Risk factors associated with the development of active tuberculosis among patients with advanced chronic kidney disease

doi:10.1016/j.jinf.2018.06.003

Journal of Infection

Volume 77, Issue 4, October 2018, Pages 291-295

https://doi.org/10.1016/j.jinf.2018.06.003 Get rights and content

Highlights

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Those with advanced kidney disease or receiving dialysis are at high risk of active TB.
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Cases occurred steadily over the period observed, regardless of time on dialysis.
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Those of Asian/Asian British or black/black British ethnicity were at highest risk.
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Testing and treating for latent TB is justified in high risk groups receiving or approaching dialysis.

Summary

Objectives

The risk of developing active TB is greater in those receiving haemodialysis. This study aimed to describe the incidence of active tuberculosis among patients referred for management of kidney disease and dialysis in a high incidence UK city, with the purpose of informing latent TB testing and treatment practice.

Methods

Information from the tuberculosis register was cross-referenced with the Department of Renal Medicine patient information system. All patients seen between 1st January 2005 and 1st October 2016 were included in the analyses with the exception of those with prior TB.

Results

68 cases of active TB were identified, an incidence of 126/100,000 patient-years (95% CI 97-169). Incidence was lowest in those with CKD 1 or 2 and rose as high as 256/100,000 patient-years (95% CI 183-374) in those receiving renal replacement therapy. 48% of cases were pulmonary and 87% of TB patients gave their ethnicity as either black/black British or Asian/Asian British, significantly more than in the non-TB renal group. Cases occurred steadily over the time period in which patients were in the cohort.

Conclusion

TB incidence was very high among those receiving renal replacement therapy or CKD 4 or 5. Most cases occurred in those of an Asian/Asian British or black/black British background. Testing and treating such patients for latent TB is justified and should include those who have been receiving renal replacement therapy for some years.

Introduction

It is estimated that around one quarter of the world's population is infected with tuberculosis (TB).¹ Over a lifetime a healthy individual with latent TB has 10–15% chance of developing active TB infection. This risk is greatly increased in those with certain forms of immunosuppression or co-morbidity. For example, it doubles or trebles in those receiving TNF-antagonists for treatment of conditions such as rheumatoid arthritis and psoriasis.² This has led the UK Medicine and Healthcare Regulatory Agency to recommend that all patients in whom treatment with TNF-antagonists is being considered are first screened for latent TB and treated if necessary.³

Patients receiving haemodialysis are known to be at increased risk of latent TB reactivation.⁴ Some studies estimate this as great as 25 times that of an otherwise healthy individual.⁵ Even patients experiencing acute kidney injury and requiring short spells of dialysis⁶ or those with chronic kidney disease (CKD) not yet requiring it have been shown to have higher rates of incident active TB.⁷ There is at present little consensus on whether to screen dialysis patients for latent TB routinely. Current UK advice recommends against the practice suggesting instead that those at high risk should be considered on a case-by-case basis⁸ whereas more recent guidance from the World Health Organization recommends testing for all patients receiving dialysis.⁹

Birmingham is the UK's second city. 24% of its population was born overseas, mostly in India and Pakistan (Office for National Statistics 2011). It has a TB incidence of 29 per 100,000/year, one of the highest outside of London, with approximately 350 active cases treated each year, 75% of whom were born overseas. This compares with a rate of 10.2 per 100,000/year in 2017 in England.¹⁰ Heart of England NHS Foundation Trust provides renal care and dialysis services to the population of East Birmingham and Solihull. In line with national guidance it does not routinely screen for latent TB. This study aimed to describe the incidence of active TB within patients referred for management of kidney disease and dialysis with the purpose of informing the unit's latent TB testing and treatment practice.

Section snippets

Methods

The Heart of England NHS Foundation Trust TB register was cross-referenced with the Department of Renal Medicine patient information system. This holds basic information on all patients referred to the renal department with kidney disease, as well as those receiving peritoneal or haemodialysis. All patients seen between 1st January 2005 and 1st October 2016 were included in the analyses with the exception of those with prior TB. Patients were considered to have come under the care of the renal

Demographics

There were 8767 patients within the renal cohort representing 53,833 patient years. The median age at entry was 66 years (mean 62 years). 71% were white, 18% Asian/Asian British and 5% black/black British. 56% were male. By the end of follow-up 24% of the cohort was at CKD 3 or less, 45% were at CKD 4 and not receiving renal replacement therapy, with 31% of the cohort receiving some form of renal replacement therapy.

Cases of active tuberculosis

68 patients developed tuberculosis during the time period studied. Those

Discussion

It is recognized that those patients with advanced kidney disease or undergoing renal replacement therapy are at high risk of developing active TB.⁴ Over the approximately 10 years of data in our study we identified 68 cases of active TB, equating to an overall incidence of 126/100,000 patient-years in the cohort (95% CI 97-169). Whilst not directly comparable, Public Health England reports an overall rate of 29/100,000 people per year for the City of Birmingham. Incidence was lowest in those

Acknowledgments

This study was performed as part of the usual work of the contributors with no additional funding.

