Renal ischaemia

Proximal tubule cells are exquisitely sensitive to vasculat disturbances and acute tubular necrosis (ATN) can occur naturally in areas of poor perfusion resulting from falling blood pressure, or vasospasm of renal vessels or arterioles. In other words hypoxia associated with partial ischaemia can cause severe damage. It is not then surprising that anoxia associated with iatrogenic, surgically induced total ischaemia produces irreversible damage within a short time unless steps are taken to prevent it. 

Iatrogenic warm ischaemia (WI) may be induced vvhen (1) the renal vessels are clamped in situ for exploratory or reconstructive surgery of the kidney (2) when the organ is removed from the donor, reconstructed invito and then replanted orthotopically and (3) when a kidney is harvested from a donor for transplantation. 

Reduction in temperature to above 0°C is the common denominator to all techniques for inhibiting warm ischaemic damage. However, hypothermia alone can only delay the onset of irreversible damage and not prevent it. Furthermore, cold can itself be damaging. Kidneys for transplantation are in clinical practice cooled to 0°-10°C either after they have been removed from 

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In rats, hepatic ischaemia is associated with reduced ATP levels but normal lipid peroxide formation. Reperfusion gives a slow recovery of ATP levels, a reduction in endogenous vitamin E and glutathione, but an increase in lipid peroxidation. Vitamin-E-treated animals showed accelerated ATP synthesis with a suppression of the increased lipid peroxidation [ 170, l7l]. Ischaemia of liver tissue reduced the metabolism of xenobiotics. Vitamin E was protectant against this effect [172]. The protective effect is related to an increase in catalytic activity of cytochrome P-450, to antioxidant and membrane-stabilizing properties [173]. In kidney tissue, prophylactic injection of vitamin E and synthetic antioxidants prevented the development of lesions during acute renal ischaemia and subsequent reperfusion. These effects were related therefore to the vitamin s antioxidant ability. 

Ishikawa I, Nakagawa M, Hayama S, Yoshida S, Date T (2005) Acute renal failure with severe loin pain and patchy renal ischaemia after anaerobic exercise (ALPE) (exercise-induced acute renal failure) in a father and child with URAT1 mutations beyond the W258X mutation. Nephrol Dial Transplant 20 1015... 

Another publication from Takeda described a series of asterric acid analogues as endothelin antagonists. These compounds, TAN-1415 derivatives, have been patented for the indications of myocardial infarction or renal ischaemia [154]. The only reported activity of the asterric acid itself and close analogues (34) is that they showed inhibition against pressor effects, induced by ET-1 in the rat, at 50 mg/kg i.v. 

Jain S, Bicknell GR, Nicholson ML. Tacrolimus has less fibrogenic potential than cyclosporin A in a model of renal ischaemia-reperfusion injury. Br J Surg 2000 87 1563-1568. 

Violet tree ((Wild Wisteria) (has produced poisoning in the Congo. The roots of this plant when taken orally or intravaginally, in search for a cure for dysmen-orrhoea, can produce renal ischaemia and death [9] A strychnine-(like substance has been found in the root additionally a high concentration of methyl salicylate (is found in the oils from the root [9, 58]. 

Pre-treatment with dexamethasone significantly attenuated neutrophil infiltration and expression of intercellular adhesion molecule-1 induced by renal ischaemia/reperfusion (Takahira etal. 2001). Treatment with nitroxyl anion releaser known as Angeli s salt abolished the beneficial effect of dexamethasone. Renal dysfunction and tubular damage induced by renal ischaemia/reperfusion were not ameliorated by pre-treatment with dexamethasone. 

Yoshioka etal. (1990) demonstrated enhancement of intrinsic antioxidant enzyme activity after renal ischaemia-reperfusion injury in the rat and protection of renal function against injuries induced by reactive oxygen species. 

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