|Year : 2003 | Volume
| Issue : 2 | Page : 145-152
|Spectrum of Tuberculosis in Dialysis Patients in Saudi Arabia
Ghulam Hassan Malik1, Suleiman Ali Al-Mohaya1, Ali Swaid Al-Harbi1, Mohammad Kechrid1, Osman Azhari1, Sabry Shetia1, Mohammad Amin Tashkandy2, Khursheed Ahmad3, Abdul Waheed Bhat4, Mohammad Ashraf Want5, PT Subramanian6, Nussrullah Abutaleb7, Ayman Karkar8
1 Security Forces Hospital Program-Riyadh, Saudi Arabia
2 Al Noor Specialist Hospital-Makkah, Saudi Arabia
3 Al-Jouf Central Hospital, Saudi Arabia
4 Ar Ar General Hospital, Saudi Arabia
5 King Fahad Hospital, Gizan, Saudi Arabia
6 Samtah General Hospital, Gizan, Saudi Arabia
7 Northwest Armed Forces Hospital, Tabuk, Saudi Arabia
8 Dammam Central Hospital, Dammam, Saudi Arabia
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| Abstract|| |
Data from different regional hospitals of Saudi Arabia were collected to know the prevalence, clinical features and results of therapy of tuberculosis, in patients on dialysis. Eight hospitals located in five different provinces of Saudi Arabia were involved. There were 132 patients with TB on dialysis of whom 75 were males (mean ages in different hospitals ranging 4258 years) and 57 were females (mean ages ranging 38-58 years). The prevalence of TB in these patients varied from 2.4 to 14.5% with an average of 7%, which is 12 times commoner than in the general population of Saudi Arabia. The presenting clinical features were fever (65%), cough (17%), weight loss (59%) and anorexia (58%). The organs/systems involved by TB were pulmonary in 73 (55.3%), lymphadenopathy in 30 (22.7%) peritoneal in 27 (20.4%) and bone in seven (5.3%). The diagnosis of TB was made by X-ray chest in 73, positive acid fast bacilli in sputum in 38, lymph node biopsy in 30, ascitic fluid examination in 20 and other tests in 17 patients. Four anti-TB drugs namely, isoniazid (INH), rifampicin (Rif), ethambutol (Eth) and pyrazinamide (Pyra) were used in 58 patients (44%) for six months; three drugs namely, INH, Rif, and Eth or Pyra were used in 61 patients (46%) for a variable period of six to 12 months. A total of 28 (21%) patients expired, eight while on therapy, one before starting the therapy and 19 after they were cured of TB. The main causes of death were sepsis in eight (28.5%), cardiovascular in seven (25%) and sudden death in six (21%). TB was not the direct cause of death in any of the patients except one, in whom it could be contributory.
Keywords: Tuberculosis, Hemodialysis, Acid fast bacilli, Saudi Arabia.
|How to cite this article:|
Malik GH, Al-Mohaya SA, Al-Harbi AS, Kechrid M, Azhari O, Shetia S, Tashkandy MA, Ahmad K, Bhat AW, Want MA, Subramanian P T, Abutaleb N, Karkar A. Spectrum of Tuberculosis in Dialysis Patients in Saudi Arabia. Saudi J Kidney Dis Transpl 2003;14:145-52
|How to cite this URL:|
Malik GH, Al-Mohaya SA, Al-Harbi AS, Kechrid M, Azhari O, Shetia S, Tashkandy MA, Ahmad K, Bhat AW, Want MA, Subramanian P T, Abutaleb N, Karkar A. Spectrum of Tuberculosis in Dialysis Patients in Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2020 Jul 12];14:145-52. Available from: http://www.sjkdt.org/text.asp?2003/14/2/145/33023
| Introduction|| |
Studies from different countries have shown that the prevalence of tuberculosis (TB) in dialysis patients is many times higher than in the general population and that it varies in different regions of the same country. ,,,, Anorexia, weight loss, low grade fever and generalized weakness, which are the main symptoms of TB, are commonly seen in patients with chronic renal failure as well. ,,,
Extrapulmonary TB is reported to be more common among dialysis patients than pulmonary TB ,,, and could play a significant role in the delay in diagnosis of TB in dialysis patients.  This delay in diagnosis and thereby, initiation of treatment, constitutes one of the main reasons for high mortality. , Studies from single centers may be biased; those with high incidence of TB may report and results from centers with low incidence may not be published.
