Is kidney injury from Plicamycin (mithramycin) reversible?

Partially reversible. Typical onset: With repeated / cumulative dosing (days to weeks)..

How should kidney function be monitored during Plicamycin (mithramycin) therapy?

Serum calcium and phosphate (risk of overshoot hypocalcemia); Liver enzymes and platelet count / coagulation (hepatic and hemorrhagic toxicity); Renal function closely during therapy.

How can kidney injury from Plicamycin (mithramycin) be prevented?

Avoid in patients with renal dysfunction Limit cumulative dose and dosing frequency (lower antihypercalcemic doses are less toxic than antitumor doses)

Who is at higher risk of kidney injury from Plicamycin (mithramycin)?

Pre-existing renal impairment; Repeated or high cumulative dosing; Concomitant nephrotoxins.

Back to explorer

Printable monograph

Antitumor antibiotic

Plicamycin (mithramycin)

Mithracin · Plica

Antitumor antibiotic · approved 1970 · 9 citations

Dated evidence· through 2017

Fairly sourced5/9 · 4 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 34y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Not met: Current through 2017
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.

An older antitumor antibiotic and bone-resorption inhibitor with cumulative, dose-limiting renal tubular toxicity.

ModerateAntitumor antibiotic (aureolic acid)

Hypercalcemia of malignancy (historical)Testicular germ-cell tumors (historical)Paget disease of bone (historical)

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Representative incidence5%

Cumulative, dose-related nephrotoxicity is a recognized dose-limiting toxicity; when used for hypercalcemia, its antiresorptive potency can overshoot to symptomatic hypocalcemia. Precise modern incidence is not well quantified because the drug is now essentially obsolete. The comparative hypercalcemia-tolerability review cited here pooled trials of at least 10 patients and reported serum creatinine elevation in 5% of plicamycin-treated patients, alongside hepatotoxicity in 26% and nausea/vomiting in 23%. The creatinine figures it gives for etidronate (8%), clodronate (5%) and pamidronate (2%) are bisphosphonate rates from the same review and are not plicamycin's.Source: Zojer, Drug Saf 1999

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

With repeated / cumulative dosing (days to weeks).

Distilled from: “With repeated / cumulative dosing (days to weeks).”

§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.

Acute Tubular Necrosis#1 · Signatureno population incidence denominator
Dose-dependent acute tubular injury / AKI; nephrotoxicity reported even after a single 25 microgram/kg dose, with pre-existing renal impairment magnifying the effect. Cumulative-dose renal toxicity historically limited its use. PMID 6227249 (opens PubMed in a new tab)
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.

5%incidence

SeverityModerate

ReversibilityPartially reversible

Evidence9 citations

Nephron map

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

Acute Tubular Necrosis

Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

§03

Kidney injury

Mechanism of kidney injury

Direct tubular epithelial toxicity affecting both proximal and distal segments impairs electrolyte handling, producing electrolyte wasting and, with cumulative exposure, frank acute tubular necrosis and a rising creatinine. Superimposed on this, its potent inhibition of osteoclastic bone resorption lowers serum calcium and phosphate, so the electrolyte picture reflects both the renal tubular lesion and the antiresorptive effect. Toxicity is cumulative and increases with repeated dosing and with pre-existing renal impairment.

Clinical presentation

Hypocalcemia (sometimes symptomatic), hypophosphatemia and hypokalemia with a rising creatinine; frequently accompanied by hepatotoxicity and a hemorrhagic diathesis (thrombocytopenia and clotting-factor effects), which together limited the drug's use.

Management

Discontinue for renal dysfunction; correct electrolyte derangements including hypocalcemia (calcium repletion) and provide supportive care. Bisphosphonates (and later denosumab) have entirely replaced plicamycin for hypercalcemia owing to its nephrotoxicity and hemorrhagic toxicity.Lesion-level management framework

Risk factors

Pre-existing renal impairment
Repeated or high cumulative dosing
Concomitant nephrotoxins

Prevention

Avoid in patients with renal dysfunction
Limit cumulative dose and dosing frequency (lower antihypercalcemic doses are less toxic than antitumor doses)

Anticancer mechanism· how it treats cancer

Aureolic-acid antitumor antibiotic that binds GC-rich DNA in the minor groove (in a magnesium-dependent fashion), displacing Sp1-family transcription factors and inhibiting RNA and protein synthesis. It also potently inhibits osteoclastic bone resorption, the basis of its historical use for hypercalcemia. Historically used for testicular germ-cell tumors and hypercalcemia of malignancy / Paget disease.

Note · The drug is no longer commercially marketed in many regions.

