What kind of kidney injury does Casdatifan cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

How should kidney function be monitored during Casdatifan therapy?

Hemoglobin and oxygen saturation (on-target anemia/hypoxia); Creatinine and, in combinations, blood pressure and urine protein/ACR; Volume status/edema.

How can kidney injury from Casdatifan be prevented?

Account for solitary kidney / reduced nephron mass common in RCC

Who is at higher risk of kidney injury from Casdatifan?

Pre-existing CKD (common in RCC after nephrectomy / solitary kidney); Combination with VEGFR-TKIs (additive hypertension/proteinuria); Baseline anemia.

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Printable monograph

HIF-2α inhibitor (investigational)

Casdatifan

· CASD

HIF-2α inhibitor (investigational) · 4 citations

Up to date· through 2026

Fairly sourced4/9 · 4 signals

Not met: 4 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2026
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

An investigational next-generation HIF-2α inhibitor for clear-cell RCC, with class-based anemia/edema effects under study.

MildHIF-2α inhibitor (investigational)

Clear-cell renal cell carcinoma (investigational)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Renal-specific data are not established. By analogy to the first-in-class HIF-2α inhibitor belzutifan, expected on-target effects include anemia (belzutifan: ~27-90% across trials) and hypoxia, plus possible fluid retention/edema; these are class effects rather than direct nephron injury. No casdatifan-specific renal incidence is published.Source: McKay et al., Am Soc Clin Oncol Educ Book 2025

Onset & rechallenge

Time to injuryVariable / unpredictable

Renal onset is not established; class anemia/hypoxia effects emerge during ongoing therapy.

Distilled from: “Not established; class anemia/hypoxia effects emerge during ongoing therapy.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

Predicted/indirect: HIF-2α inhibition reduces erythropoietin (on-target anemia) and VEGF signaling, with possible hemodynamic and fluid-balance effects. Any AKI is anticipated to be prerenal/hemodynamic rather than a structural tubular lesion. When combined with VEGFR-TKIs (e.g., cabozantinib), the TKI partner contributes hypertension and glomerular (podocyte VEGF-deprivation) proteinuria — the more renally relevant combination effect.

Clinical presentation

Anemia and hypoxia as the recognized class effects; if present, modest creatinine changes with bland sediment; in combination regimens, watch for TKI-driven hypertension and proteinuria.

Management

Supportive; manage anemia and hypoxia per class experience, treat hypertension/proteinuria if a TKI partner is used, and correct prerenal factors. No drug-specific renal therapy is defined.Lesion-level management framework

Risk factors

Pre-existing CKD (common in RCC after nephrectomy / solitary kidney)
Combination with VEGFR-TKIs (additive hypertension/proteinuria)
Baseline anemia

Prevention

Account for solitary kidney / reduced nephron mass common in RCC

Anticancer mechanism· how it treats cancer

Oral, potent, selective hypoxia-inducible factor-2α (HIF-2α) inhibitor that allosterically prevents HIF-2α/ARNT (HIF-1β) heterodimerization. HIF-2α is a key oncogenic driver in VHL-deficient clear-cell renal cell carcinoma (ccRCC); blocking it suppresses VEGF-, cyclin-D1- and EPO-driven programs. In development (ARC-20 platform; phase 3 with cabozantinib, NCT07011719); not yet approved.

Note · INVESTIGATIONAL (yearApproved set to 2026 as a near estimate per contract). No renal-specific literature; framing is conservative HIF-2α-class reasoning by analogy to belzutifan. Treat as hypothesis-level.

§04

Clinical depth

Renal dose adjustment

Not established (investigational). HIF-2α inhibitors are hepatically metabolized; meaningful renal-clearance dependence is not expected, but formal renal-impairment dosing has not been published. Many ccRCC patients have reduced nephron mass after nephrectomy, which is relevant to baseline GFR interpretation.

Dialyzability & ESKD dosing

Not characterized; a protein-bound, hepatically cleared small molecule is unlikely to be appreciably dialyzed. No ESKD dosing data.

Differential diagnosis

In combination regimens, attribute hypertension/proteinuria to the VEGFR-TKI partner (podocyte/glomerular effect) and anemia/hypoxia to the HIF-2α agent; distinguish prerenal creatinine changes from any TKI-related TMA/glomerular injury.

Monitoring

Hemoglobin and oxygen saturation (on-target anemia/hypoxia)
Creatinine and, in combinations, blood pressure and urine protein/ACR
Volume status/edema

Key trials & series

ARC-20 ccRCC platform study (monotherapy and with cabozantinib)
Phase 3 casdatifan + cabozantinib (NCT07011719)

Clinical pearls

On-target anemia and hypoxia are the hallmark HIF-2α class effects (EPO/VEGF suppression), not direct nephrotoxicity.
The renally important combination effect is the VEGFR-TKI partner's hypertension and proteinuria — monitor BP and urine protein.
A drug that treats kidney cancer while its own renal-safety profile is still being defined — reason from belzutifan by analogy.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

§05

References

4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 2021–2026 · 2 since 2024

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Guidelines & consensus· 13

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.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides 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.SIRMSIRM-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)Radiol Med 2022 · PMID 35303246Recommends 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.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies 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.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses 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.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides 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.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three 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.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes 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.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate 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.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates 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.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages 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.

Where Casdatifan sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Iberdomide

Zenbexus · Cereblon E3 ligase modulator (CELMoD)

Profile

2026 first-in-class CELMoD; no attributable lesion (renal impairment 11% vs 8% on the comparator arm) but exposure rises 1.8x below eGFR 30 off dialysis.

PRE

Mild#1 · 100% phenotype match

Dordaviprone

Modeyso · Imipridone (ONC201; DRD2/ClpP)

Profile

2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.

PRE

Mild#2 · 100% phenotype match

Belzutifan

Welireg · HIF-2α inhibitor

Profile

Anemia/hypoxia; emerging renal profile in VHL/RCC.

PRE

Mild#3 · 97% phenotype match

Denileukin diftitox

Lymphir · Immunotoxin (IL-2–diphtheria)

Profile

Capillary-leak syndrome → prerenal AKI.

PRE

Moderate#4 · 94% phenotype match

Vepdegestrant

Veppanu · PROTAC estrogen-receptor degrader

Profile

2026 first PROTAC ER degrader; no meaningful intrinsic renal signal.

PRE

Mild#5 · 89% phenotype match

Zidesamtinib

Jideytro · ROS1-selective TKI

Profile

2026 TRK-sparing ROS1 TKI; no creatinine abnormality reached the label's >=20% lab-table cutoff — unlike the class's benign pseudo-AKI rise. Renally quiet so far.

PRE

Mild#6 · 89% phenotype match

Compare Casdatifan with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Other targeted agents

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.