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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 2  |  Page : 254-259
Characteristics and outcomes of end-stage renal disease patients with active tuberculosis followed in intensive care units


1 Department of Pulmonary Diseases, Baskent University, Faculty of Medicine, Ankara, Turkey
2 Department of Nephrology, Baskent University, Faculty of Medicine, Ankara, Turkey
3 Department of General Surgery, Baskent University, Faculty of Medicine, Ankara, Turkey

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   Abstract 

Tuberculosis (TB) remains a common problem in patients with chronic renal failure. In intensive care units, misdiagnosis or delayed diagnosis of TB is common. Therefore, a description of characteristics of active TB in patients with renal failure followed in intensive care units is important to reduce mortality and transmission of the disease. This study was performed to describe the characteristics of patients with renal failure admitted to the intensive care units and having active TB and evaluate predictive factors for in hospital mortality. The hospital records of 24 patients (11 women, 13 men) having ESRD and TB between 2001-2006 were reviewed. Clinical, radiological, and laboratory data on admission were recorded. Possible parameters contributing to in-hospital mortality were obtained from the medical records. In-hospital mortality rate was 66.6%. Factors associated with mortality were decreased partial pressure of oxygen and malnutrition. Fever was reported in 8 patients and hemoptysis was reported in 3 patients. Eight patients had consolidation on chest radiograph, while 4 had normal findings Seventeen patients had pulmonary involvement, and 11 had extra pulmonary involvement. The mortality rate in TB patients followed in intensive care units is high, with 3 factors contributing to in-hospital mortality. Clinicians should consider active TB in renal failure patients being followed in the intensive care unit, even when results of a chest radiograph are normal especially in patients with unexplained poor general health or respiratory failure.

Keywords: Tuberculosis, End-stage renal disease, Intensive care units, Mortality, Risk factors

How to cite this article:
Ulasli SS, Ulubay G, Arslan NG, Sezer S, Akcay S, Eyuboglu FO, Haberal M. Characteristics and outcomes of end-stage renal disease patients with active tuberculosis followed in intensive care units. Saudi J Kidney Dis Transpl 2009;20:254-9

How to cite this URL:
Ulasli SS, Ulubay G, Arslan NG, Sezer S, Akcay S, Eyuboglu FO, Haberal M. Characteristics and outcomes of end-stage renal disease patients with active tuberculosis followed in intensive care units. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2014 Jul 31];20:254-9. Available from: http://www.sjkdt.org/text.asp?2009/20/2/254/45574

   Introduction Top


Despite the availability of effective chemo­therapy, the incidence of tuberculosis (TB) and TB-related illnesses has increased since the 1970s and has become the leading cause of death due to an infection worldwide. [1],[2] End­stage renal disease (ESRD) is known to disrupt the cell-mediated immune response for killing intracellular organisms such as Mycobacterium tuberculosis. There is an increased risk (6.9- to 52.5-fold) of TB in patients with chronic renal failure undergoing dialysis as compared with the general population.

Early diagnosis of TB reduces mortality and morbidity rates and also reduces nosocomial transmission in patients with TB. [3] However, misdiagnosis or delayed diagnosis of TB as a cause of death is common in intensive respi­ratory care units. [4],[5],[6],[7],[8] Better descriptions of the disease's clinical features could improve diag­nostic accuracy in this setting.


   Patients and Methods Top


In this retrospective cohort study, we re­viewed the hospital records of end-stage renal disease patients with microbiological diagnosis of active TB in our intensive care unit between 2001 and 2006. During that time, 24 patients (11 women, 13 men; aged 50 ± 16 years) were admitted to our intensive care unit for treat­ment of acute respiratory failure related to pul­monary TB or poor general health caused by TB. Microbiologic analysis included using di­rect light microscopy to reveal acid-fast bacilli in at least 1 Ziehl-Neelsen-stained respiratory tract secretion sample or positive cultures for the etiologic pathogen.

The following data were obtained from each patient's medical record: patient demographics (age and sex), presence of another comorbid disease or pre-existing risk factors for TB in­fection, chest radiograph patterns, symptoms, organ involvement of disease, results of blood gas analyses, duration of hospitalization, length of required mechanical ventilation in patients with respiratory failure, diagnostic methods for TB, administration of anti-TB therapy, and mortality. Respiratory failure was defined as requiring mechanical ventilation for at least 24 hours.

