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Discrepancy in calculated and measured glomerular filtration rates in patients treated with PARP inhibitors
  1. Graziela Zibetti Dal Molin1,
  2. Shannon Neville Westin2,
  3. Pavlos Msaouel3,
  4. Larissa M Gomes1,
  5. Andrea Dickens4 and
  6. Robert L Coleman2
  1. 1 Medical Oncology, Beneficencia Portuguesa de Sao Paulo, Sao Paulo, Brazil
  2. 2 Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  3. 3 Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  4. 4 Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Robert L Coleman, Department of Gynecologic Oncology and Reproductive Medicine, University of Texas; M.D. Anderson Cancer Center, Houston, TX 77030, USA; rcoleman{at}mdanderson.org

Abstract

Objective To describe discrepancies in calculated and measured glomerular filtration rate in patients using PARP (poly ADP ribose polymerase) inhibitors who had an elevation in serum creatinine levels.

Methods Retrospective cohort, single center study. Patients included were those with ovarian or endometrial cancer taking olaparib, rucaparib or niraparib, and in in whom an increased serum creatinine was identified. The study cohort included those who also underwent technetium-99m radioisotope renography (glomerular filtration rate (GFR) scan). The main objective is to describe the discrepancies in calculated glomerular filtration rate using the Cockcroft-Gault method and measured glomerular filtration rate using a GFR scan.

Results 211 patients were included in the study; 64 (30%) had on-treatment elevated serum creatinine, and 23 (36%) underwent a GFR scan. 32 GFR scans were performed (six patients had more than one scan). Using a clinical cut-off ≥50 mL/min as normal renal function, both calculated and estimated glomerular filtration rates were below normal in 6 of 32 GFR scans. In those patients undergoing a GFR scan, serum creatinine had risen a median 49% (IQR 20–66%, range 0–144%) above baseline. Discordance between a calculated low glomerular filtration rate and an estimated normal glomerular filtration rate occurred in 63% (range of glomerular filtration rate discrepancy: −46% to +237%). Despite increases in serum creatinine on therapy and a subsequent significant decline in the per patient calculated creatinine clearance (mean 65.6 mL/min vs 43.4 mL/min; p<0.0001), the estimated glomerular filtration rate from the renal scan was nearly identical to the patient’s baseline (65.6 mL/min vs 66.1 mL/min; p=0.89).

Conclusions Serum creatinine elevation in patients taking PARP inhibitors may not be associated with a true decrease in glomerular filtration rate. A high index of suspicion should be maintained for alternative causes of elevated serum creatinine in patients treated with PARP inhibitors who lack other sources of renal injury.

  • ovarian cancer
  • medical oncology
  • ovarian neoplasms
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Footnotes

  • Twitter @Shannon.Westin, @rcoledude

  • Contributors All authors contributed to writing and approving the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RLC is supported in part by the Ann Rife Cox Chair in Gynecology and the Judy Reis/Albert Pisani, MD Ovarian Cancer Research Fund and from research grants CPRIT RP120214 and the V Foundation. RLC reports grants from AstraZeneca, Roche/Genentech, Janssen, OncoMed, Merck, Clovis Oncology, Esperance, and AbbVie and reports serving as an advisor to AstraZeneca, Roche/Genentech, Janssen, OncoMed, Millennium, Merck, Clovis Oncology, Esperance, Tesaro, GamaMabs, Pfizer, Genmab, and AbbVie. SNW reports research support from AstraZeneca, ArQule,Bayer, Clovis, Cotinga Pharmaceuticals, Novartis, Roche/Genentech, and Tesaro and reports consulting advisor for AstraZeneca, Clovis, Merck, MediVation, Ovation, Pfizer,Roche/Genentech, Takeda, Tesaro.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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