The Injury Atlas
GLOM
Glomerular Injury / Proteinuria
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.
33agents
Severity mix
Severe· 4Moderate· 22Mild· 7
Reversibility
Often irreversible· 2Partially reversible· 7Variable· 8Reversible· 16
Signature offenders
9Agents for which glomerular injury / proteinuria is the defining renal lesion.
Interferon-αSubacute — weeks to months of therapy.Rare; best characterized by an 11-case biopsy series, disproportionately in Black patients (APOL1).SeverePamidronateSubacute — weeks to months of therapy.Not well quantified; the histopathologic pattern comes from case series, notably at higher-than-approved doses.SevereBevacizumabWeeks to months; dose-dependent.All-grade proteinuria ~20–40%; high-grade ~2.2%. Hypertension RR 3–7.5. Nephrotic syndrome RR 7.78.ModerateSirolimusVariable—weeks to months after initiation or dose escalation; proteinuria characteristically emerges or worsens within months after calcineurin-inhibitor withdrawal/conversion.New or worsening proteinuria occurs in a substantial minority of treated patients in transplant cohorts (more pronounced after conversion from a calcineurin inhibitor than with de novo use), but oncology-specific renal incidence is not well quantified and is described largely at the case and small-series level. Acute renal dysfunction (e.g., delayed graft recovery) is recognized but variable.ModerateDasatinibProteinuria can appear within weeks to months and increases with treatment duration and exposure.Dasatinib causes significantly more albuminuria than other TKIs. In a pharmacokinetic cohort, dasatinib users had higher urine albumin-creatinine ratios and about 10% showed severely increased albuminuria (UACR >300 mg/g) versus none on other TKIs, with the degree of proteinuria correlating with plasma exposure. Nephrotic-range proteinuria with biopsy-proven glomerular injury (FSGS, podocyte foot-process effacement, endothelial injury) is reported in cases.ModeratemTOR InhibitorsWeeks–months.Everolimus all-grade proteinuria ~10–14%, high-grade ~1–2%. Temsirolimus case-level only.MildDoxorubicinSubacute in models (over weeks); clinical events rare and variable.Adriamycin nephropathy is the canonical rodent model of podocyte injury and focal segmental glomerulosclerosis (FSGS); clinically significant glomerular disease from therapeutic dosing in patients is rare and largely case-level.MildErlotinibWeeks to months after starting therapy; proteinuria/creatinine typically improve over weeks after discontinuation in reported cases.Glomerular disease (including minimal-change-type nephrotic syndrome) and acute kidney injury are reported rarely, at the case level; pharmacovigilance data show measurable disproportionality signals for AKI/renal failure (and rare TMA) but no robust trial-based incidence.MildGefitinibWeeks to months after initiation in reported cases; proteinuria resolves over weeks to months after stopping the drug.Nephrotic syndrome (minimal-change disease and secondary membranous nephropathy patterns) and rare acute renal failure are reported only as isolated cases; not quantified in clinical-trial datasets.Mild
Also associated
24Agents that cause glomerular injury / proteinuria as a secondary pattern alongside a different signature lesion.
