What kind of kidney injury does Ixazomib cause?

Thrombotic Microangiopathy — Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

How should kidney function be monitored during Ixazomib therapy?

CBC with smear review each cycle (platelets, schistocytes); LDH and haptoglobin if cytopenias develop; ADAMTS13 activity when the TMA triad appears, to exclude TTP; Blood pressure at each visit; Serum creatinine each cycle.

Who is at higher risk of kidney injury from Ixazomib?

Prior or concurrent proteasome inhibitor exposure (especially carfilzomib); Cumulative drug exposure; Underlying multiple myeloma with paraprotein burden; Pre-existing endothelial/renal compromise.

Back to explorer

Printable monograph

Proteasome inhibitor

Ixazomib

Ninlaro · IXA

Proteasome inhibitor · approved 2015 · 8 citations · FAERS AKI reporting ROR 1.71 (95% CI 1.54–1.90, 354 AKI reports)

Up to date· through 2025

Fairly sourced6/9 · 6 signals

Met: 8 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 8y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

The first oral proteasome inhibitor, with rare reports of drug-induced thrombotic microangiopathy.

ModerateOral proteasome inhibitor

Multiple myeloma (relapsed/refractory)

§01

Signature kidney injury

Signature lesion

Thrombotic Microangiopathy

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.Source: Deng et al., Support Care Cancer 2025 (FAERS pharmacovigilance)

Onset & rechallenge

Time to injuryVariable / unpredictable

Reported after weeks to months, including with cumulative exposure; class median time to TMA onset ~8 days from a triggering cycle.

Distilled from: “Variable; reported after weeks to months of therapy, including with cumulative exposure. Class median time to TMA onset ~8 days from a triggering cycle.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Thrombotic Microangiopathy#1 · Signaturequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

§03

Kidney injury

Deep diveProteasome-inhibitor thrombotic microangiopathyWeeks into carfilzomib — often with an infection as the second hit — the microvascular endothelium tips into thrombotic microangiopathy: schistocytes and falling platelets, an acute kidney injury the drug set in motion, and an ADAMTS13 that comes back normal because this was never TTP.

Mechanism of kidney injury

Proteasome inhibition injures glomerular and microvascular endothelium, reducing endothelial production of protective factors (including VEGF and complement-regulatory proteins) and provoking platelet aggregation, microthrombi, and mechanical (microangiopathic) hemolysis. In the pooled PI-TMA literature, the median time to onset was about 8 days and most patients presented with the classic triad of hemolytic anemia (98%), thrombocytopenia (97%), and AKI (97%). Ixazomib TMA has been reported both as cumulative dose-dependent toxicity and via an immune-mediated mechanism; complement activation has been implicated, mirroring carfilzomib cases that responded to eculizumab.

Clinical presentation

Microangiopathic hemolytic anemia (schistocytes on smear, elevated LDH, undetectable haptoglobin, negative direct Coombs), thrombocytopenia, and AKI with rising creatinine, often with new or worsening hypertension. Gastrointestinal symptoms, fever, and fatigue frequently precede the laboratory triad.

Management

Discontinue ixazomib promptly when TMA is suspected; provide supportive care, transfusion as needed, and AKI management including dialysis when indicated (used in ~32% of pooled PI-TMA cases). TMA often improves after drug withdrawal (hematologic recovery ~96%, renal recovery ~93% in the pooled series). Plasma exchange has uncertain benefit in drug-induced TMA and is reserved for diagnostic uncertainty (suspected TTP); complement blockade with eculizumab has stabilized renal function in refractory proteasome-inhibitor TMA and can be considered.Lesion-level management framework

Risk factors

Prior or concurrent proteasome inhibitor exposure (especially carfilzomib)
Cumulative drug exposure
Underlying multiple myeloma with paraprotein burden
Pre-existing endothelial/renal compromise

Anticancer mechanism· how it treats cancer

Reversibly inhibits the chymotrypsin-like activity of the 20S proteasome (beta-5 subunit), causing accumulation of polyubiquitinated misfolded proteins, ER stress, and NF-kB-dependent apoptosis in malignant plasma cells. Used orally with lenalidomide and dexamethasone for relapsed/refractory multiple myeloma.

Note · TMA with ixazomib is rare and case-level; incidence is not reliably quantified. The signal is extrapolated from the proteasome-inhibitor class, where carfilzomib dominates.

§04

Clinical depth

Renal dose adjustment

No starting-dose change for mild renal impairment (CrCl >=30). For severe renal impairment (CrCl <30) or ESRD requiring dialysis, reduce the ixazomib dose from 4 mg to 3 mg. Hepatic impairment also requires reduction.

Dialyzability & ESKD dosing

Ixazomib is not meaningfully dialyzable (highly protein-bound, large volume of distribution); it may be given without regard to dialysis timing. Use the reduced 3 mg dose in dialysis-dependent patients.

