How should kidney function be monitored during Tretinoin (ATRA) therapy?

Daily weight, oxygenation and symptom assessment for differentiation syndrome during induction; WBC trend (rising count heralds the syndrome and tumor-lysis risk); Tumor-lysis labs (uric acid, potassium, phosphate, calcium, creatinine); Coagulation parameters (APL coagulopathy/DIC accompanies induction).

How can kidney injury from Tretinoin (ATRA) be prevented?

Prophylactic/early corticosteroids (e.g., prednisone/dexamethasone) in high-WBC patients Cytoreduction for hyperleukocytosis TLS prophylaxis with hydration and urate-lowering

Who is at higher risk of kidney injury from Tretinoin (ATRA)?

High or rising WBC (hyperleukocytosis); Bulky disease; Concurrent infection; Delayed corticosteroids; High baseline creatinine.

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Printable monograph

Retinoid (differentiating agent)

Tretinoin (ATRA)

Vesanoid · ATRA

Retinoid (differentiating agent) · approved 1995 · 10 citations · FAERS AKI reporting ROR 1.40 (95% CI 1.13–1.72, 89 AKI reports)

Up to date· through 2025

Deeply sourced8/9 · 7 signals

Met: 10 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 28y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

The drug that turned APL from lethal to curable — but blast maturation can unleash a capillary-leak storm and AKI.

ModerateRetinoid (differentiating agent)

Acute promyelocytic leukemia (APL)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Representative incidence25%

2–37% range across studies

Differentiation (retinoic acid) syndrome — the main route to AKI — occurs in roughly 2–37% of APL patients depending on criteria and prophylaxis (commonly cited around 25%); acute renal failure is part of its defining end-organ spectrum.Source: Woods & Norsworthy, Cancers 2023 (2–37% across series)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Usually within the first 1–3 weeks of induction, bimodal at the first and third week.

Distilled from: “Usually within the first 1–3 weeks of induction (bimodal: first week and third week).”

§02

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.

Prerenal / Hemodynamic AKI#1 · Signature24.8%PMID 18945964 (opens PubMed in a new tab)
Differentiation syndrome (capillary-leak with fluid overload and renal impairment) in 24.8% of 739 APL patients treated with ATRA plus idarubicin (PETHEMA LPA96/LPA99); severe form in 12.6%.
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

25%incidence

SeverityModerate

ReversibilityReversible

Evidence10 citations

Nephron map

Vasculature / Endothelium

Proximal Tubule

Distal Tubule / Collecting Duct

Prerenal / Hemodynamic AKI

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

§03

Kidney injury

Mechanism of kidney injury

Differentiating promyelocytes release inflammatory cytokines (and express adhesion molecules) causing a systemic capillary-leak syndrome with hypotension, third-spacing and tissue edema; the resulting hemodynamic compromise produces prerenal AKI that can progress to ischemic ATN. Pulmonary leukostasis/hyperleukocytosis and concurrent tumor lysis can compound the injury.

Clinical presentation

Fever, dyspnea/hypoxia, pulmonary infiltrates, peripheral edema, weight gain >5 kg, hypotension, pleural/pericardial effusion and acute renal failure (differentiation syndrome). A rising WBC during induction is characteristic.

Management

Start dexamethasone (10 mg IV q12h) immediately when differentiation syndrome is suspected; supportive hemodynamics, diuresis for fluid overload, oxygen. Temporarily hold ATRA for severe/refractory syndrome and resume once resolved.Lesion-level management framework

Risk factors

High or rising WBC (hyperleukocytosis)
Bulky disease
Concurrent infection
Delayed corticosteroids
High baseline creatinine

Prevention

Prophylactic/early corticosteroids (e.g., prednisone/dexamethasone) in high-WBC patients
Cytoreduction for hyperleukocytosis
TLS prophylaxis with hydration and urate-lowering

Anticancer mechanism· how it treats cancer

All-trans retinoic acid binds the ligand-binding domain of the PML-RARA fusion receptor, relieving its transcriptional repression and degrading the fusion oncoprotein to release the differentiation block — driving promyelocytic blasts to terminally mature. With arsenic trioxide it forms the chemo-free backbone of acute promyelocytic leukemia (APL) therapy.

Note · Renal injury is a manifestation of differentiation syndrome and fluid shifts rather than direct tubular toxicity. ATRA is also a recognized therapeutic and prophylactic differentiator, so the clinical art is treating the syndrome without abandoning the cure.

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Clinical depth

Renal dose adjustment

No established renal dose adjustment; standard induction is 45 mg/m²/day. Dose interruptions are driven by differentiation syndrome, pseudotumor cerebri and hepatotoxicity rather than CrCl.

Dialyzability & ESKD dosing

Not characterized; ATRA is highly protein-bound and hepatically metabolized (and autoinduces its own metabolism), so it is not expected to be appreciably dialyzed. Dialysis, if needed, treats the AKI/fluid overload, not drug levels.

Differential diagnosis

Differentiation syndrome vs sepsis/pneumonia (overlapping fever, infiltrates, hypotension), fluid overload, and pulmonary hemorrhage from APL coagulopathy. Weight gain, effusions and rising WBC favor the syndrome; prerenal/differentiation AKI is distinguished from tumor-lysis crystal nephropathy by the urate/phosphate profile.

