Comprehending the Role of Metabolic and Hemodynamic Factors Alongside Different Signaling Pathways in the...

Diabetic nephropathy (DN) is a progressive microvascular disorder of diabetes that contributes as a primary reason for end-stage renal disease worldwide. The pathological hallmarks of DN include diffuse mesangial expansion, thicker basement membrane of glomeruli, and arteriole hyalinosis. Hypertension and chronic hyperglycemia are the primary risk factors contributing to the occurrence of DN. The complex pathophysiology of DN involves the interplay amongst metabolic and hemodynamic pathways, growth factors and cytokines production, oxidative stress, and ultimately impaired kidney function. Hyperglycemia-induced vascular dysfunction is the main pathological mechanism that initiates DN. However, several other pathogenic mechanisms, such as oxidative stress, inflammatory cell infiltration, and fibrosis, contribute to disease progression. Different vasoactive hormone processes, including endothelin and renin-angiotensin, are activated as a part of the pathophysiology of DN, which also involves increased intraglomerular and systemic pressure. The pathophysiology of DN will continue to be better understood because of recent developments in genomics and molecular biology, but attempts to develop a comprehensive theory that explains all existing cellular and biochemical pathways have been thwarted by the disease's multifactorial nature. This review extensively discusses the current understanding regarding the metabolic and hemodynamic pathological mechanisms, along with other signaling pathways and molecules responsible for the pathogenesis of DN. This work will encourage a greater in-depth understanding and investigation of the present status of the biochemical mechanistic processes underlying the pathogenesis of DN, which may assist in the determination of different biomarkers and help in the design and development of novel drug candidates in the near future.