What kind of kidney injury does Inavolisib cause?

Electrolyte Disturbance — Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

How should kidney function be monitored during Inavolisib therapy?

Fasting glucose and HbA1c at baseline and periodically; Frequent glucose monitoring early in treatment and after dose changes; Serum electrolytes (including potassium and magnesium) and volume status, especially with stomatitis/diarrhea; Renal function in the setting of hyperglycemia or volume depletion.

How can kidney injury from Inavolisib be prevented?

Optimize glycemic control before the first dose Dietary counseling and early involvement of endocrinology for at-risk patients Proactive management of stomatitis and diarrhea to limit volume and electrolyte losses

Who is at higher risk of kidney injury from Inavolisib?

Pre-existing diabetes, prediabetes, or impaired fasting glucose; Obesity and metabolic syndrome; Concurrent glucocorticoids; Volume depletion from stomatitis/diarrhea (amplifies electrolyte and prerenal risk).

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Printable monograph

PI3Kα inhibitor

Inavolisib

Itovebi · PI3Kalpha inhibitor

PI3Kα inhibitor · approved 2024 · 4 citations · FAERS AKI reporting ROR 5.39 (95% CI 3.45–8.43, 20 AKI reports)

Recent· through 2024

Fairly sourced5/9 · 5 signals

Not met: 4 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 2y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2024
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.

PI3Kalpha inhibitor whose renal-relevant toxicity is metabolic, hyperglycemia and electrolyte shifts, not a defined kidney lesion

ModerateSelective PI3Kalpha (p110alpha) inhibitor/degrader

In combination with palbociclib and fulvestrant for PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with disease relapse during or within 12 months of completing adjuvant endocrine therapy

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Signature kidney injury

Signature lesion

Electrolyte Disturbance

Direct nephrotoxicity from inavolisib is not prominent and renal-specific data are limited; the headline metabolic toxicity is on-target hyperglycemia. In the INAVO120 phase 3 trial, grade 3 or 4 hyperglycemia occurred in 5.6 percent of the inavolisib group versus 0 percent with placebo, alongside higher rates of stomatitis and diarrhea (which can secondarily cause volume and electrolyte loss). A defined inavolisib-specific kidney lesion with an established electrolyte-event incidence rate is not characterized, so no headline signature rate is charted (the 5.6% grade 3/4 hyperglycemia figure is a metabolic, not electrolyte, signal).Source: 39476340

Onset & rechallenge

Time to injuryHyperacute (<24 h)

On-target hyperglycemia appears soon after dosing, sometimes peaking within hours of ingestion, and reverses within days of holding.

Distilled from: “Hyperglycemia from PI3Kalpha inhibition is an on-target effect that can appear soon after dosing, sometimes with peak glucose elevations in the hours following ingestion, and typically reverses within days of holding the drug.”

Long-term outlook & thresholds

Early-detection biomarkers

Fasting glucose from the first week — On-target PI3Kα insulin-signalling block — the same class effect as alpelisib, on a faster clock. The one number the class evidence cannot supply is the timing: in the phase III trial the median time to first hyperglycaemia was 7.0 days, roughly half alpelisib's, and hyperglycaemia drove dose interruption in 27.2% of patients (reduction 2.5%, discontinuation 0.6%). That argues for checking within the first week rather than at the first scheduled cycle visit. Everything else about this row is class-level and should be read that way. State the limit plainly: inavolisib has no renal literature at all — no AKI series, no electrolyte-event rate, no case report of kidney injury — so this marker tracks an on-target metabolic effect, and the agent's electrolyte signature rests on class inference, exactly as its own profile concedes.PMID 42202490 (opens PubMed in a new tab)

Long-term outcome and threshold data distilled from the agent's cited literature — educational, not a substitute for the primary sources.

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Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Electrolyte Disturbance#1 · Signaturequalitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

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Kidney injury

Mechanism of kidney injury

PI3Kalpha is a central mediator of insulin signaling, so on-target inhibition causes insulin resistance and hyperglycemia as a class effect, the dominant metabolic toxicity rather than a structural renal lesion. Secondary electrolyte disturbances can arise from the hyperglycemia itself (osmotic shifts and glucosuria-driven losses) and from GI toxicity (stomatitis and diarrhea causing volume depletion with potassium and magnesium loss). True direct tubular or glomerular injury is not a recognized feature of inavolisib.

Clinical presentation

Most commonly new or worsened hyperglycemia detected on glucose monitoring, occasionally severe and recalcitrant, with associated risk of dehydration. Electrolyte abnormalities and prerenal-pattern changes, when present, generally track with hyperglycemia severity and GI fluid losses rather than with an intrinsic kidney lesion.

Management

Manage hyperglycemia per protocol with lifestyle measures and antihyperglycemics (metformin is commonly first-line; insulin's effect may be partly blunted by ongoing PI3K inhibition), and interrupt or dose-modify inavolisib for severe or refractory hyperglycemia. Correct electrolyte abnormalities and replete volume losses driven by GI toxicity. Monitor renal function in the context of these metabolic and volume disturbances rather than expecting a primary nephrotoxic lesion.Lesion-level management framework

Risk factors

Pre-existing diabetes, prediabetes, or impaired fasting glucose
Obesity and metabolic syndrome
Concurrent glucocorticoids
Volume depletion from stomatitis/diarrhea (amplifies electrolyte and prerenal risk)

Prevention

Optimize glycemic control before the first dose
Dietary counseling and early involvement of endocrinology for at-risk patients
Proactive management of stomatitis and diarrhea to limit volume and electrolyte losses

Anticancer mechanism· how it treats cancer

Inavolisib is a highly potent, selective small-molecule inhibitor of the p110alpha catalytic subunit of PI3K (encoded by PIK3CA) that also promotes degradation of mutant p110alpha. By blocking and depleting oncogenic PI3Kalpha signaling it suppresses the PI3K/AKT/mTOR pathway that drives PIK3CA-mutated, HR-positive/HER2-negative breast cancer. It is used in combination with palbociclib and fulvestrant to overcome endocrine resistance.

