Delayed graft function (DGF) is a post kidney transplant complication in which kidney function and urine production is delayed for days, weeks or months. During this period, the patient must be maintained on dialysis. DGF is a consequence of ischemia reperfusion (I/R) injury as the kidney is exposed to ischemia when harvested and reperfusion once transplanted. The re-introduction of oxygenated blood underlies I/R damage. DGF occurs in up to 30% of kidney transplant recipients, which suggests that therapeutic approaches are needed to improve patient outcomes.

This study investigates the role of protein kinase C epsilon (PKCε) inhibition in maintaining kidney function in a murine model of bilateral kidney I/R. Measurements of glomerular filtration rate (GFR) and serum creatinine (Cr) were used to assess kidney function. Ischemia was induced in male C57BL/6J mice by clamping kidney pedicles bilaterally for 19 minutes followed by 96 hours of reperfusion. A cell permeable peptide that inhibits PKCε (N-myristic acid-EAVSLKPT; YT-001) interaction with downstream receptors,given at the time of reperfusion, significantly maintained GFR, blunted serum Cr elevation to a greater extent, and prevented PKCε translocation to renal epithelial cell membranes compared to the scrambled control peptide (N-Myr-LSETKPAV).

These findings suggest that YT-001 given upon the re-institution of blood flow after kidney transplant would potentially decrease the incidence of DGF and the subsequent downstream morbidity and mortality. Based upon these findings, YT-001 was granted Orphan Drug Status by the FDA in 2023.