Which anti-cancer drugs cause fanconi syndrome?

Fanconi Syndrome is the signature kidney injury of Ifosfamide, Streptozocin, Azacitidine. It is also associated with Cisplatin, Zoledronic acid, Trastuzumab deruxtecan, Lenalidomide, Vemurafenib, BRAF / MEK Inhibitors, Imatinib, Nirogacestat.

The Injury Atlas

FANC

Fanconi Syndrome

Global failure of proximal tubule reabsorption — glucosuria, phosphaturia and acidosis, classically from ifosfamide.

11agents

Deep diveIfosfamide Fanconi Deep diveBRAF/MEK tubular

Where it strikes

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

See it on the nephron

Agents’ overall severity

Each agent’s whole-drug severity grade, not the severity of this lesion specifically — an agent whose signature injury is elsewhere can still be graded severe here.

Severe· 3Moderate· 5Mild· 3

Agents’ overall reversibility

Often irreversible· 1Partially reversible· 4Variable· 2Reversible· 4

Does the kidney recover? Cross-drug outcomes

Agents’ onset window

How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.

Acute (days)· 4Subacute (weeks)· 2Delayed (weeks–months)· 1Variable· 4

Real-world reporting for this lesion

FAERS across all lesions →

Agents with a disproportionate FAERS reporting signal for fanconi syndrome (reporting odds ratio with a 95% CI lower bound above 1) — a spontaneous-reporting signal, not incidence or proven causation. FAERS carries reporting and indication biases and has no denominator.

4Corroborated

Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.

5Documented, FAERS-silent

Documented in a profile with no reporting signal. Mostly expected: naming this lesion on a report can require a biopsy, and silence is not evidence against the literature.

12Not attributable

A real reporting signal that is not evidence for this drug-lesion pair: no MedDRA term names it, the naming subset asked alone came back flat, or the 2026-08 review attributed the reporting to the population, co-therapy, or class-level literature.

7Reported by name

The terms that name this lesion are disproportionate, but no profile documents it for that agent. Most are echoed by a sibling agent in the same class. Leads for review, never lesions the atlas claims.

23 agents with a significant FANC reporting signal.

Management approach

Full framework →

Supportive electrolyte and acid–base repletion; often partially irreversible, so prevention (cumulative-dose limits) matters.

Drug-level levers

Hold or avoid further exposure once Fanconi features appear.
Respect cumulative-dose limits; use caution in young children and after prior cisplatin exposure.

Pharmacologic toolkit

Electrolyte repletion — Phosphate, bicarbonate or citrate (for proximal renal tubular acidosis), and potassium replacement.
Supportive — Monitor growth in children; some proximal tubular dysfunction persists long-term.

When to biopsy

Usually clinical (glucosuria with normal serum glucose, phosphaturia, proximal RTA); biopsy not routinely required.

Monitoring

· Phosphate, bicarbonate, potassium, glucose
· Growth in children

Grounding

Ifosfamide nephrotoxicity (Fanconi syndrome) · PMID 8418231 ↗

Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.

What the guidelines say

All guidelines →

Society and consensus recommendations that speak to fanconi syndrome.

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.

Offending agents

Any agent11 Primary (#1) only3

Signature offenders

Agents for which fanconi syndrome is the defining renal lesion.

IfosfamideAcute tubulopathy during therapy; chronic Fanconi/CKD can emerge months–years later.Subclinical tubular dysfunction is common while overt Fanconi is not, and the gap is the point. In 183 children investigated prospectively at least 5 years out — none of whom received any platinum, so the toxicity is attributable — the tubular threshold for phosphate was reduced in 24% and glycosuria detected in 37%, yet glycosuria exceeded 0.5 g/24 h in only 5%, bicarbonate and calcium were normal in every patient, and 89.5% had normal tubular function overall at a median 10 years. GFR was abnormal in 21.5%. Ifosfamide dose and time since therapy both predicted tubulopathy. Rates elsewhere span 0% to 84% depending on the definition and cohort used, so a single figure is only meaningful with its threshold attached.Severe StreptozocinWithin weeks of therapy; worsens with cumulative dose; abrupt AKI possible on re-challenge.Nephrotoxicity is the major dose-limiting toxicity; transient proteinuria, tubular dysfunction and azotemia are common and a sizable minority develop clinically significant renal impairment, though precise rates are not uniformly quantified. Reported rate: decrease in estimated glomerular filtration rate of at least 25% during treatment in 30% — 111 patients (27 prospective + 84 retrospective) with locally advanced or metastatic well-differentiated digestive… (Legoux 2021, PMID 33751987).Severe AzacitidineDuring treatment cycles (days to weeks).Proximal tubular dysfunction (proximal/type 2 renal tubular acidosis, polyuria, and glucose/amino-acid/electrolyte wasting) was described with higher-dose azacitidine; with current low-dose subcutaneous/IV regimens overt AKI is uncommon and renal incidence is not well quantified (case-level).Moderate

Also associated

Agents that cause fanconi syndrome as a secondary pattern alongside a different signature lesion.

