Kidney function in patients with ovarian cancer treated with poly (ADP-ribose) polymerase (PARP) inhibitors

Abstract

Background Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking. Methods We identified adults treated with olaparib or niraparib between 2015-2021 at a major cancer center in Boston, Massachusetts. We determined the incidence of any acute kidney injury (AKI), defined as a ≥ 1.5-fold rise in serum creatinine from baseline in the first 12 months following PARPi initiation. We calculated the percentage of patients with any AKI and sustained AKI, and adjudicated the etiologies by manual chart review. We compared trajectories in estimated glomerular filtration rate (eGFR) among PARPi-treated and carboplatin/paclitaxel-treated patients with ovarian cancer, matched by baseline eGFR. Results Of 269 patients, 60 (22.3%) developed AKI, including 43/194 (22.1%) olaparib-treated patients and 17/75 (22.7%) niraparib-treated patients. Only 9 of 269 (3.3%) had AKI attributable to the PARPi. Of the 60 patients with AKI, 21 (35%) had sustained AKI, of whom 6 had AKI attributable to the PARPi (2.2% of the whole cohort). eGFR declined within 30 days post-PARPi initiation by 9.61 ± 11.017 mL/min/1.73 m2 but recovered by 8.39 ± 14.05 mL/min/1.73 m2 within 90 days after therapy cessation. There was no difference in eGFR at 12 months post-therapy initiation in patients receiving PARPi, or controls receiving carboplatin/paclitaxel (p = .29). Conclusions AKI is common following PARPi initiation, as is a transient decline in eGFR; however, sustained AKI directly attributable to the PARPi and long-term eGFR decline are uncommon.

Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer

“…Gupt et al. compared the renal function of olaparib and niraparib, and reported that although both showed decreased renal function, there was no difference between the two drugs ( 8 ). We investigated the correlation in kidney function between maintenance treatment and chemotherapy given before maintenance treatment.…”

“…Renal function deterioration due to the use of PARP inhibitors has become a topic of discussion ( 8 ). In this study, we investigated hematological toxicity and renal function following chemotherapy and maintenance therapy among the three groups including bevacizumab.…”

Assessment of GFR in Patients with Cancer Part 2

“…PARPis may cause pseudo-AKI, but this largely resolves with drug discontinuation. 9 Measured GFR or eGFR via cystatin C does not show significant change from baseline eGFR before treatment. Despite these observations, the data on the long-term safety of PARPis are limited.…”

“…Targeted molecular anticancer agents, pseudo-AKI, and true kidney adverse effects[6][7][8][9][10] AIN, acute interstitial nephritis; ATI, acute tubular injury; ALK, anaplastic lymphoma kinase; BCR-ABL, breakpoint cluster region-abelson; BRAF, v-raf murine sarcoma viral oncogene homolog B1; CDK, cyclin-dependent kinase; MATE, multidrug and toxin extruder; MET, mesenchymal-epithelial transition; ND, not determined; OCT, organic cation transporter; PARP, poly(ADP-ribose) polymerase.GFR in Cancer Part 2, Kitchlu et al CJASN 19: 1073-1077, August, 2024 1075…”

Renal dysfunction in individuals with ovarian cancer; a review on current concepts

“…Other chemopreventive agents that may affect renal function in ovarian cancer include targeted therapies such as bevacizumab and PARP [Poly (ADPribose) polymerase] inhibitors. Bevacizumab can cause proteinuria and hypertension, which can lead to renal impairment, while PARP inhibitors may increase the risk of acute kidney injury (AKI) (23,24).…”