The present study was conducted by collecting data of TB in dialysis patients from different regions of Saudi Arabia in order to know the incidence, clinical features and results of therapy.
| Material and Methods|| |
Saudi Arabia has five provinces; the Central, Northern, Eastern, Western and Southern. A format to obtain data of TB patients on dialysis was prepared and mailed to 17 hospitals in different provinces out of which seven consented to participate in the study. The data for the study were collected from the following hospitals: Security Forces Hospital, Riyadh (Central Province), Al-Noor Hospital, Makkah (Western Province), King Fahad Central Hospital, Gizan and Samtah General Hospital, Samtah (Southern Province), North West Armed Forces Hospital, Tabuk, Central Hospital, ArAr and Central Hospital, Al Jouf (Northern Province) and Central Hospital, Dammam (Eastern Province).
The format included information about age and sex, cause of renal failure, duration on maintenance dialysis (hemodialysis or peritoneal dialysis), clinical features like fever, weight loss and anorexia with duration, and the organs/systems involved such as pulmonary, abdominal, lymph nodes, genitourinary, nervous system, musculoskeletal and others. Evidence of TB sought included radiology, sputum examination [smear and culture for acid fast bacilli (AFB)], fluid exam [peritoneal, pleural, pericardial or cerebrospinal (CSF)] and its smear and culture for AFB; tissue biopsy like lymph node, peritoneal, pleural or any other tissue involved; purified protein derivative (PPD) skin or tuberculin test. Also the anti-TB drugs received, duration and complications of therapy were noted.
The outcome as well as the cause of death, in the patients who died, were noted.
| Results|| |
The combined total number of patients on maintenance dialysis in the eight hospitals was 1791. Of these, 105 patients (5.9%) were on peritoneal dialysis (all in the same center, Security Forces Hospital Program), with a total dialysis population of 330 patients and the remainder on maintenance hemodialysis (MHD). The total number of patients on dialysis having TB, noted in eight different hospitals, was 132 (7.4%). The age and sex distribution, the duration on dialysis and the prevalence in each hosptial of TB are given in [Table - 1].
The prevalence varied in different hospitals and ranged from 2.4 to 14.5%. Al Noor Hospital in Makkah, apart from the patients from the region, provides dialysis to pilgrims from other regions and countries for varying lengths of time and was therefore, excluded duration on dialysis varied from 20 to 63 months. The main causes of renal failure in the patients on dialysis with TB in different hospitals were bilateral small kidneys of unknown cause in 35 (26.5%), chronic glomerulonephritis in 31 (23.4%), diabetes mellitus in 21 (16.6%), hypertension in 17 (12.9%), chronic pyelonephritis in 12 (9.1%) and chronic interstitial nephritis in nine patients (6.8%).
The clinical features at presentation are given in [Table - 2]. Fever was noted in 65%, cough in 16.7%, weight loss in 59% and anorexia in 58.3% of all patients. The organs/ systems involved by TB in patients on dialysis are give in [Table - 3]. Overall, pulmonary TB was noted in 73 (55.3%) cases; lymphadenopathy was the second commonest in 30 (22.7%) followed by peritoneal TB in 27 (20.4%). There were seven cases of bone TB of whom five had spinal involvement. Two organ systems were involved in 14 while two patients had involvement of three organ systems. Pulmonary TB was concomitantly present in 14 of the 16 patients with multisystem involvement.
The various parameters used for diagnosis of TB in dialysis patients and their results are given in [Table - 4]. Sputum test was positive for AFB in 38 of the 73 cases with pulmonary TB and in two of the 20 cases with peritonitis. Out of 46 cases on whom PPD skin test was performed, 25 (54.3%) were found to be positive and the frequency of positivity varied from 35 to 78% in different centers.
