Tuberculosis and kidney function impairment

Screening for latent tuberculosis infection (LTBI) is crucial for patients with end-stage renal disease on dialysis, but the risk in patients with chronic kidney disease (CKD) not on dialysis is less understood. As CKD prevalence increases globally, the link between CKD and TB infection becomes increasingly significant. A study from 2008 to 2013 examined patients over 20 years old, categorizing them into CKD stages using the MDRD equation based on serum creatinine levels. Patients with pre-existing or newly diagnosed active TB, or those with insufficient follow-up, were excluded. The analysis revealed that the incidence of TB was higher in males, who made up 45.3% of the study, and was linked to various comorbidities like heart failure, stroke, diabetes, and systemic lupus erythematosus, with obesity inversely correlated with severe kidney dysfunction.[1]

Further findings indicated that the risk of TB escalates with the progression of CKD, particularly from stage 3 onwards. Older males with conditions such as pulmonary disease, GERD, cancer, heart failure, cirrhosis, diabetes, and autoimmune disorders were at an elevated risk for TB. The study reported an increase in both incidence and hazard ratios for TB with declining kidney function, with CKD stage 5 patients showing roughly a two-fold risk compared to dialysis patients, although with some statistical uncertainty due to overlapping confidence intervals. This suggests that TB prevention strategies should be intensified for CKD patients from stage 3, aligning with WHO recommendations for active LTBI screening in dialysis patients.[1]

A retrospective cross-sectional study in Cameroon analyzed 252 TB patients treated from January 2009 to December 2020, categorizing them into those with (cases) and without (controls) CKD, matched by age, sex, and TB form. Males comprised 59% of participants, with mean ages of 44.7 and 44.6 years for CKD and non-CKD groups, respectively. Most CKD patients were at advanced stages (84.1% at stage 5 on hemodialysis, 15.8% at stage 4), with median CKD and hemodialysis durations at TB diagnosis of 24 and 19.5 months.[2]

Mortality was significantly higher in CKD patients (33.3% vs. 5.6% in controls, p<0.0001), with 27% versus 4.8% death rates within two months. Multivariate analysis confirmed CKD and thrombocytopenia as independent predictors of mortality in TB patients.[2]

A retrospective study from January 2012 to December 2018 in Chongqing, China analyzed 167 TB patients, categorizing them into HD (66), pre-HD (51), and non-CKD (50) groups. EPTB was significantly higher in HD (66.6%) and pre-HD (41.1%) groups compared to non-CKD (32.0%). In CKD patients, TB commonly affected the pleura, lymph nodes, and bone, unlike the predominantly pleural TB in non-CKD patients. CKD groups showed fewer respiratory symptoms but more gastrointestinal issues and lymphadenitis. Diagnostic tests like TB antibody and tuberculin skin tests were less positive in the HD group, and TB-PCR was significantly lower in sputum for CKD groups.[3] 

Radiological findings confirmed TB in most CKD patients, often with multi-lobe lung involvement, and pleural effusion was common across groups. Mortality was notably higher in CKD patients, with rates of 37.3% for HD, 31.9% for pre-HD, and 6.1% for non-CKD. Multivariate analysis identified age over 40, hypoalbuminemia, advanced CKD stages, and HD as independent predictors of mortality in TB patients.[3]

In a study involving 653 adults with TB disease treated between 2010 and 2018 in a large Australian hospital network, all-cause mortality was significantly associated with age, diabetes, and renal function. The hazard ratio for diabetes-linked mortality decreased from 4.8 to 1.5 after adjusting for age, indicating that much of the association was due to older age rather than diabetes alone. However, renal function showed a stronger link; mortality hazard ratios escalated dramatically with declining eGFR, reaching as high as 34.0 for patients with an eGFR below 30 ml/min.[4]

Further analysis revealed the impact of chronic kidney disease (CKD) on mortality among TB patients, with the population attributable fraction (PAF) for CKD being notably high, peaking at 57% for those with eGFR below 60 ml/min. For comparison, diabetes had a PAF of 31%. Both TB-related and non-TB-related deaths were strongly associated with low eGFR, age, and diabetes. Even after adjustments for sex, age, and diabetes, the effect of severe renal impairment (eGFR < 30 ml/min) on both types of mortality remained significant, underscoring the critical role of renal function in TB outcomes.[4]

References:

1. Shu, CC., Wei, YF., Yeh, YC. et al. The impact on incident tuberculosis by kidney function impairment status: analysis of severity relationship. Respir Res 21, 51 (2020). https://doi.org/10.1186/s12931-020-1294-5.

2. Mangamba, L.M.E., Halle, M.P., Onana, C.L.M., Tochie, J.N., Ngamby, V., Noubibou, J.C.E., Balkissou, A.D., Tewaffeu, D.G., & Ngahane, B.H.M. (2023). Impact of Chronic Kidney Disease on the Mortality of Tuberculosis Patients: A Cross-Sectional Study in Douala. Health Sciences and Disease, 24(2).

3. Xiao, J., Ge, J., Zhang, D., Lin, X., Wang, X., Peng, L. and Chen, L., 2022. Clinical characteristics and outcomes in chronic kidney disease patients with tuberculosis in China: A retrospective cohort study. International Journal of General Medicine, 15, p.6661.

4. Carr, B.Z., Briganti, E.M., Musemburi, J., Jenkin, G.A. and Denholm, J.T., 2022. Effect of chronic kidney disease on all-cause mortality in tuberculosis disease: an Australian cohort study. BMC Infectious Diseases, 22(1), p.116.