What kind of kidney injury does Procarbazine cause?

Acute Tubular Necrosis — Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate. Other reported patterns: Acute Interstitial Nephritis.

How should kidney function be monitored during Procarbazine therapy?

Tumor-lysis labs (potassium, phosphate, uric acid, calcium) in bulky disease; Urinalysis if creatinine rises (granular casts vs sterile pyuria); Signs of hypersensitivity (rash, fever, eosinophilia).

How can kidney injury from Procarbazine be prevented?

Tumor-lysis prophylaxis (hydration, urate-lowering) in high-burden disease Recognize and avoid re-challenge after hypersensitivity

Who is at higher risk of kidney injury from Procarbazine?

Bulky/chemosensitive disease (tumor lysis); Concurrent nephrotoxins in combination regimens (cisplatin, methotrexate, nitrosoureas); Volume depletion; Prior hypersensitivity to procarbazine.

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Printable monograph

Hydrazine alkylating agent

Procarbazine

Matulane · Procarb

Hydrazine alkylating agent · approved 1969 · 4 citations

Aging evidence· through 2021

Fairly sourced5/9 · 4 signals

Not met: 4 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 38y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
Not 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.

A classic lymphoma alkylator listed among the cytotoxics with recognized renal complications.

ModerateHydrazine alkylating agent

Hodgkin lymphoma (MOPP and variants)Brain tumors (PCV regimen)

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Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Not well quantified at the drug-specific level. Procarbazine appears in classic onconephrology reviews of the renal complications of cytotoxic therapy as an agent with recognized renal/urological complications, and it is part of multi-agent lymphoma regimens in which acute renal failure (often multifactorial — tumor lysis, volume depletion, combined nephrotoxins) is described. Discrete procarbazine-attributable nephrotoxicity is largely case-/review-level rather than quantified.Source: Healy & Clarkson, Aust N Z J Med 1983 (renal complications of cytotoxic therapy)

Onset & rechallenge

Time to injuryVariable / unpredictable

Tumor-lysis AKI within days in bulky disease; hypersensitivity-type injury after re-exposure.

Distilled from: “Variable; tumor-lysis-related AKI within days of starting in bulky disease, hypersensitivity-type injury after re-exposure.”

RechallengeHigh recurrence risk

Hypersensitivity-type injury has been described after re-exposure.

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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.

Acute Tubular Necrosis#1 · Signaturequalitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Acute Interstitial NephritisSecondaryqualitative — no citable incidence
Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.

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Kidney injury

Mechanism of kidney injury

As a hydrazine alkylator activated to reactive methylating and oxidizing intermediates (including hydrogen-peroxide generation), procarbazine can in principle injure renal tubular epithelium via alkylation and oxidative stress (an acute tubular pattern). Being an MAO inhibitor and a frequent hypersensitivity sensitizer, it can also contribute to a hypersensitivity/allergic acute interstitial nephritis pattern. In practice, kidney injury during procarbazine-containing regimens is usually multifactorial — tumor lysis, volume depletion, hypercalcemia, and co-administered nephrotoxins (cisplatin, methotrexate, nitrosoureas) — so isolating a pure procarbazine lesion is difficult and the published renal evidence is conservative and case-/review-based.

Clinical presentation

When implicated, a subacute creatinine rise; an ATN pattern would show granular casts and tubular proteinuria, whereas an interstitial/hypersensitivity pattern may accompany rash, fever, eosinophilia, and sterile pyuria. Hypersensitivity reactions to procarbazine are otherwise well recognized (pulmonary, dermatologic).

Management

Supportive: hydration, correct electrolytes and treat tumor lysis; hold the drug for significant AKI or hypersensitivity. For suspected interstitial nephritis, discontinue and consider corticosteroids with nephrology input. Within combination regimens, identify and address the dominant contributor.Lesion-level management framework

Risk factors

Bulky/chemosensitive disease (tumor lysis)
Concurrent nephrotoxins in combination regimens (cisplatin, methotrexate, nitrosoureas)
Volume depletion
Prior hypersensitivity to procarbazine

Prevention

Tumor-lysis prophylaxis (hydration, urate-lowering) in high-burden disease
Recognize and avoid re-challenge after hypersensitivity

Anticancer mechanism· how it treats cancer

Oral hydrazine-derivative alkylating agent that is metabolically activated (CYP- and oxidation-dependent) to reactive methyldiazonium species that methylate DNA and generate hydrogen peroxide, causing DNA strand breaks. A monoamine-oxidase inhibitor with dietary/drug interactions. Long-standing component of lymphoma regimens (MOPP) and brain-tumor therapy (PCV).

Note · Renal-specific literature is thin and historical; kidney injury in procarbazine regimens is typically multifactorial. Classification here (ATN signature with possible hypersensitivity interstitial nephritis) is conservative and class-/case-based rather than quantified.

