Amsacrine
Amsidine · Topoisomerase II inhibitor (acridine)
Predominantly hepatobiliary elimination; renal clearance minor, kidney risk mainly tumor lysis in AML; reduce dose in organ impairment.
LYTEXTAL
Moderate#1 · 74% phenotype match
Infigratinib
Truseltiq · INFI
FGFR inhibitor · approved 2021 · 7 citations
Up to date· through 2025
Fairly sourced5/9 · 5 signals
- Met: 7 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 8y)
- Met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Met: Current through 2025
- 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 FGFR inhibitor whose hyperphosphatemia is an on-target pharmacodynamic biomarker — manage it, do not ignore it.
ModerateFGFR inhibitor
Previously treated, unresectable or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement
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Signature kidney injury
Signature lesion
Representative incidence77%
Hyperphosphatemia is the most common adverse event and the defining FGFR class effect — it occurred in 83 of 108 patients (~77%, any grade) in the pivotal trial. Infigratinib-specific nephrocalcinosis/calciphylaxis rates are not quantified (case reports/series only).Source: Javle et al., Lancet Gastroenterol Hepatol 2021
Onset & rechallenge
Time to injurySubacute (~1–6 weeks)
Early (first cycle); reversible and dose-dependent, normalizing during the 7-day off-drug interval.
Distilled from: “Early (first cycle); reversible and dose-dependent, normalizing during the 7-day off-drug interval of the 21-on/7-off cycle.”
Long-term outlook & thresholds
Early-detection biomarkers
- Serum phosphate — FGFR1 target engagement — blocked FGF23 signalling lets the proximal tubule reabsorb filtered phosphate. Read this one carefully, because it runs opposite to a nephrotoxicity marker: hyperphosphataemia is the on-target class effect of FGFR1 inhibition, 48 of 67 patients (71.6%) had it on at least one test, serum phosphorus correlated positively with drug concentration, and the paper's finding is that it tracks BETTER antitumour response. It is a pharmacodynamic readout of drug exposure, not a tubular-injury assay, and no infigratinib study measures a renal endpoint against it. It earns a place here for one reason: the phosphate number drives a real management algorithm (diet, binders, hold, dose-reduce) whose purpose is to keep the calcium–phosphate product away from the range that deposits in tissue, which is the only sense in which watching it protects the kidney.PMID 32847703 (opens PubMed in a new tab)
Long-term outcome and threshold data distilled from the agent's cited literature — educational, not a substitute for the primary sources.
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Renal toxicities, ranked
This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.
Hyperphosphatemia ~77% (83/108) - on-target FGFR class effect and most common AE
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
77%incidence
SeverityModerate
ReversibilityReversible
Evidence7 citations
Nephron map
Proximal Tubule
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Tubular Lumen
Electrolyte Disturbance
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
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Kidney injury
Mechanism of kidney injury
On-target disruption of the FGF23-alpha-Klotho axis. Normally bone-derived FGF23 binds the FGFR1/alpha-Klotho complex in the proximal tubule, downregulating apical sodium-phosphate cotransporters NaPi-2a (SLC34A1) and NaPi-2c (SLC34A3) to promote urinary phosphate excretion. FGFR inhibition blocks this signal, so NaPi-2a/2c are no longer suppressed and renal phosphate reabsorption rises, producing class-effect hyperphosphatemia. Sustained elevation (raised calcium-phosphate product) drives nephrocalcinosis, calcinosis cutis and vascular calcification. This is a metabolic/transporter effect, not primary tubular cytotoxicity.
Clinical presentation
Usually an asymptomatic rise in serum phosphate; severe or prolonged elevation can cause cramps and soft-tissue/cutaneous calcification (rarely calcinosis cutis/calciphylaxis). Onset is early — within the first cycle (days to weeks); cutaneous calcification has been reported as early as ~10 days.
Management
Stepwise: intensify the phosphate binder (e.g. sevelamer) → if still markedly elevated, hold the drug → dose-reduce on rechallenge (125 mg to 100 to 75 mg) → discontinue for refractory/severe (e.g. >10 mg/dL) or symptomatic hyperphosphatemia or soft-tissue calcification. Keep the calcium-phosphate product down and avoid vitamin D loading.Lesion-level management framework
Risk factors
- Higher dose/exposure
- Pre-existing CKD or reduced GFR and baseline hyperphosphatemia
- High dietary phosphate
- Concurrent vitamin D or phosphate supplementation
Prevention
- Low-phosphate diet (~600-800 mg/day) from the start
- Avoid vitamin D loading
- Start an oral phosphate binder when phosphate exceeds the label threshold (~7.0 mg/dL)
Anticancer mechanism· how it treats cancer
Oral, selective, ATP-competitive inhibitor of FGFR1-3 that targets oncogenic FGFR2 fusions and rearrangements in cholangiocarcinoma.
Note · The 2021 accelerated approval was contingent on confirmatory PROOF 301; infigratinib was subsequently withdrawn from the US cholangiocarcinoma market — verify current availability before clinical use. The hyperphosphatemia mechanism remains reference-grade and class-defining.
