Avaliação das alterações renais induzidas por álcool e tabaco em modelos experimentais e biópsias humanas

Abstract

Alcohol consumption and smoking are important risk factors for chronic kidney disease (CKD); however, the pathophysiological mechanisms underlying renal injury resulting from isolated or combined exposure remain incompletely understood. This study investigated, from a translational perspective, the effects of alcohol and cigarette smoke on renal function and structure by integrating an experimental model with human clinicopathological data. This was a quantitative, exploratory, and analytical study with an experimental and epidemiological design. A total of 197 human renal biopsies from the biobank of the Kidney Research Center (CePRim) were analyzed, correlating histopathological findings with exposure profiles and associated comorbidities. In parallel, female Wistar rats were allocated to Control, Alcohol, Tobacco, and Alcohol + Tobacco groups (n = 12/group) and underwent biochemical, functional, histological, and renal cytokine assessments. In the experimental model, combined exposure resulted in lower body weight gain, reduced serum urea (p < 0.001), and increased plasma AST (p < 0.0001), in addition to reduced creatinine clearance in all exposed groups (p < 0.0001), increased 24-hour proteinuria, and tubulointerstitial alterations, including mononuclear inflammatory infiltrate, tubular atrophy, and early fibrotic remodeling. In the clinical assessment, systemic arterial hypertension showed a high prevalence in the combined-exposure group (71.4%). Logistic regression analysis indicated that alcohol consumption and smoking were not independent predictors of advanced structural renal injury; however, alcohol consumption was independently associated with greater severity of mononuclear inflammatory infiltrate in females (OR = 4.98; p = 0.028). Hypertension and diabetes mellitus (DM), in turn, were the main determinants of tubular atrophy (OR = 2.08 and OR = 3.02, respectively) and interstitial fibrosis (OR = 2.04 and OR = 2.66, respectively), while hypertension was also associated with reduced creatinine clearance (OR = 2.53). In conclusion, alcohol and tobacco may act as renal sensitizing factors, promoting early inflammatory and tubulointerstitial alterations, whereas the consolidation of structural and functional renal damage appears to be predominantly associated with the coexistence of metabolic and hemodynamic comorbidities, particularly hypertension and DM.