Introducere. Fibroza renală reprezintă etapa ireversibilă a leziunilor renale cronice, iar expunerea la substanţe ne-frotoxice este subestimată. Agenţii toxici - farmacologici (AINS, antibiotice), industriali (metale grele, solvenţi), de mediu (pesticide) - declanşează răspunsuri patologice ce duc la fibroză progresivă. Scop. Identificarea mecanismelor comune implicate în tranziţia de la leziune toxică la fibroză renală, clasificarea substanţelor cu potenţial fibrogenic pentru a identifica căi de intervenţie terapeutică. Material şi metode. S-a efectuat o analiză critică a literaturii ştiinţifice din ultimii ani (2015-2025), integrând date din studii experimentale, clinice şi epidemiologice. Au fost analizate acţiunea agenţilor nefrotoxici asupra mecanismelor moleculare (TGF-p/Smad, Wnt/0-catenină, NLRP3), stresului oxidativ, inflamaţiei cronice şi activării miofibroblastelor. Rezultate. Majoritatea substanţelor nefrotoxice, indiferent de origine, induc leziuni tubulare urmate de inflamaţie cronică şi fibroză prin mecanisme comune: activarea căii TGF-0/ Smad, stres oxidativ, disfuncţie mitocondrială şi recrutarea miofibroblastelor. Inflamozomul NLRP3 şi hipoxia cronică contribuie suplimentar la progresie. Vârstnicii, pacienţii cu diabet sau hipertensiune sunt mai susceptibili. Biomarkerii KIM-1, NGAL, TGF-p şi PIIINP urinar sunt valoroşi în evaluarea riscului fibrotic. Exozomii urinari şi microARN-urile, precum miR-21 şi miR-29, sunt propuşi ca noi instrumente de diagnostic precoce şi monitorizare a fibrozei renale. Concluzii. Substanţele toxice de diverse origini induc fibroză renală prin mecanisme comune, ceea ce deschide oportunităţi pentru intervenţii ţintite antifibrotice. Prevenţia, farma-covigilenţa şi terapiile direcţionate molecular pot contribui la reducerea impactului nefrotoxicităţii asupra sănătăţii publice.
Introduction. Renal fibrosis represents the irreversible stage of chronic kidney injury, and exposure to nephrotoxic substances is underestimated. Toxic agents - pharmacological (NSAIDs, antibiotics), industrial (heavy metals), environmental (pesticides) - trigger pathological responses that lead to progressive fibrosis. Objective. Identification of the mechanisms involved in the transition from toxic injury to renal fibrosis, classification of fibrogenic agents in order to identify therapeutic intervention pathways. Material and methods. A critical analysis of the scientific literature from recent years (2015-2025) was conducted, integrating data from experimental, clinical, and epidemiological studies. The action of nephrotoxic agents on molecular mechanisms (TGF-ß/Smad, Wnt/ß-catenin, NLRP3), oxidative stress, chronic inflammation, and myofibroblast activation was analyzed. Results. Most nephrotoxic substances, regardless of their origin, induce tubular injury followed by chronic inflammation and fibrosis through common mechanisms: activation of the TGF-ß/Smad pathway, oxidative stress, mitochondrial dysfunction, and myofibroblast recruitment. The NLRP3 inflammasome and chronic hypoxia further contribute to disease progression. Elderly individuals, as well as patients with diabetes or hypertension, are more susceptible. Biomarkers such as KIM-1, NGAL, urinary TGF-ß, and PIIINP are valuable for assessing fibrotic risk. Urinary exosomes and microRNAs (miR-21, miR-29), have been proposed for early diagnosis and monitoring. Conclusion. Toxic substances of diverse origin induce renal fibrosis through common mechanisms, which opens up opportunities for targeted antifibrotic interventions. Prevention, pharmacovigilance, and molecularly targeted therapies can reduce the impact of nephrotoxicity on public health.
