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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
RENAL DATA FROM THE ARAB WORLD  
Year : 2017  |  Volume : 28  |  Issue : 6  |  Page : 1362-1368
The diagnosis of tuberculosis in dialysis patients


1 Department of Nephrology, Dialysis and Transplantation, Tunis, Tunisia
2 Department of Pneumology, La Rabta Hospital, Tunis, Tunisia
3 Department of Infectiology, La Rabta Hospital, Tunis, Tunisia
4 Department of Research Laboratory of Kidney Diseases (LR00SP01), Charles Nicolle Hospital; Department of Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia

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Date of Web Publication18-Dec-2017
 

   Abstract 


The incidence of tuberculosis (TB) is high in patients undergoing chronic dialysis than it is in the general population. The diagnosis of TB is often difficult and extrapulmonary involvement is predominant. This study investigates the spectrum of clinical presentations and outcome in dialysis patients during a nine-year period. TB was diagnosed in 41 patients. Anti-TB drugs, adverse effects of therapy, and outcome were noted. Thirty-eight patients (92.6%) were on hemodialysis and three were on peritoneal dialysis (7.3%). The mean age at diagnosis was 50.8 years and the male/female ratio was 1.16. Four patients had a history of pulmonary TB. Extrapulmonary involvement was observed in 32 (78 %) patients. The bacteriological confirmation was made in 41.46% and histological confirmation was made in 26.83%, and in the rest, the diagnosis was retained on the criterion presumption. Nineteen patients (46.34%) developed adverse effects of antitubercular drugs. Eight patients (19.51%) died during the study from TB or adverse effects of treatment. Low urea reduction ratio and female sex were associated with poor prognosis in our study. The clinical manifestations of TB in patients on dialysis are quite nonspecific, making timely diagnosis difficult, and delaying the initiation of curative treatment, which is a major determinant of the outcome.

How to cite this article:
Jebali H, Barrah S, Rais L, Kheder R, Khouja N, Mhiri SN, Beji M, Abdelmalek R, Tiouiri H, Smaoui W, Beji S, Hmida FB, Fatma LB, Zouaghi MK. The diagnosis of tuberculosis in dialysis patients. Saudi J Kidney Dis Transpl 2017;28:1362-8

How to cite this URL:
Jebali H, Barrah S, Rais L, Kheder R, Khouja N, Mhiri SN, Beji M, Abdelmalek R, Tiouiri H, Smaoui W, Beji S, Hmida FB, Fatma LB, Zouaghi MK. The diagnosis of tuberculosis in dialysis patients. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Apr 25];28:1362-8. Available from: http://www.sjkdt.org/text.asp?2017/28/6/1362/220882



   Introduction Top


Tuberculosis (TB) remains a major health problem, particularly in endemic regions.[1]

Worldwide, TB infection in dialyzed patients ranges from 5%–25% and a 6.9–52.5-fold risk of TB is reported as compared to the general population.[2],[3] In a previously published Tunisian prospective study, the authors found 10% as a rate of active TB among hemodialysis (HD) patients; this rate represents 15 times of the general population TB incidence in our country (23/100,000).[4],[5] Several factors related to dialysis contribute to impairment of cell-mediated immunity, including nutritional abnormalities (reduction of protein intake and micronutrient deficiency), iron overload, and bio-incompatibility of the dialysis system. In addition, frequent hospital contact, older age of dialysis recipients, diabetes mellitus, low body mass index (BMI), and the use of immunosuppressive drugs are additional factors which contribute to the higher prevalence of TB in these patients.[6],[7],[8] The diagnosis of TB disease is often delayed in dialysis patients due to nonspecific symptoms.[2],[9] This causes the delay in initiation of TB treatment which adversely patient outcomes.[10],[11]

There are limited data about the prevalence and the patient characteristics of TB cases among dialysis patients in Tunisia. The aim of this study was to evaluate clinical characteristics, diagnostic tests, treatment modalities, and outcomes of TB among patients with end-stage renal disease undergoing chronic dialysis.


   Patients and Methods Top


This was a retrospective study and included all patients with diagnosed with TB undergoing either HD or peritoneal dialysis (PD) over a period of nine years between April 2007 and July 2016. We identified 41 cases of TB. We analyzed the clinical and laboratory features at the time of TB diagnosis including epidemiological characteristics and signs suggestive of a pulmonary or extrapulmonary involvement.

