Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
JAK1/2 inhibitor
Ruxolitinib
Jakafi · RUXO
A JAK1/2 inhibitor for myelofibrosis whose kidney risks are tumor-lysis and dose-adjustment, not direct toxicity.
MildJAK1/2 inhibitor · approved 2011
MyelofibrosisPolycythemia veraGraft-versus-host disease
Signature kidney injury
Prerenal / Hemodynamic AKI
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.
Source: Verstovsek et al., J Hematol Oncol 2023
Mechanism of kidney injury
No characterized direct nephron injury. Plausible renal stress is indirect: tumor-lysis-type metabolic derangements early after starting therapy in high-burden disease (urate/phosphate intratubular deposition), infection/cytopenia-related complications causing prerenal/ischemic AKI, and a ruxolitinib-withdrawal syndrome (cytokine rebound with hemodynamic instability, occasionally a capillary-leak-like picture) on abrupt discontinuation.
Clinical presentation
Usually a bland renal picture; if tumor lysis occurs, hyperuricemia/hyperphosphatemia with creatinine rise; prerenal AKI in the setting of infection or volume depletion; abrupt-withdrawal symptom flare with hemodynamic compromise.
Onset
Any tumor-lysis risk is early (first cycles); withdrawal syndrome occurs within days of stopping; otherwise no defined renal onset.
Reversibility
Reversible
Anticancer mechanism
Oral ATP-competitive JAK1/JAK2 inhibitor that dampens dysregulated JAK-STAT signaling (driven by JAK2 V617F and related mutations), reducing splenomegaly, inflammatory cytokines and constitutional symptoms. Approved for intermediate/high-risk myelofibrosis, polycythemia vera, and acute/chronic graft-versus-host disease.
Management
Supportive; standard tumor-lysis management if it occurs, treat infections, correct prerenal factors, and adjust dose for renal function. For withdrawal syndrome, resume ruxolitinib and provide hemodynamic support. No drug-specific renal therapy; intrinsic nephrotoxicity has not been established.
Risk factors
- Bulky/high-burden myelofibrosis (TLS risk at initiation)
- Pre-existing CKD (requires dose adjustment)
- Infection and cytopenia-related volume depletion
- Abrupt discontinuation (withdrawal syndrome)
Prevention
- TLS awareness/hydration at initiation in high-burden disease
- Renal dose adjustment per label
- Avoid abrupt cessation; taper when stopping
- Monitor creatinine, electrolytes and uric acid
Note · ASON-flagged. Well-established agent but with no significant direct renal toxicity; the prerenal/TLS framing is conservative and supported by the long-term safety review.
Clinical depth
Renal dose adjustment
Renal dosing is required: the starting dose is reduced in moderate-to-severe renal impairment and in ESKD. In myelofibrosis/PV with platelets 100-150 x10^9/L and severe impairment (CrCl 15-29), and in dialysis-dependent ESKD, the label specifies reduced starting doses; in ESKD on hemodialysis, give a single reduced dose after dialysis on dialysis days. Always titrate to platelets and response.
Dialyzability & ESKD dosing
Ruxolitinib and its active metabolites are not efficiently removed by hemodialysis; dose AFTER dialysis on HD days. Highly protein-bound, hepatically (CYP3A4) metabolized small molecule.
Differential diagnosis
Distinguish early tumor-lysis AKI, infection/cytopenia-related prerenal AKI, and withdrawal-syndrome hemodynamic AKI from any unrelated intrinsic renal disease; the drug is rarely the direct nephrotoxic cause.
Monitoring
- CBC (platelets, neutrophils, hemoglobin) — dose is platelet-driven
- Creatinine/eGFR to guide dosing; electrolytes and uric acid at initiation in high-burden disease
- Infection surveillance (including reactivation: HBV, TB, herpes zoster)
Key trials & series
- COMFORT-I/II — registrational myelofibrosis trials (clinical context)
- 10-year safety review (Verstovsek, J Hematol Oncol 2023) — cytopenia/infection-dominant profile
Clinical pearls
- Don't stop ruxolitinib abruptly — withdrawal can precipitate a cytokine-rebound, capillary-leak-like crisis; taper instead.
- Dose-reduce and dose AFTER dialysis in renal impairment/ESKD; it is not meaningfully dialyzed.
- The renal risks are TLS at start and dosing logistics, not a tubulopathy.
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.
LandmarkTen years of treatment with ruxolitinib for myelofibrosis: a review of safety.Verstovsek S et al. · J Hematol Oncol 2023 · PMID 37501130Comprehensive 10-year safety review; toxicity is cytopenia/infection-dominant with no defining direct renal signal.PMIDAcute Kidney Injury in Patients With Cancer: A Review of Onconephrology.Gudsoorkar P et al. · Adv Chronic Kidney Dis 2021 · PMID 35190106Onconephrology review covering tumor-lysis-related AKI relevant to myeloproliferative therapy initiation.PMIDTumor Lysis Syndrome.Barbar T et al. · Adv Chronic Kidney Dis 2021 · PMID 35190110Focused TLS review supporting prophylaxis/monitoring at cytoreductive therapy initiation.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onconephrology review framing kinase-inhibitor renal effects and the need for renal dose adjustment.
Related agents
Other agents sharing the same signature kidney injury.