Radiographic patterns were classified as nor­mal findings, consolidation, miliary pattern, pleural effusion, parenchymal cavity, fibrosis, and hilar or mediastinal lymphadenopathy. The number of lobes involved on the radiographs also was recorded. Septic shock was defined as sepsis with hypotension that, despite adequate fluid resuscitation, required vasopressor thera­py. In addition, perfusion abnormalities inclu­ded lactic acidosis, altered mental status, and acute lung injury in septic shock. [9]

Risk factors for TB infection included known contact with a person with active TB; abuse of either alcohol or drugs; diabetes mellitus re­quiring oral or parenteral hypoglycemic thera­py; end-stage renal disease requiring dialysis; type of dialysis; presence of malnutrition (body mass index < 20 kg/m 2 ); gastrectomy; hemato­logic disease; drug-induced immunosuppression by corticosteroids, chemotherapy, or other im­munomodulating drugs used to treat organ transplant patients; advanced age or collagen­vascular disorders.


   Results Top


Patient characteristics

The patients' characteristics are shown in [Table 1]. None of the patients had primary TB according to radiologic and clinical features. The patients had been receiving maintenance dialysis (mean renal failure duration, 64 months; hemodialysis/peritoneal dialysis, 23/1). Seven patients (29%) had received renal transplan­tation (mean transplant duration = 77 ± 64 months), with all organ recipients receiving standard immunosuppressive therapy including steroids, tacrolimus, and mycophenolate mofetil or cyclosporine (mean immunosuppressive the­rapy duration, 77 months).

Mean patient body temperature on admission was 37.9°C ± 0.9°C (range, 36.2°C-39.9°C). Fever was reported in 8 patients (33%; 4 patients did not have a fever before anti-TB treatment), and hemoptysis was reported in 3 patients (12%; [Table 2]). Seventeen patients had pulmonary involvement, and 11 had extra pulmonary involvement (lymph node, n= 1; lymph node plus central nervous system, n= 2; pleura, n= 3; small intestine, n= 1; knee, n= 1; kidney, n= 2; and vertebrae and central ner­vous system, n= 1). Four patients had both pulmonary and extra pulmonary involvement.

Eight patients (36%) had consolidation on chest radiograph, while 4 (18%) had a miliary pattern, 4 (18%) had pleural effusion, 1 (4.5%) had cavitation, and 4 (18%) had normal fin­dings. Bedside flexible bronchoscopic proce­dures (endobronchial biopsy in 3, bronchial lavage in 10) were performed in 11 patients with abnormal chest radiograph findings.

TB was diagnosed by direct light microscopy examination of respiratory tract secretion sam­ple (n= 17) including sputum or bronchial la­vage samples, bacilli in the gastric fluid (n= 1), positive sputum or bronchial lavage cultures (n= 5), or positive bone marrow polymerized chain reaction (n= 1). TB was diagnosed on biopsy specimens in 13 patients, with caseating granulomas in 7 of those. Treatment in all 24 patients included either oral or parenteral ad­ministration of 3 or more first-line anti-TB drugs: isoniazid, rifampin, pyrazinamide, and ethambutol. One patient received steroids (1 mg/kg/day) because of the presence of TB me­ningitis. None of the patients received second­line anti-TB drugs. One patient receiving iso­niazid (INH) had a seizure as an adverse effect.

Mortality

Sixteen patients (66%) who required invasive mechanical ventilation for respiratory failure died following admission to the ICU at a mean of 25 ± 14 days. Partial oxygen pressure in arterial blood samples was 45 ± 8 mmHg. Most patients (75%) had another comorbid di­sease such as systemic hypertension (n= 13), congestive heart failure (n= 1), malignancy (n= 1), both systemic hypertension and dia­betes mellitus (n= 3). Six of 16 patients (40%) who died had consolidation on chest radio­graphs, 3 (20%) had a miliary pattern, 3 (20%) had pleural effusions, 2 (13.3%) had fibrosis, and 2 (13.3%) had normal chest radiographs. Ventilator associated pneumonia from other microorganisms occurred in 6 patients [Table 3].

Univariate analyses identified the risk factors for TB that were significantly associated with mortality [Table 4]. The most significant among these were malnutrition, serum creatinine le­vel, and partial arterial pressure of oxygen. Disease presentation and treatment did not correlate with mortality. Co infection with other microorganisms also was not a risk factor for mortality.


