Pathophysiology of ischemic acute tubular necrosis

Abstract

Ischemia is an important cause of acute tubular necrosis. In spite of fluctuations in hydration and blood pressure, kidney tries to auto regulate glomerular perfusion with the help of myogenic reflex, tubuloglomerular feedback, and renin- angiotensin system. Other protective features are medullary pericytes, higher capacity for glycolysis in medulla, and capacity of kidney to be preconditioned. Poor fluid intake or increased fluid loss, bleeding, low cardiac output state, and sepsis-induced vasodilatation cause renal hypoperfusion. Diseased renal vessels, old age, diabetes, nonsteroidal anti-inflammatory drug (NSAID) predispose to ischemia. When ischemia is severe, compensatory renal mechanisms are overwhelmed and renal failure ensues. In pre-renal failure, function quickly normalizes if perfusion is restored. But with worse insult, renal tubular cells actually get injured and necrosed. In its most extreme form, ischemia leads to bilateral renal patchy or complete cortical necrosis. Pathophysiology of ischemic acute renal failure is not as simple as ischemia. Today it is considered an inflammatory disease. Innate and acquired immunity, tubular and endothelial factors, leukocytes, mitochondrial biogenesis, apoptosis, all are involved. Organ cross-talk of acute kidney injury (AKI) explains multiorgan involvement and increased mortality. After a maintenance phase, restoration of tubular epithelium takes place after dedifferentiation and proliferation of surviving tubular cells. Resolving and protectins may initiate resolution. When new tubular cell regains polarization and function, renal function gradually returns to normal. Sometimes recovery may be incomplete. The detailed understanding of pathophysiology and underlying mediators is helping in identifying various biomarkers for early diagnosis of AKI and also in exploring novel therapeutic options.