Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
PARP inhibitor
Olaparib
Lynparza · OLAP
A PARP inhibitor that raises creatinine by blocking tubular transporters, mimicking - but not causing - true GFR loss.
MildPARP inhibitor · approved 2014
Ovarian cancerBreast cancerPancreatic cancerProstate cancer
Signature kidney injury
Prerenal / Hemodynamic AKI
Olaparib commonly causes a reversible, dose-dependent rise in serum creatinine. In a 66-patient study, median creatinine rose ~14% (and creatinine-based eGFR fell ~13%) on treatment, while cystatin C and cystatin C-based eGFR were unchanged - indicating no true GFR decline. Thrombotic microangiopathy is a rare, case-level event for the PARP-inhibitor class.
Source: Bruin et al., Eur J Clin Pharmacol 2021
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Glomerulus
Vasculature / EndotheliumGlomerular & peritubular capillaries
Proximal Tubule
Prerenal / Hemodynamic AKI
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Mechanism of kidney injury
Olaparib inhibits renal tubular transporters (notably OCT2-mediated uptake and MATE1/MATE2-K-mediated efflux) that secrete creatinine, raising serum creatinine and lowering creatinine-based eGFR while measured/cystatin C-based GFR is preserved - a pseudo-AKI. Rare TMA reflects endothelial injury and is mechanistically distinct from this transporter effect.
Clinical presentation
Isolated, reversible creatinine elevation with stable cystatin C-based eGFR and clear discordance between creatinine- and cystatin C-derived eGFR. Rare TMA presents with microangiopathic hemolysis, thrombocytopenia, and AKI. Anemia is the most common overall toxicity and can prompt renal workup.
Onset
Creatinine rise within weeks of starting therapy; reverses on discontinuation.
Reversibility
Reversible
Anticancer mechanism
Inhibits poly(ADP-ribose) polymerase (PARP1/2), trapping PARP on DNA single-strand breaks and exploiting synthetic lethality in homologous-recombination-deficient (e.g., BRCA1/2-mutated) tumors. Used in ovarian, breast, pancreatic, and prostate cancers.
Management
Most creatinine elevations require no intervention and reverse on discontinuation; confirm preserved true GFR with cystatin C when clinically important (e.g., dosing of co-administered renally cleared drugs). Investigate alternative causes - including rare TMA - if cytopenias or hemolysis accompany the AKI.
Risk factors
- Pre-existing chronic kidney disease (complicates creatinine interpretation)
- Concurrent drugs affecting tubular creatinine secretion (e.g., trimethoprim, cimetidine)
Prevention
- Recognize the benign, transporter-mediated nature of the creatinine rise
- Use cystatin C-based eGFR to assess true renal function when needed
- Avoid unnecessary dose changes for isolated creatinine elevation
Note · The hallmark creatinine rise is a transporter (OCT2/MATE) artifact, not true nephrotoxicity; TMA is rare.
Clinical depth
Renal dose adjustment
No starting-dose change for mild renal impairment (CrCl 51-80). For moderate impairment (CrCl 31-50), reduce the dose (e.g., to 200 mg twice daily) per labeling. Severe impairment/ESKD (CrCl <30) is not recommended due to limited data; if used, monitor closely.
Dialyzability & ESKD dosing
Olaparib is protein-bound and predominantly hepatically metabolized (CYP3A); dialyzability is not well characterized and it is not relied upon for clearance. Avoid in dialysis-dependent ESKD given sparse data.
Differential diagnosis
The defining distinction is pseudo-AKI (creatinine up, cystatin C-based eGFR stable) versus true AKI. If hemolysis and thrombocytopenia accompany the creatinine rise, evaluate for PARP-inhibitor TMA rather than a transporter artifact.
Monitoring
- Serum creatinine periodically (interpret with the OCT2/MATE artifact in mind)
- Cystatin C-based eGFR when true GFR matters
- CBC for anemia/thrombocytopenia (and to flag possible TMA)
Key trials & series
- Bruin et al. olaparib creatinine vs cystatin C study (mechanistic, 2021)
- SOLO-1 (first-line maintenance in BRCA-mutated ovarian cancer; safety dataset)
Clinical pearls
- Olaparib’s creatinine rise is an OCT2/MATE transporter artifact - check cystatin C before assuming true GFR loss.
- Use cystatin C-based eGFR when dosing other renally cleared drugs in olaparib-treated patients.
- A creatinine rise with new hemolysis/thrombocytopenia is not the artifact - work up for TMA.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIThrombotic MicroangiopathyPseudo-AKI
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkA real or apparent decrease in glomerular filtration rate in patients using olaparib?Bruin MAC et al. · Eur J Clin Pharmacol 2021 · PMID 33319340Shows olaparib raises creatinine ~14% via transporter inhibition without affecting cystatin C-based GFR.PMIDSpotlight on olaparib in the treatment of BRCA-mutated ovarian cancer: design, development and place in therapy.Lorusso D et al. · Drug Des Devel Ther 2018 · PMID 29881257Reviews olaparib mechanism (PARP trapping, synthetic lethality), development, and tolerability.PMIDOlaparib First-Line Maintenance Monotherapy in BRCA-Mutated Epithelial Ovarian Cancer: Descriptive Analysis of the First French Real-World Data Study.Bellier C et al. · Drugs Real World Outcomes 2023 · PMID 36630055Real-world SOLO-1-era safety experience; dominant toxicities are hematologic (anemia), with no new renal signal.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2024 · PMID 38095483Onconephrology review covering targeted-agent renal effects and chemotherapy-associated TMA.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology class context for targeted-agent renal effects and pseudo-AKI.PMIDPharmacological nephrotoxicity profile in a comprehensive cancer center: What changed in two decades and predictors for the need for haemodialysis and mortality.Ferreira A et al. · Nefrologia (Engl Ed) 2025 · PMID 40783302Cancer-center AKI series contextualizing modern targeted-agent contributions to drug-induced AKI.
Related agents
Other agents sharing the same signature kidney injury.