PARP inhibitors and the Kidney

Poly (ADP-ribose) polymerases (PARPs) are crucial in repairing DNA after a damaging event. However, several studies indicate that more extensive DNA disruption causes overactivity of PARP and can ultimately lead to cellular necrosis particularly in the setting of ischemia- related or sepsis-related acute kidney injury (AKI). Though the anti-cancer effects of PARP inhibitors (PARPis) are well known, especially in cases of Breast Cancer gene mutations, there exists a potential for the use of these drugs in treating ischemic AKI. Though the beneficial effects of PARPis in attenuating ischemic AKI has been shown in animal models, testing has yet to be done in humans. Studies have also found that PARPis interact with proximal tubular transporter channels and cause a physiologic increase serum creatinine, however the long- term effects on kidney function, proteinuria and hematuria are unclear. The use of PARPis in patients with chronic kidney disease (CKD) and malignancy may result in the amplification of adverse effects such as anemia and thrombocytopenia. Safe dosing of these agents in patients with advanced CKD and end stage kidney disease (ESKD) is yet to be determined as these populations were excluded from clinical trials. This manuscript reviews the current data on the kidney effects of PARPis and opens the door to further research in this arena.