Various anti-TB drug therapy regimens were used by the different hospitals. Four drugs, isoniazid (INH), rifampicin (Rif), ethambutol (Eth) and pyrazinamide (Pyra) were used in 58 patients (44%) initially for two months followed by only INH and Rif for further four months to complete a six month therapy. Three drugs (INH, Rif and Eth or Pyra) were used in 61 cases (46%). Modified drug regimen was used in three patients who developed hepatitis while on INH and Rif.
Twenty-eight (21%) of the 132 patients died during the study period. Eight patients expired while on therapy, one died before starting the therapy and 19 died after they were cured of TB. Sepsis, the commonest cause of death, was noted in eight (28.5%) followed by cardiovascular in seven (25%) and sudden death in six (21%). Tuberculosis was thought to have contributed as the cause of death in only one patient while in the remaining 27, TB was not considered the direct cause of death.
| Discussion|| |
The prevalence of TB in dialysis patients is closely related to, and several times higher than, its prevalence in the general population. ,,,, In the present study, the prevalence of TB in dialysis patients in different regional hospitals varied from 2.4 to 14.5% (mean = 7.0%). In a survey of TB in Saudi Arabia using positive Mantoux test as the indicator, the mean annual risk was estimated to be 0.56%.  Thus, on an average, TB in dialysis population is many times commoner than that in the general population; 12 times higher in San Francisco,  10 times higher in Brooklyn, New York  and 6-16 times higher in Japan.  The wide range of immunological derangements that are postulated to increase the susceptibility of dialysis patients to TB include impaired cellular immunity  , suppressed mitogenic response of lymphocytes  and defects in leukocyte function following exposure to dialysis membranes.  Protein malnutrition and zinc and pyridoxine deficiency also may predispose dialysis patients to TB. 
Some of the immune defects previously attributed to uremia may be partly due to the exposure of blood to the dialysis membrane.
Himmelfarb and Hakim found that granulocyte phagocytic activity, natural killer cell function and lymphocyte interleukin-2 (IL2) receptor densities may be impaired to a greater extent when dialysis is performed using unsubstituted cellulose membranes than when using synthetic membranes. 
The reasons for differences in the prevalence of Tb in dialysis patients in different regions of Saudi Arabia are not clear. The highest prevalence (14.5%) has been reported from the Security Forces Hospital in the Central Province. The likely explanations would be the higher index of suspicion and the more sophisticated and invasive methods used to diagnose Tb in the regions with higher prevalence. Al Kassimi in an epidemiological study of TB in Saudi Arabia found the annual risk of infection of 0.5% in Riyadh to be similar to rest of the country. 
Collectively, there was a slight male predominance (57%) in our study. Predominance of both males , and females , has been reported in different studies. The duration on dialysis of our patients, at the time of developing TB, varied from one month to 17 years with a mean duration from 20 to 63 months in different centers. In previous reports, the majority of cases were diagnosed within one year on dialysis. ,, In the present study, the duration on dialysis was not related to the development of TB, indicating thereby that despite maintenance dialysis, immunity remains suppressed.
Fever, cough, weight loss and anorexia were reported in varying frequencies from different centers in the present series [Table - 3]. Common constitutional symptoms reported in other studies were fever, anorexia, weight loss and generalized weakness. , Extrapulmonary TB has been noted in more than 40% of dialysis patients with TB in many studies. ,,,, Mitwalli have reported on six out of seven patients who had extrapulmonary TB.  Similarly, in another study from Brooklyn, New York, Lundin et al noted that seven out of eight cases had extrapulmonary TB. 3 The reasons for increase in the frequency of extrapulmonary TB are not clear. In HIV-infected individuals extrapulmonary tuberculosis is seen more commonly as a result of hematogenous dissemination which could also explain the predominance of extrapulmonary TB in dialysis patients.  However, awareness and advancement in the methodology of diagnosis could be contributory since, compared to pulmonary TB, more invasive methods are needed to diagnose extrapulmonary TB. The high incidence of extrapulmonary TB in dialysis patients may be the cause for delay in diagnosis as suggested by Andrew et al. 
