Role of Inflammation in Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD). Although the pathogenesis of DN is multifactorial, local inflammatory stress may result from both the metabolic and hemodynamic derangements observed in DN. Inflammatory markers such as Interleukin-18 and Tumor Necrosis Factor (TNF)-alpha are increased in the serum of patients with diabetes and DN. This occurs at a very early stage of disease, and correlates with the degree of albuminuria. Recent data suggest that standard pharmacologic interventions for DN, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, may have anti-inflammatory properties that are independent of their hemodynamic effect. Although inflammation is traditionally thought of as a process resulting in macrophage infiltration, current scientific progress has lead to the novel idea that even cells distant from the blood stream, such as podocytes, can produce cytokines and can express molecules that are part of the co-stimulatory pathway. A strong translational research effort is currently aimed at defining the role of such molecules in cells other than lymphocytes and macrophages. Experimental animal models have recently provided evidence that some acute phase markers of inflammation such as intracellular cell adhesion molecule-1 (ICAM-1), TNF-alpha and Monocytes Chemoattractant Protein-1 (MCP-1) may have a causative role in the development of DN. Here, we review the current evidence supporting the role of inflammation in the early phases of clinical and experimental DN. A complete understanding of inflammatory pathways activated in DN may lead to the discovery of earlier and more reliable markers of DN than albuminuria and the identification of novel therapeutic targets.

An Aqueous-Ethanol Extract ofLiriope spicatavar.proliferaAmeliorates Diabetic Nephropathy through Suppression of Renal Inflammation

“…ICAM-1 is also present on the membranes of macrophages and lymphocytes [21]. ICAM-1 expression is increased in models of type 1 and 2 diabetes [22, 23] and can be induced by hyperglycemia, advanced glycosylation end products, oxidative stress, hyperlipidemia, hyperinsulinemia, and proinflammatory cytokines [24]. Like ICAM-1, MCP-1 is also increased significantly in DN, and expression levels correlate with the number of infiltrating interstitial macrophages.…”

Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

“…It is a novel biomarker that has been studied in detail in preclinical ischemia-reperfusion models and has been proved to play an important role in renal injury induced by acute ischemia-reperfusion in mice [6]. Numerous reports indicate that CKD patients have elevated serum or urine levels of IL-18 and its correlation with decreased renal function [7–9]. The aim of this research was to investigate the relationship of serum IL-18 levels with histopathological severity and renal prognosis in IgA nephropathy.…”

Oryeongsan suppressed high glucose-induced mesangial fibrosis

“…In diabetic patients with nephropathy, the levels of ICAM-1 and MCP-1 recruiting inflammatory immune cells of macrophages and granulocytes were elevated [14]. It was shown that MCP-1 appeared to be responsible for diabetic ECM accumulation and early inflammation in diabetic nephropathy pathogenesis [36].…”

“…There is accumulating evidence demonstrating that the diabetic nephropathy is closely related to mesangial inflammation [14]. The activation of NF-κB may play a pivotal role in the progression of renal injury by inflammatory factors in diabetes [37].…”

“…Growing evidences demonstrated that activation of nuclear factor-kappa B (NF-κB) and subsequently coordinated expression of gene products may play an important role in the pathogenesis of diabetic nephropathy [14]. Mononuclear macrophage infiltration and abnormal expression of inflammatory mediators including intercellular adhesion molecule-1 (ICAM-1), MCP-1, TGF-β1, can be observed in nephridial tissue in the early stages of diabetic nephropathy [15].…”