How should kidney function be monitored during Alpelisib therapy?

Fasting glucose and HbA1c at baseline, then fasting glucose weekly for 2 weeks, every 2 weeks for 8 weeks, then periodically; Ketones/anion gap if marked hyperglycemia or SGLT2 inhibitor used; Weight and volume status.

How can kidney injury from Alpelisib be prevented?

Optimize and document fasting glucose and HbA1c before starting Patient education on hydration and hyperglycemia symptoms Early metformin; SGLT2 inhibitors are increasingly used to blunt the insulin-feedback loop (watch euglycemic DKA) Dose interrupt/reduce alpelisib for grade 3/4 hyperglycemia per label

Who is at higher risk of kidney injury from Alpelisib?

Baseline diabetes, prediabetes, elevated HbA1c or BMI; Concurrent glucocorticoids; Older age and pre-existing CKD; Inadequate hydration/antihyperglycemic management.

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Printable monograph

PI3Kα inhibitor

Alpelisib

Piqray · ALP

PI3Kα inhibitor · approved 2019 · 7 citations

Recent· through 2024

Fairly sourced5/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 6y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2024
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.

PI3K-alpha inhibitor whose on-target hyperglycemia can drive osmotic diuresis and prerenal AKI — a metabolic, not structural, kidney threat.

ModerateTargeted PI3K-pathway era

PIK3CA-mutated, HR-positive, HER2-negative advanced or metastatic breast cancer (with fulvestrant)PIK3CA-related overgrowth spectrum (PROS)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Hyperglycemia is essentially on-target and very common: any-grade hyperglycemia ~64% and grade 3/4 hyperglycemia ~36.6% in SOLAR-1, with diabetic ketoacidosis reported rarely in pharmacovigilance. The renal injury is secondary (osmotic diuresis/volume depletion or DKA) rather than a direct lesion; a discrete AKI incidence is not well quantified.Source: Andre et al., N Engl J Med 2019 (SOLAR-1; 36.6% grade 3/4 hyperglycemia — a metabolic, not renal-injury, rate); Rugo et al., Ann Oncol 2020

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Hyperglycemia typically within the first 1–2 weeks; prerenal AKI follows volume depletion or a hyperglycemic crisis.

Distilled from: “Hyperglycemia typically within the first 1-2 weeks; prerenal AKI follows volume depletion or a hyperglycemic crisis.”

Long-term outlook & thresholds

Early-detection biomarkers

Fasting plasma glucose, with baseline HbA1c as the pre-treatment risk stratifier — On-target PI3Kα-mediated insulin resistance — the kidney is downstream, via osmotic diuresis or a hyperglycaemic crisis. Among 247 patients at a single centre — 100 of them (40.5%) on a clinical trial, the rest as standard care — 61.5% developed hyperglycaemia of any grade and 29.2% reached grade 3–4, with a median 16 days to onset. Those are whole-cohort figures, and the split inside the cohort is the point: standard-care patients reached 80.3% any-grade and 40.2% grade 3–4 against 34.0% and 13.0% on trial, so the window is short and the rate in ordinary practice runs far above the trial figures. Baseline HbA1c is the unusual part: it was significantly associated both with developing hyperglycaemia and with needing an alpelisib dose reduction or discontinuation, which makes it a gate before the first dose rather than a monitoring test — and the authors conclude that optimising glycaemic status before starting should be routine. This is a metabolic marker, not a renal one: no study measures a kidney biomarker against it, and the glucose is watched to prevent the crisis that would injure the kidney, not to detect a lesion.PMID 37743730 (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.

§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.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Acute Tubular NecrosisSecondaryqualitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityReversible

Evidence7 citations

Nephron map

Vasculature / Endothelium

Proximal Tubule

Distal Tubule / Collecting Duct

Prerenal / Hemodynamic AKI

Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

Inhibiting p110-alpha blocks insulin's own PI3K-dependent signaling, producing on-target insulin resistance with hyperglycemia and a compensatory hyperinsulinemic state (the hyperglycemia paradoxically reactivates tumor PI3K, the rationale for SGLT2 inhibitors as adjuncts). Marked hyperglycemia causes a glucose osmotic diuresis with renal sodium and water loss, volume contraction and prerenal azotemia; severe cases progress to hyperosmolar states or DKA with true AKI. The kidney lesion is therefore hemodynamic/metabolic rather than a direct tubular or glomerular toxicity.

Clinical presentation

Rising fasting glucose within days to a few weeks of starting therapy, polyuria, polydipsia and weight loss; rising creatinine with a bland sediment, high urine osmolality and low FeNa typical of a prerenal state. In extreme cases: hyperosmolar hyperglycemic state or ketoacidosis with anion-gap metabolic acidosis and acute tubular injury.

Management

Treat the hyperglycemia aggressively (metformin first-line; add SGLT2 inhibitor, insulin or others for grade 3/4), maintain euvolemia with fluids, and hold or reduce alpelisib until glucose is controlled. Manage DKA/HHS with IV fluids and insulin; the AKI generally resolves with restoration of volume and glycemic control. Involve endocrinology for refractory hyperglycemia.Lesion-level management framework

Risk factors

Baseline diabetes, prediabetes, elevated HbA1c or BMI
Concurrent glucocorticoids
Older age and pre-existing CKD
Inadequate hydration/antihyperglycemic management

Prevention

Optimize and document fasting glucose and HbA1c before starting
Patient education on hydration and hyperglycemia symptoms
Early metformin; SGLT2 inhibitors are increasingly used to blunt the insulin-feedback loop (watch euglycemic DKA)
Dose interrupt/reduce alpelisib for grade 3/4 hyperglycemia per label

Anticancer mechanism· how it treats cancer

Selective oral inhibitor of the p110-alpha catalytic isoform of class I PI3K (PIK3CA). In PIK3CA-mutated hormone-receptor-positive, HER2-negative breast cancer it blocks PI3K/AKT/mTOR signaling downstream of the activated receptor, restoring sensitivity to endocrine therapy (fulvestrant).