CisplatinAcute — creatinine peaks ~day 4–7; magnesium wasting can persist for months.AKI in ~20–35% per cycle (classic teaching: ~1 in 3). Hypomagnesemia in 40–100%.Severe Zoledronic acidAcute — days to weeks after infusion(s).Nephrotoxicity is the dose-limiting toxicity but largely avoidable; no precise population rate. Reported rate: renal toxicity in 17% — 852 patients with symptomatic newly diagnosed multiple myeloma and at least one lytic bone lesion who received at least… (Raje 2018, PMID 29429912).Moderate Trastuzumab deruxtecanVariable; reported during ongoing therapy, sometimes resolving over months after discontinuation.Renal data are emerging and under-published. AKI/proteinuria are reported at case level; a reversible proximal-tubule Fanconi syndrome (glucosuria, phosphate/potassium wasting, non-anion-gap acidosis) has been described and attributed to the deruxtecan payload. Renal-specific incidence is not quantified.Moderate LenalidomideVariable; azotemia reported from weeks to several months after initiation.AKI/azotemia is uncommon but recognized, described mainly in case series of plasma-cell dyscrasias with underlying renal insufficiency; not reliably quantified as an incidence. Rare Fanconi syndrome and TMA are reported. Because ~80% of lenalidomide is renally cleared as unchanged drug, accumulation in renal impairment is the dominant driver of toxicity, including myelosuppression.Moderate VemurafenibEarly — most cases arise within the first weeks to three months of therapy (all AKI events in the Teuma cohort occurred in the first trimester of treatment); later onset is uncommon.Clinically meaningful AKI is a recognized but variably quantified effect, and vemurafenib is the strongest renal offender of the BRAF/MEK class. Small serum-creatinine rises are common and usually low-grade; overt AKI produced the first case series of 8 patients with significant-to-severe renal insufficiency (Launay-Vacher, Cancer 2014) and 132 vemurafenib AKI reports to FDA FAERS over 3 years, far exceeding dabrafenib's 13 (Jhaveri, JAMA Oncol 2015). The monotherapy denominator comes from a retrospective single-center cohort of 74 patients with BRAF-V600-mutant metastatic melanoma, with creatinine measured before treatment, monthly on treatment and 3 months after stopping: 44 of 74 (59.5%) met the KDIGO threshold of a 1.5-fold creatinine rise, and 40 of those 44 (91%) were stage 1. Read that figure with its definition attached — it is creatinine-based, and BRAF/MEK inhibitors also blunt tubular creatinine secretion, so a share of any such cohort is pseudo-AKI rather than tubular injury; the authors biopsied two stage-1 patients to demonstrate real tissue damage. Men were over-represented among the AKI-positive patients (75% versus 40%). Adding a MEK inhibitor lowers it substantially: in the companion cobimetinib cohort 9 of 38 (24%) developed AKI, all within three months and mostly stage 1-2, about a 60% reduction versus monotherapy.Moderate BRAF / MEK InhibitorsAcute–subacute during therapy.Pharmacovigilance shows vemurafenib > dabrafenib. Mild creatinine elevation common, serious AKI uncommon. Reported rate: acute kidney injury in 21% — 199 patients who received dabrafenib/trametinib in a single large US healthcare system between 2010 and 2019… (Seethapathy 2022, PMID 33355659).Mild ImatinibEdema early; tubular dysfunction and eGFR decline develop over months to years.Periorbital/peripheral edema and fluid retention are common. Clinically meaningful renal injury is uncommon: long-term front-line imatinib is associated with a modest, measurable decline in eGFR over years, while proximal tubular dysfunction (hypophosphatemia, aminoaciduria, rare Fanconi syndrome) and AKI (including rare urate nephropathy from disease cytoreduction) are described at the case level.Mild NirogacestatDuring therapy; not well characterized.Hypophosphatemia occurred in 42% of nirogacestat-treated patients in the DeFi trial, alongside other electrolyte disturbances; the characteristic DeFi-trial toxicities were diarrhea, rash, nausea, fatigue and ovarian dysfunction. Beyond the phosphate signal, renal-specific incidence is not well quantified.Mild

See these on the Toxic-Ties graph All 14 lesions