Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
PARP inhibitor
Rucaparib
Rubraca · Ruca
A PARP inhibitor whose creatinine bump is mostly a transporter artifact, not true kidney injury.
MildPARP inhibitor · approved 2016
Ovarian cancer (maintenance / treatment)BRCA-mutated metastatic castration-resistant prostate cancer
Signature kidney injury
Prerenal / Hemodynamic AKI
Early reversible serum-creatinine elevation is common and partly drug-specific: rucaparib is a recognized inhibitor of renal cation transporters, and a pooled meta-analysis found markedly higher odds of creatinine rise vs placebo across the class, but grade >=3 renal events were rare (<1%).
Source: Gasowska-Bodnar et al., Cancers 2026
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / EndotheliumGlomerular & peritubular capillaries
Proximal Tubule
Distal Tubule / Collecting Duct
Prerenal / Hemodynamic AKI
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Mechanism of kidney injury
Rucaparib inhibits the proximal-tubular cation transporters MATE1, MATE2-K, and OCT2 that secrete creatinine (and also OCT1 and BCRP), raising serum creatinine without a true reduction in glomerular filtration — a transporter-mediated 'pseudo-AKI' rather than tubular injury. True intrinsic nephrotoxicity is uncommon.
Clinical presentation
Asymptomatic mild creatinine increase early in therapy, typically plateauing and reversible; no proteinuria or active sediment. Cystatin C-based eGFR remains at baseline, confirming the transporter mechanism. Transaminase elevation is a separate, common early laboratory effect.
Onset
Within the first weeks of treatment.
Reversibility
Reversible
Anticancer mechanism
Inhibits and traps PARP1/2/3 on DNA, producing synthetic lethality in homologous-recombination-deficient (BRCA-mutant) tumors. Used in ovarian cancer and BRCA-mutated metastatic castration-resistant prostate cancer.
Management
Usually observation; confirm a stable cystatin C before attributing the rise to true AKI or changing dose. Persistent or progressive elevation, proteinuria, or active sediment warrants standard AKI workup and consideration of alternative causes.
Risk factors
- Pre-existing CKD (lower reserve)
- Concurrent transporter-inhibiting drugs (e.g. cimetidine, trimethoprim)
Prevention
- Recognize transporter-mediated pseudo-AKI before acting on the number
- Baseline creatinine and periodic monitoring
- Use cystatin C-based eGFR when true GFR is uncertain
Note · Creatinine rise is predominantly a transporter artifact; true nephrotoxicity is uncommon. Cystatin C-based GFR can clarify ambiguous cases.
Clinical depth
Renal dose adjustment
No starting-dose adjustment for mild-moderate renal impairment (CrCl >=30 mL/min); not studied in CrCl <30 mL/min or dialysis — use with caution. Modest exposure increases occur with moderate impairment but rarely require dose change.
Dialyzability & ESKD dosing
Highly protein-bound small molecule; not expected to be appreciably dialyzed. No established ESKD dosing.
Differential diagnosis
Transporter-mediated pseudo-AKI (stable cystatin C, bland urinalysis, no oliguria) vs true AKI from prerenal causes, ATN, or AIN. A flat cystatin C with a rising creatinine is essentially diagnostic of the transporter effect.
Monitoring
- Serum creatinine at baseline and each cycle; cystatin C-based eGFR if true GFR is in doubt
- CBC for anemia/thrombocytopenia/neutropenia
- Liver enzymes (early transaminase rise is common)
Key trials & series
- ARIEL3 (recurrent ovarian maintenance)
- TRITON2 / TRITON3 (BRCA-mutated mCRPC)
- Gasowska-Bodnar 2026 class creatinine meta-analysis
Clinical pearls
- Rucaparib raises creatinine by blocking MATE/OCT2 secretion — check cystatin C before calling it AKI or stopping the drug.
- The creatinine rise appears within weeks, then plateaus and reverses on discontinuation.
- An early transaminase bump is also expected and usually self-limited — do not conflate it with progressive organ injury.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte WastingPseudo-AKI
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkPARP Inhibitors and the Risk of Serum Creatinine Elevation in Ovarian Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Gasowska-Bodnar A et al. · Cancers (Basel) 2026 · PMID 42073552Pooled RCT analysis showing PARP-inhibitor creatinine elevation likely reflects inhibition of tubular creatinine secretion, not true GFR loss.PMIDExploring and comparing renal adverse effects between PARP inhibitors based on a real-world analysis of post-marketing surveillance data.Xu Q et al. · Front Med (Lausanne) 2024 · PMID 39493722Real-world comparison of renal adverse-event signals across individual PARP inhibitors including rucaparib.PMIDTargeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.Mach T et al. · Can J Kidney Health Dis 2022 · PMID 35756332Mechanistic review of targeted-therapy creatinine elevation via tubular-secretion inhibition; cystatin C as confirmatory test.PMIDRucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.Coleman RL et al. · Lancet 2017 · PMID 28916367Pivotal ARIEL3 maintenance trial; the registrational safety dataset in which the early reversible creatinine rise is observed.PMIDThe forefront of ovarian cancer therapy: update on PARP inhibitors.Mirza MR et al. · Ann Oncol 2020 · PMID 32569725Class-level efficacy/safety review of the pivotal PARP-inhibitor ovarian trials.PMIDCurrent Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch 2021 · PMID 34840210Onconephrology review of renal complications of molecular targeted therapies including small-molecule inhibitors.
Related agents
Other agents sharing the same signature kidney injury.