Note · The renal link is indirect: alpelisib causes profound on-target hyperglycemia, and AKI arises from osmotic diuresis/volume depletion or a hyperglycemic crisis rather than a direct renal lesion. The hyperglycemia figures are real and quantified.

§04

Clinical depth

Renal dose adjustment

No dose adjustment for mild-moderate renal impairment; not studied in severe impairment (CrCl <30) or ESKD. Dose modification is driven by hyperglycemia and rash, not by baseline GFR.

Dialyzability & ESKD dosing

Highly protein-bound small molecule; not expected to be meaningfully dialyzable and no ESKD dosing established.

Differential diagnosis

Distinguish osmotic-diuresis prerenal AKI (low FeNa, high urine osmolality, hyperglycemia) from intrinsic ATN, contrast injury, and fulvestrant-unrelated causes. The tight temporal link to hyperglycemia and rapid reversal with glucose/volume correction is the clue.

Monitoring

Fasting glucose and HbA1c at baseline, then fasting glucose weekly for 2 weeks, every 2 weeks for 8 weeks, then periodically
Ketones/anion gap if marked hyperglycemia or SGLT2 inhibitor used
Weight and volume status

Key trials & series

SOLAR-1 (Andre, NEJM 2019) — registrational RCT defining the grade 3/4 hyperglycemia signal
Rugo et al. (Ann Oncol 2020) — detailed time-course and management of alpelisib hyperglycemia

Clinical pearls

Hyperglycemia is on-target, not idiosyncratic — anticipate it in every patient and pre-arm a glucose plan.
SGLT2 inhibitors are mechanistically attractive (they break the insulin-feedback loop) but risk euglycemic DKA — monitor ketones.
The kidney injury is hemodynamic: fix the glucose and the volume and the creatinine follows.
A hyperglycemic crisis (HHS/DKA) is the scenario that converts prerenal azotemia into true ATN.

§05

References

6 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2018–2024 · 2 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.

Case reports — ranked by strength· 1

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedTumor lysis Syndrome in a Patient with Metastatic Breast Cancer Treated with Alpelisib.Handy C et al. · Breast Cancer (Auckl) 2021 · PMID 34483661Case report of tumor lysis syndrome with acute renal function impairment developing 12 days after starting alpelisib/fulvestrant, recovering to baseline without renal replacement therapy.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Dec 2025) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

The effect of severe renal impairment (CLcr < 30 mL/min) on alpelisib pharmacokinetics is unknown [see Clinical Pharmacology (12.3)] . No dose adjustment is recommended for patients with mild to moderate renal impairment (CLcr 30 to < 90 mL/min).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 8,666 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

Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
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.
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.

SIADH / Hyponatremia

ROR 1.3895% CI 1.04–1.85· 46 reports

FAERS outcomes & reporting trend· 14.1% of reports w/ death · 19.5% w/ hospitalization

14.1%

Reported with a death outcome

1,224 of 8,666 reports

19.5%

Reported with hospitalization

1,686 of 8,666 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 8,666 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 0.8695% CI 0.66–1.12· 54 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Gastrointestinal

Diarrhoea1,356Nausea861Vomiting489Stomatitis343Dry Mouth211

General / constitutional

Fatigue852Weight Decreased526Asthenia346Pyrexia273Pain249

Metabolic & electrolyte

Hyperglycaemia1,509Decreased Appetite548Dehydration197

Skin

Rash1,391Pruritus281Alopecia223

Endocrine

Diabetes Mellitus246

Respiratory

Dyspnoea200

Nervous system

Headache193

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 Alpelisib 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

Pacritinib

Vonjo · JAK2/ACVR1 inhibitor

Profile

JAK2/ACVR1 inhibitor; diarrhea-driven prerenal AKI and electrolyte loss.

PRELYTEATN

Moderate#1 · 89% phenotype match

Gedatolisib

Revtorpyk · Pan-PI3K inhibitor

Profile

2026 IV pan-PI3K + mTORC1/2 (breast); on-target hyperglycemia and low-grade Na/K/Mg drift — creatinine up 14% vs 8% control, grade 3-4 rare.

LYTEPRE

Mild#2 · 78% phenotype match

Lifileucel

Amtagvi · Tumor-infiltrating lymphocyte (TIL) therapy

Profile

2024 cellular therapy; high-dose IL-2 conditioning → capillary leak AKI.

PREATNLYTE

Moderate#3 · 77% phenotype match

Avutometinib

Avmapki (co-packaged with defactinib as Avmapki Fakzynja) · RAF/MEK inhibitor

Profile

RAF/MEK clamp; CK elevation/rhabdomyolysis and tubular electrolyte wasting.

LYTEATNPRE

Moderate#4 · 77% phenotype match

Neratinib

Nerlynx · HER2 / pan-EGFR TKI

Profile

Severe diarrhea → prerenal AKI; loperamide prophylaxis.

PRELYTE

Moderate#5 · 73% phenotype match

Capivasertib

Truqap · AKT inhibitor

Profile

2023 breast-cancer AKT inhibitor; AKI with diarrhea/hyperglycemia.

PRELYTE

Moderate#6 · 72% phenotype match

Compare Alpelisib 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
6Alpelisib· this agentPRE — 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.

Who studies this

The leading contributors to Alpelisib’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Alpelisib; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 5 clinical records among all 6 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.