The Injury Atlas
FANC
Fanconi Syndrome
Global failure of proximal tubule reabsorption — glucosuria, phosphaturia and acidosis, classically from ifosfamide.
7agents
Severity mix
Severe· 2Moderate· 3Mild· 2
Reversibility
Often irreversible· 1Partially reversible· 1Variable· 2Reversible· 3
Signature offenders
2Agents for which fanconi syndrome is the defining renal lesion.
IfosfamideAcute tubulopathy during therapy; chronic Fanconi/CKD can emerge months–years later.Subclinical proximal tubulopathy is near-universal; overt Fanconi ~5% (range 1.4–30%), higher in young children.SevereStreptozocinWithin 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. A single re-challenge after a stable course can still precipitate acute renal failure.Severe
Also associated
5Agents that cause fanconi syndrome as a secondary pattern alongside a different signature lesion.
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).ModerateTrastuzumab 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.ModerateLenalidomideVariable; 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.ModerateImatinibEdema 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.MildNirogacestatDuring therapy; not well characterized.Electrolyte and phosphate disturbances (including hypophosphatemia) are reported among adverse events; the characteristic DeFi-trial toxicities were diarrhea, rash, nausea, fatigue and ovarian dysfunction. Renal-specific incidence is not well quantified.Mild