Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
JAK/ACVR1 inhibitor
Momelotinib
Ojjaara · MOME
A JAK1/2 plus ACVR1 inhibitor that improves anemia in myelofibrosis — with no established direct kidney toxicity.
MildJAK1/2 + ACVR1 inhibitor · approved 2023
Myelofibrosis with anemia
Signature kidney injury
Prerenal / Hemodynamic AKI
No established intrinsic nephrotoxicity. As a JAK-inhibitor-class agent, dominant toxicities are hematologic (thrombocytopenia), infection, and (notably) peripheral neuropathy; renal injury is not a defining signal. Tumor-lysis at initiation and prerenal factors are the indirect renal considerations.
Source: Duminuco et al., Cancers (Basel) 2023
Mechanism of kidney injury
No characterized direct nephron injury. The ACVR1/hepcidin mechanism targets systemic iron metabolism, not the kidney. Renal stress, when present, is indirect (tumor-lysis at initiation in high-burden disease, infection/cytopenia-related prerenal AKI). Renal dose adjustment is advised in significant impairment.
Clinical presentation
Generally a bland renal picture; creatinine changes track intercurrent illness and volume status; metabolic derangements if tumor lysis occurs early.
Onset
Any tumor-lysis risk is early; otherwise no defined renal onset.
Reversibility
Reversible
Anticancer mechanism
Oral inhibitor of JAK1/JAK2 and ACVR1 (ALK2). ACVR1 inhibition lowers hepcidin via the BMP6/ACVR1/SMAD axis, increasing iron availability and improving anemia — distinguishing it from other JAK inhibitors. Approved for intermediate/high-risk myelofibrosis with anemia.
Management
Supportive; tumor-lysis management if it occurs, treat infection, correct prerenal factors. No drug-specific renal therapy; intrinsic nephrotoxicity has not been established.
Risk factors
- High-burden myelofibrosis (TLS risk at initiation)
- Pre-existing CKD
- Infection/cytopenia-related volume depletion
Prevention
- TLS awareness/hydration at initiation in high-burden disease
- Monitor creatinine, electrolytes and uric acid
- Renal-appropriate dosing per label
Note · 2023 approval; renal-specific literature is absent. The cited review covers the ACVR1/anemia mechanism and JAK-inhibitor class; the prerenal/TLS renal framing is conservative class reasoning.
Clinical depth
Renal dose adjustment
No dose adjustment is needed for mild-to-severe renal impairment per the registrational program; momelotinib is hepatically metabolized (with an active metabolite). Data in dialysis are limited. Dose modification is driven primarily by cytopenias rather than renal function.
Dialyzability & ESKD dosing
Not characterized; highly protein-bound, hepatically cleared. Not expected to be meaningfully dialyzed. No ESKD-specific dosing guidance.
Differential diagnosis
Separate early tumor-lysis AKI and infection/cytopenia-related prerenal AKI from unrelated intrinsic renal disease; the drug itself is not an established nephrotoxin.
Monitoring
- CBC with platelets (dose-limiting thrombocytopenia)
- Creatinine, electrolytes and uric acid at initiation in high-burden disease
- Peripheral neuropathy assessment and infection/HBV reactivation surveillance
Key trials & series
- MOMENTUM and SIMPLIFY-1 — registrational myelofibrosis-with-anemia trials (clinical context)
Clinical pearls
- Momelotinib's distinguishing trick is lowering hepcidin (ACVR1) to improve anemia — a non-renal mechanism.
- Watch for peripheral neuropathy, a class-distinct momelotinib toxicity.
- Renal risk is indirect (TLS, prerenal); no renal dose reduction is required for impairment.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis.Duminuco A et al. · Cancers (Basel) 2023 · PMID 38201581Reviews momelotinib's JAK/ACVR1 mechanism and class; supports the iron-metabolism (non-renal) target and class toxicity expectations.PMIDAcute Kidney Injury in Patients With Cancer: A Review of Onconephrology.Gudsoorkar P et al. · Adv Chronic Kidney Dis 2021 · PMID 35190106Onconephrology review of tumor-lysis-related AKI relevant to myelofibrosis therapy initiation.PMIDTumor Lysis Syndrome.Barbar T et al. · Adv Chronic Kidney Dis 2021 · PMID 35190110TLS review supporting prophylaxis/monitoring at cytoreductive initiation in high-burden disease.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onconephrology review framing kinase-inhibitor renal/electrolyte effects and dosing considerations.
Related agents
Other agents sharing the same signature kidney injury.