What kind of kidney injury does Idelalisib cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Acute Interstitial Nephritis.

How should kidney function be monitored during Idelalisib therapy?

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).

How can kidney injury from Idelalisib be prevented?

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

Who is at higher risk of kidney injury from Idelalisib?

Younger, treatment-naive patients (paradoxically higher autoimmune toxicity); Pre-existing CKD or diuretic use; Concurrent nephrotoxins; Inadequate volume repletion during diarrhea.

Back to explorer

Printable monograph

PI3Kδ inhibitor

Idelalisib

Zydelig · IDE

PI3Kδ inhibitor · approved 2014 · 6 citations

Aging evidence· through 2021

Fairly sourced4/9 · 4 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 7y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
Not met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

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

Relapsed chronic lymphocytic leukemia (with rituximab)Relapsed follicular B-cell non-Hodgkin lymphoma and small lymphocytic lymphoma

§01

Signature kidney injury

Signature lesion

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)

Onset & rechallenge

Time to injuryDelayed (>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.

Distilled from: “Diarrhea/colitis often delayed — a median of several months into therapy; transaminitis is typically earlier (first weeks).”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Acute Interstitial NephritisSecondaryqualitative — no citable incidence
Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.

§03

Kidney injury

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.

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.Lesion-level management framework

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

Anticancer mechanism· how it treats cancer

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.

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.

§04

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) 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 & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Interstitium

Supporting tissue around the tubules

Injury signatures

Prerenal / Hemodynamic AKI Acute Interstitial Nephritis

§05

References

6 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2014–2021 · 2 since 2019

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Guidelines & consensus· 13

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.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides 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.SIRMSIRM-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)Radiol Med 2022 · PMID 35303246Recommends 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.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies 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.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses 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.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides 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.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three 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.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes 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.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate 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.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates 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.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages 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.

Where Idelalisib sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Duvelisib

Copiktra · PI3Kδ/γ inhibitor

Profile

Colitis and diarrhea → prerenal AKI.

PREAIN

Mild#1 · 100% phenotype match

Sacituzumab govitecan

Trodelvy · Antibody-drug conjugate (Trop-2/SN-38)

Profile

Diarrhea-driven prerenal AKI; emerging direct signals.

PREAINATN

Moderate#2 · 54% phenotype match

Elotuzumab

Empliciti · Anti-SLAMF7 mAb

Profile

Kidney-neutral antibody; unchanged PK in severe impairment and dialysis; no renal dose adjustment.

PRE

Mild#3 · 53% phenotype match

Radium-223 dichloride

Xofigo · Radiopharmaceutical (alpha-emitter)

Profile

Bone-seeking alpha emitter; minimal direct renal toxicity.

PRE

Mild#4 · 53% phenotype match

Pexidartinib

Turalio · CSF1R inhibitor

Profile

Boxed hepatotoxicity; secondary renal effects.

PRE

Mild#5 · 53% phenotype match

Tisotumab vedotin

Tivdak · Antibody-drug conjugate (tissue factor/MMAE)

Profile

Ocular/bleeding toxicity dominates; renal involvement essentially unreported.

PRE

Mild#6 · 53% phenotype match

Compare Idelalisib with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across PI3K / AKT inhibitors

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

1DuvelisibPRE — Prerenal / Hemodynamic AKIMild
2GedatolisibLYTE — Electrolyte DisturbanceMild
3Idelalisib· this agentPRE — Prerenal / Hemodynamic AKIMild
4CopanlisibHTN — HypertensionModerate
5CapivasertibPRE — Prerenal / Hemodynamic AKIModerate
6AlpelisibPRE — Prerenal / Hemodynamic AKIModerate
7InavolisibLYTE — Electrolyte DisturbanceFAERS AKIModerate

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.