Avaliação do inflamassoma NLRP3, interleucina 1β (IL-1β) e interleucina 18 (IL- 18) na Nefropatia Diabética em pacientes idosos e adultos

Abstract

Diabetic Nephropathy (DN) is one of the major chronic complications of Diabetes Mellitus and represents one of the most frequent causes of chronic kidney disease and progression to endstage renal disease. Although metabolic and hemodynamic alterations are traditionally recognized as central to the pathophysiology of DN, growing evidence indicates that inflammatory mechanisms play a decisive role in the development and progression of renal lesions associated with the disease. In this context, the NLRP3 inflammasome and the proinflammatory cytokines IL-1β and IL-18 have been widely investigated due to their involvement in the activation and perpetuation of renal inflammation. The present study aimed to evaluate the expression of the NLRP3 inflammasome and the cytokines IL-1β and IL-18 in the glomerular and interstitial compartments of renal biopsies from elderly and non-elderly patients with DN, in order to better understand the involvement of this inflammatory axis in the pathophysiology of the disease. A total of 80 renal biopsies from patients with DN were analyzed, including 28 from elderly individuals and 52 from non-elderly individuals, as well as 22 control samples obtained from autopsies. Analyses were performed using immunohistochemical techniques, followed by semiquantitative evaluation of immunostaining. The results demonstrated a significant increase in NLRP3 inflammasome immunostaining in all glomerular cell types evaluated, including mesangial cells, endothelial cells, and podocytes, as well as in the interstitial compartment of patients with DN when compared to the control group. Consistently, a marked increase in IL-1β and IL-18 immunostaining was observed in the same compartments, with particular emphasis on mesangial cells and podocytes. Comparative analysis between age groups revealed no statistically significant differences between elderly and non-elderly patients, a finding that was also observed when comparing histological classes of DN with the inflammatory markers evaluated in both age groups. In endothelial cells, a positive and significant correlation was observed between NLRP3 and IL-1β expression in both age groups. Additionally, in the non-elderly group, a positive and significant correlation between NLRP3 and IL-18 was identified in podocytes and in the renal interstitium. In this group, mesangial and interstitial NLRP3 expression also showed a positive and significant correlation with serum creatinine levels. Interstitial IL-1β immunostaining likewise correlated positively and significantly with serum creatinine levels in both age groups. In contrast, IL-18 did not show a significant correlation with serum creatinine levels, and the remaining markers did not demonstrate relevant associations with other clinical parameters evaluated. Taken together, these findings suggest that activation of the NLRP3 inflammasome and the expression of IL-1β and IL-18 contribute significantly to the maintenance of the inflammatory state and to the decline of renal function in DN, regardless of age. Therefore, the NLRP3/IL-1β/IL-18 axis emerges as an important mechanism in the pathophysiology of the disease, highlighting its potential as a prognostic marker and a promising therapeutic target in DN.