Busulfan
Myleran · Alkylator
Conditioning-regimen TMA risk.
TMA
ModerateOpen →
Proteasome inhibitor
Bortezomib
Velcade · Bort
The proteasome inhibitor that more often rescues the myeloma kidney than harms it — with rare TMA/glomerular injury.
ModerateProteasome inhibitor (first generation) · approved 2003
Multiple myelomaMantle cell lymphoma
Signature kidney injury
Thrombotic Microangiopathy
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.
Source: Mizuno et al., CEN Case Rep 2021 (case); Deng et al., Support Care Cancer 2025 (FAERS)
Mechanism of kidney injury
Net renal effect is usually beneficial via rapid suppression of nephrotoxic free light chains, mitigating intratubular cast nephropathy. Rarely, endothelial injury produces a systemic thrombotic microangiopathy or a localized glomerular microangiopathy (proposed via VEGF/NF-κB-related endothelial perturbation), with proteinuria and AKI even in the absence of systemic MAHA.
Clinical presentation
Usually stable or improving renal function in myeloma. Rare TMA: microangiopathic hemolysis, thrombocytopenia, AKI. Rare glomerular microangiopathy: increasing (often albumin-predominant) proteinuria with AKI and biopsy-confirmed endothelial injury, sometimes alongside monoclonal immunoglobulin deposition disease.
Onset
Rare adverse renal events occur during therapy (days to weeks); the beneficial light-chain reduction is often rapid.
Reversibility
Variable
Anticancer mechanism
Reversible (boronate) inhibitor of the chymotrypsin-like activity of the 20S proteasome, causing accumulation of misfolded proteins, NF-κB pathway modulation and apoptosis in myeloma cells. A backbone of multiple myeloma therapy and used in mantle cell lymphoma.
Management
For TMA/glomerular microangiopathy, hold/discontinue, provide supportive care and obtain nephrology evaluation (kidney biopsy for unexplained proteinuria/AKI); otherwise continue with standard myeloma renal management, leveraging bortezomib's light-chain-lowering benefit.
Risk factors
- Underlying myeloma renal disease/MIDD
- Pre-existing endothelial injury
- Concurrent nephrotoxins
Prevention
- Monitor renal function, urine protein and CBC
- Maintain hydration and manage myeloma renal drivers (light chains, calcium, volume)
Note · In contrast to carfilzomib, bortezomib's dominant renal story is benefit (reversing cast nephropathy). TMA and glomerular microangiopathy are rare, case-level signals.
Clinical depth
Renal dose adjustment
No renal dose adjustment required at any level of renal function, including dialysis (bortezomib is hepatically metabolized via CYP-mediated deboronation). This renal-sparing profile is a key reason it anchors regimens for myeloma with kidney involvement.
Dialyzability & ESKD dosing
Not appreciably dialyzed; on dialysis days, administer after the HD session per label. No supplemental dose required.
Differential diagnosis
In a bortezomib-treated myeloma patient, rising creatinine is far more often cast nephropathy/myeloma activity (improving with treatment) than drug toxicity. Reserve a drug-TMA/microangiopathy diagnosis for hemolysis/thrombocytopenia or new heavy proteinuria with supportive biopsy, and exclude MIDD and amyloid.
Monitoring
- Serum creatinine and serum free light chains to track the (usually beneficial) renal response
- CBC, LDH and haptoglobin if TMA is suspected
- Urine protein for the rare glomerular microangiopathy
Key trials & series
- Mizuno CEN Case Rep 2021 (biopsy-proven glomerular microangiopathy)
- Deng Support Care Cancer 2025 (FAERS PI-TMA; bortezomib weaker signal than carfilzomib)
Clinical pearls
- Bortezomib usually helps the myeloma kidney - it lowers nephrotoxic light chains and needs no renal dose adjustment, including on dialysis.
- Contrast with carfilzomib: bortezomib's TMA signal is real but rare and much weaker.
- New heavy proteinuria on bortezomib warrants biopsy - glomerular microangiopathy and MIDD are on the differential.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Thrombotic MicroangiopathyGlomerular Injury / Proteinuria
Beyond the kidney
Class-level context for the major non-renal toxicities of proteasome inhibitors.
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (bortezomib)
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- Heart failure / hypertension (carfilzomib)
Hematologic
Cytopenias, thrombosis, TMA
- Thrombocytopenia
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkBortezomib-induced glomerular microangiopathy complicated with monoclonal immunoglobulin deposition disease.Mizuno S et al. · CEN Case Rep 2021 · PMID 33909224Biopsy-proven bortezomib-induced glomerular microangiopathy without systemic TMA, alongside MIDD.PMIDProteasome inhibitor-associated thrombotic microangiopathy: a real-world retrospective and pharmacovigilance database analysis.Deng Z et al. · Support Care Cancer 2025 · PMID 39939437FAERS analysis quantifying PI-TMA, showing bortezomib carries a much weaker TMA signal than carfilzomib.PMIDThrombotic microangiopathy associated with proteasome inhibitors.Lodhi A et al. · Clin Kidney J 2015 · PMID 26413293Reviews proteasome-inhibitor-associated TMA, including bortezomib.PMIDAdvances in the Treatment of Relapsed and Refractory Multiple Myeloma in Patients with Renal Insufficiency: Novel Agents, Immunotherapies and Beyond.Bozic B et al. · Cancers (Basel) 2021 · PMID 34680184Reviews bortezomib's favorable use in renal insufficiency and reversal of myeloma cast nephropathy.PMIDAnticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep 2017 · PMID 29318217Onconephrology reference for vascular/glomerular drug-induced injury and myeloma kidney.
Related agents
Other agents sharing the same signature kidney injury.