Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
PI3Kδ inhibitor
Idelalisib
Zydelig · IDE
First-in-class PI3K-delta inhibitor whose immune-mediated colitis and severe diarrhea can dehydrate patients into prerenal AKI.
MildFirst-generation B-cell PI3K inhibitor · approved 2014
Relapsed chronic lymphocytic leukemia (with rituximab)Relapsed follicular B-cell non-Hodgkin lymphoma and small lymphocytic lymphoma
Signature kidney injury
Prerenal / Hemodynamic AKI
Severe immune-mediated diarrhea/colitis occurs in roughly 14-20% (grade 3+) and transaminitis is common; secondary prerenal AKI from volume loss is not separately quantified. Direct renal lesions are rare.
Source: Furman et al., N Engl J Med 2014; Coutre et al. safety analyses
Mechanism of kidney injury
PI3K-delta inhibition impairs regulatory T-cell function, producing a class-characteristic autoimmune-type inflammatory toxicity — colitis/enteritis, hepatitis and pneumonitis. The kidney is injured indirectly: profuse secretory diarrhea and reduced intake cause extracellular volume depletion and prerenal azotemia; severe sustained hypoperfusion can tip into ischemic ATN. Rare immune-mediated interstitial nephritis is biologically plausible within this autoimmune toxicity spectrum.
Clinical presentation
Watery, sometimes severe diarrhea (often after months of therapy), weight loss, orthostatic hypotension; creatinine rises with a low FeNa and concentrated urine. Concurrent transaminitis is a clue to the broader immune-toxicity syndrome.
Onset
Diarrhea/colitis often delayed — a median of several months into therapy; transaminitis is typically earlier (first weeks).
Reversibility
Reversible
Anticancer mechanism
Oral selective inhibitor of the p110-delta isoform of PI3K, which is expressed predominantly in leukocytes. Blocking PI3K-delta disrupts B-cell receptor signaling and survival in chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma.
Management
For severe diarrhea/colitis: interrupt idelalisib, exclude infection, rehydrate, and use systemic corticosteroids (e.g. budesonide or prednisone) for immune-mediated colitis. Restore volume to reverse prerenal AKI; if creatinine does not improve with euvolemia, consider AIN and a steroid trial. Permanently discontinue for life-threatening toxicity.
Risk factors
- Younger, treatment-naive patients (paradoxically higher autoimmune toxicity)
- Pre-existing CKD or diuretic use
- Concurrent nephrotoxins
- Inadequate volume repletion during diarrhea
Prevention
- Counsel on early reporting of diarrhea; rule out infection (including CMV) before attributing to drug
- Aggressive oral/IV rehydration during diarrheal episodes
- Scheduled LFT and CBC monitoring per REMS-style schedule
- Prompt drug interruption for grade 3+ diarrhea/colitis
Note · Renal involvement is indirect — driven by immune-mediated colitis/diarrhea and volume depletion rather than a primary renal lesion; rare AIN is plausible within the autoimmune toxicity spectrum.
Clinical depth
Renal dose adjustment
No specific renal dose adjustment is defined; metabolism is hepatic (CYP3A/aldehyde oxidase). Caution and monitor in CKD; dose changes are driven by colitis, hepatotoxicity and cytopenias.
Dialyzability & ESKD dosing
Extensively protein-bound; not meaningfully dialyzable. No established ESKD dosing.
Differential diagnosis
Distinguish prerenal AKI (low FeNa, responds to volume) from C. difficile or CMV colitis-driven losses, drug-induced AIN (pyuria, WBC casts, eosinophiluria) and hepatorenal physiology from concurrent hepatotoxicity.
Monitoring
- LFTs every 2 weeks for the first 3 months, then periodically
- Stool frequency and volume status; weight
- Serum creatinine/electrolytes during diarrheal episodes
- Infection surveillance (PJP prophylaxis; CMV monitoring)
Key trials & series
- Furman et al. (NEJM 2014) — registrational idelalisib + rituximab CLL trial
- Lampson et al. (Blood Adv 2019) — immune-mediated hepatotoxicity/colitis characterization
Clinical pearls
- Idelalisib toxicity is autoimmune in flavor — colitis, hepatitis and pneumonitis cluster together.
- Always exclude CMV/infectious colitis before steroids for presumed immune colitis.
- The kidney injury is almost always volume-mediated; rehydration is the primary therapy.
- Watch for PJP and CMV — boxed/serious infection warnings accompany this drug.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Interstitium
Supporting tissue around the tubules
Injury signatures
Prerenal / Hemodynamic AKIAcute Interstitial Nephritis
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkIdelalisib and rituximab in relapsed chronic lymphocytic leukemia.Furman RR et al. · N Engl J Med 2014 · PMID 24450857Registrational trial establishing efficacy and the diarrhea/colitis and transaminitis safety profile.PMIDIdelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity.Lampson BL et al. · Blood Adv 2019 · PMID 30967392Characterizes the immune-mediated hepatotoxicity/colitis that drives volume loss and prerenal injury.PMIDIdelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia.Zelenetz AD et al. · Lancet Oncol 2017 · PMID 28139405Phase 3 safety data including infection and GI toxicity informing risk-benefit.PMIDIdelalisib for the treatment of chronic lymphocytic leukemia.Pleyer C et al. · Leuk Lymphoma 2018 · PMID 29764250Review of toxicity management including diarrhea/colitis monitoring.PMIDIdelalisib in relapsed/refractory chronic lymphocytic leukaemia: a UK real-world experience (RETRO-idel).Eyre TA et al. · Br J Haematol 2021 · PMID 34121184Real-world toxicity and tolerability data outside trial conditions.PMIDIdelalisib: First Global Approval.Keating GM et al. · Target Oncol 2015 · PMID 25637459Approval profile summarizing pharmacology and class safety.
Related agents
Other agents sharing the same signature kidney injury.