TB infection has become a global healthy issue. In 2018, TB had affected 10 million individuals, of whom 1.5 million died, thus imposing a massive burden on the public health system according to the World Health Organization (WHO) [20]. Because of early diagnosis and direct observation of treatment by using anti-tuberculosis agents with advanced public health services in Taiwan, a decreasing trend in TB infection was observed; the case rate decreased from 73 cases per 100,000 population to 36.7 cases per 100,000 population from 2005 to 2019 [21].
We included a large number of patients with PKD and observed them for a long time in our study. Our findings showed a signficantly higher incidence rate of TB in the PKD group (495.4 per 100,000 person-years) than in the non-PKD group (276.8 per 100,000 person-years). In the multivariate analysis after adjusting for confounders, namely sex, age, index year, and comorbidities, the PKD cohort had a 1.91-fold higher risk of TB than did the non-PKD cohort. When stratified by sites involving TB, such as pulmonary (PTB) and extrapulmonary (EPTB) sites, a 3.40-fold higher risk of EPTB was observed in the patients with PKD (aHR = 2.44, 95% CI = 1.46–4.08). Similarily, a 2.69-fold higher risk of TB was observed in the patients with PKD after excluding any underlying diseases, including diabetes, alcohol consumption, and liver disease, which may contribute to TB infection in the general population. Our findings suggest that PKD is associated with a higher TB infection risk, particularly EPTB infection, which has never been known previously. In addition, our findings may provide indirect evidence implicating PKD underlying abnormal immunological function.
Risk factors for TB infection can be divided into impaired host immunity and increased exposure. For example, impaired immunity with HIV infection poses a high risk of TB infection, including EPTB or miliary TB infection, and a low CD4 lymphocyte count is a key risk factor for TB relapse [2223]. Several predisposing factors are associated with TB infection. The risk of TB infection is high in patients with diabetes [24], solid organ transplant [25], renal disease [26], COPD [27], hematologic malignancies [28], diseases under long-term glucocoticoid treatment or tumor necrosis factor treatment [2930], undernutrition [31], or smoking and alcohol consumption [3233].
TB is prevalent worldwide, and male patients are particularly prone. Male patients have an approximately two-fold increased risk of TB infection [20]. Compared with female patients, more social exposure in male patients accounted for these findings. In the present study, the male patients in the PKD group were associated with an 1.8-fold higher risk of TB infection than did those in the control group, which supports the previous findings. Male sex is supposed to be associated with more rapid progression in PKD1-gene mutant patients with ADPKD [34]. Notably, the observation that female patients with PKD have a 2.2-fold increased risk of TB infection needs to be eluciated further.
Underlying comorbidities in PKD patients can aggravate the risk of TB infection. In this study, we observed that the PKD patients with hypertension (aHR = 1.89, 95% CI = 1.35–2.64), hyperlipidemia (aHR = 4.18, 95% CI = 1.46–11.94), and diabetes mellitus (aHR = 1.92, 95% CI = 1.01–3.66) had a high risk of TB infection; however, those with alcohol-related disease, chronic kidney disease, chronic liver disease, COPD, diabetes, bacterial infection, viral infection, and pneumoconiosis did not have a significantly increased risk of TB infection in the study.
In cases with TB infection in renal transplantations, more than one-third of the renal transplant patients developed TB infection during the first year post- transplantation [35]. High-dose immunosuppresant agents after the initial renal transplantation might interfere with T-cell function; for example, cyclosporin suppressed purified protein derivative-specific CD4 T-cell reactivity and the production of interleukin-2 and interferon-gamma [36].
Similarily, patients with PKD in the first year of follow-up have a high risk of TB, which implies that underlying immunodysregulation may likely contribute to the findings of our study.