Abordagem de estudos que relaionam lesões podocitárias mediadas por hiperglicemia: uma revisão sistemática

Abstract

Introduction/Rationale: Podocytes are epithelial cells that together with the endothelium and basement membrane form the glomerular filtration barrier. Changes in these structures lead to impaired glomerular function and are related to several kidney diseases, one of which is diabetic nephropathy (DN), which manifests as a diabetic complication. Currently, many studies are being aimed at identifying the mechanisms of DN, however, its pathogenesis is not fully elucidated. Objective: Thus, the present study aims to discuss, through a systematic review, the types of podocyte lesions associated with DN Methods: A systematic secondary study was carried out in scientific databases Medline (PubMed), Scopus, “Web of Science”, “OneFile” and gray literature. Searches were performed using the keywords ''Diabetic Nephropathies Biopsy AND Podocytes'' and their corresponding synonyms, delimiting the records between the period from 2001 to 2021. Observational studies that associated podocyte lesions in biopsy with diabetic nephropathy were considered for the selection. The analysis of methodological quality and consistency of evidence were evaluated for eligible studies. The data were discussed in a qualitative narrative way. Results: It was possible to select 28 studies according to the eligibility criteria. The mean evaluated for methodological quality was 91.46%. The frequency of scientific productions is heterogeneous, but showed a positive correlation in the study period (rho = 0.63; p=0.004). The most evaluated model in the relationship between podocyte injury and diabetes mellitus was the mouse (37.78%; CI = 23.61% to 51.95%), followed by analyzes of materials in humans (33.33%; CI = 19 .56% to 47.10%). Hyperglycemia has been shown to be related to reticular stress, redox destabilization, activation of important signaling pathways such as mTorc1 linked to podocyte hypertrophy, morphological and functional changes and cellular apoptosis mediated by the Wnt/β-catenin pathway, imbalance of matrix proteins such as BPM- 7 or even capsular thickening by increased production of podocyte proteins mediated by the interaction of TGF-β1, reduction of nephrin followed by pro-inflammatory processes associated with autocrine signaling of IL1β / IL-1R1. Conclusions: Several pathways integrate and participate in the molecular processes of podocyte lesions observed in diabetes mellitus, which contribute to the pathophysiology of nephropathy. Hyperglycemia leading to redox imbalance and inflammatory mechanisms seem to be the main events linked to podocyte lesions, however gaps still need to be investigated in primary studies, as they may enable better strategies to contain the harmful effects of hyperglycemia on renal function.