With nearly 800,000 new cases reported year and being one of the 30 nations with the highest incidence of TB in the world, the situation for TB prevention and control is still quite dire. This places the country second among statutory infectious diseases[15, 16]. To meet the action goals, set forth in our Action Plan to Stop TB (2019–2022), which call for reducing the national incidence of TB to less than 55/100,000 and controlling the mortality rate to less than 3/100,000 by 2022, it is necessary to step up screening efforts to find patients as quickly as possible. To prevent problems including bladder contracture, hydronephrosis, and spontaneous bladder rupture brought on by UTB, clinicians require a quick and reliable test for early diagnosis and treatment of individuals with the condition.
There are many items that are checked in a urine routine, including protein, occult blood, RBC, WBC, amino acids, ketone bodies, and glucose. The most likely cause of renal TB is an increase of white blood cells in the urine, but an increase of WBC in the urine does not necessarily indicate renal TB, but rather a reaction to the infection of the urinary system by pathogenic microorganisms[17]. In the present study, the number of microscopic WBC was significantly higher (717.7 ± 933.5) and the WBC positivity rate for UTB was 94.6% and was significantly higher than that of Non-UTB at 52.2%, P < 0.001, which is consistent with the finding that infection with MTB caused an increase in WBC in the study by Amar R. Shah et al[18]. Hematuria, which occurs between 70% and 80% of the time, is another significant symptom of UTB. Urinary frequency, urgency, and painful urination are frequently present alongside it. Hematuria typically results from bladder lesions; however, kidney damage can also be the cause. In this study, the number of microscopic WBCs was significantly higher (252.6 ± 460.9) and the RBC positivity rate of UTB was 71.4%, which was significantly higher than the Non-UTB positivity rate of 21.7%, P < 0.001. Although a portion of the urine routine may be abnormal in UTB patients, this aberration is non-specific and may also be present in other kidney-related disorders. As a result, anomalies in urine routine cannot rule out UTB, but UTB can present alongside them. In the present study, we also found that the specificity of WBC was 78.6%, but the NPV was only 47.8%, which was not of high diagnostic value for UTB.
UTB is almost always secondary to pulmonary TB infection. UTB will manifest after MTB enters the bloodstream and enters the kidneys. If the patient's resistance is still weak at this time, the disease will develop rapidly, and in serious cases, it will lead to bilateral kidney lesions, which will cause Crea, UA, and Urea to increase[19]. In the present study, Urea (5.66 ± 2.67), Crea (96.03 ± 56.22) and UA (395.04 ± 143.70) levels were elevated in UTB compared to Non-UTB, and the positive rate of Crea was significantly higher, P < 0.05. Urea levels may also increase in other situations, such as upper gastrointestinal bleeding[20]. Although abnormalities in Crea, UA, and Urea occur in patients with UTB, the diagnosis of UTB requires a comprehensive judgment. If the Crea is high, it is possible that it is not caused by UTB. If the kidney function was normal before, and the Crea is high after having UTB, it is likely that the kidney function is destroyed by UTB, which causes the Crea to rise. As a result, it is not suggested to diagnose UTB purely based on impaired renal function.
TB-DOT, a serological test, TB antibody measurement, positive for having been infected or currently infected with MTB[21]. In this study, the positive rate of TB-DOT was 87.88%, which was significantly higher than that of Non-UTB, P < 0.001; its sensitivity and specificity were 85.7% and 78.6%, respectively, and its diagnostic efficacy was still not high.
T-SPOT.TB is also commonly used to diagnose UTB, and MTB-specific T cells specifically secrete γ- interferon. The T-SPOT.TB test is based on the principle of γ-interferon release assay (TB-IGRA), which is an enzyme-linked immunospot technique for the specific detection of TB effector T cells in the subject to diagnose whether the subject is infected with MTB. The test is early, rapid, inexpensive, biosafe, and has a wide range of applications. Existing studies have shown that it also has a very high sensitivity and detection rate in the diagnosis of TB, with a sensitivity and specificity of 84.0% and 99.1%, respectively, in children with TB and 83. 7% and 80. 2%[22], respectively, in patients with co-infected HIV TB[23]. The sensitivity and specificity of the T-SPOT.TB in this study were 77.4% and 100.0%, respectively, which is more consistent with the findings of C.H. Liao et al[24], but its diagnostic efficacy was still not particularly high. However, studies have shown that peripheral blood T-SPOT.TB has its own defects and is susceptible to the influence of peripheral blood T-lymphocyte count[25], which often leads to false-negative results. The sensitivity of T-SPOT.TB is constrained by the fact that several non-TB pathogen infections also encourage T cells to secret interferon, and individuals with the latent and infected phases of the disease are difficult to diagnose. Although each of these tests has pros and cons of its own, they are all helpful in the early identification of UTB.
The results of this study showed that, among the tests, the positive rate and specificity of Urea and UA were too low; the sensitivity of Crea, RBC and PH was average, but the specificity was poor; the sensitivity and specificity of WBC and TB-DOT were average; and the sensitivity of T-SPOT.TB was poor, but it had a high positive rate and specificity, which showed that each individual test was diagnostic of UTB efficacy was not high, see Fig. 2, Tables 2 and 3. And, by correlation analysis, urinary routine as long as WBC was correlated with T-SPOT.TB (r = 0.270, P < 0.05) and TB-DOT (r = 0.251, P > 0.05) and was not statistically significant with TB-DOT; Crea in renal function was only correlated with T-SPOT.TB (r=-0.201, P < 0.05), see Fig. 4 and Table 5. However, in the parallel combined assay, the sensitivity of Crea + TB-DOT + T-SPOT.TB (100.0%) was the highest but its specificity (45.7%) was lower; the specificity of WBC + Crea + TB-DOT + T-SPOT.TB (100.0%) was higher but its sensitivity (35.1%) was worse; WBC + TB-DOT + T-SPOT.TB had a slightly lower sensitivity (93.1%) than Crea + T-SPOT.TB (94.1%), but its specificity and PPV (77.8%, 87. 1%) were higher than Crea + T-SPOT.TB (40.8%, 35.6%), as shown in Table 6. And the AUC of WBC + TB-DOT + T-SPOT.TB (0.930), was significantly higher than any of the single tests as well as other parallel combined tests, see Figs. 2 and 4, Tables 4 and 7. Therefore, this study suggests that the practical significance of combining the three methods of WBC in urine and TB-DOT and T-SPOT.TB in blood for diagnosis is greater. However, the focus of this trial analyzed the laboratory diagnosis of UTB and did not analyze drug resistance in UTB patients, which will be the focus of our next study.
Therefore, for the diagnosis and treatment of UTB, laboratory testing is crucial. Numerous new detection techniques have arisen in recent years because of the advancement of molecular biology. A single detection method has a low detection effect, but the combined use of several detection methods can increase the accuracy of its detection, reduce the time it takes to detect, and make it easier to diagnose and treat UTB early.
In conclusion, in the early identification of UTB, the sensitivity of T-SPOT.TB or TB-DOT tests are much higher than that urine routine and renal function tests. The parallel combination of WBC, TB-DOT, and T-SPOT.TB has better diagnostic efficacy for UTB, which is beneficial for rapid clinical diagnosis of UTB.