Inflammation in Renal Diseases: New and Old Players

Abstract

Inflammation, a process intimately linked to renal disease, can be defined as a complex network of interactions between renal parenchymal cells and resident immune cells, such as macrophages and dendritic cells, coupled with recruitment of circulating monocytes, lymphocytes, and neutrophils. Once stimulated, these cells activate specialized structures such as Toll-like receptor and Nod-like receptor (NLR). By detecting danger-associated molecules, these receptors can set in motion major innate immunity pathways such as nuclear factor ĸB (NF-ĸB) and NLRP3 inflammasome, causing metabolic reprogramming and phenotype changes of immune and parenchymal cells and triggering the secretion of a number of inflammatory mediators that can cause irreversible tissue damage and functional loss. Growing evidence suggests that this response can be deeply impacted by the crosstalk between the kidneys and other organs, such as the gut. Changes in the composition and/or metabolite production of the gut microbiota can influence inflammation, oxidative stress, and fibrosis, thus offering opportunities to positively manipulate the composition and/or functionality of gut microbiota and, consequentially, ameliorate deleterious consequences of renal diseases. In this review, we summarize the most recent evidence that renal inflammation can be ameliorated by interfering with the gut microbiota through the administration of probiotics, prebiotics, and postbiotics. In addition to these innovative approaches, we address the recent discovery of new targets for drugs long in use in clinical practice. Angiotensin II receptor antagonists, NF-ĸB inhibitors, thiazide diuretics, and antimetabolic drugs can reduce renal macrophage infiltration and slow down the progression of renal disease by mechanisms independent of those usually attributed to these compounds. Allopurinol, an inhibitor of uric acid production, has been shown to decrease renal inflammation by limiting activation of the NLRP3 inflammasome. So far, these protective effects have been shown in experimental studies only. Clinical studies will establish whether these novel strategies can be incorporated into the arsenal of treatments intended to prevent the progression of human disease.

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

“…However, persistent inflammation promotes the synthesis of fibrogenic factors, thus leading to renal fibrosis (Xiao et al, 2014). Inflammatory cytokines, such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and IL-6, can directly mediate renal fibrosis through inflammatory infiltration, fibroblast activation and synthesis and degradation of ECM (Andrade et al, 2019;Gorjipour et al, 2019;Shrikant, 2019). Our results showed that NE-THCQ inhibited inflammatory infiltration in H&E staining analysis and reduced the levels of serum IL-1b and IL-6 in vivo.…”

High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study

“…The common causes for AKI include renal ischemia/reperfusion injury, systemic inflammatory processes/sepsis, hemodynamic impairment, and nephrotoxicity [7]. Among them, inflammation plays a critical role, and several experimental studies have demonstrated an important contribution of intra-renal and systemic inflammation in promoting parenchymal injury, repair, and fibrosis of the kidney [8][9][10]. Growing attention has been focused on C-reactive protein (CRP), a simply detectable inflammation biomarker, as a possible predictor of AKI and it has been recently recognized that CRP actively contributes in the pathogenesis and progression of AKI, by exacerbating local inflammation, impairing the proliferation of damaged tubular epithelial cells, and promoting the fibrosis of injured renal tissue [11][12][13][14][15].…”

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers

“…Observations made in culture cells in vitro, experimental animals in vivo, and kidney tissue from CSFs suggest that CaOx crystals can adhere to tubular epithelial cells, become transcytosed to the renal interstitium, and undergo dissolution within cells [8,11,12,[25][26][27]. The kidney harbors a variety of resident immune cells including macrophages and lymphocytes [28]. CaOx crystal deposition can activate renal immune cells to increase release of chemokines and pro-in ammatory cytokines, which in turn can recruit additional in ammatory cells including monocytes and neutrophils to the site [11,12,28,29].…”

“…The kidney harbors a variety of resident immune cells including macrophages and lymphocytes [28]. CaOx crystal deposition can activate renal immune cells to increase release of chemokines and pro-in ammatory cytokines, which in turn can recruit additional in ammatory cells including monocytes and neutrophils to the site [11,12,28,29]. EVs secreted by these immune cells can serve as a biomarker of their presence and activation, and may also serve signaling functions in vivo, including antigen presentation, immune suppression, and tissue remodeling [30].…”