Of the seven cases of bone TB, five had involvement of the spine. Although all five recovered with anti-TB drugs, three of these patients developed paraplegia with significant morbidity, indicating the importance of early diagnosis and treatment. El-Shahawy et al described two patients of TB of the spine in patients with end-stage renal disease one of whom developed paraplegia.  In a study of 12 patients of TB in dialysis patients, six (50%) had miliary TB all of whom died and the diagnosis could be made only on autopsy in four.  Five patients in the present study had miliary TB, all of whom recovered, emphasizing the benefit of early diagnosis and initiation of therapy. Two cases with pyrexia of unknown origin were empirically treated with anti-TB drugs with satisfactory response. A similar diagnosis of occult TB in dialysis patients has been made after positive response to anti-TB drugs by many authors. ,,,
A total of 16 patients had two or three systems involved, 14 of whom (87.5%) had concomitant pulmonary TB. The high proportion of pulmonary TB in these patients is highly suggestive of the initial focus being present in the lungs. Also, the pulmonary form was noted in 86% of TB cases in the general population in Saudi Arabia.  Additionally, the origin of extrapulmonary TB is generally from an initial focus in the lung.  Similar involvement of two or more systems involved by TB has been reported in other studies. , Tuberculin test was positive in 35% of the patients in whom it was performed, comparable to the 40-60% noted in other studies. ,, However, a positive tuberculin test in dialysis patients forms an indication for TB prophylaxis  and its importance cannot be underestimated.
In our study, short course (6 months) chemotherapy with four first-line drugs (INH +Rif +Eth +Pyra) was used in 48 patients, three drugs (INH +Rif and Pyra or Eth) were used in nine and two drugs (INH +Rif) in six patients; all showed satisfactory response. In an earlier study, short course chemotherapy with four drugs resulted in recovery of all six patients in whom it was used.  Thus, short course chemotherapy with four drugs seems to be a viable option of therapy for TB in dialysis patients.
Of the 132 patients studied, 28 (21%) expired, eight of whom died while on therapy. One patient with coronary artery disease, who died after angioplasty, pulmonary TB could be contributory to the mortality. Some earlier studies have reported a mortality in TB patients on dialysis to be 47-100% ,,. In more recent studies, a 100% recovery with anti-TB therapy has been reported. , Studies reporting a high mortality were mostly conducted in 1970's when potent anti-TB drugs were not widely available. Also, a high index of suspicion with early diagnosis and treatment may have changed the outcome.
In conclusion, there was a marked variation (2.4-14.5%) in the prevalence of TB in dialysis patients in different regions and on an average it was 12 times commoner than that in general population. A high index of suspicion is needed for early diagnosis. Extrapulmonary TB was noted in 45% of cases. Short course (6 months) chemotherapy seems a viable option although more studies are needed to prove its efficacy.
Mortality is insignificant with early diagnosis and treatment is insignificant.
| Acknowledgment|| |
The authors feel grateful to Ms. Sesita J. Benedicto for the secretarial assistance in preparing the manuscript.
