The Injury Atlas See it on the nephron Does the kidney recover? Cross-drug outcomesSchematic · not to scale Representative per-agent thrombotic microangiopathy incidence where a published figure is citable — open an agent's name for its profile and cited source, or hover its dot for the source inline. Agents without a citable figure are omitted; a tier without a number is not the same as a low number.
TMA
Thrombotic Microangiopathy
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.
44agents
Where it strikes
Vasculature / Endothelium
Glomerular & peritubular capillaries
Glomerulus
Filtration barrier (podocytes + endothelium)
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· 7Moderate· 26Mild· 11
Agents’ overall reversibility
Often irreversible· 3Partially reversible· 9Variable· 15Reversible· 17
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)· 15Delayed (weeks–months)· 12Variable· 13
Real-world reporting for this lesion
FAERS across all lesions →Agents with a disproportionate FAERS reporting signal for thrombotic microangiopathy (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.
27Corroborated
Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.
9Documented, 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.
4Not 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.
47Reported 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.
5-FluorouracilAtezolizumabAzacitidineBendamustineBevacizumabBleomycinBlinatumomabBortezomibBrentuximab vedotinBusulfanCapecitabineCarboplatinCarfilzomibCarmustine (BCNU)CetuximabCisplatinClofarabineCyclophosphamideCytarabineDacarbazineDactinomycin (actinomycin D)DasatinibDecitabineDinutuximabDocetaxelDostarlimabDoxorubicinDurvalumabElotuzumabErlotinibEtoposideEverolimusFludarabineGemcitabineGemtuzumab ozogamicinIbritumomab tiuxetanIdarubicinIfosfamideImatinibInotuzumab ozogamicinInterleukin-2 (high-dose)IsatuximabIxazomibLenalidomideLenvatinibLifileucelLorlatinibMelphalanMethotrexate (high-dose)Mitomycin CMitoxantroneMogamulizumabNaxitamabNivolumabOxaliplatinPaclitaxelPanitumumabPazopanibPegaspargasePembrolizumabPemetrexedPentostatinPolatuzumab vedotinPonatinibRamucirumabRituximabRuxolitinibSirolimusSorafenibSunitinibTafasitamabTemsirolimusThalidomideThiotepaTopotecanTrabectedinVincristineVinorelbine
78 agents with a significant TMA reporting signal.
§Mechanism, step by step
How anti-cancer drugs cause thrombotic microangiopathy
One lesion, two mechanistic routes — direct endothelial toxicity and VEGF withdrawal — converging on the glomerular capillary. Scroll to follow the injury from the endothelial surface to the sheared red cells on the smear.
At the bedside
VEGF-TMA deep dive →TMA is a final common pathway — the workup turns on the cause. Narrow the differential, then estimate the pretest probability of TTP before reaching for plasma exchange. After hematopoietic cell transplant, see the dedicated TA-TMA page.
What's driving this TMA?
Thrombotic microangiopathy is a final common pathway — the treatment turns entirely on the cause. Select a driver.
ADAMTS13
Normal / near-normal
How to tell
A temporal link to a culprit nephrotoxin. VEGF inhibitors give a renal-limited, proteinuric picture; gemcitabine, mitomycin C, carfilzomib, and calcineurin inhibitors give more systemic disease.
The trigger
The offending drug — dose-dependent/cumulative (VEGF, mitomycin, gemcitabine) or immune (quinine). Gemcitabine's mechanism is unsettled; its best-documented risk is cumulative-dose, so it is grouped with the dose-dependent agents here.
Directed treatment
Stop the offending agent — the single most important step. Blood-pressure control; complement blockade only for severe, systemic, or refractory disease. Not plasma exchange as reflex.
PLASMIC score
Bendapudi 2017 · PMID 28259520Pretest probability of severe ADAMTS13 deficiency (TTP) in an adult with thrombotic microangiopathy. Answer each feature — a Yes scores one point. The score appears once all seven are answered.
Answer all seven criteria to see the score and risk band (0/7 answered).
Educational aid only — not medical advice. The PLASMIC score supplements, and does not replace, ADAMTS13 activity testing and clinical judgment.
