable. Four of the patients who did not receive drainage experienced renal loss. Therefore, early double-J insertion before anti-TB treatment prevented the worsening of obstruction and renal loss. We kept the double-J stent and PCN drainage during anti-TB treatment for 6 months, which is the same protocol used by Shin et al.[12] We therefore suggest that early ureteral stenting or PCN and scheduled changes for obstruction are as important as medical treatment for urinary TB.

There are several limitations to this study. First, observation bias may be present due to its retrospective design. Second, this study included a relatively small sample size, and larger studies or multicenter analysis should be performed in the future to confirm our findings. Third, we used eGFR to assess the patients' renal function, and renal scintigraphy for infected kidneys was not performed. Therefore, pre- and posttreatment renal function for infected kidneys could not be evaluated. Further studies with renal scintigraphy may be considered in the future.


  Conclusion Top


Urinary TB has vague clinical manifestations, and the diagnosis is often delayed. The importance of early internal urinary drainage cannot be overemphasized. Early diagnosis and internal ureteral stenting can effectively prevent renal loss.

Acknowledgments

The authors thank the staff at the Department of Urology of Mackay Memorial Hospital for their assistance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
Wein AJ, Kavoussi LR, Novick AC, Ghoneim IA, Rabets JC, Mawhorter SD, et al. Campbell-Walsh urology. 10th ed. Philadelphia, PA: Elsevier Saunders; 2012.  Back to cited text no. 2
    
3.
Carl P, Stark L. Indications for surgical management of genitourinary tuberculosis. World J Surg 1997;21:505-10.  Back to cited text no. 3
    
4.
Centers of Disease Control ROC. Taiwan Tuberculosis Control Report; 2013. Available from: http://www.cdc.gov.tw/english/infectionreport.aspx?treeid=3847719104be0678&nowtreeid=ffb51203f16bfe57. [Last accessed on 2015 Dec 25].  Back to cited text no. 4
    
5.
Cek M, Lenk S, Naber KG, Bishop MC, Johansen TE, Botto H, et al. EAU guidelines for the management of genitourinary tuberculosis. Eur Urol 2005;48:353-62.  Back to cited text no. 5
    
6.
Nakane K, Yasuda M, Deguchi T, Takahashi S, Tanaka K, Hayami H, et al. Nationwide survey of urogenital tuberculosis in Japan. Int J Urol 2014;21:1171-7.  Back to cited text no. 6
    
7.
Lenk S, Schroeder J. Genitourinary tuberculosis. Curr Opin Urol 2001;11:93-8.  Back to cited text no. 7
    
8.
Muttarak M, ChiangMai WN, Lojanapiwat B. Tuberculosis of the genitourinary tract: Imaging features with pathological correlation. Singapore Med J 2005;46:568-74.  Back to cited text no. 8
    
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Figueiredo AA, Lucon AM, Arvellos AN, Ramos CO, Toledo AC, Falci R Jr, et al. A better understanding of urogenital tuberculosis pathophysiology based on radiological findings. Eur J Radiol 2010;76:246-57.  Back to cited text no. 9
    
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Wang LJ, Wu CF, Wong YC, Chuang CK, Chu SH, Chen CJ, et al. Imaging findings of urinary tuberculosis on excretory urography and computerized tomography. J Urol 2003;169:524-8.  Back to cited text no. 10
    
11.
Leung TK, Lu CT, Ling CM, Lee CC, Chang PN, Lee SK, et al. Imaging of renal tuberculosis in Eastern Taiwan: Correlation with clinical course and different communities. Kaohsiung J Med Sci 2003;19:271-7.  Back to cited text no. 11
    
12.
Shin KY, Park HJ, Lee JJ, Park HY, Woo YN, Lee TY, et al. Role of early endourologic management of tuberculous ureteral strictures. J Endourol 2002;16:755-8.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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