| Abstract|| |
Immunocompromised patients such as those with end-stage kidney failure undergoing hemodialysis (HD) are at increased risk of developing tuberculosis (TB). For this reason, routine TB screening of HD patients with tuberculin test has been recommended. The Center for Disease Control and Prevention (CDC) has recommended that patients with chronic renal failure should undergo annual skin testing for TB with tuberculin [purified protein derivative (PPD)], with an induration of ≥10 mm at 48 h depicting a positive reaction. The aim of this study was to compare the results of two different doses of PPD in dialysis patients. This descriptive and comparative multicenter study was performed on 255 patients on chronic dialysis in Tabriz, Iran. These patients did not have the PPD test done within the preceding one year. Patients were divided into two groups randomly and conventional or double-dose tuberculin test was performed using the Mantoux technique with 5 IU (group 1) and 10 IU (group 2) of PPD. Results were interpreted 48-72 h after injection. Patients were divided into those with less than 10 mm and those with ≥10 mm duration. Mean age was 44.6 ± 15 years (M/F = 1.5/1). The mean duration on dialysis was 39 ± 7 months. There was no significant difference regarding the age, gender, duration on dialysis, causes of chronic kidney disease, erythrocyte sedimentation rate, C-reactive protein and serum albumin between the two groups. The mean induration was 4.6 mm and 7.7 mm in groups 1 and 2, respectively. There was induration ≥10 mm in 19.6% and 25.5% of group 1 and 2, respectively, which showed a significant difference (P <0.05). In conclusion, because of the high frequency of TB in dialysis patients, an annual tuberculin test may be recommended. Our study showed that the double-dose tuberculin test may be a better substitute to the conventional test in dialysis patients.
|How to cite this article:|
Khosroshahi H T, Shojaie E A, Habibzadeh D, Hajipour B. Comparison of 5 IU and 10 IU tuberculin test results in patients on chronic dialysis. Saudi J Kidney Dis Transpl 2012;23:823-6
|How to cite this URL:|
Khosroshahi H T, Shojaie E A, Habibzadeh D, Hajipour B. Comparison of 5 IU and 10 IU tuberculin test results in patients on chronic dialysis. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2022 Aug 14];23:823-6. Available from: https://www.sjkdt.org/text.asp?2012/23/4/823/98171
| Introduction|| |
Immunocompromised patients such as those with chronic kidney disease (CKD) requiring hemodialysis (HD) are at increased risk of developing tuberculosis (TB). In addition, patients receiving HD spend prolonged periods of time together in health-care facilities, thereby increasing the potential for TB transmission if a patient has active disease. The risk of TB is higher (6.9-52.5-fold) in patients with CKD when compared with the general population. 
Diagnosis is usually difficult in those patients due to non-specific clinical presentation with fever of unknown origin, fatigue and loss of weight, with tuberculin skin test (TST) being usually negative (anergy) and with a low probability of microbiologic evidence of TB by direct observation of acid-resistant bacilli or culturing the organism. 
Screening patients at high risk for development of TB and use of therapy for latent TB infection (LTBI) to prevent the development of active TB is a well-accepted strategy for TB control. The gold standard screening tool used to detect dormant or latent TB is the tuberculin test, which owes its popularity to its ease of administration and high sensitivity. ,
Although guidelines recommend screening these patients for LTBI, the TST is believed to be insensitive in end-stage kidney disease (ESKD) patients, and TST negativity rate is high. False-negative TST of ESKD patients might be due to the immunocompromised condition.  In addition, the TST might be falsely positive in persons with a history of previous non-tuberculous mycobacterium (NTM) infection or vaccination with Bacillus Calmette-Guerin (BCG). 
