PI3Kδ inhibitor
Idelalisib
Zydelig · IDE
PI3Kδ inhibitor · approved 2014 · 6 references
First-in-class PI3K-delta inhibitor whose immune-mediated colitis and severe diarrhea can dehydrate patients into prerenal AKI.
- Signature injury
- Prerenal / Hemodynamic AKI
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Diarrhea/colitis often delayed — a median of several months into therapy; transaminitis is typically earlier (first weeks).
Signature kidney injury & incidence
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 (PMID 24450857; registrational idelalisib + rituximab CLL trial); Lampson et al., Blood Adv 2019 (PMID 30967392; grade >=3 colitis/diarrhea 15%, first-line); Coutré et al., Leuk Lymphoma 2015 (PMID 25726955; expert-panel review of idelalisib diarrhea/colitis)
Reported injury signatures: Prerenal / Hemodynamic AKI, Acute Interstitial Nephritis.
Renal toxicity profile
- Prerenal / Hemodynamic AKIPrimary
- Acute Interstitial NephritisSecondary
Onset timing & rechallenge
Delayed (>6 weeks / cumulative) — Diarrhea/colitis is often delayed to a median of several months into therapy, while transaminitis tends to appear earlier, in the first weeks. Prose gives no concrete day counts.
Mechanism of kidney injury
Clinical presentation
Management
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
- Prompt drug interruption for grade 3+ diarrhea/colitis
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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.
Anticancer mechanism
Note
Guidelines & consensus
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
- ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
- SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
- KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
- ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
- ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
- ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
- KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
- KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
- KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
- KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525
References
6 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.Furman RR et al. · N Engl J Med · 2014 · PMID 24450857
- 2.Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia.Lampson BL et al. · Blood Adv · 2019 · PMID 30967392
- 3.Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial.Zelenetz AD et al. · Lancet Oncol · 2017 · PMID 28139405
- 4.Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia.Pleyer C et al. · Leuk Lymphoma · 2018 · PMID 29764250
- 5.A retrospective observational study to evaluate the clinical outcomes and routine management of patients with chronic lymphocytic leukaemia treated with idelalisib and rituximab in the UK and Ireland (RETRO-idel).Eyre TA et al. · Br J Haematol · 2021 · PMID 34121184
- 6.Idelalisib: a review of its use in chronic lymphocytic leukaemia and indolent non-Hodgkin's lymphoma.Keating GM et al. · Target Oncol · 2015 · PMID 25637459