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Clinical depth
Renal dose adjustment
Standard 125 mg daily for 21 of 28 days. No dedicated adjustment is established for mild-moderate renal impairment, but reduced GFR raises hyperphosphatemia risk and warrants closer monitoring; severe-impairment data are limited.
Dialyzability & ESKD dosing
Not established; highly protein-bound and CYP3A4-metabolized, so it is not expected to be meaningfully dialyzable.
Differential diagnosis
Distinguish from other FGFR inhibitors (pemigatinib, erdafitinib, futibatinib — same class effect), CKD/AKI phosphate retention, tumor lysis, exogenous phosphate load, hypoparathyroidism, vitamin D toxicity and pseudohyperphosphatemia (paraprotein/hemolysis).
Monitoring
- Serum phosphate at baseline and regularly (at least monthly) with a threshold-based binder/hold algorithm
- Serum calcium and renal function
- Ophthalmologic monitoring for serous retinopathy (FGFR class effect; outside renal scope)
Key trials & series
- Pivotal phase 2 (Javle, Lancet Gastroenterol Hepatol 2021) — hyperphosphatemia in ~77%
- PROOF 301 confirmatory phase 3 (Makawita, Future Oncol 2020) — design/rationale
Clinical pearls
- Hyperphosphatemia is an on-target pharmacodynamic biomarker of FGFR inhibition, not idiosyncratic — but it must be managed.
- It is the most common adverse event (~77% any grade) and the defining class effect of all FGFR1-3 inhibitors.
- Manage proactively with a low-phosphate diet plus threshold-triggered binders; the 7-day off-drug window aids reversal.
- The feared downstream harm is calcium-phosphate deposition (nephrocalcinosis, calcinosis cutis, calciphylaxis) — keep the calcium-phosphate product down and avoid vitamin D loading.
Beyond the kidney — non-renal toxicities· 2 organ systems
Class-level context for the major non-renal toxicities of the FGFR inhibitor class.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Central serous retinopathy
Dermatologic
Rash, HFS, SJS/TEN, vitiligo
- Nail/skin changes, hand-foot syndrome
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References
7 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
7 references · 2017–2025 · 1 since 2023Primary (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.
- 1.LandmarkInfigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study.Javle M et al. · Lancet Gastroenterol Hepatol · 2021 · PMID 34358484Pivotal/registrational phase 2; hyperphosphatemia the most common adverse event (83/108).
- 2.Targeted Therapy for Advanced or Metastatic Cholangiocarcinoma: Focus on the Clinical Potential of Infigratinib.Yu J et al. · Onco Targets Ther · 2021 · PMID 34720591Drug-focused review of mechanism, program and approval context.
- 3.The Klotho proteins in health and disease.Kuro-O M et al. · Nat Rev Nephrol · 2019 · PMID 30455427Authoritative review of the FGF23-alpha-Klotho-FGFR axis governing renal phosphate handling.
- 4.Pleiotropic Actions of FGF23.Erben RG et al. · Toxicol Pathol · 2017 · PMID 29096595FGF23/FGFR1/alpha-Klotho in the proximal tubule suppressing NaPi-2a/2c — basis of hyperphosphatemia.
- 5.Calcinosis Cutis With Selective Fibroblast Growth Factor Receptor Inhibitors: A Case Report and Review of Literature.Ghimire B et al. · Cureus · 2025 · PMID 40486452FGFR-inhibitor hyperphosphatemia-driven soft-tissue calcification with binder/hold management.
- 6.Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial.Makawita S et al. · Future Oncol · 2020 · PMID 32580579Design/rationale of the confirmatory phase 3 PROOF 301 (first-line vs gemcitabine/cisplatin).
- 7.Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Prud'homme GJ et al. · Front Aging · 2022 · PMID 35903083Klotho as an obligate FGF23 co-receptor regulating renal phosphate excretion.
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 Infigratinib 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Erdafitinib
Balversa · FGFR inhibitor
Hyperphosphatemia is an on-target class effect.
LYTE
Moderate#2 · 73% phenotype match
Futibatinib
Lytgobi · FGFR inhibitor
Hyperphosphatemia, class effect.
LYTE
Moderate#3 · 73% phenotype match
Pemigatinib
Pemazyre · FGFR inhibitor
Hyperphosphatemia; nephrocalcinosis risk.
LYTE
Moderate#4 · 73% phenotype match
Mechlorethamine
Mustargen · Alkylating agent (nitrogen mustard)
Tumor lysis in bulky lymphoma is the main renal hazard; modern topical gel has no detectable systemic absorption.
LYTEXTAL
Moderate#5 · 71% phenotype match
Melphalan flufenamide (melflufen)
Pepaxto · Peptide-conjugated alkylator
Delivers melphalan intracellularly; BRIDGE supports a reduced 30 mg dose in moderate renal impairment.
ATNLYTE
Moderate#6 · 57% phenotype match
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 FGFR inhibitors
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.
- 1ErdafitinibLYTE — Electrolyte DisturbanceModerate
- 2FutibatinibLYTE — Electrolyte DisturbanceModerate
- 3PemigatinibLYTE — Electrolyte DisturbanceModerate
- 4Infigratinib· this agentLYTE — Electrolyte DisturbanceModerate
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.