Cytarabine

Crystal / Obstructive Nephropathy.

Intrinsic tubular nephrotoxicity is uncommon; the major renal risk is AKI from tumor lysis syndrome during leukemia/lymphoma cytoreduction, reported at case and series level including fatal TLS. Direct cytarabine-nephrotoxicity primary literature is genuinely sparse.

Source: Seymour et al., Cancer 2002

Reported injury signatures: Crystal / Obstructive Nephropathy, Prerenal / Hemodynamic AKI, Electrolyte Disturbance, SIADH / Hyponatremia.

1. Crystal / Obstructive NephropathyPrimary
2. Prerenal / Hemodynamic AKISecondary
3. Electrolyte DisturbanceSecondary
4. SIADH / HyponatremiaRareOne episode in a 1979 single-agent high-dose series; co-therapy and leukemic ADH production explain most reporting.

Acute (~1–7 days) — Hours to days after initiating therapy in high-burden disease.

• High tumor burden / high blast count
• High baseline uric acid and LDH
• Volume depletion and pre-existing renal impairment
• Bulky/aggressive lymphoma (e.g., Burkitt)

• TLS prophylaxis: aggressive hydration plus allopurinol or rasburicase by risk

• TLS panel (uric acid, K, phosphate, calcium, creatinine) frequently during induction
• Neurologic/cerebellar exam with high-dose cytarabine, especially if renal function declines
• Urine output and volume status

• Seymour Cancer 2002 (cisplatin-fludarabine-cytarabine salvage) - cytarabine-containing regimen with fatal TLS
• KDIGO onco-nephrology controversies conference (Malyszko Kidney Int 2020) - AKI/TLS in hematologic malignancy
• British/expert TLS management guidance (rasburicase, hydration)

• The renal threat is the tumor, not the drug: anticipate and prophylax TLS at induction in high-burden AML/lymphoma.
• With HIGH-dose cytarabine, a falling CrCl is a cerebellar-toxicity red flag - reduce dose and examine for nystagmus/ataxia.
• Rasburicase plus hydration is the workhorse for cytarabine-era TLS-AKI, which is usually reversible.
• A single-agent high-dose cytarabine series recorded one SIADH episode (1979); most SIADH in cytarabine regimens belongs to vincristine/cyclophosphamide partners or leukemic ADH production.

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 Summaries may be superseded; consult the current full text and individualize to the patient.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
• TLS Expert Panel (2008) — Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based reviewPrevention 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.J Clin Oncol · PMID 18509186
• TLS Consensus Panel (2010) — Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensusStratify 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.Br J Haematol · PMID 20331465
• BCSH (2015) — Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in HaematologyRisk-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.Br J Haematol · PMID 25876990
• Cairo-Bishop (2004) — Tumour lysis syndrome: new therapeutic strategies and classificationDefines 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.Br J Haematol · PMID 15384972
• 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