§04

Clinical depth

Renal dose adjustment

Contraindicated/avoided in significant renal impairment because nephrotoxicity is cumulative and dose-related; lower doses are used for hypercalcemia than for antitumor effect. No validated renal dose-adjustment schema exists given its obsolescence — the practical guidance is avoidance when renal function is impaired.

Dialyzability & ESKD dosing

Not characterized; dialysis is not used for dosing. Hemodialysis would be employed only to manage AKI complications, not to remove the drug.

Differential diagnosis

Hypocalcemia here reflects both antiresorptive overshoot and tubular electrolyte wasting; distinguish from hungry-bone syndrome and from hypomagnesemia-driven hypocalcemia. The rising creatinine of cumulative ATN must be separated from prerenal azotemia of hypercalcemia-related volume depletion (which improves with hydration).

Monitoring

Serum calcium and phosphate (risk of overshoot hypocalcemia)
Liver enzymes and platelet count / coagulation (hepatic and hemorrhagic toxicity)
Renal function closely during therapy

Key trials & series

Historical hypercalcemia-of-malignancy series comparing plicamycin with emerging bisphosphonates

Clinical pearls

Plicamycin is a teaching relic: cumulative tubular toxicity plus a hemorrhagic diathesis is why bisphosphonates supplanted it.
When it was used for hypercalcemia, the danger was overshooting into symptomatic hypocalcemia.
Avoid entirely in renal impairment — the nephrotoxicity is dose-cumulative.

Beyond the kidney — non-renal toxicities· 2 organ systems

Class-level context for the major non-renal toxicities of the Antitumor antibiotic class.

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Mitomycin / bleomycin pulmonary toxicity

Hematologic

Cytopenias, thrombosis, TMA

Cumulative myelosuppression

§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 · 1992–2017 · 1 since 2015

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· 2

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 · LimitedNephrotoxicity following single dose mithramycin therapy.Benedetti RG et al. · Am J Nephrol 1983 · PMID 6227249Case report of acute renal dysfunction (nephrotoxicity) following a single 25 mcg/kg dose of mithramycin in a patient with hypercalcemia and underlying renal impairment.CaseC · Limited[Acute fatal hepatorenal failure during treatment with mithramycin].Hémon Y et al. · Ann Fr Anesth Reanim 1985 · PMID 3160268Case report of acute fatal renal failure with anuria (alongside hepatic failure) developing during mithramycin treatment of malignant hypercalcemia.

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 Plicamycin (mithramycin) 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

Nedaplatin

Aqupla · Platinum agent

Profile

Second-gen platinum with reduced renal toxicity vs cisplatin.

ATNLYTE

Moderate#1 · 78% phenotype match

Melphalan flufenamide (melflufen)

Pepaxto · Peptide-conjugated alkylator

Profile

Delivers melphalan intracellularly; BRIDGE supports a reduced 30 mg dose in moderate renal impairment.

ATNLYTE

Moderate#2 · 75% phenotype match

Telisotuzumab vedotin (Teliso-V)

Emrelis · c-Met ADC (MMAE)

Profile

c-Met MMAE antibody-drug conjugate; proximal tubular ATN risk extrapolated from the ADC/MMAE class.

ATNLYTE

Moderate#3 · 74% phenotype match

Trabectedin

Yondelis · Marine alkylating agent

Profile

Rhabdomyolysis → pigment nephropathy; hepatotoxicity.

ATNLYTE

Moderate#4 · 71% phenotype match

Enfortumab vedotin

Padcev · Antibody-drug conjugate (Nectin-4/MMAE)

Profile

Emerging AKI and electrolyte signals in urothelial cancer.

ATNLYTEPRE

Moderate#5 · 62% phenotype match

Trastuzumab deruxtecan

Enhertu · Antibody-drug conjugate (HER2/DXd)

Profile

Emerging AKI/proteinuria reports — under-published.

ATNFANCLYTE

Moderate#6 · 62% phenotype match

Compare Plicamycin (mithramycin) 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 Antitumor antibiotics

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.

1IdarubicinXTAL — Crystal / Obstructive NephropathyMild
2BleomycinPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
3DoxorubicinGLOM — Glomerular Injury / ProteinuriaFAERS AKIMild
4MitoxantroneXTAL — Crystal / Obstructive NephropathyFAERS AKIMild
5Plicamycin (mithramycin)· this agentATN — Acute Tubular NecrosisModerate
6Dactinomycin (actinomycin D)LYTE — Electrolyte DisturbanceModerate
7Mitomycin CTMA — Thrombotic MicroangiopathySevere

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.