The Center for Disease Control and Prevention (CDC) has recommended that patients with chronic renal failure undergo annual skin testing for TB with tuberculin [purified protein derivative (PPD)], with induration of >10 mm at 48 h depicting a positive reaction (CDC 2000). , To date, no large study has been carried out regarding the incidence of myco-bacterial infection in CKD patients in Iran. This study was performed to compare the results of the tuberculin test with 5 U and 10 U in patients on chronic dialysis.
| Materials and Methods|| |
This descriptive comparative study was performed on 255 patients with chronic kidney diseases on chronic dialysis and three times a week in two university hospitals in Tabriz, Iran.
These patients did not have PPD exposure during the previous one year for preventing any interference in results and adjustment of cases for better grouping.
- Patients having active TB at the time of inclusion in the study
- All pediatric patients as these patients before and after transplant were followed-up in the Department of Pediatrics
- Patients who had been given TB prophylaxis in various trials done at our center during the study period.
Patients were divided into two groups randomly according to standard or double-dose tuberculin injection, and were tuberculin tested using the Mantoux technique with 0.1 mL (five tuberculin units, group 1) or 0.2 mL (10 tuberculin units, group 2) of PPD intradermally injected into the volar surface of the forearm without atriovenous fistula in the TB research center Tabriz Iran. Results were interpreted 48-72 h after injection. Areas of indurations were measured with a fiberglass measuring tape and patients were divided into <10 mm and ≥10 mm in duration groups.
| Statistical Analysis|| |
Statistical analysis was performed using SPSS for windows version 13. Statistical analysis was done using the independent t test and k square test.
| Results|| |
We selected 255 CKD patients on chronic HD (M/F = 52/48). [Table 1] shows the. Etiology of renal failure in these patients. Mean age was 44.6 ± 15 years (M/F = 1.5/1). The mean duration on dialysis was 39 ± 7 months. Mean Hb was 9.7 ± 1.9 g/dL, mean serum albumin 4.03 ± 0.57 g/dL and mean serum phosphate was 5.9 ± 2.1 mg/dL.
|Table 1: Etiology of renal failure in the selected hemodialysis patients.|
Click here to view
In group 1, the mean age of the patients was 40.2 ± 14.8 years, with a male to female ratio of 1/1. The mean duration on dialysis was 30.6 ± 41.3 months. Mean Hb was 9.2 ± 1.8 g/dL, mean serum albumin was 4.2 ± 0.46 g/dL and mean ESR was 40.1 ± 25.4.
In group 2, the mean age of these patients was 52.7 ± 16.4 years, with a male to female ratio of 63/37. The mean duration on dialysis was 35.7 ± 36.5 months. Mean serum albumin was 3.9 ± 0.6 g/dL. Mean Hb was 10.3 ± 1.8 and mean ESR was 39.4 ± 28.6. For induration over ≥5 mm, there was a significant difference between group 1 (32%) and group 2 (243%) [Table 2]. There was no significant difference regarding the sex, duration on dialysis, serum albumin, Hb and ESR between the two groups.
|Table 2: Comparison of indurations in two different doses of PPD in the two groups of hemodialysis patients.|
Click here to view
Positive = Indurations ≥10 mm
Negative = Indurations < 10 mm
There are significant differences between mean indurations in the two groups in the study (P < 0.05).
[Table 1] shows that in comparing the two groups of this study, negative indurations in single dose are high and positive indurations are low compared with double dose.
| Discussion|| |
In an endemic area for TB, giving prophylaxis to every patient going for maintenance hemodialysis followed by renal transplant may not be justified. Thus, we need to detect patients who are at a significant risk of developing TB. In this regard, TST is at present the accepted and widely employed test for the diagnosis and management of LTBI.  The dose of tuberculin used in the United Kingdom and Australia is 10 U, while in the United States 5 U is used.  In Iran, the conventional dose used is 5U. Few data are available on tuberculin skin testing in HD patients. In a recent study, there was a high prevalence of positive PPD test among patients on maintenance dialysis. In that study, 35% of the dialysis patients were PPD positive and 65% were negative. However, 81% of the PPD negative patients were anergic.  In another study, PPD test was positive in 27.8% and negative in 11.1% of the dialysis patients, but about 52.8% of these patients were anergic.  Others have reported a positive test in 62% of their cases. , In our study, about 33.6% of dialysis patients were PPD positive. We did not perform tests for isolation of anergic patients in this study. None of these patients had clinical or radiographic signs of active TB, which is comparable with the Podual and Hammes study.  We performed the tuberculin test with 10 IU in dialysis patients and compared the results with 5 IU tuberculin test results. To the best of our knowledge, there is no other comparative study regarding the tuberculin dose in dialysis patients. Our study showed a significant difference in the mean size of induration between the groups. In a recent study, there was high prevalence of PPD positively among patients on maintenance dialysis. In that study, 21% of the dialysis patients were PPD positive and 79% were negative.
