Emerging therapeutic strategies for transplantation-induced acute kidney injury: protecting the organelles and the vascular bed

Vascular and inflammatory mineralocorticoid receptors in kidney disease

“…This effect was associated with the prevention of kidney fibrosis and the AKI-to-CKD transition. 36,49,58 In addition, the protective effect against the chronic sequelae of ischaemic AKI was also observed in the Large White Pig; 3 months after the AKI episode, MRA-treated pigs displayed no signs of kidney fibrosis and normal levels of plasma creatinine and urinary protein excretion vs the untreated pigs, in which fibrosis and proteinuria were evident. 35 In addition, eplerenone has been shown to reduce MCP-1 expression and glomerular macrophage infiltration in glomerulonephritis induced by anti-Thy1.1 antibodies.…”

“…36,49,58 In addition, the protective effect against the chronic sequelae of ischaemic AKI was also observed in the Large White Pig; 3 months after the AKI episode, MRA-treated pigs displayed no signs of kidney fibrosis and normal levels of plasma creatinine and urinary protein excretion vs the untreated pigs, in which fibrosis and proteinuria were evident. 36,49,58 A benefit of MR inhibition has also been described in rodent models of diabetic kidney disease. Spironolactone prevented kidney fibrosis, glomerular injury and reduced oxidative stress in animals in which type 1 diabetes was induced by streptozotocin injection.…”

“…36 The role of myeloid MRs in CKD progression was also evaluated in a mouse model of glomerulonephritis in which MR deficiency in myeloid cells reduced cystatin C levels, crescent numbers, fibrosis, tubular damage and the inflammatory infiltrate in the kidney. 36,49,58 A benefit of MR inhibition has also been described in rodent models of diabetic kidney disease. 57 The benefit of MR antagonism in rodent models of AKI has been translated to the pre-clinical Large White Pig model in which Soludactone ® (potassium canrenoate, a soluble mineralocorticoid receptor antagonist [MRA]) administration prevented the acute dysfunction and injury caused by ischaemic AKI, as shown by reduced levels of plasma creatinine and urinary tubular injury biomarkers, including proteinuria, NGAL, KIM-1, L-FABP and NAG.…”

Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis

“…As we know, oxidative stress is a well-known hallmark of IRI-induced AKI, which is believed to be one of the critical factors causing kidney injury during ischemia-reperfusion [ 21 ]. DNA damage, a deleterious event that occurs in the genome, may be induced under many conditions such as oxidative stress or free radical insult, irradiation, and UV exposure [ 22 ].…”

Targeting oxidative stress, a crucial challenge in renal transplantation outcome

“…An emerging field demonstrates the role of oxidative stress in I/R (7) and more particularly the overproduction of ROS and RNS that indistinctly react with local proteins, lipids or nucleotides. More and more studies are focused on their roles in current clinical and pharmacological treatments, and new approaches and molecules emerged as potentially efficient to limit or blunt I/R deleterious consequences (8). In this review, we will described ROS and RNS origin (Figure 1) and effect along I/R by focusing on kidney transplantation, finally we will present several new interesting approaches developed in preclinical models to limit ROS and RNS impact at various step of kidney transplantation protocols.…”