   Discussion Top


Sixteen TB patients died between 2 and 180 days after admission to the ICU (mortality rate, 66.6%). Univariate analyses showed that, malnutrition and respiratory failure was inde­pendently associated with patient in-hospital mortality. The association between respiratory failure and a higher mortality rate agrees with prior studies that show high mortality rates (47%-80%) for TB patients who required me­ chanical ventilation. [2],[10]

According to World Health Organization re­cords, the number of TB patients in Turkey in 2000 was 18 038 out of a total of 66 668 000 persons with an incidence of 0.0027%. [11] If TB is not endemic in a community, exposure of older persons and children to Mycobacterium bacilli may lead to primary TB. Otherwise, in endemic areas like Turkey, reactivation is the main mechanism of infection in adults owing to the high exposure risk. [12]

Pulmonary TB characterized by lymphadeno­pathy, pleural effusions, and zone infiltrates in the lower lung or mid lung on chest radiograph represent a primary disease from a recently ac­quired infection, whereas upper lobe infiltrates and cavities represent secondary or reactivation of the disease. [13],[14],[15] In ESRD patients the clinical features of TB are usually atypical, mi­micking the primary disease with lower lung or mid lung zone infiltrates without cavities. [15]

All of our patients were older than 18 years. Twelve of our patients had fibrosis or hilar or apical calcified lesions, indicating primary in­fection in the past; 11 of them had extra pulmonary TB. Thus, reactivation of TB was the most common form seen in our study.

Previous studies show that the mortality is increased when TB coexists with chronic sick­nesses such as infection with HIV, diabetes mellitus, chronic heart failure, rheumatoid arth­ritis (low dose prednisone therapy), sarcoidosis (prior prednisone therapy), alcohol abuse, COPD, malignancy, chronic pancreatitis, and solid-organ transplantation. [2],[13],[16],[17],[18],[19]

It is well known that patients with ESRD and those on chronic dialysis have at least a 10- to 40-fold greater risk of developing TB com­pared with persons in the general population [15],[20] and use of bio-incompatible membranes may contribute by causing polymorphic nuclear dysfunction, such as chemotaxis, adhe­rence, and phagocytosis. [15]

Extra pulmonary involvement of mycobacte­rial infections is more frequent than isolated pulmonary involvement in ESRD patients [15] possibly due to the impaired cellular immunity in such patients. The incidence of extra pulmo­nary involvement in ESRD patient's ranges from 40% to 80% in recent studies. [21],[22],[23],[24] Consistent with those studies, 45.8% of our pa­tients had extrapulmonary involvement. Multi drug-resistant TB was not present in our patient population in contrast to TB mor­tality studies that involved younger and primarily outpatient populations. [25],[26] Our patient population did not have a past medical history of active TB or medical treatment for TB, which could explain this difference.

Malnourished patients are particularly vulne­rable to pulmonary infection. Starvation signi­ficantly depresses the phagocytic ability of pulmonary alveolar macrophages, which play important roles in the local cellular defenses of the lung. [27] In our study, 12 patients were malnourished, 13 had hypoalbuminemia, and 9 had general debilitation due to co morbidities. Univariate analysis also suggested an associa­tion between malnutrition and TB related mor­tality, nevertheless, it is unclear whether mal­nutrition was a cause or an effect.

In conclusion, we found a high mortality rate in TB patients followed in the intensive care units and identified respiratory failure requi­ring mechanical ventilation, and malnutrition, as risk factors for mortality. To reduce delayed diagnosis and mortality, TB should be con­sidered in ESRD patients admitted to the ICU for unexplained or non responding infections.