Management approach
Full framework →Stop the culprit drug — the single most important step — with supportive care; complement-pathway-directed therapy for severe, refractory, or complement-mediated cases.
Drug-level levers
- Discontinue the offending agent promptly; re-exposure risk is high.
- Distinguish dose-dependent/toxic TMA (e.g. mitomycin C, gemcitabine, VEGF inhibitors, carfilzomib) from complement-mediated TMA — the latter is the one most likely to respond to complement blockade.
- Switch out of class for ongoing therapy — drug-induced TMA tends to recur on rechallenge.
- Control hypertension aggressively.
Pharmacologic toolkit
- C5 inhibition (eculizumab, ravulizumab) — First-line complement blockade for severe or drug-discontinuation-refractory TMA; eculizumab achieved renal recovery in ~80% of reported drug-induced cases (gemcitabine, carfilzomib, bevacizumab). Ravulizumab is the longer-acting C5 alternative. Cover/vaccinate against encapsulated organisms before dosing.
- Narsoplimab (anti-MASP-2, lectin pathway) — Targets the lectin pathway driving transplant-associated (HSCT) TMA; its pivotal single-arm trial reported a 61% response. FDA-approved in late 2025 as Yartemlea (narsoplimab-wuug) — the first therapy indicated for HSCT-associated TA-TMA, in adults and children ≥2 years — though access/cost considerations apply and responses vary.
- Emerging complement inhibitors — Iptacopan (factor B), pegcetacoplan (C3), crovalimab and danicopan are under investigation; second-line selection after a suboptimal C5-inhibitor response is increasingly guided by complement biomarkers (e.g. sC5b-9).
- Supportive care — Transfusion, blood-pressure control, and dialysis as needed.
- Plasma exchange — Generally ineffective for drug-induced TMA (unlike TTP) and not routinely recommended.
When to biopsy
Consider when the diagnosis is unclear; but the peripheral smear (schistocytes), LDH, haptoglobin, and platelet count usually establish TMA noninvasively.
Monitoring
- · CBC, schistocytes, LDH, haptoglobin
- · Creatinine and blood pressure
- · Urine protein
- · Complement activation markers (e.g. sC5b-9) where complement-mediated TMA is suspected
Grounding
- Eculizumab in drug-induced TMA — scoping review, Thromb Res 2023 · PMID 36871347 ↗
- Narsoplimab (anti-MASP-2) for HSCT-associated TMA — pivotal trial, J Clin Oncol 2022 · PMID 35439028 ↗
- Complement as a target in HSCT-related TMA — review, Pharmaceuticals 2022 · PMID 35890144 ↗
- Biomarker-guided TA-TMA management — Front Med 2025 · PMID 40406401 ↗
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 thrombotic microangiopathy.
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.
Cited incidence across agents
Where the literature gives a representative thrombotic microangiopathy figure, the agents ranked highest first. Hover a dot for its cited note.
Offending agents
Signature offenders
13Agents for which thrombotic microangiopathy is the defining renal lesion.
