Little is known as to what causes ischemic injury in the<unk> s; however, several physical insults are stated to be activated during injury. Physical stress such as infarction, surgery and transplant may produce<unk> . Dietary habits and genetics could cause ischemic injury, as well. Diseases such as sepsis can cause<unk>  too. Infarction or Physical Injury Infarction is defined as the blockage of blood flow in tissues or organs, which may cause necrosis or death of a group of cells in the tissue. In studies of mice models, clamping of the<unk>  may result in<unk> . Renal Surgery and Transplant Renal surgery and coronary artery bypass grafting can produce renal ischemia and reperfusion injury. This could lead to an acute<unk>  injury. Moreover, renal ischemia can cause the delay of graft function after renal transplant and can cause rejection of the transplant. Dietary Habits In studies of mice models, a high-fat diet can induce greater injury to the<unk>  with renal ischemia-reperfusion as compared to mice with normal diet. This is because in a high-fat diet model, accumulation of phospholipids resulted in enlarged lysosomes within proximal tubular cells. This accumulation of phospholipids lead to an increase aggregation of ubiquitin in the<unk>  cells. When this happens, autophagy becomes exaggerated and results in malfunction of the mitochondria and inflammation of the tissue. Atherosclerosis A common cause of ischemic renal disease is atherosclerosis. Atherosclerosis is a specific type of arteriosclerosis. Arteriosclerosis is defined as the thickening or stiffening or both of the blood vessels; more specifically, atherosclerosis refers to the buildup of cholesterol and fats in the artery walls. Because the blood vessels carry oxygen and nutrients throughout the body, having atherosclerosis restrict blood flow and consequently prevent necessary nutrients to reach the<unk> s. This accounts for 60-97% of renal arterial lesions, which could lead to the occlusion of the renal artery and ischemic atrophy of the<unk> s. Genetics Several genetic pathways that lead to apoptosis of<unk>  cells have been implicated in mice models and in-vitro assays. These are proapoptotic genes that can be categorized in two: extrinsic and intrinsic pathways. The extrinsic pathway are directly induced upon renal ischemic injury, while intrinsic pathways are dependent on mitochondrial signaling pathways. Moreover, several genes have been implicated as risk factors in the development of ischemic injury. Extrinsic Pathway Activation of pro-caspase 8 initiates apoptosis via signaling from cell-surface death receptors such as Fas proteins and their ligands FADD and DAXX. This series of signaling cascade generally regulates programmed cell-death or apoptosis. Upregulation of Fas and FADD protein has occurred in mice models after a 24h period of ischemic injury. This is also shown in cell-based assays wherein tubule cells are monitored after ischemic-like injury. This shows that the Fas-pathway may play a role in the pathogenesis of the apoptosis of tubule cells during the early ischemic-reperfusion period. The role of DAXX is still unclear; however, DAXX mediates both Fas-dependent and TGF-beta-induced apoptosis and renal induction of TGF-beta is well documented in renal ischemia studies. Intrinsic Pathway Activation of pro-caspase 9 is dependent on mitochondrial signaling pathways which are regulated by the Bcl-2 family of proteins. Activation of Bcl-2 proteins such as Bax and Bak triggers a signaling cascade that results in the release of cytochrome c into the cytosol. This then activates pro-caspase 9 and results in apoptosis of the cells. Genetic Risk Factors Polymorphisms in genes have been shown to increase or decrease risk of renal ischemic injury. Genes such as Apolipoprotein E (APO E), which controls cholesterol metabolism, NADPH Oxidase which regulates oxidative stress, Angiotensin-converting enzyme (ACE) for vasomotor regulation, HSP72 which helps in tolerance of ischemic injury, Interleukin cytokines which is an inflammation modulator, and VEGF which regulates angiogenesis or the formation of blood vessels have all been shown to have significant effects in acute<unk>  injury. Apolipoprotein E Apolipoprotein E are proteins that metabolize fats in the body. In studies of patients undergoing coronary artery bypass grafting, carriers of APO-E e4 allele was found to have a decreased risk of acute<unk>  injury compared to non-carriers of the allele. NADPH Oxidase NADPH Oxidase regulates oxidative stress by conjugating with reactive oxygen species in cells. Polymorphisms in NADPH Oxidase p22phox and with the T allele has been shown to have a greater risk of dialysis and mortality. Angiotensin-converting Enzyme Angiotensin-converting enzyme regulates vasomotor movement by controlling blood pressure going through the<unk> s. Similarly to the APO-E polymorphism, patients with the D-allele for ACE has an increased risk of acute<unk>  injury after coronary artery bypass grafting, as well. HSP72 In infant studies, it was shown that HSP72 gene with the G allele gave an increased risk for acute<unk>  injury. Interleukin Researchers have found that IL-17C is activated in<unk>  injury. In hypoxia-induced studies of mice, an upregulation of the synthesis of IL-17C was evident upon oxygen loss in the<unk> . Moreover, Knockout variants of the IL-17C decreased the inflammation caused by activation of IL-17C.Using antibodies and siRNA against IL-17C also provided the same results. Also, studies of IL-60174GG showed that carriers of this polymorphism have a higher creatinine levels in the blood; however, carriers of the G-allele of IL-10 have a decreased risk of death after organ failure. VEGF Unlike with HSP72 polymorphism, infant studies show that VEGF with a homozygous A allele resulted in reduced risk for acute<unk>  injury. Examples of Signs and Symptoms of<unk> . On the left shows the difference in the size of the<unk> s resulting from<unk> .<unk>  may result in a shrinkage of the<unk>  to about 2cm or more. The top right shows the disruption of the mitochondria due to dysfunctions, This leads to a release of proapoptotic proteins such as cytochrome c and results in cell death. The lower right shows inflammation of the glomeruli of the<unk> s. This schematic diagram was drawn using BioRender.com
Kidney ischemia
Renal ischemia
Renal colic
Pyonephrosis
Renal papillary necrosis
Obstructive uropathy
Renal cortical necrosis
Acute kidney injury