Is kidney injury from Hydroxyurea reversible?

Reversible. Typical onset: Very early (within 12-24 hours of high-dose treatment)..

How should kidney function be monitored during Hydroxyurea therapy?

CBC with differential frequently during cytoreduction; Uric acid, phosphate, potassium, calcium and creatinine during high-dose/rapid cytoreduction.

How can kidney injury from Hydroxyurea be prevented?

IV hydration to maintain high urine flow Allopurinol or rasburicase in at-risk patients

Who is at higher risk of kidney injury from Hydroxyurea?

High blast count / bulky proliferative disease; High-dose hydroxyurea cytoreduction; Volume depletion; Baseline hyperuricemia or renal impairment.

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Printable monograph

Ribonucleotide reductase inhibitor

Hydroxyurea

Hydrea · HU

Ribonucleotide reductase inhibitor · approved 1967 · 7 citations · FAERS AKI reporting ROR 1.73 (95% CI 1.53–1.96, 263 AKI reports)

Aging evidence· through 2020

Fairly sourced6/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 17y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Not met: Current through 2020
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 old ribonucleotide reductase inhibitor that, at high doses, can lyse blasts fast enough to flood the tubules.

MildRibonucleotide reductase inhibitor

Chronic myeloid leukemia / myeloproliferative neoplasmsHyperleukocytic acute leukemias (cytoreduction)Polycythemia vera and essential thrombocythemia

§01

Signature kidney injury

Signature lesion

Crystal / Obstructive Nephropathy

Acute tumor lysis syndrome from hydroxyurea is rare and reported at case level, almost exclusively with high-dose cytoreduction of leukemias carrying a high blast burden. Standard-dose hydroxyurea is not characteristically nephrotoxic.Source: Seki et al., Ann Pharmacother 2003

Onset & rechallenge

Time to injuryHyperacute (<24 h)

Very early — within 12–24 hours of high-dose treatment (tumor lysis).

Distilled from: “Very early (within 12-24 hours of high-dose treatment).”

§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.

Crystal / Obstructive Nephropathy#1 · Signaturequalitative — no citable incidence
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence7 citations

Nephron map

Vasculature / Endothelium

Distal Tubule / Collecting Duct

Tubular LumenThe urine flow path

Crystal / Obstructive Nephropathy

Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

§03

Kidney injury

Mechanism of kidney injury

At high doses, rapid cytolysis of a proliferative blast population releases uric acid, phosphate and potassium; intratubular uric-acid and calcium-phosphate crystal/cast precipitation plus volume depletion produces obstructive and prerenal/ischemic AKI (tumor lysis nephropathy). Hydroxyurea itself is largely renally excreted but is not intrinsically tubulotoxic at usual doses.

Clinical presentation

Hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia and a rising creatinine within hours to a day of high-dose dosing, often accompanied by falling blast counts.

Management

Aggressive hydration, urate-lowering therapy (rasburicase for high-risk or established hyperuricemia) and electrolyte correction; hold high-dose hydroxyurea and provide supportive care, with hemodialysis for refractory hyperkalemia, hyperphosphatemia or oliguric AKI.Lesion-level management framework

Risk factors

High blast count / bulky proliferative disease
High-dose hydroxyurea cytoreduction
Volume depletion
Baseline hyperuricemia or renal impairment

Prevention

IV hydration to maintain high urine flow
Allopurinol or rasburicase in at-risk patients

Anticancer mechanism· how it treats cancer

Inhibits ribonucleotide reductase by quenching the tyrosyl free radical at its active site, depleting deoxyribonucleotides and arresting cells in S phase. Used to cytoreduce myeloproliferative neoplasms and the hyperleukocytosis of acute leukemias, and to raise fetal hemoglobin in sickle cell disease.

Note · Because the drug is renally cleared, dose reduction is needed in CKD to avoid excess myelosuppression rather than nephrotoxicity.

§04

Clinical depth

Renal dose adjustment

Hydroxyurea is predominantly renally excreted. The label and pharmacokinetic data support reducing the starting dose in renal impairment (commonly halving the dose when CrCl < 60 mL/min and using marked reductions or avoidance in ESKD) to prevent excessive myelosuppression; titrate to blood counts.

Dialyzability & ESKD dosing

Yes — hydroxyurea is a small (76 Da), water-soluble molecule that is readily removed by hemodialysis. In dialysis-dependent patients, dosing is commonly given after the HD session and reduced; counts must be followed closely.

Differential diagnosis

Tumor lysis nephropathy (urate/phosphate surge after rapid blast kill) versus leukostasis-related AKI in hyperleukocytosis versus prerenal azotemia from poor intake. Crystalluria (urate) on microscopy supports tumor lysis.

Monitoring

CBC with differential frequently during cytoreduction
Uric acid, phosphate, potassium, calcium and creatinine during high-dose/rapid cytoreduction

Key trials & series

Seki et al. case series of high-dose hydroxyurea-precipitated acute tumor lysis (Ann Pharmacother 2003)

Clinical pearls

Hydroxyurea nephrotoxicity is essentially tumor lysis at high cytoreductive doses, not chronic tubular injury.
Because the drug is dialyzable and renally cleared, reduce the dose and dose post-HD in dialysis patients to avoid profound cytopenias.
Hydration and urate-lowering therapy before aggressive cytoreduction are the key preventive steps.