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Clinical depth

Renal dose adjustment

No well-validated renal dosing algorithm; use caution in renal impairment given active metabolite handling, and consider dose reduction with close monitoring. Hepatic impairment and MAO-inhibitor drug/dietary interactions are the better-defined dosing concerns.

Dialyzability & ESKD dosing

Dialyzability not well characterized; the parent drug is short-lived and extensively metabolized. No established ESKD dosing — manage clinically with attention to active metabolites.

Differential diagnosis

In a procarbazine regimen, separate tumor-lysis AKI, prerenal volume depletion, and co-administered platinum/methotrexate/nitrosourea nephrotoxicity from a drug-specific tubular or hypersensitivity interstitial lesion; rash/fever/eosinophilia and sterile pyuria point to interstitial nephritis.

Monitoring

Tumor-lysis labs (potassium, phosphate, uric acid, calcium) in bulky disease
Urinalysis if creatinine rises (granular casts vs sterile pyuria)
Signs of hypersensitivity (rash, fever, eosinophilia)

Key trials & series

Healy & Clarkson Aust N Z J Med 1983 cytotoxic renal-complications review (lists procarbazine)
Historical MOPP and PCV regimen experience

Clinical pearls

AKI during a procarbazine-containing regimen is usually multifactorial — look for tumor lysis, volume depletion, and partner nephrotoxins before blaming procarbazine.
Procarbazine is a recognized hypersensitivity sensitizer; rash/fever/eosinophilia with a creatinine rise suggests interstitial nephritis — stop and consider steroids.
It is an MAO inhibitor — the dominant safety teaching is dietary/drug interactions, with renal injury a secondary, conservative concern.
Give tumor-lysis prophylaxis in bulky lymphoma where procarbazine regimens are used.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Interstitium

Supporting tissue around the tubules

Injury signatures

Acute Tubular Necrosis Acute Interstitial Nephritis

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the Hydrazine alkylating agent class.

Ophthalmic

Keratopathy, uveitis, retinopathy

Visual disturbance (crizotinib)

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

CNS effects (lorlatinib)

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References

4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 1983–2021 · 1 since 2019

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.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Sep 2024) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING It is recommended that MATULANE be given only by or under the supervision of a physician experienced in the use of potent antineoplastic drugs. Adequate clinical and laboratory facilities should be available to patients for proper monitoring of treatment.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 4,488 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.
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 outcomes & reporting trend· 7.2% of reports w/ death · 12.9% w/ hospitalization

7.2%

Reported with a death outcome

323 of 4,488 reports

12.9%

Reported with hospitalization

580 of 4,488 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 4,488 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 1.1795% CI 0.85–1.61· 38 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Gastrointestinal

Nausea973Vomiting304Constipation265Diarrhoea135Stomatitis63

General / constitutional

Fatigue829Pyrexia80Asthenia71Pain67Weight Decreased62

Blood & lymphatic

Platelet Count Decreased239White Blood Cell Count Decreased229Neutropenia132Thrombocytopenia100Anaemia62

Nervous system

Headache172Dizziness104Neuropathy Peripheral63Paraesthesia63

Skin

Rash148Urticaria103Alopecia52

Metabolic & electrolyte

Decreased Appetite177

Guidelines & consensus· 14

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.

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 Procarbazine 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

Cobimetinib

Cotellic · MEK inhibitor

Profile

Real-world AKI signal with BRAF partners.

ATNAIN

Mild#1 · 82% phenotype match

Encorafenib

Braftovi · BRAF inhibitor

Profile

Class tubular signal; usually mild.

ATNAIN

Mild#2 · 82% phenotype match

Nimustine (ACNU)

Nidran · Nitrosourea (alkylating)

Profile

Water-soluble nitrosourea; renal risk inferred at class level; cumulative delayed tubulointerstitial injury; DLT is myelosuppression.

CINATNLYTE

Moderate#3 · 63% phenotype match

Fotemustine

Muphoran · Nitrosourea (alkylating)

Profile

Class delayed cumulative tubulointerstitial/ATN; usually mild; acute signal often really cisplatin.

CINATNLYTE

Moderate#4 · 62% phenotype match

Samarium-153 lexidronam

Quadramet · Bone-seeking radiopharmaceutical (153Sm-EDTMP)

Profile

Renally excreted; dominant toxicity is reversible myelosuppression; caution in renal impairment.

ATN

Moderate#5 · 55% phenotype match

BRAF / MEK inhibitors (vemurafenib · dabrafenib · trametinib)

BRAF/MEK inhibitor

Profile

Tubulointerstitial AKI; vemurafenib strongest.

ATNAINLYTE

Mild#6 · 53% phenotype match

Compare Procarbazine 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 Alkylating 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.

Who studies this

The leading contributors to Procarbazine’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 Procarbazine; 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 7 clinical records among all 22 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.