GemcitabineDelayed — months of cumulative exposure.~0.015–2.2%; best single estimate ~0.31% cumulative. Historically high mortality.SevereMitomycin CDelayed — after cumulative dosing, sometimes after therapy ends.Dose-dependent, generally 4–15%; risk rises sharply at cumulative dose ≥30 mg/m². >50% historical mortality.SevereVEGFR Tyrosine Kinase InhibitorsHypertension within days–weeks; proteinuria over weeks–months.Hypertension ~17–50%; proteinuria 8–73% across agents (all-grade ~18.7%, high-grade ~2.4%).ModerateClofarabineEarly, typically within the first treatment cycle (days).A systemic inflammatory response syndrome (SIRS) / capillary-leak syndrome with associated AKI was reported in roughly 4% of treated children in the registration program; hypotension was among the most common grade 3 or greater adverse events in the pivotal phase II trial. Precise renal incidence is not well quantified and most AKI data are case-level.ModerateRamucirumabWithin the first one to two cycles (weeks).Hypertension and proteinuria are common class effects; nephrotic syndrome is a less frequent but reported event, sometimes after only 1-2 doses and typically accompanied by hypertension.ModerateZiv-afliberceptWithin weeks to a few months of therapy.Hypertension and proteinuria are common class effects; in the registrational VELOUR trial, grade 3-4 hypertension and proteinuria were notably more frequent with aflibercept plus FOLFIRI than with FOLFIRI alone. Nephrotic-range proteinuria and renal thrombotic microangiopathy are documented, including with the ophthalmic formulation, indicating a direct VEGF-trap mechanism.ModerateLenvatinibWithin the first weeks of therapy (hypertension early; proteinuria over weeks).Hypertension is among the most common adverse events; in the SELECT thyroid-cancer trial hypertension occurred in about 68% (grade >=3 ~42%) and proteinuria in roughly 31%. In KEYNOTE-B61 (lenvatinib plus pembrolizumab) grade 3-4 hypertension occurred in ~23%. Proteinuria is a frequent renal AE with lenvatinib.ModerateCabozantinibWithin weeks of starting therapy.Hypertension and proteinuria are common; in pivotal RCC trials (e.g., METEOR, CABOSUN) hypertension was among the most frequent adverse events with grade >=3 rates around 15-28%. Cabozantinib is one of the TKIs most often associated with proteinuria, with case reports of nephrotic syndrome.ModerateRegorafenibWithin the first weeks of therapy.Hypertension is a common, frequently grade 3 adverse event (in the CORRECT trial hypertension occurred in about 28%, grade 3 ~7%); proteinuria also occurs as a VEGF-pathway class effect. Drug-specific quantitative renal data are otherwise limited.ModerateVandetanibWithin the first weeks of therapy.In the pivotal phase III ZETA trial, any-grade hypertension occurred in about 32% of vandetanib-treated patients versus 5% with placebo; proteinuria occurs as an antiangiogenic class effect.ModerateTivozanibWithin the first weeks of therapy.In the phase III TIVO-3 trial, hypertension was the most common grade 3-4 treatment-related adverse event, occurring in about 20% of tivozanib-treated patients; proteinuria occurs as a VEGFR class effect but is comparatively less prominent.ModerateAtezolizumabTypically weeks to a few months after initiation (median time to checkpoint-inhibitor AKI is on the order of 3-4 months, characteristically later than classic drug AIN).Across the checkpoint-inhibitor class, any acute kidney injury occurs in roughly 15-17% of treated patients in cohort studies, while clinically significant immune-related AKI (most often acute interstitial nephritis) affects a smaller subset (commonly a few percent). Meta-analysis suggests anti-PD-L1 agents like atezolizumab carry somewhat lower AKI risk than anti-PD-1 agents; PD-L1-specific rates are not precisely separated.ModerateDurvalumabWeeks to several months after starting therapy.As with the PD-1/PD-L1 class, any AKI occurs in roughly 15-17% of treated patients, with immune-related AIN representing a smaller, clinically significant fraction (a few percent). Anti-PD-L1 agents trend toward lower AKI risk than anti-PD-1 agents; durvalumab-specific rates are not separately well quantified.ModerateAvelumabWeeks to months after initiation.Immune-related nephritis follows the PD-1/PD-L1 class pattern: any AKI in roughly 15-17% of patients and clinically significant immune-related AIN in a smaller subset. Anti-PD-L1 