§05

References

6 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

6 references · 2003–2020 · 2 since 2018

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· 1

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 · LimitedHydroxyurea and splenic irradiation-induced tumour lysis syndrome: a case report and review of the literature.Chen SW et al. · J Clin Pharm Ther 2005 · PMID 16336296Elderly CML patient developed acute tumour lysis syndrome with renal failure requiring haemodialysis after hydroxyurea and splenic irradiation.

FDA label — boxed warning & renal dosing· renal impairment

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

Renal impairment — from the label

The exposure to hydroxyurea is higher in patients with creatinine clearance of less than 60 mL/min or in patients with end-stage renal disease (ESRD). Reduce dosage and closely monitor the hematologic parameters when hydroxyurea capsules is to be administered to these patients [ see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ].

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 21,026 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· 5 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

Electrolyte Disturbancecorroborated · ROR 1.9 — on the terms that name the lesion (ROR 3.25)
Crystal / Obstructive Nephropathycorroborated · ROR 1.67
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Acute Tubular Necrosis

ROR 2.2495% CI 1.47–3.40· 22 reports

SIADH / Hyponatremia

ROR 1.9895% CI 1.69–2.31· 159 reports

Electrolyte Disturbance

ROR 1.9095% CI 1.71–2.11· 361 reports

Crystal / Obstructive Nephropathy

ROR 1.6795% CI 1.36–2.05· 93 reports

Hemorrhagic Cystitis

ROR 1.6695% CI 1.38–1.99· 115 reports

FAERS outcomes & reporting trend· 15% of reports w/ death · 38% w/ hospitalization

15%

Reported with a death outcome

3,147 of 21,026 reports

38%

Reported with hospitalization

7,993 of 21,026 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 21,026 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 1.7395% CI 1.53–1.96· 263 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Blood & lymphatic

Sickle Cell Anaemia With Crisis1,486Anaemia1,045Haemoglobin Decreased939Platelet Count Decreased696Platelet Count Increased648

General / constitutional

Fatigue1,547Pyrexia929Pain862Asthenia757Malaise618

Gastrointestinal

Diarrhoea1,409Nausea1,306Vomiting680Abdominal Pain478

Nervous system

Headache1,068Dizziness733

Musculoskeletal

Arthralgia539Pain In Extremity518

Respiratory

Dyspnoea825

Immune / infection

Pneumonia768

Metabolic & electrolyte

Decreased Appetite503

Skin

Rash484

Guidelines & consensus· 18

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.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.TLS Expert PanelGuidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based reviewJ Clin Oncol 2008 · PMID 18509186Prevention is the best management: hydration plus prophylactic rasburicase for high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk, and monitoring for low-risk; for established TLS add aggressive hydration and diuresis plus allopurinol or rasburicase for hyperuricemia. Urinary alkalinization is NOT recommended.TLS Consensus PanelRecommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensusBr J Haematol 2010 · PMID 20331465Stratify each patient as low/intermediate/high TLS risk using tumor type, bulk/stage, proliferation rate, baseline laboratory TLS, and renal impairment/involvement, then match prophylaxis intensity (monitoring vs allopurinol vs rasburicase) to the assigned risk level.BCSHGuidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in HaematologyBr J Haematol 2015 · PMID 25876990Risk-adapted prophylaxis and management of TLS in haematological malignancy: hydration with allopurinol for lower-risk and rasburicase for high-risk patients, with monitoring of electrolytes and renal function to prevent and treat AKI.Cairo-BishopTumour lysis syndrome: new therapeutic strategies and classificationBr J Haematol 2004 · PMID 15384972Defines the Cairo-Bishop criteria distinguishing laboratory TLS (>=2 metabolic abnormalities: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia within 3 days before to 7 days after therapy) from clinical TLS (laboratory TLS plus AKI, cardiac arrhythmia, or seizure), with a severity grading scheme adopted by subsequent guidelines.

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 Hydroxyurea 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

Nelarabine

Arranon · Purine analog

Profile

Tumor lysis in T-ALL.

XTALPRELYTE

Mild#1 · 100% phenotype match

Cladribine

Leustatin · Purine analog

Profile

Tumor lysis; high-dose nephrotoxicity.

XTALPRELYTE

Mild#2 · 100% phenotype match

Fludarabine

Fludara · Purine analog

Profile

Tumor lysis; accumulates in renal impairment.

XTALPRELYTE

Moderate#3 · 95% phenotype match

Etoposide

Etopophos · Topoisomerase II inhibitor

Profile

Tumor lysis; renally cleared.

XTALPRELYTE

Mild#4 · 89% phenotype match

Pomalidomide

Pomalyst · Immunomodulatory drug (IMiD)

Profile

Tumor lysis; usable in renal impairment.

PRELYTEXTAL

Mild#5 · 89% phenotype match

Thalidomide

Thalomid · Immunomodulatory drug (IMiD)

Profile

Tumor lysis and bradycardia.

PRELYTEXTAL

Mild#6 · 89% phenotype match

Compare Hydroxyurea 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 Antimetabolites

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.

Who studies this

The leading contributors to Hydroxyurea’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Hydroxyurea; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 108 clinical records among all 155 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.