| References|| |
|1.||Sasaki S, Akiba T, Suenaga M, et al. Ten years' survey of dialysis-associated tuberculosis. Nephron 1979;24:141-5 [PUBMED] |
|2.||Belcon MC, Smith EK, Kahana LM, Shimizu AG. Tuberculosis in dialysis patients.Clin Nephrol 1982;17:14-8 |
|3.||Lundin AP, Adler AJ, Berlyne GM, Friedman EA. Tuberculosis in patients undergoing maintenance hemodialysis. Am J Med 1979;67:597-602 [PUBMED] [FULLTEXT]|
|4.||Rutsky EA, Rostand SG. Mycobacteriosis in patients with chronic renal failure. Arch Intern Med 1980;140:57-61 [PUBMED] |
|5.||Andrew OT, Schoenfeld PY, Hopewell PC, Humphreys MH. Tuberculosis in patients with end-stage renal disease. Am J Med 1980; 68:59-65 [PUBMED] [FULLTEXT]|
|6.||Cengiz K. Increased incidence of tuberculosis in patients undergoing hemodialysis. Nephron 1996; 73: 421-4 [PUBMED] |
|7.||Mitwalli A. Tuberculosis in patients on maintenance dialysis. Am J Kidney Dis 1991;18:579-82 [PUBMED] |
|8.||Taskapan H, Utas C, Oymak FS, Gulmez I, Ozesmi M. The outcome of tuberculosis in patients on chronic hemodialysis. Clinical Nephrology 2000;54:134-7 |
|9.||Raviglione MC, O'Brien RJ. Tuberculosis. In Fauci AS, Braunwald E, Isselbacher K, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL (eds.) Harrison's Principles of Internal Medicine. McGraw-Hill, New York 1998;p. 1007 |
|10.||Al Kassimi FA. Review of Tuberculosis in Saudi Arabia. Saudi Med J. 1994;15(3): 192-5 |
|11.||Byron PR, Mallick NP, Taylor G. Immune potential in human uraemia. 2 changes after regular haemodialysis therapy. J Clin Pathol 1976;29:770-2 |
|12.||Newberry WM, Sanford JP. defective Cellular immunity in failure: Depression of reactivity of lymphocytes to phytohemagglutinin by renal renal failure serum. J Clin Invest 1971; 50:1262-71 [PUBMED] [FULLTEXT]|
|13.||Pereira BJ, Dinarello CA. Production of Cytokines and Cytokine inhibitory proteins in patients on dialysis. Nephrol Dial Transplant 1994;2:60-71 |
|14.||Tolkoff-Rubin NE, Rubin RH. Uremia and host defenses. N Engl J Med 1990;322: 770-2 [PUBMED] |
|15.||Himmelfarb J, Hakim RM. Biocompatibility and risk of infection in hemodialysis patients. Nephrol Dial Transplant 1994;9 [Supplement 2], 138-44 |
|16.||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 |
|17.||El-Shahawy MA, Gadallah MF, Campese VM. Tuberculosis of the spine (Potts' spine) in patients with end stage renal disease. Am J Nephrol 1994;14:55-9 [PUBMED] |
|18.||Papadimitriou M, Memmos D, Metaxas P. Tuberculosis in patients on regular haemodialysis. Nephron 1979; 24:53-7 [PUBMED] |
|19.||Hussein MM, Baker N and Roujouleh. Tuberculosis in patients undergoing maintenance dialysis. Nephrol Dial Transplant 1990;5:584-7 |
|20.||Sri SS. Clinical Features of all forms of Pulmonary Tuberculosis: In Textbook of Pulmonary and Extrapulmonary Tuberculosis. Edition 1993 Mehta Offset Works, New Delhi, India, pp 46-50 |
|21.||Shohaib S, Scrimgeour EM, Shaerya F. Tuberculosis in active dialysis patients in Jeddah. Am J Nephrol 1999;19:34-7 |
|22.||Cengiz K. Should tuberculosis prophylaxis be given for the chronically dialyzed patients. Nephron 2000; 86:411-3 [PUBMED] |
|23.||Al-Homrany M. Successful therapy of Tuberculosis in hemodialysis patients. Am J Nephrol 1997;17:32-5 [PUBMED] |
|24.||Pradhan RP, Katz LA, Nidus BD, Matalon R, Eisinger RP. Tuberculosis in dialyzed patients. JAMA 1974;229:798-800 [PUBMED] |
|25.||Amedia C, Oettinger CW. Unusual presentation of tuberculosis in chronic hemodialysis patients. Clin Nephrol 1977;8:363-6 [PUBMED] |
Ghulam Hassan Malik
Department of Internal Medicine, Security Forces Hospital Program, P.O. Box 3643, Riyadh 11481
[Table - 1], [Table - 2], [Table - 3], [Table - 4]