What kind of kidney injury does Pegaspargase cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Acute Tubular Necrosis.

How should kidney function be monitored during Pegaspargase therapy?

Antithrombin activity and fibrinogen (and serum asparaginase activity where available); Amylase/lipase, glucose and triglycerides; LFTs/bilirubin and coagulation (PT/PTT); Renal function and uric acid at induction.

How can kidney injury from Pegaspargase be prevented?

Hydration and central-line care; tumor-lysis prophylaxis at induction Consider antithrombin replacement and/or LMWH thromboprophylaxis in higher-risk patients

Who is at higher risk of kidney injury from Pegaspargase?

Adolescent/young-adult or adult age and high-risk ALL; Higher cumulative dose and central venous catheters; Concurrent steroids, thrombophilia, obesity, hypertriglyceridemia.

Back to explorer

Printable monograph

Enzyme (asparaginase)

Pegaspargase

Oncaspar · PEGA

Enzyme (asparaginase) · approved 1994 · 8 citations · FAERS AKI reporting ROR 2.83 (95% CI 2.50–3.21, 247 AKI reports)

Aging evidence· through 2020

Deeply sourced7/9 · 6 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 17y)
Met: Beyond single case reports
Met: High-impact journal
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 enzyme whose kidney injury is never direct — find the mediating thrombosis, pancreatitis, or tumor lysis.

MildEnzyme (asparaginase)

Acute lymphoblastic leukemia (first-line multi-agent regimens; and in patients with hypersensitivity to native asparaginase)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Direct nephrotoxicity is not recognized; AKI is indirect and uncommon. Symptomatic thrombosis occurs in ~1.5-5% of children and is higher (~5-10%+) in adults/adolescents-and-young-adults, and clinical pancreatitis in ~5-10%. A drug-specific AKI incidence is not quantified (it is a downstream complication, not a tracked endpoint).Source: Place et al., Lancet Oncol 2015

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Toxicities cluster during induction/first doses; AKI usually reversible with treatment of the underlying thrombosis or pancreatitis.

Distilled from: “Toxicities cluster during induction/first doses; AKI is usually reversible with treatment of the underlying thrombosis or pancreatitis.”

§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 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

§03

Kidney injury

Mechanism of kidney injury

Indirect, predominantly pre-renal/hemodynamic and vascular: (1) asparaginase-associated thrombosis from depletion of liver-synthesized antithrombin, protein C/S, fibrinogen and plasminogen creates a prothrombotic state (including renal-vein/venous thrombosis); (2) pancreatitis with third-spacing and hypovolemia causes prerenal AKI/ATN; (3) hypertriglyceridemia/hyperviscosity and induction tumor lysis add further mechanisms. There is no characteristic direct tubular lesion.

Clinical presentation

Falling antithrombin and fibrinogen during therapy; thrombosis usually during induction/first weeks (often CNS sinus or DVT, occasionally renal vein with flank pain, hematuria and a rising creatinine). Pancreatitis presents with abdominal pain and lipase/amylase >3x ULN days to weeks after a dose.

Management

Treat the mediating event: therapeutic anticoagulation (usually LMWH) for thrombosis — note that antithrombin depletion blunts heparin efficacy, so antithrombin repletion may be needed — and hold asparaginase during acute thrombosis. Permanently discontinue for severe/necrotizing or recurrent pancreatitis. Resuscitate volume for prerenal AKI.Lesion-level management framework

Risk factors

Adolescent/young-adult or adult age and high-risk ALL
Higher cumulative dose and central venous catheters
Concurrent steroids, thrombophilia, obesity, hypertriglyceridemia

Prevention

Hydration and central-line care; tumor-lysis prophylaxis at induction
Consider antithrombin replacement and/or LMWH thromboprophylaxis in higher-risk patients

Anticancer mechanism· how it treats cancer

PEGylated E. coli L-asparaginase that hydrolyzes circulating L-asparagine (and some glutamine). Acute lymphoblastic leukemia (ALL) blasts lack asparagine synthetase and depend on extracellular asparagine, so depletion starves them, halting protein synthesis and inducing apoptosis. PEGylation extends the half-life (~5-7 days) and lowers immunogenicity, allowing every-2-week dosing.

Note · Established (1994) agent; renal events are downstream of thrombosis/pancreatitis/tumor lysis and not separately quantified.

§04

Clinical depth

Renal dose adjustment

The enzyme is cleared by reticuloendothelial/proteolytic mechanisms, not renally excreted, so no renal dose adjustment is required. Hold or adjust for pancreatitis, serious thrombosis/hemorrhage, or severe hypersensitivity — not for creatinine.

Dialyzability & ESKD dosing

Not meaningfully dialyzable (a large PEGylated protein); hemodialysis is not used for removal.

