The role of mesenchymal activation and immune-inflammatory responses in the pathogenesis of drug-induced chronic tubulointerstitial renal injury (an experimental study)

Drug-induced kidney injuries are a preventable yet common cause of acute and chronic renal failure. Studying their mechanisms of development, diagnosis, and prevention is essential for improving renal outcomes.
Aim. To identify the dynamics and pathogenetic mechanisms of chronic tubulointerstitial kidney injury during prolonged administration of anti-tuberculosis drugs used for treating sensitive tuberculosis.
Materials and Methods. The experiment was conducted on 50 male outbred white rats weighing 250–260 g. Experimental and control groups (10 rats each) were formed. The control group comprised a baseline and two dynamic control subgroups. The experimental group received a combination of anti-tuberculosis drugs: isoniazid, rifampicin, ethambutol, and pyrazinamide. The study duration was 120 days. The following markers were assessed semi-quantitatively: CD3, CD20, and vimentin.
Results. In a previous study, prolonged administration of anti-tuberculosis drugs induced chronic tubulointerstitial nephritis in rats. To elucidate the underlying mechanisms, immunohistochemical analysis was performed. On day 60, the number of CD3+ cells in the interstitium of the experimental group was 17.9 [16.65; 20.35] compared to 3.1 [2.75; 3.4] in the control group (p < 0.01); by day 120, it increased to 19.6 [18.45; 21.1]. A similar trend was observed for CD20+ cells: 21.6 [19.6; 24.0] on day 60 and 26.5 [23.25; 28.65] on day 120 (p < 0.05). The proportion of vimentin-positive tubules increased to 35.4 % [31.9; 37.95] on day 60 and to 58.9 % [54.15; 63.4] on day 120. Functional impairment was confirmed biochemically.
Conclusion. Long-term anti-tuberculosis treatment induced progressive chronic tubulointerstitial renal injury in rats, characterized histologically by tubular epithelial dystrophy, inflammation, and necrosis. Injury progression was driven by activation of the epithelial-mesenchymal transition, marked by significantly increased vimentin expression in the interstitium and tubular epithelium.

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