In many clinical settings the duration of renal ischemia and therefore the outcome of acute renal failure cannot be determined adequately. Renal ischemia reperfusion injury (IRI) is known to shorten telomeres and upregulate stress-induced genes such as the cyclin-dependent kinase (CDK) inhibitor p21. So far, the expression and role of CDK inhibitors as well as mouse telomerase reverse transcriptase (mTERT) has not been investigated in a model with variable lasting ischemic periods. Male C57Bl/6 mice were subjected to renal IRI by clamping both renal pedicles for 10, 20, 30 and 45 minutes and the kidneys were reperfused for 3, 24 and 48 hours. Expression of different CDK inhibitors and mTERT was evaluated. Mice developed signs of acute renal failure linear to the duration of the ischemic period. Real-time PCR revealed that mTERT was only significantly upregulated in kidneys after short ischemic periods (20 minutes). p21 was constantly upregulated in kidneys after long ischemic intervals (30 and 45 minutes), but not in kidneys, which were clamped for shorter periods. Mainly, tubular cells contributed to the observed increase in p21 expression. Targeting p21 via the selective p53 inhibitor pifithrin- was able to prevent acute renal failure when administered immediately before ischemia. The expression of another CDK inhibitor, namely p16, was differentially regulated depending on the time of reperfusion. We detected mTERT and p21 as "indicator" genes for short and long ischemic intervals, respectively. These two proteins might also be possible new therapeutic targets in the treatment and prevention of acute renal failure.