Differential diagnosis

Tumor-lysis urate/phosphate nephropathy, sepsis/ATN, nephrotoxic co-medications (vancomycin, contrast, methotrexate), pancreatitis-related hypovolemia, renal-vein/venous thrombosis, leukemic infiltration and hyperviscosity.

Monitoring

Antithrombin activity and fibrinogen (and serum asparaginase activity where available)
Amylase/lipase, glucose and triglycerides
LFTs/bilirubin and coagulation (PT/PTT)
Renal function and uric acid at induction

Key trials & series

DFCI 05-001 (Place, Lancet Oncol 2015) — pivotal phase 3 establishing IV pegaspargase front-line
CCG-1962 (Kurre, J Pediatr Hematol Oncol 2002) — companion randomized registrational study

Clinical pearls

AKI is almost never direct drug toxicity — find the mediating event (thrombosis, pancreatitis, or induction tumor lysis).
Antithrombin is the linchpin: depleted antithrombin both causes the prothrombotic state and blunts heparin — check and replete it when anticoagulating.
It is an enzyme — not renally cleared and not dialyzable; dose tracks toxicity, not creatinine.
Hold rather than dose-reduce for serious events; discontinue for severe pancreatitis.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Prerenal / Hemodynamic AKI Acute Tubular Necrosis

§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 · 2003–2020 · 1 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 · LimitedAtypical haemolytic uraemic syndrome as a complication of induction chemotherapy for acute lymphoblastic leukaemia.Chandra D et al. · J Clin Pathol 2004 · PMID 15166281Fatal haemolytic uraemic syndrome (thrombotic microangiopathy with acute renal failure) in a child during ALL induction chemotherapy, with the aetiology attributed to L-asparaginase (or vincristine).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 12,172 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· 4 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.

SIADH / Hyponatremia

ROR 3.4895% CI 2.98–4.07· 161 reports

Electrolyte Disturbance

ROR 3.0895% CI 2.76–3.44· 335 reports

Hemorrhagic Cystitis

ROR 3.0395% CI 2.54–3.63· 121 reports

Thrombotic Microangiopathy

ROR 2.1295% CI 1.35–3.32· 19 reports

FAERS outcomes & reporting trend· 12.8% of reports w/ death · 61.4% w/ hospitalization

12.8%

Reported with a death outcome

1,557 of 12,172 reports

61.4%

Reported with hospitalization

7,469 of 12,172 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 12,172 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 2.8395% CI 2.50–3.21· 247 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury247

Blood & lymphatic

Febrile Neutropenia1,584Febrile Bone Marrow Aplasia677Neutropenia572Thrombocytopenia406Anaemia310

Gastrointestinal

Vomiting603Abdominal Pain512Pancreatitis412Nausea404Mucosal Inflammation339

Immune / infection

Sepsis562Pneumonia362Bacterial Infection345Septic Shock336Hypersensitivity331

General / constitutional

Pyrexia777

Hepatobiliary

Hyperbilirubinaemia373Alanine Aminotransferase Increased274

Vascular

Hypotension464

Cardiac

Tachycardia331

Nervous system

Headache258

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 Pegaspargase 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

Tasonermin

Beromun · Recombinant TNF-α (cytokine)

Profile

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

PREATN

Moderate#1 · 94% phenotype match

Binimetinib

Mektovi · MEK inhibitor

Profile

Creatinine rise; rhabdomyolysis reports.

ATNPRE

Mild#2 · 89% phenotype match

Sotorasib

Lumakras · KRAS G12C inhibitor

Profile

Newer agent; renal data emerging.

PREATN

Mild#3 · 89% phenotype match

Tretinoin (ATRA)

Vesanoid · Retinoid (differentiating agent)

Profile

Differentiation syndrome → capillary leak and AKI.

PREATN

Moderate#4 · 83% phenotype match

Tagraxofusp

Elzonris · IL-3 immunotoxin

Profile

Capillary-leak syndrome → AKI.

PREATN

Moderate#5 · 83% phenotype match

Talquetamab

Talvey · Bispecific (GPRC5D×CD3)

Profile

CRS-related AKI — emerging.

PREATN

Moderate#6 · 83% phenotype match

Compare Pegaspargase 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 Cytokines & enzymes

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.

1AsparaginasePRE — Prerenal / Hemodynamic AKIMild
2Pegaspargase· this agentPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
3TasonerminPRE — Prerenal / Hemodynamic AKIModerate
4Interleukin-2 (high-dose)PRE — Prerenal / Hemodynamic AKIFAERS AKIModerate
5Interferon-αGLOM — Glomerular Injury / ProteinuriaSevere

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.