GemcitabineDelayed — months of cumulative exposure.Estimates span three orders of magnitude by ascertainment. The only figure with a real denominator is the manufacturer safety-database review: 12 cases against 78,800 patient exposures, a crude 0.015% (range 0.008–0.078%). The product characteristics give 0.01%. Against that, a single center reported 2.7% — four of its five cases on nab-paclitaxel/gemcitabine, where a pharmacokinetic interaction is suspected. Historically high mortality: of 23 cases with reported outcome in the literature tally, 11 died within a few weeks, death directly attributed to HUS in two.SevereMitomycin CDelayed — after cumulative dosing, sometimes after therapy ends.Dose-dependent, generally 4–15%; nearly every case in the landmark 85-patient registry had received a cumulative total dose above 60 mg. >50% historical mortality.SevereCarfilzomibVariable — frequently early (first cycles), but TMA can also appear later, sometimes after a treatment break and re-escalation.Renal complications are common and a recognized class concern: in a 114-patient real-world cohort, ~17% had carfilzomib-attributable renal events (TMA ~5%, albuminuria >1 g/day ~6%, otherwise-unexplained grade >=3 AKI ~5%), occurring mostly early and unpredictably. On the prospective CARDAMON trial 8 patients experienced TMA (6 of 8 hypertensive at presentation, 7 of 8 with AKI); after a protocol amendment adding aggressive hypertension management, carfilzomib step-up dosing at the start of maintenance and dexamethasone premedication, the rate fell from 4.2 to 1.6 events per 1,000 patient-cycles with no further maintenance events. Pharmacovigilance (FAERS) shows carfilzomib carries by far the strongest TMA signal among proteasome inhibitors.SevereMoxetumomab pasudotoxCycle-related: CLS within the first days of a cycle; HUS often during/after cycles 2-3.Boxed warning for capillary-leak syndrome (CLS) and hemolytic-uremic syndrome (HUS)/TMA. In the pivotal phase 3 trial HUS occurred in ~7.5% and CLS in ~5%; reviews cite roughly 9% each. Fatal CLS has been reported (in a pediatric ALL case).SevereTegafur-uracil (UFT)Variable; TMA/HUS typically emerges after weeks to months of cumulative exposure.Direct renal injury from UFT is rare and largely class-level. Fluoropyrimidine-associated thrombotic microangiopathy / hemolytic-uremic syndrome is a rare, mostly case-report-level event, frequently in combination regimens (e.g., with mitomycin C). No reliable drug-specific incidence rate is established.SevereBusulfanWeeks after conditioning/transplant.Transplant-associated thrombotic microangiopathy (TA-TMA) with renal involvement complicates a subset of conditioning regimens; high-dose busulfan (e.g., 16 mg/kg) has been identified as an independent risk factor for post-transplant TMA, and high busulfan exposure also drives sinusoidal obstruction syndrome/VOD.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 can occur at any point during therapy, from weeks to several months after initiation; 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.ModerateIxazomibVariable; reported after weeks to months of therapy, including with cumulative exposure. Class median time to TMA onset ~8 days from a triggering cycle.Drug-induced thrombotic microangiopathy (TMA) is a rare, case-level event for ixazomib and is not reliably quantified. In a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS, 2004-2023), proteasome inhibitors as a class were significantly associated with TMA (225 cases in 213 exposed individuals; ROR 1.71), but carfilzomib dominated the signal (58.7% of exposed individuals, 125 of 213; ROR 17.97), with bortezomib and ixazomib contributing far fewer reports. The ixazomib signal is therefore extrapolated largely from the class.ModerateDoxifluridineVariable; class-level TMA typically after prolonged cumulative exposure.No drug-specific nephrotoxicity incidence is established. Renal risk is inferred at the fluoropyrimidine-class level (rare TMA/HUS); direct doxifluridine renal injury reports are sparse.ModerateCarmofur (HCFU)Variable; class-level TMA after cumulative exposure.No established drug-specific renal incidence. Renal risk is class-level (rare fluoropyrimidine TMA/HUS). Carmofur's characteristic serious toxicity is leukoencephalopathy, not nephrotoxicity.ModerateOxaliplatinAcute if immune-mediated (often on re-challenge).Lowest nephrotoxic potential of the platinums; AKI is rare and case-level, in some cases immune-mediated.Mild5-FluorouracilTMA often delayed (weeks to months); prerenal effects acute with GI toxicity.Intrinsic nephrotoxicity is low; the recognized vascular renal complication is thrombotic microangiopathy/hemolytic-uremic syndrome, classically with mitomycin C, with 5-FU as a frequent co-agent. In TTP/HUS series the most common antecedent chemotherapy is mitomycin C plus 5-FU.Mild
Also associated
31Agents that cause thrombotic microangiopathy as a secondary pattern alongside a different signature lesion.