§04

Clinical depth

Renal dose adjustment

Per the FDA label: no change for mild impairment (eGFR 60-89 mL/min, CKD-EPI); reduce from the 9 mg once-daily standard to 6 mg once daily for moderate (eGFR 30-59) and 3 mg once daily for severe (eGFR <30) impairment. Additional dose modification in practice is driven by hyperglycemia and GI toxicity.

Dialyzability & ESKD dosing

Not characterized. As a small-molecule oral agent, dialytic clearance data are not available; management of hyperglycemic emergencies follows standard metabolic principles.

Differential diagnosis

Distinguish on-target PI3Kalpha-inhibitor hyperglycemia from new-onset diabetes, steroid-induced hyperglycemia, and stress hyperglycemia. Electrolyte and creatinine changes should be attributed to hyperglycemia and GI fluid losses (prerenal physiology) rather than to a primary inavolisib nephrotoxic lesion, which is not an established entity.

Monitoring

Fasting glucose and HbA1c at baseline and periodically
Frequent glucose monitoring early in treatment and after dose changes
Serum electrolytes (including potassium and magnesium) and volume status, especially with stomatitis/diarrhea
Renal function in the setting of hyperglycemia or volume depletion

Key trials & series

INAVO120 (NCT04191499; Jhaveri/Turner et al., N Engl J Med 2024): phase 3, inavolisib plus palbociclib-fulvestrant vs placebo plus palbociclib-fulvestrant in PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer; median PFS 15.0 vs 7.3 months (HR 0.43), with grade 3 or 4 hyperglycemia 5.6 percent vs 0 percent
Phase I/Ib dose-finding (NCT03006172; Jhaveri et al., J Clin Oncol 2024): established the inavolisib plus palbociclib plus endocrine therapy combination; most frequent treatment-related AEs were stomatitis, hyperglycemia, and diarrhea

Clinical pearls

Watch for secondary electrolyte and volume problems from stomatitis and diarrhea, which can produce prerenal changes that mimic kidney injury.
Renal-specific literature for inavolisib is limited; the class hyperglycemia evidence (e.g., alpelisib) carries most of the mechanistic weight.

Where it strikes· nephron segments & injury signatures

Nephron segments

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

Injury signatures

Electrolyte Disturbance

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References

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

Evidence accrual

4 references · 2022–2024 · 4 since 2022

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.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Apr 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

Reduce the dosage in patients with moderate (eGFR 30 to < 60 mL/min) and severe (eGFR < 30 mL/min) renal impairment [see Dosage and Administration (2.5) ] . No dosage modification is recommended in patients with mild renal impairment (eGFR 60 to < 90 mL/min).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 527 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 1 signal

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Electrolyte DisturbanceNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.

SIADH / Hyponatremia

ROR 2.4895% CI 1.03–5.99· 5 reports

FAERS outcomes & reporting trend· 4.7% of reports w/ death · 33.6% w/ hospitalization

4.7%

Reported with a death outcome

25 of 527 reports

33.6%

Reported with hospitalization

177 of 527 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 527 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 5.3995% CI 3.45–8.43· 20 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury20

Gastrointestinal

Diarrhoea92Nausea54Stomatitis39Vomiting19Dry Mouth15

Metabolic & electrolyte

Hyperglycaemia133Decreased Appetite26Dehydration13

Blood & lymphatic

Neutropenia37White Blood Cell Count Decreased35Platelet Count Decreased24Thrombocytopenia24Anaemia16

General / constitutional

Fatigue54Asthenia28Weight Decreased23

Skin

Alopecia15Rash14

Nervous system

Headache16

Endocrine

Diabetes Mellitus12

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 Inavolisib 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

Denosumab

Xgeva · Anti-RANKL antibody

Profile

Severe hypocalcemia in low GFR; not directly nephrotoxic.

LYTE

Moderate#1 · 86% phenotype match

Necitumumab

Portrazza · Anti-EGFR antibody

Profile

Severe hypomagnesemia, class effect.

LYTE

Moderate#2 · 86% phenotype match

Amivantamab

Rybrevant · EGFR-MET bispecific antibody

Profile

EGFR-mediated electrolyte (magnesium) wasting; an emerging acute interstitial nephritis signal is also clinician-flagged.

LYTEAIN

Moderate#3 · 65% phenotype match

Erdafitinib

Balversa · FGFR inhibitor

Profile

Hyperphosphatemia is an on-target class effect.

LYTE

Moderate#4 · 63% phenotype match

Futibatinib

Lytgobi · FGFR inhibitor

Profile

Hyperphosphatemia, class effect.

LYTE

Moderate#5 · 63% phenotype match

Pemigatinib

Pemazyre · FGFR inhibitor

Profile

Hyperphosphatemia; nephrocalcinosis risk.

LYTE

Moderate#6 · 63% phenotype match

Compare Inavolisib 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
3IdelalisibPRE — Prerenal / Hemodynamic AKIMild
4CopanlisibHTN — HypertensionModerate
5CapivasertibPRE — Prerenal / Hemodynamic AKIModerate
6AlpelisibPRE — Prerenal / Hemodynamic AKIModerate
7Inavolisib· this agentLYTE — 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.