Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Anti-CD38 antibody
Daratumumab
Darzalex · Dara
An anti-CD38 antibody that improves outcomes even in renal impairment — tumor lysis is its main kidney caveat.
MildAnti-CD38 antibody · approved 2015
Multiple myeloma (newly diagnosed and relapsed/refractory)AL amyloidosis
Signature kidney injury
Prerenal / Hemodynamic AKI
Direct nephrotoxicity is uncommon; tumor lysis can occur with high tumor burden. Crucially, daratumumab-based regimens IMPROVE outcomes (PFS, and OS in relapsed disease) in myeloma patients with renal insufficiency, including dialysis-dependent patients, and can drive renal recovery.
Source: Jiang et al., Hematology 2024 (meta-analysis: PFS/OS benefit in renal insufficiency)
Mechanism of kidney injury
Rapid plasma-cell killing in high-burden disease can release uric acid/phosphate, causing tumor-lysis AKI; otherwise renal effects are hemodynamic (e.g., infusion-reaction-related). By rapidly controlling myeloma and lowering the nephrotoxic free light-chain load, daratumumab reduces cast-nephropathy/light-chain–mediated kidney injury — so its net renal effect in myeloma is frequently favorable.
Clinical presentation
Usually stable or improving renal function as myeloma responds (renal recovery, including dialysis independence in some cases); occasionally tumor-lysis labs with bulky disease. Infusion reactions are common (especially first infusion) but not directly nephrotoxic.
Onset
Tumor lysis (if any) early; renal benefit accrues over treatment as paraprotein/free light chains fall.
Reversibility
Reversible
Anticancer mechanism
Anti-CD38 IgG1κ monoclonal antibody killing myeloma plasma cells via complement-dependent cytotoxicity, ADCC, antibody-dependent phagocytosis, direct apoptosis and immunomodulation (depleting CD38+ regulatory cells); a backbone of newly diagnosed and relapsed/refractory multiple myeloma and AL amyloidosis regimens.
Management
Standard TLS management if it occurs; no renal dose adjustment required — usable across renal-function strata, including dialysis. The therapeutic goal is rapid disease control to recover renal function.
Risk factors
- High tumor burden
- Baseline cast nephropathy / high free light-chain burden
- Volume depletion
Prevention
- TLS risk assessment with hydration and urate-lowering therapy in high-burden disease
- Continue/optimize myeloma therapy to protect and recover renal function
- Infusion-reaction premedication
Note · Net effect on the kidney is often favorable in myeloma (renal response/recovery); tumor lysis is the principal direct renal risk. Daratumumab also interferes with serologic crossmatch (binds CD38 on red cells), a transfusion-medicine pitfall relevant to renal-impaired/transfused patients.
Clinical depth
Renal dose adjustment
No renal dose adjustment; antibody clearance is target-mediated/reticuloendothelial, not renal. Standard IV or subcutaneous dosing is used regardless of CrCl, including in dialysis-dependent patients per trial and case data.
Dialyzability & ESKD dosing
Not dialyzed — a large IgG1 antibody not removed by HD/PD; full standard dosing in ESKD. Renal recovery off dialysis has been reported with daratumumab-based therapy.
Differential diagnosis
Distinguish a creatinine change from the underlying myeloma kidney disease (cast nephropathy, light-chain effects, hypercalcemia) and tumor lysis from a true drug effect (rare). Improving renal function usually reflects disease response, not toxicity.
Monitoring
- Serum free light chains / paraprotein and renal function (track renal response)
- TLS labs in high-burden disease at initiation
- Infusion-reaction monitoring (first infusion highest risk)
- Note daratumumab interference with indirect antiglobulin (Coombs) crossmatch — inform the blood bank
Key trials & series
- Jiang et al., Hematology 2024 — meta-analysis (10 RCTs, 5003 patients): PFS/OS benefit in renal-impaired myeloma
- Leypoldt et al. (GMMG-DANTE), Cancers 2023 — daratumumab-bortezomib-dexamethasone in severe renal impairment (GFR <30/dialysis); 67% renal response
- Palladini et al. (ANDROMEDA), Blood 2020 — daratumumab-CyBorD in AL amyloidosis with organ (incl. renal) response
Clinical pearls
- Daratumumab is renal-friendly: it improves outcomes and can recover renal function (even off dialysis) by clearing nephrotoxic light chains — no dose adjustment for CrCl.
- Tumor lysis in high-burden disease is the main direct renal caveat — prophylax at initiation.
- Daratumumab binds CD38 on red cells and confounds the antibody crossmatch — always alert the blood bank before transfusion.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkEfficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.Jiang H et al. · Hematology 2024 · PMID 39248713Meta-analysis (10 RCTs, 5003 patients): daratumumab improves PFS/OS in renal-impaired myeloma.PMIDEvaluation of anti-CD38 monoclonal antibody-based immunotherapy in multiple myeloma with renal insufficiency: a systematic review and meta-analysis.Bai H et al. · Ther Adv Hematol 2025 · PMID 39963097Meta-analysis: anti-CD38 antibodies (daratumumab/isatuximab) improve survival in myeloma with renal insufficiency.PMIDDaratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial.Leypoldt LB et al. · Cancers (Basel) 2023 · PMID 37760637Prospective trial dedicated to severe renal impairment/dialysis: 67% overall and 67% renal response.PMIDDaratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA.Palladini G et al. · Blood 2020 · PMID 32244252ANDROMEDA run-in with organ (including renal) response data in AL amyloidosis.PMIDAnti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes.Leleu X et al. · Ann Hematol 2022 · PMID 35943588Mechanistic and clinical review of daratumumab/isatuximab including renal-impairment evidence.PMIDEmergencies in Hematology: Why, When and How I Treat?Duminuco A et al. · J Clin Med 2024 · PMID 39768494Tumor lysis syndrome pathophysiology and AKI management.
Related agents
Other agents sharing the same signature kidney injury.