Tuberculosis Infection in Patients with Chronic Kidney Disease

Introduction

Tuberculosis (TB) was the second most common infectious agent-related cause of death worldwide, after COVID-19 in 2022, and it caused almost twice as many fatalities as human immunodeficiency virus/acquired immunodeficiency syndrome HIV/AIDS.¹ Patients with chronic kidney disease (CKD) are more likely to reactivate TBI, and dialysis facilities may be a source of TB transmission.^2,3 The risk of active TB is 7.8–25.0 times higher in patients undergoing hemodialysis (HD) than in the general population.⁴ However, the diagnosis of TB is usually delayed in patients undergoing dialysis.⁵ Interferon-Gamma Release Assay (IGRA) and the Tuberculin Skin Test (TST) are used to detect tuberculosis infection (TBI). We investigated the prevalence of TBI in patients with CKD using IGRA and explored its relationship with CKD stages, dialysis duration, and Bacillus calmette-guérin (BCG) vaccination.

Materials and Methods

Adult patients with CKD attending the outpatient department (OPD) and inpatient department (IPD) of MY Hospital, Indore, were enrolled over a period of 1 year from 11th September 2023 to 11th September 2024. Patients with malignancy or immunocompromised status due to any other chronic disease (HIV, hepatitis B, and hepatitis C); patients on immunosuppression, and those who did not give consent were excluded.

The protocol was approved by the ethical committee of MGM Medical College and MY Hospital (EC/MGM/Sept-23/108). All the included patients underwent IGRA QuantiFERON-TB Gold (QFT-G), fourth generation. The sample collected was incubated for 16-24 h, after which centrifugation was done and plasma harvested to measure interferon gamma by ELISA. Investigations were done in all included cases. The following investigations were done to rule out active TBI: as appropriate, sputum AFB, serology, and chest radiograph. IGRA-positive patients were referred for tuberculosis preventive treatment according to National Tuberculosis Elimination Program (NTEP) Guidelines. Indeterminate results, if any, were retested. The data was captured in the customized proforma, transferred to Microsoft Excel, and analyzed statistically using SPSS-25. Quantitative variables were expressed as mean ± SD or median ± IQR. Qualitative data were expressed as percentages and proportions. Pearson’s Chi-square and Fisher’s Exact statistical tests were used to infer an association, and p value <0.05 was considered statistically significant.

Results

Around 250 patients were selected out of 312 enrolled patients (62 patients were excluded based on the exclusion criteria). The mean age was 49.64 ± 11.491 years, and 56.4% were men. The majority of patients were on hemodialysis; only 53.6% had any recorded BCG vaccination status (history and BCG scar), and 80.8% were receiving dialysis for <1 year. Fibrotic lesions or residual post-TB sequelae were found in 3.2% of the patients with alterations on chest X-ray. IGRA came positive in 44 patients with CKD (17.6% - 95% CI: 12.9%–22.3%) [Figure 1, Table 1]. Most IGRA-positive individuals, 36 out of 44 (81.8%), were in CKD Stage 5. Statistical analysis showed no significant association between IGRA results and CKD stage (p >0.05) [Figure 2, Table 2]. Among IGRA-positive individuals, 63.6% were unvaccinated, whereas only 36.4% had received BCG [Figure 3, Table 3]. Regarding the duration of dialysis, there was a significant relationship for IGRA positivity (p <0.001). Almost four times as many IGRA-positive patients as IGRA-negative patients underwent CKD dialysis for >1 year, with half of the former group having this condition [Figure 4, Table 4].

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Figure 1:

Distribution of study subjects according to IGRA test.

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Figure 2:

Comparison between CKD Stage and IGRA test results.

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Figure 3:

Comparison between BCG Vaccination and IGRA test results.

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Figure 4:

Comparison between Dialysis Duration and IGRA test.

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Discussion

The IGRA demonstrated a positivity rate of 17.6% (95% CI: 12.9%–22.3%). Although most patients who were IGRA-positive (81.8%), were in stage 5 of CKD, statistical analysis revealed no meaningful correlation between IGRA results and stage. IGRA positivity rates vary across studies but generally range between 28% and 46%. Lee et al. (2010)⁶ found that 34.4% of patients with CKD are positive for QFT-G test, whereas Hussein et al. (2017)⁷ and Maden et al. (2011)⁸ found positivity rates of 35.1% and 39.6%, respectively. CKD is defined as abnormalities in the structure or function of the kidney which persist for at least three months and have health implications by KDIGO.⁹ Seyhan et al. (2010)¹⁰ reported 43% positivity rates, and Sayarlıoğlu et al. (2011)¹¹ reported a similar rate of 45%. Jahdali et al. (2013)¹² reported QFT-G positivity in 32.5% of patients, including 66.7% of confirmed TB cases. Chung et al. (2010)³ revealed a 45.9% positivity with QFT and 60.4% positivity with TB ELISpot (T-SPOT).

The IGRA-positive results did not differ significantly according to the CKD stage, suggesting that the in vitro measurement of interferon-gamma release from T-cells (i.e., IGRA) is a dependable and unaffected diagnostic method in all stages of CKD. The IGRA showed a significant inverse association with BCG vaccination. This tendency in favor of the greater specificity of IGRA to TB-specific antigens uninfluenced by past BCG exposure is in line with substantial among-test statistics, suggesting IGRA is less likely to result in false positives in vaccinated populations and is a better tool for diagnosing true TBI, particularly in areas where BCG vaccination is common Chung et al. (2010)³ observed a statistically significant increase in TST positivity after previous BCG vaccination (p = 0.018), with no effect on QFT or T-SPOT. Higher dialysis vintage and increased exposure to health care are typically associated with higher rates of latent infection detected by IGRA. Binay et al. (2023)¹³ found that a positive T-SPOT TB result was substantially associated with longer hemodialysis duration (p = 0.029), implying cumulative exposure or immunological shift over time. Conversely, Hussein et al. (2017)⁷ found no statistically significant association between duration of dialysis and positivity of QFT-G (p = 0.08), showing that the association may vary and be affected by other host factors. Putri et al. (2022)¹⁴ demonstrated that the TB-specific IFN-γ responses in IGRA-positive patients may be suppressed by one session of HD, suggesting that the timing of IGRA examination is essential. Their research suggested that IGRA should be performed before dialysis sessions. Xuan et al. (2024)¹⁵ demonstrated that the sensitivity of TBI detection significantly improved by up to 8.81% with the addition of renal function markers, serum creatinine, and eGFR, thereby detecting about 23% of untreated TBI cases. These findings highlight both physiological and methodological limitations of IGRA in CKD populations and underscore the need for either optimized timing of testing or integration of renal biomarkers.

To conclude, this study supports the use of IGRA as a useful tool for identifying TBI in patients with CKD, including those with advanced disease.