Selumetinib
Koselugo · MEK inhibitor
Creatinine rise in neurofibromatosis.
PRELYTE
Mild#1 · 77% phenotype match
Teniposide
Vumon · VM-26
Podophyllotoxin (topo II) · approved 1992 · 5 citations
Aging evidence· through 2021
Fairly sourced5/9 · 4 signals
- Not met: 5 citations
- Not met: 12+ references
- Met: Accrued over 10+ years (span: 40y)
- 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 highly protein-bound podophyllotoxin whose renal relevance is pharmacokinetic — low renal clearance and exposure, not direct nephron injury.
Mild1992 podophyllotoxin
Refractory childhood acute lymphoblastic leukemia (combination therapy)Selected CNS tumors and other malignancies (regimen-dependent)
§01
Signature kidney injury
Signature lesion
Minimal direct nephrotoxicity. Teniposide is highly protein-bound with low renal clearance (only ~5-20% of a dose is recovered in urine versus a larger fraction for etoposide), so the kidney is a minor elimination route and direct renal injury is not a characteristic toxicity. Renal relevance is pharmacokinetic/exposure-related and not quantified as a discrete nephrotoxicity rate.Source: Clark, Semin Oncol 1992
Onset & rechallenge
Time to injuryVariable / unpredictable
No characteristic renal onset; pharmacokinetic exposure effects are immediate but clinically modest.
Distilled from: “No characteristic renal onset; pharmacokinetic exposure effects are immediate but clinically modest.”
§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.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
§03
Kidney injury
Mechanism of kidney injury
No well-defined direct tubular toxin mechanism. Because teniposide is extensively protein-bound and undergoes limited renal excretion, renal dysfunction has modest effects on its clearance relative to etoposide; the practical concern is altered exposure (and free-fraction shifts with hypoalbuminemia) rather than structural nephron injury. Electrolyte and prerenal changes, when seen, reflect supportive-care context rather than direct toxicity.
Clinical presentation
Direct renal presentation is uncommon. Any renal-related findings are typically electrolyte disturbances or prerenal physiology in intensive leukemia therapy. Hypersensitivity/infusion reactions and myelosuppression dominate the clinical toxicity profile.
Management
No drug-specific renal antidote is needed. Provide supportive care, correct electrolytes and volume, and individualize dosing for organ dysfunction. Manage the dominant toxicities (hypersensitivity, myelosuppression) per protocol.Lesion-level management framework
Risk factors
- Hypoalbuminemia (raises free drug fraction)
- Severe renal or hepatic impairment (altered clearance)
- Concomitant nephrotoxins or prerenal insults in intensive regimens
Prevention
- Account for protein binding and hypoalbuminemia when dosing
Anticancer mechanism· how it treats cancer
Teniposide (VM-26) is a semisynthetic podophyllotoxin derivative and topoisomerase II poison: it stabilizes the enzyme-DNA cleavable complex, producing double-strand DNA breaks and arrest in late S/early G2 phase. More potent and more highly protein-bound than its analog etoposide, it is used chiefly in childhood acute lymphoblastic leukemia (often refractory disease) and has activity in selected CNS and other tumors.
Note · Contrast with etoposide: teniposide's higher protein binding, longer terminal half-life, and lower renal/plasma clearance mean renal dysfunction perturbs its handling less — the teaching point is PK/clearance, not nephrotoxicity.
§04
Clinical depth
Renal dose adjustment
No standardized renal dose-reduction schema is well established given low renal clearance; use caution and consider individualized reduction in severe renal or hepatic impairment and with marked hypoalbuminemia. Follow local protocol.
Dialyzability & ESKD dosing
Not meaningfully dialyzable: extensive (>99%) plasma protein binding and a relatively small free fraction make removal by hemodialysis negligible. Do not rely on dialysis for clearance.
Differential diagnosis
In a leukemia patient with rising creatinine, look first to tumor lysis syndrome, sepsis/prerenal states, nephrotoxic co-medications, and contrast — teniposide itself is rarely the direct cause. Its renal footprint is pharmacokinetic.
Monitoring
- CBC (myelosuppression is dose-limiting)
- Serum albumin (affects free drug fraction)
- Infusion-reaction monitoring
Key trials & series
- Clark 1992 — clinical pharmacology of podophyllotoxin derivatives: teniposide has greater protein binding, longer half-life, and reduced plasma and renal clearance vs etoposide
- Clark & Slevin 1987 — comparative clinical pharmacokinetics of etoposide and teniposide (only ~5-20% of teniposide excreted/recovered, vs more for etoposide)
Clinical pearls
- Only about 5-20% of a teniposide dose appears in urine, so the kidney is a minor exit route.
- Hypoalbuminemia raises the free fraction — a more relevant dosing concern than direct nephrotoxicity.
Where it strikes· nephron segments & injury signatures
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
§05
References
4 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
4 references · 1987–2021 · 1 since 2019Primary (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.
- 1.Toxicity of the topoisomerase II inhibitors.Seiter K · Expert Opin Drug Saf · 2005 · PMID 15794715Review of topoisomerase II inhibitor toxicity covering teniposide and its administration in renal insufficiency, supporting the drug's modest renal-PK profile.
- 2.LandmarkClinical pharmacology and schedule dependency of the podophyllotoxin derivatives.Clark PI · Semin Oncol · 1992 · PMID 1411635States teniposide has greater protein-binding affinity, longer half-life, and reduced plasma and renal clearance than etoposide — the basis for its PK-driven renal relevance.
- 3.The clinical pharmacology of etoposide and teniposide.Clark PI et al. · Clin Pharmacokinet · 1987 · PMID 3297462Comparative PK review documenting that only ~5-20% of teniposide is excreted/recovered (vs more for etoposide), confirming minimal renal elimination.
- 4.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107Onconephrology reference framing which conventional cytotoxics carry meaningful kidney risk, contextualizing teniposide's low direct nephrotoxic profile.
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.
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 Teniposide 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Gallium nitrate
Ganite · Antineoplastic metal salt
Dose-limiting acute tubular necrosis; potentiated by dehydration and concurrent nephrotoxins.
ATNPRELYTE
Moderate#2 · 67% phenotype match
Enfortumab vedotin
Padcev · Antibody-drug conjugate (Nectin-4/MMAE)
Emerging AKI and electrolyte signals in urothelial cancer.
ATNLYTEPRE
Moderate#3 · 67% phenotype match
Daratumumab
Darzalex · Anti-CD38 antibody
Tumor lysis; usable in renal impairment.
PRELYTE
Mild#4 · 66% phenotype match
Isatuximab
Sarclisa · Anti-CD38 antibody
Tumor lysis in myeloma.
PRELYTE
Mild#5 · 66% phenotype match
Octreotide
Sandostatin · Somatostatin analog
Kidney-neutral/possibly renoprotective; renally cleared, caution in severe CKD/dialysis.
LYTEPRE
Mild#6 · 66% phenotype match
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 Topoisomerase inhibitors
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.
- 1TopotecanPRE — Prerenal / Hemodynamic AKIMild
- 2Teniposide· this agentLYTE — Electrolyte DisturbanceMild
- 3IrinotecanPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 4EtoposideXTAL — Crystal / Obstructive NephropathyFAERS AKIMild
- 5AmsacrineLYTE — Electrolyte DisturbanceModerate
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.