Diagnosis of TB was based on the following criteria: (1) positive culture of any specimen or a tissue for Mycobacterium tuberculosis and (2) histopathological evidence of M. Tuberculosis (granulomatous with caseating necrosis). In cases without bacteriological or pathological confirmation, TB was defined as clinical (unexplained fever, impaired general condition), biological (high C-reactive protein (CRP), hypoalbuminemia, lymphocyte predominance, and exudative effusion of peritoneal, pericardial, and pleural fluid), imaging (pleural lesions, pulmonary lesions) and/or histopathological (noncaseating granulomas), and/or positive tuberculin skin test (TST) and/or history of active TB, and the exclusion of other diseases. TST was carried out by the intradermal method and was read 48-72 hours later. Positivity was defined as an induration diameter ≥10 mm. Malnutrition was defined as BMI <20 kg/m2 and hypoalbuminemia <30 g/L. Iron overload was defined as hyperferritinemia >500 μg/L.

Treatment response was evaluated according to improvement of the general condition, functional signs, radiological signs, and biological data.


   Statistical Analysis Top


Data were analyzed using the Statistical Package for the Social Sciences for Windows version 11.0 (SPSS Inc., Chicago, IL., USA). The results were expressed in terms of number of cases and/or percentage for categorical variables and in terms of averages for quantitative variables. We used Chi-square test for the comparison of percentages and test analysis of ANOVA variances for comparison of averages. P <0.05 was considered statistically significant.


   Results Top


Forty-one cases of TB were diagnosed during the study period. The average age of this population was 50.8 years ± 15.23 (22–85 years). Twenty-two patients (53.6%) were male and 19 (46.3%) were female. Of these, 38 patients (92.6 %) were on HD and three (7.3 %) on PD. The mean interval between the onset of dialysis and the time of diagnosis of TB was about 1.7 years (range: 1 week–9.2 years). Comorbidities, primary renal disease, and corticoids and/or immunosuppressive therapy are summarized in [Table 1]. Four patients (9.7%) had a prior history of a pulmonary TB. Thirty-two patients (78%) have been vaccinated against TB. The most common clinical features were weight loss (97.5 %), anorexia (97.5 %), and fever (51.2 %). The main biological characteristics of our patients are summarized in [Table 2]. High CRP (>10 mg/L) was noted in 39 patients (95.12%). Hypoalbuminemia (<30 g/L) was noted in 12 cases (29.2%).
Table 1: Epidemiological features

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Table 2: Biological features.

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Hematological abnormalities included anemia in 85.3% (35 patients), hyperleukocytosis in 21.95% (9 patients), and leukopenia in 4.8% of cases (2 patients). Six patients had hypercalcemia and parathyroid hormone levels below 150 pg/mL (14.63%). An analysis of peritoneal, pericardial, and pleural fluids showed lymphocyte predominance and exudative effusion in all cases. TST was performed on all patients before initiation of therapy. A positive result was seen in 15 patients (36.5%).

The clinical presentation of TB was varied in our study population. It was unifocal in 29 patients (70.73%), bifocal in nine patients (21.95%), and three patients had multisystem involvement (7.3%). Extrapulmonary TB was observed in 78% of cases (32 patients). Isolated pulmonary TB was noted in 21.95% of cases (9 patients), whereas eight patients presented pulmonary TB associated with another placement [Table 3] and [Table 4]. The mean interval between the onset of symptoms and TB diagnosis was about 113.52 days (30–360 days). Confirmation of TB was done in 68.3% of cases (28 patients), 17 cases (41.46%) on bacteriological findings, and 11 cases (26.83%) on histological findings [Table 3]. In the remaining cases (13 patients, 31.7%), the diagnosis of TB was made on strong clinical, laboratory, histopathological, and/or radiological suspicion.
Table 3: TB diagnosis.

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Table 4: Comparison with the literature.

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Thirty-nine patients were treated with rifampicin, isoniazid, ethambutol, and pyrazinamide, whereas two patients received rifampicin, isoniazid, and pyrazinamide. Planned for all patients involved the use of all antitubercular drugs in the first two months, isoniazid and rifampicin treatment continued thereafter. The mean duration of treatment was 198.3 days (4–365 days). Nonadherence of treatment was observed in 34.1% of cases (14 patients). The determination of acetylator phenotype was carried out on 25 patients. Twenty-one patients were slow acetylators, whereas four patients had fast phenotype. The mean dose of isoniazid for slow group was 130 mg/day (ranging from 50 mg and 200 mg/day), and the mean dose for fast group was 200 mg/day (ranging from 150 mg and 300 mg/day). Nineteen patients developed adverse effects (46.34%). Cutaneous manifestations of drug allergy and hypersensitivity occurred in seven patients; all drugs were stopped and restarted gradually with good tolerance. Hepatotoxicity developed in six patients (cytolysis in 2, cholestasis in 2, and acute liver failure in 2), requiring cessation of all drugs in two patients, and adjustment of doses in two cases. Hematologic abnormalities were observed in six patients (aggravation of anemia in 4, leukopenia in 1, and thrombocytopenia in 1 patient). Five patients presented with reversible digestive disorders and required cessation of isoniazid in one case. Several patients presented more than one adverse effect. According to acetylator phenotype, 11 slow acetylators developed adverse effects related to isoniazid and only one fast acetylator presented digestive disorders.