agents trend toward lower AKI risk than anti-PD-1 agents; avelumab-specific renal incidence is not separately quantified and rests on class-level pharmacovigilance and meta-analysis data.ModerateCemiplimabWeeks to months after initiation.Follows the PD-1/PD-L1 class profile: any AKI in roughly 15-17% of patients, with immune-related AIN in a smaller clinically significant subset. As an anti-PD-1 agent it may carry somewhat higher AKI risk than anti-PD-L1 agents, and pharmacovigilance data show an immune-nephropathy signal; cemiplimab-specific renal incidence is not separately quantified.ModerateDostarlimabWeeks to months after initiation.Consistent with the PD-1/PD-L1 class: any AKI in roughly 15-17% of treated patients, with immune-related AIN in a smaller clinically significant subset. As a newer anti-PD-1 agent, dostarlimab-specific renal incidence is not separately quantified.ModerateTrastuzumab emtansine (T-DM1)Variable; reported after initiation, over weeks to months of therapy.Renal toxicity is rare and case-level. FDA adverse-event analyses flagged renal events with trastuzumab-based therapy, and biopsy-proven cases (collapsing focal segmental glomerulosclerosis; TMA-like microvascular injury) have been reported. Incidence is not quantified.ModerateBortezomibRare adverse renal events occur during therapy (days to weeks); the beneficial light-chain reduction is often rapid.Bortezomib is generally renal-friendly and often improves renal function in myeloma by rapidly reducing light-chain-driven cast nephropathy; it requires no renal dose adjustment. Thrombotic microangiopathy and glomerular microangiopathy are rare, case-level events, and pharmacovigilance shows a far weaker TMA signal than carfilzomib.ModerateIbrutinibHypertension develops over weeks–months (can be early); tumor lysis is early (first cycle); glomerular/interstitial lesions are case-level over weeks to months.New or worsened hypertension is common (~26% in a real-world CLL cohort comparing it with acalabrutinib; higher with longer follow-up). AKI at CLL presentation and with tumor lysis is well described. Drug-attributable AKI from interstitial nephritis or glomerular endotheliosis is case-level.ModerateDatopotamab deruxtecan (Dato-DXd)Not well characterized (recent approval); by class analogy a subacute tubular pattern during cumulative dosing.Renal signal is theoretical and not yet quantified, extrapolated from the ADC class. In TROPION-PanTumor01 and the phase III TROPION-Breast01 the dominant toxicities were mucosal (stomatitis ~50%) and ocular events, nausea, and interstitial lung disease; grade ≥3 treatment-related adverse events were actually lower than chemotherapy (~21%), and kidney-specific events were not prominent.ModerateFruquintinibWithin weeks of starting therapy (hypertension often earliest).Hypertension and proteinuria are characteristic VEGFR-TKI class effects; in the FRESCO-2 safety analysis hypertension was among the most frequent grade ≥3 adverse events, with proteinuria also reported. Renal-specific TMA is rare but described across the VEGF-inhibitor class.ModerateNintedanibOver months of therapy in reported cases.Renal effects are uncommon; proteinuria and rare biopsy-proven renal thrombotic microangiopathy have been reported, consistent with VEGF-pathway inhibition. Renal incidence is not well quantified (case-level), and much of the published renal experience comes from pulmonary-fibrosis rather than oncology cohorts.MildBelantamab mafodotinVariable; renal events reported during prolonged therapy. Ocular toxicity is often detectable within the first cycles.Renal-specific data are emerging and sparse; direct nephrotoxicity is not an established signal. In myeloma, AKI more often reflects the underlying disease (cast nephropathy, hypercalcemia, volume status) than the ADC. A case of focal segmental glomerulosclerosis after belantamab mafodotin (confounded by severe COVID-19) has been reported. The defining toxicity is ocular keratopathy (71-77% in DREAMM-2).MildAdagrasibEarly — within the first weeks of therapy.Renal effects are usually mild: a creatinine rise (partly from inhibited tubular creatinine secretion) plus prerenal AKI from GI losses. The KRYSTAL-1 registrational program reported renal-related lab changes; a dedicated PubMed-indexed pseudo-AKI/albuminuria study for adagrasib does not yet exist, so the precise incidence is unquantified.Mild