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Cited by (17)

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study
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Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease.
Observational cohort study.
A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or “other” glomerular diseases in British Columbia, Canada.
Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria.
A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB.
The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis.
The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and >6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]).
A relatively low number of events contributed to uncertainty in risk estimates.
Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population.
Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.
Tuberculosis treatment delay and nosocomial exposure remain important risks for patients undergoing regular hemodialysis
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Citation Excerpt :
As demonstrated in the present study, isolation and TB treatment cannot completely eliminate nosocomial transmission due to extended delays in diagnosing active TB, and LTBI intervention can prevent TB from activating and further spreading to other patients.34 Both the tuberculin skin and IGRA tests are less sensitive in patients with ESRD than in those without ESRD.35 Thus, a negative test result does not definitively indicate the absence of LTBI.
Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case–control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients.
Adult (aged ≥20 years) patients with incident ESRD over 2000–2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio.
Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p < 0.001). Nosocomial exposure increased active TB risk (adjusted odds ratio [OR; 95% confidence interval, CI]: 1.60 [1.55–1.66] per month of exposure), particularly when the exposure time was either within 6 months before the index case was diagnosed or 6–15 months before the ESRD patient became an incident active TB case. For patients with active TB, cough-related medication prescriptions (proxy for cough symptoms) exponentially increased over 6 months before TB treatment.
Nosocomial exposure attributed to delay in the diagnosis of index pulmonary TB is important in TB transmission among patients undergoing regular hemodialysis. Additional studies investigating how TB can be diagnosed and treated early are warranted.
Our study revealed that nosocomial exposure, attributed to delay in pulmonary TB diagnosis, is important in TB transmission among patients undergoing regular hemodialysis. Strategies to diagnose and treat TB early are crucial to infection control, and they warrant further investigations.
INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease
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CKD correlates with increased risk of pulmonary tuberculosis.102 The risk further increases in those receiving HD.103 All patients of CKD with active TB should be treated with four agents.104
Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20–21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.
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Use of tumor necrosis factor α inhibitors for conditions, such as rheumatoid arthritis, is also associated with progression to TB disease.68 Additional risk factors for progression to TB disease include diabetes mellitus (19.1% of reported TB cases) and other non-HIV immunocompromising conditions, including end-stage renal disease and history of solid organ transplantation (7.5%).12,69–80 As the US TB control program enters a new decade, a combination of old and new approaches is needed to maintain and accelerate progress toward eliminating TB in the United States.
Latent tuberculosis infection and non-infectious co-morbidities: Diabetes mellitus type 2, chronic kidney disease and rheumatoid arthritis
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The risk of acquiring LTBI or of developing active TB is high in patients with CKD because, apart from the immunity problems already described, comorbidities such as diabetes are common and these further increase this risk. Incidence of TB increases further with advancing stage of CKD: a study that included more than 8000 patients with CKD in the United Kingdom found an incidence of 126 cases of active TB per 100,000 patient-years (95% CI 97–169), and the incidence was lower in those patients with stage 1 CKD (92 per 100,000 patient-years) compared with those who received dialysis (257 per 100,000 patient-years) (Moran et al., 2018). Outcomes, including risk of death, are also worse among patients with TB who are on dialysis.
The prevalence of non-communicable diseases is increasing worldwide, which coincides with the persistence of infectious diseases including tuberculosis. These can synergistically affect individual and population health. Three non-communicable diseases that are relevant because of their associated morbidity, mortality and disability are type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis. There is some evidence that patients with these conditions are at increased risk of acquiring latent tuberculosis infection (LTBI) and of this progressing to active disease. Unfortunately, evidence on accurate testing and effective prophylactic treatment in these populations is lacking. This review discusses current evidence and recommendations for management of LTBI in these patients.
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View full text

Risk factors associated with the development of active tuberculosis among patients with advanced chronic kidney disease

Highlights

Summary

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Demographics

Cases of active tuberculosis

Discussion

Acknowledgments

Clin Microbiol Infect

J Infect

The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling

PLoS Med

Risk of tuberculosis in patients with chronic immune-mediated inflammatory diseases treated with biologics and tofacitinib: a systematic review and meta-analysis of randomized controlled trials and long-term extension studies

Rheumatology (Oxford)

Risk of active tuberculosis in chronic kidney disease: a systematic review and meta-analysis

Int J Tuberc Lung Dis

Risk of tuberculosis in dialysis patients: a population-based study

Int J Tuberc Lung Dis

Increased risk of active tuberculosis following acute kidney injury: a nationwide, population-based study

PLoS ONE (Public Library of Science)

Increased risk of tuberculosis in patients with end-stage renal disease: a population-based cohort study in Taiwan, a country of high incidence of end-stage renal disease

Epidemiol Infect