Interferon-αSubacute — weeks to months of therapy.Rare; best characterized by an 11-case biopsy series, disproportionately in Black patients (APOL1).SevereIpilimumabDelayed and variable: typically weeks to several months after initiation. Median time to AKI in biopsy cohorts was roughly 3 months (about 91 days; ~4 cycles); combination ipilimumab/nivolumab nephritis can appear after only one or two doses, and onset after drug discontinuation has been described.Clinically significant kidney injury from ipilimumab monotherapy is uncommon; renal immune-related adverse events are reported in roughly 1-2% of patients on single-agent checkpoint blockade. The dominant driver of elevated incidence is combination therapy: in real-world ICI cohorts any-cause AKI reaches about 16-17%, but only a minority is true immune-mediated nephritis. The combination of ipilimumab plus nivolumab carries a substantially higher and more severe AKI risk than either single agent. In a pooled analysis of biopsy-proven ICI-related acute tubulointerstitial nephritis, all patients on dual ICI blockade developed stage 3 AKI versus about half on a single agent, and complete renal recovery was less likely with dual blockade.SevereBevacizumabWeeks to months; dose-dependent.In a 72-trial meta-analysis (21,902 bevacizumab cases vs 20,608 controls), all-grade proteinuria was 18% (95% CI 11.7–26.6%) and high-grade 2.4% (1.8–3.2%); all-grade hypertension was 25.3% (21.5–29.5%). Relative to controls the risk ratios were 3.37 for all-grade and 5.49 for high-grade proteinuria. A separate 16-trial meta-analysis put high-grade proteinuria at 2.2% and nephrotic syndrome at RR 7.78, with renal cell carcinoma carrying the highest cumulative incidence (10.2%).ModerateVEGFR Tyrosine Kinase InhibitorsHypertension within days–weeks; proteinuria over weeks–months.Hypertension ~17–50%; proteinuria 8–73% across agents (the cited review's ranges; it reports no single pooled proteinuria rate).ModerateCarmustine (BCNU)Delayed - months to years after cumulative exposure; conditioning-associated TMA appears within weeks.Insidious, cumulative-dose chronic nephrotoxicity; in classic high-cumulative-dose series the majority of long-term survivors develop reduced renal function, with small scarred kidneys. Acute injury is uncommon except via infusion hypotension or as part of conditioning-associated TMA/HUS.ModerateBendamustineTLS within hours to days of the first cycle; TMA delayed and rare.Direct nephrotoxicity is uncommon; the principal renal risk is acute kidney injury from tumor lysis syndrome in high-burden disease, classically during the first cycle. TLS with renal failure is documented from the first reported case onward; TMA is rare and 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 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. A meta-analysis of 15 trials (4,451 patients) put the summary all-grade hypertension incidence at 42.4%.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.ModeratePonatinibHypertension can emerge early; arterial occlusive events accrue over months, with dose reduction mitigating risk.Ponatinib carries a black-box warning for arterial occlusive and thrombotic events and has the highest cardiovascular event rate among CML TKIs (about 41% in one comparative cohort; cumulative arterial occlusive events ~31% over 5 years in the PACE trial). Treatment-emergent hypertension is common; renal injury is largely a downstream consequence of hypertension and vascular disease.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 the most frequent treatment-related adverse event of special interest, occurring in 28.9% of fruquintinib-treated patients all-grade and 10.7% at grade ≥3, with proteinuria also reported (1.3% of patients required a dose reduction for it). Renal-specific TMA is rare but described across the VEGF-inhibitor class.ModerateLutetium-177 DotatateDelayed — radiation nephropathy evolves over months to years after treatment; the amino-acid-related hyperkalemia is acute (during infusion).Clinically significant nephrotoxicity is uncommon when amino-acid renoprotection is used: in the NETTER-1 and large Erasmus/Rotterdam cohorts, no therapy-related long-term renal failure was attributed to lutetium-177 dotatate, and the typical long-term GFR decline is modest (~2 mL/min/year). In a 74-patient single-agent 177Lu-octreotate cohort with dedicated