PARP inhibitor
Rucaparib
Rubraca · Ruca
PARP inhibitor · approved 2016 · 7 references
A PARP inhibitor whose creatinine bump is mostly a transporter artifact, not true kidney injury.
- Signature injury
- Pseudo-AKI
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Within the first weeks of treatment.
Signature kidney injury & incidence
Pseudo-AKI — representative incidence ~19.7%.
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%). Reported rate: elevated serum creatinine in 19.7% — Pooled safety population of seven studies of rucaparib monotherapy in patients with recurrent high-grade ovarian… (Adrianto 2024, PMID 39266137).
Source: Adrianto et al., Taiwan J Obstet Gynecol 2024
Reported injury signatures: Pseudo-AKI.
Onset timing & rechallenge
Subacute (~1–6 weeks) — Onset within the first weeks of treatment.
Mechanism of kidney injury
Clinical presentation
Management
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
- Use cystatin C-based eGFR when true GFR is uncertain
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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.
Anticancer mechanism
Guidelines & consensus
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525
References
7 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Efficacy and safety of rucaparib in patients with recurrent high-grade ovarian carcinoma: A systematic review and meta-analysisAdrianto N et al. · Taiwan J Obstet Gynecol · 2024 · PMID 39266137
- 2.PARP 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 42073552
- 3.Exploring 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 39493722
- 4.Targeted 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 35756332
- 5.Rucaparib 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 28916367
- 6.The forefront of ovarian cancer therapy: update on PARP inhibitors.Mirza MR et al. · Ann Oncol · 2020 · PMID 32569725
- 7.Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch · 2021 · PMID 34840210