Role of the Immune System in Diabetic Kidney Disease

Abstract

Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies. In addition, increased levels of circulating pro-inflammatory cytokines have been linked to disease progression. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease. Although no current therapies for DKD are directly based on immune modulation many of the therapies in clinical use have anti-inflammatory effects along with their primary actions. Macrophages emerge as the most likely beneficial immune cell target and compounds which reduce macrophage infiltration to the kidney have shown potential in both animal models and clinical trials.

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

“…The molecular mechanisms involved have also been elucidated, including oxidative stress [13,14], activation of nuclear factor kappa-B (NF-κB) [14], and production of related cytokines such as tumor necrosis factor (TNF) [13][14][15] and Toll-like receptor (TLR) activation [16]. Accordingly, targeting of macrophages has been extensively studied as an anti-inflammatory strategy [17]. In a recent review, we provided thorough information on the experimental and clinical studies reporting the beneficial effects of agents targeting inflammation pathways, such as monocyte protein-1 (MCP-1/CCL2), its receptor CCR2 (chemokine ligand 2/C-C-motif chemokine receptor type 2), IL-1β, and JAK/STAT (Janus kinase/signal transducer and activator of transcription), as well as Nrf2 (nuclear factor erythroid 2 related factor 2) inducers, e.g., bardoxolone methyl [18].…”

“…Although these studies have addressed circulating or urinary IL-17A levels in DN patients, local renal levels of IL-17A have not been investigated yet. Importantly, infiltration of immune cells is a key feature of DN [17]. Activated T cells (CD4+ and CD8+) are mainly located in the renal interstitium of diabetic kidneys [44][45][46].…”

Perspectives of Plasmapheresis in the Treatment of Kidney Diseases

“…Among them we can mention peralin (pyraline) arising from the interaction of glucose with amino groups of proteins. In addition, the level of circulating proinflammatory cytokines contributing to the progression of kidney damage is increasing [47]. The accumulation of uric acid and glycated hemoglobin, as well as oxidative stress with increased activity of the renin-angiotensin-aldosterone system is important [48,49].…”

Epac ameliorates tubulointerstitial inflammation in diabetic nephropathy via C/EBPβ/SOCS3/STAT3 pathway

“…DN has not been traditionally considered an inflammatory disease until recently. Emerging data have demonstrated that tubulointerstitial inflammation is strongly correlated with the development and progression of DN (2,3). Macrophage infiltration in the kidney tissues has been postulated to be a prominent pathological feature and key inflammatory mediator during the progression of DN.…”