Renal insufficiency in patients on PARP inhibitors: Case-based review of possible mechanisms and management

Abstract

Background: PARP inhibitors are a new class of drugs that are being widely used in treatment of various cancers including advanced ovarian cancer. Based on new promising data and impending approvals, it is expected that there will be an increased use of this class of drugs in gynecologic malignancies and many other solid tumors. Therefore, it is extremely important to familiarize oneself with the toxicity profile associated with this class of drugs. One such adverse event is a rather frequently reported elevation of serum creatinine, which could be a false elevation rather a true renal toxicity as we try to demonstrate in this case presentation. Case presentation: Herein we report the case of a patient who experienced elevated creatinine while on maintenance PARPi. After comprehensive work up which ruled out other common etiologies, temporal relation to initiation of PARPi therapy, and the fact that creatinine returned to baseline when PARPi was interrupted; it was deemed that creatinine elevation using conventional methods was directly related to that drug. As we further demonstrate in our case presentation, this creatinine elevation may not represent a true reduction in glomerular filtration rate (GFR) due to PARPi on-target interference with creatinine transporter enzymes, and alternate measures GFR may be more appropriate for these patients. Conclusion: Serum creatinine may provide a false reduction of GFR in patients receiving PARPi and providers should be aware of this phenomenon since lack of recognition of this finding may unnecessarily result in dose interruptions or discontinuation of an effective life-prolonging treatment for many patients.