Differential diagnosis

Distinguish drug-induced TMA from myeloma-related causes of AKI (cast nephropathy, hypercalcemia, paraprotein-associated TMA) and from TTP (check ADAMTS13) and atypical HUS (complement). The temporal link to PI dosing, normal ADAMTS13, and improvement on drug withdrawal favor PI-TMA.

Monitoring

CBC with smear review each cycle (platelets, schistocytes)
LDH and haptoglobin if cytopenias develop
ADAMTS13 activity when the TMA triad appears, to exclude TTP
Blood pressure at each visit
Serum creatinine each cycle

Key trials & series

TOURMALINE-MM1 (phase 3 ixazomib-Rd vs placebo-Rd in relapsed/refractory myeloma)
FAERS proteasome-inhibitor TMA pharmacovigilance analysis (Deng et al. 2025)

Clinical pearls

Carfilzomib carries by far the largest proteasome-inhibitor TMA signal; ixazomib reports are rare and the risk is largely class-extrapolated.
Look for the MAHA triad: schistocytes, undetectable haptoglobin, and thrombocytopenia with AKI.
Eculizumab has rescued renal function in refractory PI-TMA, supporting a complement-mediated component.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Glomerulus

Filtration barrier (podocytes + endothelium)

Injury signatures

Thrombotic Microangiopathy

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the Proteasome inhibitor class.

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

Peripheral neuropathy (bortezomib)

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

Heart failure / hypertension (carfilzomib)

Hematologic

Cytopenias, thrombosis, TMA

Thrombocytopenia

§05

References

6 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

6 references · 2017–2025 · 2 since 2023

Primary (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.

Case reports — ranked by strength· 2

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.

CaseB · ModerateDrug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature.Monteith BE et al. · Clin Lymphoma Myeloma Leuk 2020 · PMID 32807717Case series on proteasome inhibitor-associated drug-induced thrombotic microangiopathy (including ixazomib) presenting with hemolytic anemia, thrombocytopenia, and renal organ damage.CaseC · LimitedIxazomib-induced thrombotic microangiopathy resolving without complement pathway inhibition: a case report.Lafont T et al. · Leuk Lymphoma 2025 · PMID 39565042Case report of ixazomib-induced thrombotic microangiopathy with renal involvement that resolved without eculizumab/complement inhibition.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Aug 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. ( 2.4 , 8.7 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 28,609 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 2 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Thrombotic Microangiopathycorroborated · ROR 1.66

Electrolyte Disturbance

ROR 1.7695% CI 1.60–1.93· 455 reports

Thrombotic Microangiopathy

ROR 1.6695% CI 1.19–2.31· 35 reports

FAERS outcomes & reporting trend· 18.5% of reports w/ death · 30.6% w/ hospitalization

18.5%

Reported with a death outcome

5,284 of 28,609 reports

30.6%

Reported with hospitalization

8,748 of 28,609 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 28,609 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 1.7195% CI 1.54–1.90· 354 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Gastrointestinal

Diarrhoea3,156Nausea1,841Vomiting1,108Constipation967

General / constitutional

Fatigue1,918Asthenia915Malaise749Pyrexia734Peripheral Swelling704

Blood & lymphatic

Thrombocytopenia1,046Platelet Count Decreased1,003Neutropenia671Anaemia643White Blood Cell Count Decreased578

Immune / infection

Pneumonia1,934Covid-19611

Nervous system

Neuropathy Peripheral1,451Dizziness567

Skin

Rash1,087

Respiratory

Dyspnoea636

Metabolic & electrolyte

Decreased Appetite585

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 Ixazomib 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.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Busulfan

Myleran · Alkylator

Profile

Conditioning-regimen TMA risk.

TMA

Moderate#1 · 78% phenotype match

Moxetumomab pasudotox

Lumoxiti · Immunotoxin (anti-CD22 PE38)

Profile

Boxed warning for capillary-leak syndrome and hemolytic-uremic syndrome / TMA.

TMAPRE

Severe#2 · 68% phenotype match

Bortezomib

Velcade · Proteasome inhibitor

Profile

Rare TMA; reverses myeloma cast nephropathy.

TMAGLOM

Moderate#3 · 65% phenotype match

Ziv-aflibercept

Zaltrap · VEGF trap

Profile

Hypertension and proteinuria like bevacizumab.

HTNGLOMTMA

Moderate#4 · 57% phenotype match

Bevacizumab

Avastin · Anti-VEGF antibody

Profile

Proteinuria, hypertension, glomerular TMA.

GLOMHTNTMA

Moderate#5 · 57% phenotype match

Ramucirumab

Cyramza · Anti-VEGFR2 antibody

Profile

Hypertension and proteinuria, class effect.

HTNGLOMTMA

Moderate#6 · 57% phenotype match

Compare Ixazomib with its nearest agents

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 Other targeted agents

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.

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.

Who studies this

The leading contributors to Ixazomib’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Ixazomib; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 17 clinical records among all 21 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.