long-term follow-up, CTCAE grade >=3 nephrotoxicity occurred in one patient (1.3%) — who also had arterial hypertension and prior chemotherapy — while a slower GFR decline was more common; the more feared long-term toxicity is delayed MDS/AML (~1-2%).ModerateDinutuximabInfusion-associated and acute — pain, capillary leak and blood-pressure swings occur during/around each infusion.Severe neuropathic pain is near-universal, and capillary-leak syndrome and hypertension are common, sometimes severe, infusion-associated toxicities (driven partly by concurrent IL-2). The resulting fluid shifts and prerenal AKI are managed proactively but not separately quantified.ModerateTislelizumabDelayed: commonly weeks to several months after initiation (often 8-12+ weeks); can occur after multiple cycles or after a single dose, and rarely after drug discontinuation.Drug-specific renal data are sparse: the registrational ESCC trials (RATIONALE-302, RATIONALE-306) did not report nephritis as a notable adverse event, and no tislelizumab-specific biopsy series exists. Reasoning from the PD-1 class, immune-mediated acute interstitial nephritis (the class signature) is uncommon at roughly 1-3% of treated patients, while any-cause AKI in real-world ICI cohorts is far higher (16-17%) but mostly prerenal/non-immune rather than true ICI-nephritis.ModerateIvonescimabVEGF-pathway proteinuria/hypertension typically within the first weeks-to-cycles; checkpoint-inhibitor AIN usually delayed, often 8-16 weeks (range days to >1 year).Renal-specific data are immature for this newly approved agent; no dedicated nephrotoxicity series exists. In registrational trials, grade >=3 VEGF-related adverse events (a class category encompassing proteinuria, hypertension, and hemorrhage) occurred in roughly 3% of patients (HARMONi-A: 5/161, 3.1%) — against 4/161 (2.5%) in the chemotherapy-alone arm of the same trial, a one-patient difference that is not separable from background. Grade >=3 immune-related adverse events (the checkpoint-inhibitor category that includes AIN) occurred in ~6-9% across trials, though kidney-specific irAE rates were not separately tabulated. Clinically significant AKI was uncommon.ModerateSunitinibHypertension typically appears early (within the first treatment cycle/weeks); proteinuria develops over weeks to months, and biopsy-proven TMA in case series presented on average around 2 years (range ~7-36 months) into therapy.In a systematic review/meta-analysis of 4,999 patients across 13 trials, all-grade hypertension occurred in ~21.6% and high-grade hypertension in ~6.8% of sunitinib-treated patients, with a significantly increased risk of renal dysfunction versus controls (RR ~1.36); risk varied by tumor type and dosing schedule. Proteinuria is common but less consistently quantified, and severe glomerular lesions (thrombotic microangiopathy, nephrotic-range proteinuria) are reported mainly at the case-series level. Reported figures are class-consistent with other VEGF-pathway inhibitors.ModerateAxitinibHypertension typically emerges early, frequently within days to the first few weeks of starting therapy. Proteinuria tends to develop over weeks of continued exposure and is dose-related. Severe glomerular lesions (TMA, nephrotic syndrome) are usually later and more variable in timing.Hypertension is the dominant and best-quantified renal-relevant signal. In the randomized phase III AXIS trial, treatment-emergent all-causality hypertension occurred in 40.4% of axitinib-treated patients (vs 29.0% with sorafenib), with grade 3 hypertension in 15.3% and grade 4 in 0.3%. A real-world VEGFR-TKI cohort in metastatic RCC similarly found hypertension to be the single most common anti-angiogenesis-related adverse event (about 48.6% in TKI-naive patients across the class). Proteinuria is the next most common renal effect; across the VEGF-inhibitor class mild/asymptomatic proteinuria is reported in roughly 21% to 63% of patients, with heavy (nephrotic-range) proteinuria in up to about 6.5% of RCC patients, and axitinib-specific proteinuria rates have been higher in some populations (e.g., Japanese cohorts). Thrombotic microangiopathy and other glomerular lesions (FSGS-like injury, podocytopathy, hyaline occlusive glomerular microangiopathy) are reported at the severe, biopsy-level end of the spectrum but are not precisely quantified for axitinib specifically.ModeratePazopanibProteinuria