 
   References Top

1.Arslan H, Ergin F, Oner-Eyuboglu F, et al. Tuberculosis in renal transplant recipients. Transplant Proc 2003;35:2680-1.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Andrew OT, Schoenfeld PY, Hopewell PC, et al. Tuberculosis in patients with end-stage renal disease. Am J Med 1980;68:59-65.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Braun MM, Cote TR, Rabkin CS. Trends in death with tuberculosis during the AIDS era. JAMA 1993;269:2865-8.  Back to cited text no. 3    
4.De Backer W. Renal failure and lung: Pulmo­nary manifestations of systemic diseases. Eur Respir 2006;34:102-11.  Back to cited text no. 4    
5.Chuang FR, Lee CH, Wang IK, et al. Extra­pulmonary tuberculosis in chronic hemodia­lysis patients. Ren Fail 2003;25:739-46.  Back to cited text no. 5  [PUBMED]  
6.Erbes R, Oettel K, Raffenberg M, et al. Cha­racteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care. Eur Respir J 2006;27:1223-8.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Enarson DA, Chiang CY, Murray JF. Global epidemiology of tuberculosis. In: Rom WN, Garay SM, (eds). Tuberculosis. Philadelphia, Lippincott Williams and Wilkins. 2004;13-30.  Back to cited text no. 7    
8.Frame RN, Johnson MC, Eichenhorn MS, et al. Active tuberculosis in the medical intensive care unit: A 15 year retrospective analysis. Crit Care Med 1987;15:1012-4.  Back to cited text no. 8  [PUBMED]  
9.Hopewell PC. Tuberculosis and other myco­bacterial infections. In: Murray JF, Nadel JA, Broaddus VC, Mason R, (eds). Murray and Nadel's Textbook of Respiratory Medicine. Philadelphia, WB Saunders.2005;979-1043.  Back to cited text no. 9    
10.Hui C, Wu CL, Chan MC, et al. Features of severe pneumonia in patients with undiagnosed pulmonary tuberculosis in an intensive care unit. J Formos Med Assoc 2003;102:563-9.  Back to cited text no. 10  [PUBMED]  
11.Kotloff RM, Ahya VN, Crawford SW. Pulmo­nary complications of solid organ and hema­topoietic stem cell transplantation. Am J Respir Crit Care Med 2004;177:22-48.  Back to cited text no. 11    
12.Levy H, Kallenbach JM, Feldman C, et al. Acute respiratory failure in active tuberculosis. Crit Care Med 1987;15:221-5.  Back to cited text no. 12  [PUBMED]  
13.Malik GH, Al-Harbi AS, Al-Mohaya S, et al. Eleven years of experience with dialysis asso­ciated tuberculosis. Clin Nephrol 2002;58:356-62.  Back to cited text no. 13  [PUBMED]  
14.Mathur P, Sacks L, Auten G, et al. Delayed diagnosis of pulmonary tuberculosis in city hospitals. Arch Intern Med 1994;154:306-10.  Back to cited text no. 14  [PUBMED]  
15.Munford RS. Sepsis, severe sepsis, and septic shock. In: Mandell GL, Douglas RG, Bennet JE, (eds). Principles and practice of infectious diseases. New York, Churchill Livingstone. 1990;1:906-26.  Back to cited text no. 15    
16.McMurray DN, Barrow RA. Immunosuppression and alteration of resistance to pulmonary tuberculosis in guinea pigs by protein under­nutrition. J Nutr 1992;122:738-43.  Back to cited text no. 16    
17.Shennib H, Chiu RC, Mulder DS, et al. Depre­ssion and delayed recovery of alveolar macro­phage function during starvation and refeeding. Surg Gynecol Obstet 1984;158:535-40.  Back to cited text no. 17  [PUBMED]  
18.Oner-Eyuboglu AF, Akcay MS, Arslan H, et al. Extrapulmonary involvement of mycobacte­rial infections in dialysis patients. Transplant Proc 1999;31:3199-201.  Back to cited text no. 18    
19.Ozkara S, Aktas Z, Ozkan S, et al. National Guide for Tuberculosis Control in Turkey (in Turkish) 1998;7-55.  Back to cited text no. 19    
20.Pablos-Mendez A, Sterling TR, Frieden TR. The relationship between delayed or incomplete treatment and all-cause mortality in patients with tuberculosis. JAMA 1996;276:1223-8.  Back to cited text no. 20    
21.Penner C, Roberts D, Kunimoto D, et al. Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation. Am J Respir Crit Care Med 1995;151:867-72.  Back to cited text no. 21  [PUBMED]  
22.Piersen DJ Respiratory considerations in the patient with renal failure. Respir Care 2006;51:413-22.  Back to cited text no. 22    
23.Rao VK, Iademarco EP, Fraser VJ, et al. Delays in the suspicion and treatment of tuberculosis among hospitalized patients. Ann Intern Med 1999;130:404-11.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Sacks LV, Pendle S. Factors related to in­hospital deaths in patients with tuberculosis. Arch Intern Med 1998;158:1916-22.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]
25.Stoneburner R, Laroche E, Prevots R, et al. Survival in a cohort of human immuno­deficiency virus-infected tuberculosis patients in New York City: Implications for the expansion of the AIDS case definition. Arch Intern Med 1992;152:2033-7.  Back to cited text no. 25  [PUBMED]  
26.WHO. 2002 WHO Global Tuberculosis Control Report. Geneva, World Health Organization  Back to cited text no. 26    
27.Zahar JR, Azoulay E, Klement E, et al. Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure. Intensive Care Med 2001;27:513-20.  Back to cited text no. 27  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Sevinc Sarinc Ulasli
Department of Pulmonary Diseases, Baskent University, Fevzi Cakmak Cad, 5 sok, No 48, Postal Code 06490, Besevler, Ankara
Turkey
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PMID: 19237814

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