The studies by Smirnoff  and Anthony  had shown that 81% of the PPD-negative patients were anergic.
In another study, PPD test was positive in 27.8% and negative in 11.1% of dialysis patients, but about 52.8% of these patients were anergic. 
In our study, about 21% of dialysis patients were PPD positive. We did not perform tests for isolation of anergic patients in this study. None of these patients had clinical or radiographic signs of active TB, similar to other comparable studies.
In conclusion, there is an increasing prevalence of TB among dialysis patients. The prognosis is very much dependent on early diagnosis and treatment. Renal physicians should be aware of the unusual presentation and localization, and also include TB in the differential diagnosis of any patients having non-specific symptoms such as anorexia, fever and weight loss. PPD should be performed on dialysis patients annually. Tuberculin test with 10 IU shows better immunologic response when compared with 5 IU. It is necessary that patients with indurations ≥10 must be considered or take prophylaxis anti-TB agent before transplantation of the kidney.
Tests for anergy are strongly indicated in patients with negative PPD results to confirm the true negatives.
| References|| |
|1.||Hussein MM, Mooij JM, Roujouleh H. Tuberculosis and chronic renal disease. Semin Dial 2003;16:38-44. |
|2.||Woeltje KF, Mathew A, Rothstein M, Seiler S, Fraser VJ. Tuberculosis infection and anergy in hemodialysis patients. Am J Kidney Dis 1998; 31:848-52. |
|3.||Akcay A, Erdem Y, Altan B, Usalan C, Agca E, Yasavul U. The booster phenomenon in 2-step tuberculin skin testing of patients receiving long term Hemodialyses. Am J Infect control 2003;31:371-4. |
|4.||Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:221-47. |
|5.||Smirnoff M, Patt C, Seckler B, Adler JJ. Tuberculin and anergy skin testing of patients receiving long-term hemodialysis. Chest 1998; 113:25-7. |
|6.||Wang L, Turner MO, Elwood RK, Schulzer M, FitzGerald JM. A meta-analysis of the effect of Bacille-Calmette-Guerin vaccination on tuberculin skin test measurements. Thorax 2002; 57:804-9. |
|7.||Eyuboglu AF, Akcay MS, Arslan H, Demirhan B, Kalpaklioglu AF. Extra pulmonary Involvement of mycobacterium Infections in Dialysis patients. Transplant Proc 1999;31:3199-201. |
|8.||Agarwal SK, Gupta S, Bhowmik D, Mahajan S. Tuberculin skin test for the diagnosis of latent tuberculosis during renal replacement therapy in an endemic area: a single center study. Indian J Nephrol 2010;20:132-6. |
|9.||Poduval RD, Hammes MD. Tuberculosis screening in dialysis patients- is the tuberculin test effective? Clin Nephrol 2003;59:436-40. |
|10.||Khosroshahi HT, Shoja EA, Beiglu LG, Hassan AP. Tuberculin testing of kidney allograft recipients and donors before transplantation. Transplant Proc 2006;38:1982-4. |
|11.||Jerant AF, Bannon M, Rittenhouse S. Identification and management of tuberculosis. Am Fam Physician 2000;61:2667-78, 2681-82. |
Young Researchers Club, Tabriz Branch, Islamic Azad University, Tabriz
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]