Blockade of TNFα after ischemia reperfusion injury ameliorates renal prognosis

Recently, acute kidney injury (AKI) is thought to develop a predisposition toward chronic kidney disease. But the detailed mechanism of the disease progression after AKI is unknown. We made two ischemia-reperfusion injury (IRI) mice models, repaired kidney model and atrophic kidney model, and studied the mechanism that kidney after IRI became atrophy. We found that the atrophy kidney model had two peaks of apoptosis 3 and 14 days after IRI, whereas the repaired kidney model had only one apoptosis peak 3 days after IRI. We showed that the second apoptosis is responsible for the kidney atrophy. Moreover, apoptotic ligands, TNFα and FasL were upregulated at the same time of two apoptosis peaks on the atrophic kidney, and blockade of them before IRI prevented kidney from falling into atrophy. Surprisingly, inhibition of the second apoptosis by anti-TNFα antibody protected from renal atrophy. We propose that apoptosis might play a major role in AKI progression and blockade of TNFα after IRI will be a new therapeutic approach for AKI. Mice were subjected for 0, 45, and 60 min of unilateral IRI. Mice kidneys were collected at day 1 and 3 after IRI for RNA extraction and hybridization on Affymetrix microarrays. There are 6 samples, 1day IRI45(1), 1day IRI60(2), 1day IRI0(3), 3day IRI45(4), 3day IRI60(5), 3day IRI0(6).