Ramucirumab
Cyramza · Anti-VEGFR2 antibody
Hypertension and proteinuria, class effect.
HTNGLOMTMA
ModerateOpen →
PARP inhibitor
Niraparib
Zejula · Nira
The PARP inhibitor with a distinctive hypertension signal — a class outlier on blood pressure.
MildPARP inhibitor · approved 2017
Ovarian cancer (maintenance)Fallopian tube / primary peritoneal cancerBRCA-altered metastatic castration-resistant prostate cancer
Signature kidney injury
Hypertension
Representative incidence17%
Hypertension is a characteristic, class-distinctive adverse event: a FAERS pharmacovigilance plus RCT meta-analysis estimated ~16.9% any-grade hypertension, disproportionately higher with niraparib than other PARP inhibitors. A small reversible serum-creatinine rise is also seen across the class (pooled OR for creatinine elevation ~5 vs placebo), but grade >=3 nephrotoxicity is <1%.
Source: Chen et al., Gynecol Oncol 2024
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
GlomerulusFiltration barrier (podocytes + endothelium)
Vasculature / EndotheliumGlomerular & peritubular capillaries
Proximal Tubule
Hypertension
On-target loss of endothelial nitric oxide from VEGF-pathway blockade — so consistent it marks drug activity.
Mechanism of kidney injury
Hypertension is thought to be an off-target effect of niraparib — possible inhibition of dopamine/norepinephrine reuptake transporters (DAT/NET) with sympathetic activation and altered vascular tone — distinguishing it from olaparib/rucaparib; intrinsic nephron injury is not characteristic. The mild creatinine elevation shared across the class reflects inhibition of proximal-tubular cation transporters (MATE1/MATE2-K, OCT2) that secrete creatinine, raising serum creatinine without a true fall in GFR ('pseudo-AKI').
Clinical presentation
New or worsened hypertension (occasionally hypertensive crisis), often within the first cycles; modest asymptomatic creatinine rise without proteinuria, active sediment, or other tubular markers. Anemia and thrombocytopenia dominate the non-renal toxicity profile and drive most dose holds.
Onset
Hypertension typically emerges within the first weeks to months of therapy.
Reversibility
Reversible
Anticancer mechanism
Inhibits poly(ADP-ribose) polymerase (PARP1/2) and traps the enzyme on damaged DNA, exploiting homologous-recombination deficiency (synthetic lethality). Used as maintenance in ovarian cancer and, with abiraterone, in BRCA-altered metastatic castration-resistant prostate cancer.
Management
Manage hypertension with standard antihypertensives (often a calcium-channel blocker or ACE inhibitor/ARB); dose-interrupt then reduce for medically uncontrolled BP, and discontinue for hypertensive crisis. Isolated creatinine rise without other findings usually needs only monitoring; consider cystatin C-based eGFR before attributing a true GFR fall.
Risk factors
- Pre-existing hypertension
- Cardiovascular disease
- Concurrent agents that raise blood pressure
Prevention
- Baseline and serial blood-pressure monitoring (weekly first 2 months, then periodically)
- Optimize/initiate antihypertensives before and during therapy
- Periodic creatinine checks
Note · Hypertension is the headline renal-relevant signal; serious nephrotoxicity is uncommon. Creatinine rise may overstate true GFR loss (transporter effect).
Clinical depth
Renal dose adjustment
No formal renal dose adjustment for mild-moderate impairment; not studied in CrCl <30 mL/min or on dialysis (use with caution). Individualized starting dose (200 mg) is recommended by weight (<77 kg) and platelet count (<150,000/µL) for hematologic, not renal, safety.
Dialyzability & ESKD dosing
Small molecule but highly protein-bound (~83%) with a large volume of distribution; not expected to be meaningfully removed by hemodialysis. No validated ESKD dosing — extrapolate cautiously and prioritize cytopenia monitoring.
Differential diagnosis
Distinguish drug-induced hypertension from pain-, steroid-, or volume-related BP elevation and from VEGF-pathway hypertension if on combination therapy. For the creatinine bump, distinguish transporter-mediated pseudo-AKI (stable cystatin C, bland sediment, no oliguria) from true AKI (rising cystatin C, proteinuria, active sediment).
Monitoring
- Blood pressure and heart rate at least weekly for the first 2 months, then at least monthly
- CBC weekly for the first month (thrombocytopenia/anemia/neutropenia), then monthly
- Serum creatinine at baseline and periodically; cystatin C if a true GFR change is in question
Key trials & series
- PRIMA/ENGOT-OV26 (first-line ovarian maintenance — hypertension signal)
- NOVA (recurrent ovarian maintenance)
- MAGNITUDE (niraparib + abiraterone in mCRPC — hypertension among most common grade >=3 events)
- Chen 2024 FAERS + RCT meta-analysis (class-distinctive hypertension)
Clinical pearls
- Among PARP inhibitors, niraparib is the hypertension outlier — check and treat BP proactively rather than reflexively dose-reducing the drug.
- A small early creatinine rise is usually a transporter artifact; cystatin C-based eGFR avoids unnecessary biopsies and dose changes.
- Thrombocytopenia, not nephrotoxicity, is the dose-limiting toxicity — individualize the starting dose by weight and platelets.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
HypertensionPrerenal / Hemodynamic AKI
Evidence
8 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkHypertension associated with niraparib in cancer patients: A pharmacovigilance analysis based on the FAERS database and meta-analysis of randomized controlled trials.Chen W et al. · Gynecol Oncol 2024 · PMID 38295607FAERS + RCT meta-analysis quantifying niraparib-specific hypertension (~16.9%) vs other PARP inhibitors.PMIDNiraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer.Chi KN et al. · J Clin Oncol 2023 · PMID 36952634Phase III MAGNITUDE trial reporting hypertension among the most common grade >=3 adverse events.PMIDNiraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trial.Reiss KA et al. · Lancet Oncol 2022 · PMID 35810751Randomized trial listing hypertension among the most common grade >=3 treatment-related events.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 meta-analysis: PARP inhibitors increase creatinine elevation (OR ~5) but severe nephrotoxicity <1%; likely tubular transport effect.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 39493722FAERS disproportionality analysis of PARP-inhibitor renal adverse events; median onset 15 days, mostly reversible creatinine elevation.PMIDThe forefront of ovarian cancer therapy: update on PARP inhibitors.Mirza MR et al. · Ann Oncol 2020 · PMID 32569725Authoritative review of the phase III PARP-inhibitor maintenance trials (SOLO-1, PRIMA, PAOLA-1, VELIA) framing class 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 35756332Names PARP inhibitors among targeted agents that raise creatinine via tubular-secretion inhibition; cystatin C clarifies true GFR.PMIDNavigating the Complexities of Cancer Treatment-Induced Hypertension.Arriola-Montenegro J et al. · J Cardiovasc Dev Dis 2025 · PMID 40558670Onconephrology/cardio-oncology review of anticancer drug-induced hypertension mechanisms and management.
Related agents
Other agents sharing the same signature kidney injury.