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Hypomethylating agent

Decitabine

Dacogen · Decit

Hypomethylating agent · approved 2006 · 6 references

A hypomethylating cytidine analog whose marrow clearance can ignite tumor lysis and prerenal AKI.

Signature injury
Crystal / Obstructive Nephropathy
Severity
Mild
Reversibility
Reversible
Onset
Early after a treatment cycle (days) for tumor lysis; TMA over weeks.

Signature kidney injury & incidence

Crystal / Obstructive Nephropathy.

Tumor lysis syndrome with AKI is a recognized but uncommon complication when bulky/proliferative disease responds; renal incidence specific to decitabine is not well quantified (case-level). Rare biopsy-proven renal thrombotic microangiopathy has been reported.

Source: Qin et al., Medicine (Baltimore) 2020 (TMA case); TLS reviews

Reported injury signatures: Crystal / Obstructive Nephropathy, Prerenal / Hemodynamic AKI, Electrolyte Disturbance, Thrombotic Microangiopathy.

Renal toxicity profile

  1. Crystal / Obstructive NephropathyPrimary
  2. Prerenal / Hemodynamic AKISecondary
  3. Electrolyte DisturbanceSecondary
  4. Thrombotic MicroangiopathySecondary

Onset timing & rechallenge

Variable / unpredictable — Tumor-lysis AKI early (days) after a cycle; TMA over weeks.

Mechanism of kidney injury

Rapid cytoreduction of responsive marrow releases uric acid, phosphate and potassium; intratubular uric-acid and calcium-phosphate precipitation, combined with volume depletion, produces obstructive/crystal-related and prerenal-ischemic AKI (tumor lysis nephropathy). Separately, rare biopsy-proven decitabine-associated thrombotic microangiopathy reflects endothelial injury with glomerular fibrin thrombi, crescents and tubular necrosis.

Clinical presentation

Hyperuricemia, hyperphosphatemia, hyperkalemia and a rising creatinine within days of a responding cycle in tumor lysis; in the rare TMA presentation, nephrotic-range proteinuria, hematuria, schistocytes/thrombocytopenia and AKI develop over weeks.

Management

Treat tumor lysis with aggressive hydration, rasburicase (preferred when urate is high or the patient is at high risk) or allopurinol, and correction of hyperkalemia/hyperphosphatemia; hold the drug and provide supportive care for AKI, with hemodialysis for refractory metabolic derangements. For suspected TMA, discontinue decitabine; reported cases recovered after withdrawal with supportive care (plasma exchange is generally not effective for drug-induced TMA).

Risk factors

  • High/proliferative tumor burden
  • Pre-existing renal impairment
  • Volume depletion
  • Hyperuricemia at baseline

Prevention

  • IV hydration to maintain brisk urine output
  • Tumor lysis prophylaxis (allopurinol or rasburicase) in at-risk patients

Renal dose adjustment

No formal renal dose adjustment is established in the label; decitabine is largely metabolized by deamination (cytidine deaminase) rather than renal excretion. Use caution in significant renal impairment given limited data and monitor renal function closely.

Dialyzability & ESKD dosing

Not well characterized; the short plasma half-life and rapid deamination limit the rationale for dialytic dosing. Hemodialysis is used to treat AKI/metabolic complications, not to adjust drug levels.

Differential diagnosis

Separate tumor lysis nephropathy (urate/phosphate surge, uric-acid:creatinine >1, calcium-phosphate or urate crystals) from decitabine-associated TMA (microangiopathic hemolysis, thrombocytopenia, schistocytes, biopsy fibrin thrombi) and from prerenal azotemia. In MDS, also consider disease-related glomerulonephritis.

Monitoring

  • Uric acid, phosphate, potassium and calcium during early responding cycles
  • CBC with smear and LDH/haptoglobin if TMA is suspected
  • Serum creatinine through the first responding cycles

Key trials & series

  • Decitabine phase III MDS registration trial (Kantarjian, Cancer 2006)
  • Qin et al. biopsy-proven decitabine-associated renal TMA case (Medicine 2020)

Clinical pearls

  • The chief renal hazard of a hypomethylating agent is the tumor lysis it can precipitate when bulky disease responds, not the molecule itself.
  • Rasburicase is preferred over allopurinol when baseline uric acid is high or G6PD status is normal and risk is high.
  • A microangiopathic picture (low platelets, schistocytes, LDH) after weeks of therapy should prompt drug discontinuation rather than plasma exchange.

Anticancer mechanism

Deoxycytidine analog phosphorylated to its triphosphate and incorporated directly into DNA, where it forms an irreversible covalent complex with DNA methyltransferase, causing enzyme depletion, genome-wide hypomethylation and reactivation of silenced tumor-suppressor genes; at higher concentrations it is also directly cytotoxic. Used for myelodysplastic syndromes and acute myeloid leukemia.

Note

Direct decitabine nephrotoxicity is case-level; the dominant renal risk is treatment-related tumor lysis rather than intrinsic tubular toxicity.

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) — Conventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupCisplatin 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.Kidney Int · PMID 41881107
  • 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

6 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Decitabine-induced kidney thrombotic microangiopathy with glomerular crescents formation and tubular necrosis: A case report.Qin AB et al. · Medicine (Baltimore) · 2020 · PMID 33120841
  2. 2.Clinical reasoning: a 69-year-old man with leukocytosis and hemorrhagic brain lesions.Scott KM et al. · Neurology · 2014 · PMID 24982042
  3. 3.Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus.Cairo MS et al. · Br J Haematol · 2010 · PMID 20331465
  4. 4.Expert consensus guidelines for the prophylaxis and management of tumor lysis syndrome in the United States: Results of a modified Delphi panel.Perissinotti AJ et al. · Cancer Treat Rev · 2023 · PMID 37579533
  5. 5.Anticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep · 2017 · PMID 29318217
  6. 6.Onconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin · 2020 · PMID 32853404
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.