The mean period of follow-up was 9.32 months (3 days to 3 years). Clinical response was achieved in 82.9% (34 patients) [Table 4]. One patient developed reactivation of pulmonary TB after cessation of treatment. Fifteen patients (36.58%) died during the treatment from TB or adverse effects related to the treatment in eight patients (multiorgan failure in 5, acute liver failure in 1, isoniazid intoxication in 1, and acute respiratory failure in 1 patient, respectively). The remaining deaths were related to cardiovascular and/or cerebrovascular events. For the patients treated according to the criteria of presumption, clinical response was achieved in 84.61% (11/13) of cases. Overall survival at one year was 62% [Figure 1]. Univariate analysis showed that the female sex (P = 0.009), and urea reduction ratio <65% (P = 0.026) were negative prognosis factors in our patients [Table 5].
Figure 1: Survival curve.

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Table 5: Prognosis factor.

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   Discussion Top


In this study, we diagnosed 41 active TB patients undergoing chronic dialysis treatment for a period of nine years. Our data suggested that TB diagnosis was often difficult in these patients. In fact, the mean interval between the onset of symptoms and TB diagnosis was about 113.52 days in our patients, and diagnosis of TB was made on presumption criteria in 31.7% of cases.

In our study, 26.83% of patients were diabetic and 12.19% were on immunosuppressive treatment. The majority of our patients had iron overload and malnutrition

In our study, 9.7% of patients had a history of active pulmonary TB. This frequency varies according to the authors between 0% and 27%. TB infection in chronic dialysis patients is probably secondary to reactivation of latent TB.[12] A negative TST due to its poor sensitivity in these patients cannot be used to eliminate the possibility of latent or active TB.[13],[14],[15],[16] In our study, only 36.5% of patients with a clinical diagnosis of TB presented positive TST.

In this study, impaired general condition and fever were noted in 97.56% and 51.22% of cases, respectively, while increasing CRP and anemia were noted in 95.12% and 85.3%, respectively. Lymphocyte-predominant exudates were presented in all cases with pleural, pericardial, or peritoneal TB in our series. On the other hand, hypercalcemia could be a sign of TB in dialysis patients caused by an increased form of Vitamin D released by granulomas. In our study, six patients developed hypercalcemia (14.63%).[17]

In our study, urinary, pleural, and lymphadenitis were the more frequent location, whereas bifocal or multifocal TB occurred in 12 patients. In our study, the bacterial diagnosis was of TB which was positive in only 17 (41.46%) of pulmonary cases [Table 3]. In our study population, histological examination was positive in 11/41 patients (26.83%) [Table 3]. Dialysis patients do not seem to have the capacity to develop caseous lesions or even granulomatous lesions,[18],[19] and the absence of bacteriological or histological confirmation should not exclude TB infection.[20],[21] Therefore, initiation of antitubercular therapy must be discussed if patients presented with unexplained debilitating symptoms, for example, nonspecific fever, anorexia fatigue, cough, or weight loss associated with specific signs such as lymph node enlargement and pleural or peritoneal effusion lesions.[20],[21],[22],[23] Thirteen patients in our series were treated according to presumptive criteria with good response in the majority of cases.

Treatment of TB in dialysis patients may be complicated by an increased risk of toxicity from antitubercular drugs.[24] There are many possible adverse effects including hepatitis, skin rash, digestive disorders, and hematologic complications. Hepatotoxicity and allergic manifestations were the most frequent adverse effects in our series. Our result showed that the mortality of dialysis patients presenting TB remain high. Delay in diagnosis and initiation of treatment, nonobservance of treatment, and the frequency of serious adverse effects of antitubercular drugs were associated with worse prognosis. The low urea reduction ratio was identified as a negative prognostic factor in our study. This finding was explained probably by the association between dialysis adequacy and nutritional status and inflammation.

Due to the retrospective nature of this study, we could not gather more information regarding risk factors, additional comorbidities, or diagnostic procedures.


   Conclusion Top


Our study highlights the predominance of extrapulmonary TB in dialysis patients and the frequency of adverse effects from antitubercular treatment and death related to TB or treatment. This study demonstrates the challenges posed for diagnosing TB in this population despite high index of suspicion.



 
   References Top

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Ko YC, Lee CT, Cheng YF, et al. Hypercalcaemia and haemophagocytic syndrome: Rare concurrent presentations of disseminated tuberculosis in a dialysis patient. Int J Clin Pract 2004;58:723-5.  Back to cited text no. 17
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Correspondence Address:
Sana Barrah
Department of Nephrology, Dialysis and Transplantation, La Rabta Hospital, Tunis
Tunisia
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DOI: 10.4103/1319-2442.220882

PMID: 29265048

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