and hypertension typically emerge within weeks to a few months of starting therapy; TMA case reports describe onset within the first weeks to ~2 months.Proteinuria is common but usually low-grade, and reported any-grade rates span roughly 15% to 80% depending on the population and how proteinuria was ascertained. In a pooled secondary analysis of two phase III trials of pazopanib or sunitinib in metastatic RCC (n=1392, Sorich 2016), any-grade proteinuria occurred in 15.0% and grade 3/4 in 3.7% — a trial adverse-event figure covering both agents, not a pazopanib-specific rate. In a single-center first-line mRCC cohort, proteinuria was reported in 80% of the pazopanib-treated patients (Land 2016), most grade 1-2 and managed with continued monitoring at the same dose. Assume proteinuria is the expectation rather than the exception on pazopanib and schedule urine protein monitoring accordingly. Hypertension is one of the most frequent class effects, with severe (grade 3-4) hypertension a recognized class risk. Thrombotic microangiopathy is rare and largely case-level; biopsy-proven renal-limited and systemic TMA/TTP-like presentations have been reported.ModerateNivolumabCharacteristically delayed compared with other drug-induced AIN: median time from ICI initiation to AKI was about 14 weeks (IQR 6-37) in a 138-patient multicenter cohort, and 91 days in the original series; onset ranges from weeks to many months and can follow drug discontinuation.Clinically significant ICI-attributed AKI is uncommon but not rare. A 2023 systematic review/meta-analysis of real-world data (18 studies, ~12,000 ICI-treated patients) found a pooled incidence of all-cause AKI during ICI therapy of about 16%, but AKI specifically attributed to the ICI of roughly 3.5%. Risk is higher with combination ICI regimens (e.g., nivolumab-ipilimumab) than with PD-1 monotherapy. Among biopsied ICI-AKI, acute tubulointerstitial nephritis is the dominant lesion (>90%); glomerular lesions and thrombotic microangiopathy are reported but uncommon.ModeratePembrolizumabDelayed and highly variable, typically weeks to months after initiation; multicenter cohorts reported median onsets around 14-16 weeks. Can occur after a single dose or after many months, and may recur on rechallenge.In real-world cohorts of patients receiving immune checkpoint inhibitors, any AKI is common (roughly 16-18%), but AKI attributable to the checkpoint inhibitor itself (ICPi-AKI) is less frequent. A single-center cohort reported AKI in 16.5% of ICI-treated patients with checkpoint-attributable nephrotoxicity in a minority, while a larger real-world study found ICPi-AKI in about 3.6%. Acute interstitial nephritis is the dominant biopsy lesion (>80% in the largest multicenter series). These figures are pooled across PD-1/PD-L1/CTLA-4 agents rather than pembrolizumab-specific.ModerateEverolimusSubacute — proteinuria typically emerges over the first weeks to months of therapy; thrombotic microangiopathy usually appears within weeks to months, often in the setting of concurrent calcineurin-inhibitor or anti-VEGF exposure.Proteinuria is a class effect of mTOR inhibitors, and with systematic monitoring it is close to universal. A retrospective review of 129 first-line metastatic renal-cell patients found any-grade proteinuria in 81% overall and in 96% of the everolimus arm (44 patients) — the highest of the three regimens compared, against 80% on pazopanib and 64% on bevacizumab. Almost all of it was minor: the study's grade 3-4 proteinuria (24%, 6 patients) occurred entirely in the bevacizumab group, none in the everolimus arm, and 35 of the everolimus patients (80%) simply continued at the same dose under monitoring. So the striking number is detection, not injury — heavy proteinuria and overt podocytopathy remain uncommon, and most nephrotic-range and biopsy-proven FSGS data are still extrapolated from the sirolimus/transplant literature. A phase II trial combining everolimus with bevacizumab reported grade 3-4 proteinuria of 25%, which reflects the added anti-VEGF effect and overstates everolimus alone. Thrombotic microangiopathy is rare and drawn mainly from case reports, typically with concomitant calcineurin-inhibitor or anti-VEGF exposure.ModerateSorafenibHypertension typically emerges within the first few weeks of treatment; proteinuria develops over weeks to months of continued