Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
PARP inhibitor
Talazoparib
Talzenna · Tala
A potent, renally cleared PARP-trapper — renal impairment raises exposure and dosing must adjust.
MildPARP inhibitor · approved 2018
gBRCA-mutated HER2-negative breast cancerMetastatic castration-resistant prostate cancer (with enzalutamide)
Signature kidney injury
Prerenal / Hemodynamic AKI
Renal clearance is a major elimination route (~two-thirds of dose), so exposure rises with declining renal function: dedicated PK studies show higher AUC and more myelosuppression in moderate-severe impairment, mandating dose reduction. Class-level mild creatinine elevation may occur; severe intrinsic nephrotoxicity is uncommon.
Source: Durairaj et al., Clin Pharmacokinet 2021
Mechanism of kidney injury
Talazoparib is substantially renally cleared, so reduced GFR increases drug exposure (and hematologic toxicity) rather than causing direct tubular injury — the dominant renal issue is pharmacokinetic. As with the class, any modest creatinine rise can reflect inhibition of tubular creatinine secretion rather than true filtration loss.
Clinical presentation
Usually no overt nephrotoxicity; the renal concern is pharmacokinetic — higher exposure with anemia, thrombocytopenia, and neutropenia in patients with reduced renal function. Mild reversible creatinine changes are possible.
Onset
The pharmacokinetic effect is present from initiation in patients with reduced renal function; cytopenias accrue over the first cycles.
Reversibility
Reversible
Anticancer mechanism
One of the most potent PARP-trapping inhibitors; exploits homologous-recombination deficiency for synthetic lethality. Used in germline BRCA-mutated HER2-negative breast cancer and, with enzalutamide, in metastatic castration-resistant prostate cancer.
Management
Reduce the starting dose for moderate (CrCl 30-59: 0.75 mg daily) and severe (CrCl 15-29: 0.5 mg daily) renal impairment per label; manage cytopenias with dose holds/reductions, transfusion, and growth-factor support.
Risk factors
- Moderate to severe renal impairment (exposure)
- Concurrent myelosuppressive therapy
- Concurrent P-gp/BCRP inhibitors
Prevention
- Renal-function-based starting-dose adjustment
- Monitor blood counts closely in CKD
- Baseline and periodic creatinine
Note · Principal renal issue is dosing in CKD (exposure), not intrinsic nephrotoxicity.
Clinical depth
Renal dose adjustment
Breast-cancer monotherapy: CrCl 60-89 no change; CrCl 30-59 reduce to 0.75 mg once daily; CrCl 15-29 reduce to 0.5 mg once daily. With enzalutamide in mCRPC, label-specific lower doses apply. Not studied on dialysis or in CrCl <15 mL/min.
Dialyzability & ESKD dosing
Renally cleared but highly protein-bound; dialyzability not formally established and no validated ESKD dose — avoid or use only with intensive hematologic monitoring.
Differential diagnosis
Cytopenias in a CKD patient on talazoparib usually reflect drug over-exposure (PK), not marrow infiltration or a separate renal lesion. A mild creatinine rise is more likely transporter-mediated than true AKI.
Monitoring
- CBC monthly (and more often after dose changes) — anemia is the most common grade >=3 event
- Serum creatinine/eGFR at baseline and periodically to guide dosing
Key trials & series
- EMBRACA (gBRCA HER2-negative breast cancer)
- TALAPRO-2 (talazoparib + enzalutamide in mCRPC)
- Durairaj 2021 dedicated renal-impairment PK study
Clinical pearls
- Talazoparib is the renally cleared PARP inhibitor — reduce the dose for CrCl <60 mL/min and watch counts, since exposure (and anemia) climbs as GFR falls.
- The principal renal issue is dosing in CKD, not de novo kidney injury.
- Confirm an ambiguous creatinine rise with cystatin C before attributing GFR decline.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIPseudo-AKI
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkThe Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors.Durairaj C et al. · Clin Pharmacokinet 2021 · PMID 33686631Dedicated PK study showing increased talazoparib exposure with renal impairment, supporting dose adjustment.PMIDPopulation Pharmacokinetics of Talazoparib in Patients With Advanced Cancer.Yu Y et al. · J Clin Pharmacol 2019 · PMID 31489639Population PK identifying renal function as a covariate on talazoparib clearance.PMIDPARP 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 42073552Class-level evidence that PARP-inhibitor creatinine rise is usually mild and transporter-mediated.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 renal adverse-event comparison across PARP inhibitors, contextualizing talazoparib safety.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 35756332Frames cystatin C as the confirmatory test for targeted-therapy creatinine elevation.PMIDTalazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.Litton JK et al. · N Engl J Med 2018 · PMID 30110579Pivotal EMBRACA trial: registrational efficacy/safety dataset (anemia-dominant hematologic toxicity relevant to CKD dosing).
Related agents
Other agents sharing the same signature kidney injury.