Monitoring

Daily weight, oxygenation and symptom assessment for differentiation syndrome during induction
WBC trend (rising count heralds the syndrome and tumor-lysis risk)
Tumor-lysis labs (uric acid, potassium, phosphate, calcium, creatinine)
Coagulation parameters (APL coagulopathy/DIC accompanies induction)

Key trials & series

Lo-Coco et al., NEJM 2013 — APL0406 (ATRA + arsenic trioxide vs ATRA-chemotherapy; established the chemo-free standard)
Woods & Norsworthy (Woods AC et al.), Cancers 2023 — FDA review quantifying differentiation-syndrome incidence and renal failure

Clinical pearls

At the first hint of differentiation syndrome, give dexamethasone immediately — do not wait for confirmation; renal failure is part of the syndrome.
A rising WBC during ATRA induction is expected blast maturation but signals differentiation-syndrome and tumor-lysis risk.
The AKI is hemodynamic (capillary leak), not direct tubulotoxicity — manage the syndrome and the kidney recovers.

Beyond the kidney — non-renal toxicities· 2 organ systems

Class-level context for the major non-renal toxicities of the Retinoid (differentiating agent) class.

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Differentiation syndrome

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

QT prolongation

§05

References

7 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

7 references · 2011–2025 · 2 since 2023

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.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedNephrotic-range proteinuria in a child with retinoic acid syndrome.Sethna CB et al. · Pediatr Nephrol 2012 · PMID 22081164Child on ATRA developed transient nephrotic-range proteinuria during two episodes of retinoic acid (differentiation) syndrome, resolving with ATRA discontinuation and dexamethasone.CaseC · LimitedThrombotic complications in acute promyelocytic leukemia during all-trans-retinoic acid therapy.Pogliani EM et al. · Acta Haematol 1997 · PMID 9158667Reversible acute renal failure attributed to renal vessel occlusion during ATRA therapy, highlighting the procoagulant/hemodynamic renal complication of ATRA in APL.CaseC · LimitedGranulomatous tubulointerstitial nephritis induced by all-trans retinoic acid.Tomita N et al. · Anticancer Drugs 2001 · PMID 11604554First reported case of ATRA-induced granulomatous tubulointerstitial nephritis causing acute renal failure in an APL patient, distinct from ATRA syndrome or thrombosis.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Aug 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: EMBRYO-FETAL TOXICITY and DIFFERENTIATION SYNDROME Tretinoin capsules can cause embryo-fetal loss and malformations when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Females of reproductive potential must have a negative pregnancy test before initiating tretinoin capsules. Advise females of reproductive potential to use two effective methods of contraception during treatment with tretinoin capsules and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with tretinoin capsules and for 1 week after the last dose [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)] . Differentiation Syndrome, which can be life-threatening or fatal, occurred in about 26% of patients with APL who received tretinoin capsules. At first signs or symptoms of this syndrome, immediately initiate high-dose corticosteroid therapy and hemodynamic monitoring until resolution of signs and symptoms. Consider withholding tretinoin capsules for moderate and severe Differentiation Syndrome until resolution [see Warnings and Precautions (5.2)] . WARNING: EMBRYO-FETAL TOXICITY and DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity: tretinoin capsules can cause embryo-fetal loss and…

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 8,792 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 2 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.

Hypertension

ROR 1.6795% CI 1.48–1.88· 266 reports

Crystal / Obstructive Nephropathy

ROR 1.5495% CI 1.11–2.14· 36 reports

FAERS outcomes & reporting trend· 9.9% of reports w/ death · 19.4% w/ hospitalization

9.9%

Reported with a death outcome

867 of 8,792 reports

19.4%

Reported with hospitalization

1,706 of 8,792 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 8,792 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 1.4095% CI 1.13–1.72· 89 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Gastrointestinal

Vomiting498Nausea453Diarrhoea414Abdominal Pain Upper374

Skin

Rash477Erythema412Pruritus354Dry Skin318

Nervous system

Headache434Paraesthesia409Dizziness334Taste Disorder322

General / constitutional

Pain598Fatigue369

Psychiatric

Depression350

Musculoskeletal

Arthralgia329

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 Tretinoin (ATRA) 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

Tagraxofusp

Elzonris · IL-3 immunotoxin

Profile

Capillary-leak syndrome → AKI.

PREATN

Moderate#1 · 100% phenotype match

Sotorasib

Lumakras · KRAS G12C inhibitor

Profile

Newer agent; renal data emerging.

PREATN

Mild#2 · 95% phenotype match

Talquetamab

Talvey · Bispecific (GPRC5D×CD3)

Profile

CRS-related AKI — emerging.

PREATN

Moderate#3 · 89% phenotype match

Teclistamab

Tecvayli · Bispecific (BCMA×CD3)

Profile

CRS-associated AKI in myeloma — emerging signal.

PREATN

Moderate#4 · 89% phenotype match

Tasonermin

Beromun · Recombinant TNF-α (cytokine)

Profile

Isolated-limb-perfusion agent; systemic leakage → SIRS/hypotension → prerenal AKI.

PREATN

Moderate#5 · 88% phenotype match

Arsenic trioxide

Trisenox · Differentiating agent

Profile

Differentiation syndrome; QT prolongation.

PREATNLYTE

Moderate#6 · 84% phenotype match

Compare Tretinoin (ATRA) 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.