exposure. Nephrotic syndrome and thrombotic microangiopathy are variable, generally appearing after weeks to months but occasionally sooner.Hypertension is the dominant renal-vascular signal: a systematic review/meta-analysis of 9 trials (4,599 patients) reported an all-grade incidence of 23.4% (95% CI 16.0-32.9%) and high-grade (grade 3-4) incidence of 5.7% (Wu 2008), and a larger meta-analysis of 93 trials (20,494 patients) gave concordant figures of 21.3% all-grade and 5.9% high-grade, with higher rates in renal-cell and thyroid cancer and rising incidence with longer treatment duration (Yang 2017). Proteinuria is a VEGF-pathway class effect: across VEGF-signaling inhibitors mild/asymptomatic proteinuria is reported in roughly 21-63% and heavy (nephrotic-range) proteinuria in up to about 6.5% of renal-cell carcinoma patients (Izzedine 2009); drug-specific quantitative proteinuria data for sorafenib alone are more limited. Nephrotic-range proteinuria and renal-limited thrombotic microangiopathy are documented but uncommon.ModeratemTOR InhibitorsWeeks–months.Everolimus commonly causes all-grade proteinuria, with high-grade uncommon; mTOR-inhibitor proteinuria/FSGS is well described. Temsirolimus case-level only.MildCapecitabineAcute, during cycles with GI toxicity; TMA delayed and rare.Intrinsic nephrotoxicity is uncommon; the main renal issue is prerenal AKI from drug-induced diarrhea and volume depletion. Renal impairment increases toxicity - in the PK study, all patients with severe impairment (CrCl <30) had grade 3-4 adverse events - so labeling mandates dose adjustment by creatinine clearance and, below CrCl 30, establishes no dose (avoid unless no alternative).MildDecitabineEarly after a treatment cycle (days) for tumor lysis; TMA over weeks.Tumor lysis syndrome with AKI is a recognized but uncommon complication when bulky/proliferative disease responds; renal incidence specific to decitabine is not well quantified (case-level). Rare biopsy-proven renal thrombotic microangiopathy has been reported.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. Separately, doxorubicin — especially the pegylated liposomal formulation — is an increasingly recognized but underreported cause of kidney-limited thrombotic microangiopathy (a vascular/endothelial lesion), described in biopsy-proven case reports and drug-induced-TMA series.MildNintedanibOver 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.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. Reported rate: proteinuria in 3% — Erlotinib-MONOTHERAPY comparator arm of 4 randomized controlled trials in EGFR-mutation-positive advanced NSCLC (Deng 2022, PMID 35985780).MildOlaparibCreatinine rise within weeks of starting therapy; reverses on discontinuation.Olaparib commonly causes a reversible, dose-dependent rise in serum creatinine. In a 66-patient study, median creatinine rose ~14% (and creatinine-based eGFR fell ~13%) on treatment, while cystatin C and cystatin C-based eGFR were unchanged - indicating no true GFR decline. Thrombotic microangiopathy is a rare, case-level event for the PARP-inhibitor class. Reported rate: creatinine-defined acute kidney injury within 12 months of olaparib initiation in 22.1% — Adults with ovarian cancer treated with olaparib at a single major Boston cancer center, 2015-2021 (n=194… (Gupta 2023, PMID 37074956).MildDocetaxelFluid retention develops cumulatively (often after several cycles / cumulative dose); hypersensitivity reactions occur during infusion.Docetaxel has low direct renal toxicity. Its characteristic fluid-retention syndrome (peripheral edema, effusions, weight gain) reflects increased capillary permeability rather than tubular injury; AKI directly attributable to docetaxel is uncommon and not well quantified, and the drug has been used successfully even in kidney-transplant recipients.MildRuxolitinibAny tumor-lysis risk is early (first cycles); withdrawal syndrome occurs within days of stopping; otherwise no defined renal onset.No established intrinsic nephrotoxicity. Over a decade of safety data show cytopenias and infections (including opportunistic) as the dominant toxicities. Renal concerns are indirect: rare tumor-lysis at treatment initiation in bulky myelofibrosis, the need for dose reduction in renal impairment, and a recognized ruxolitinib-withdrawal syndrome on abrupt cessation — rather than direct tubular injury.Mild