Gedatolisib

Electrolyte Disturbance.

No discrete drug-specific incidence of gedatolisib acute kidney injury is published; the renal-relevant signal is laboratory-level. In the VIKTORIA-1 triplet arm the FDA label's laboratory table reports increased creatinine in 14% (grade 3-4 0.8%) versus 8% (0.8%) on fulvestrant alone, decreased sodium in 21% (grade 3-4 1.6%), decreased potassium in 19% (1.6%) and decreased magnesium in 19% (0%) — all-grade drift, with severe events rare. The dominant metabolic effect is on-target hyperglycemia: increased fasting glucose in 46% of triplet-arm and 57% of doublet-arm patients on the label's laboratory table, while grade >=3 treatment-related hyperglycemia in the VIKTORIA-1 publication was 2.3% in both gedatolisib arms (Hurvitz, J Clin Oncol 2026) — markedly gentler than daily oral PI3K-alpha inhibition. In a phase II HER2-positive combination, any-grade hyperglycemia was 25.0% with grade 3 in 2.3% (Kim, ESMO Open 2026).

Source: No drug-specific AKI incidence; label lab-table electrolyte/creatinine drift is all-grade and low-grade. Grade >=3 hyperglycemia 2.3% in VIKTORIA-1 (Hurvitz 2026); any-grade 25% in a HER2+ phase II (Kim 2026)

Reported injury signatures: Electrolyte Disturbance, Prerenal / Hemodynamic AKI.

1. Electrolyte DisturbancePrimary
2. Prerenal / Hemodynamic AKISecondary

Subacute (~1–6 weeks) — Fasting glucose moves within the first weekly infusions; electrolyte drift appears on routine chemistries across early cycles rather than as an acute event.

• Pre-existing diabetes, prediabetes or elevated baseline HbA1c (amplifies on-target hyperglycemia)
• Volume depletion from stomatitis-limited intake, diarrhea or decreased appetite
• Concurrent diuretics or other electrolyte-wasting drugs
• Baseline CKD — the label reports no clinically significant pharmacokinetic differences at eGFR >=45 mL/min/1.73 m2 (MDRD equation) and states the effect of eGFR <45, or dialysis, on pharmacokinetics is unknown
• Concurrent corticosteroids or other hyperglycemia-promoting medications

• Assess fasting glucose and HbA1c before the first infusion and optimize glycemic control before starting — the baseline gate the label builds dosing on
• Correct baseline electrolyte abnormalities before starting therapy
• Ensure adequate hydration when fasting glucose rises, per the label's hyperglycemia management instructions
• Initiate or intensify anti-hyperglycemic treatment early rather than after osmotic symptoms develop
• Review co-medications for additive electrolyte loss or hyperglycemia before each cycle

• Fasting glucose before each infusion during early cycles, then periodically per label; HbA1c to track control
• Basic chemistries including sodium, potassium, magnesium and creatinine on the routine schedule
• Volume status during stomatitis, diarrhea or poor intake
• Blood counts per the palbociclib partner's requirements (the dominant grade 3-4 toxicity in the triplet)

• VIKTORIA-1 (Hurvitz, J Clin Oncol 2026) — phase III, n=392: gedatolisib triplet median PFS 9.3 vs 2.0 months for fulvestrant (HR 0.24), doublet 7.4 months (HR 0.33); grade >=3 treatment-related hyperglycemia 2.3% in both gedatolisib arms — the registrational trial and the source of the label's laboratory table.
• Phase Ib first-line triplet (Wesolowski, Clin Cancer Res 2025) — gedatolisib plus palbociclib and letrozole, n=41: median PFS 48.4 months; most frequent grade 3/4 events neutropenia 61%, rash 39%, stomatitis 29% — no renal signal.
• HER2-positive phase II (Kim, ESMO Open 2026) — trastuzumab plus gedatolisib, n=44: oral mucositis 90.9% (grade >=3 15.9%) and hyperglycemia 25.0% (grade 3 2.3%) as the leading toxicities.

• Think glucose first: pan-PI3K blockade inhibits insulin signaling, and the kidney trouble it causes is downstream of hyperglycemia and volume, not a lesion in the nephron.
• The intermittent IV schedule is why its grade >=3 hyperglycemia (2.3% in VIKTORIA-1) sits far below daily oral PI3K-alpha inhibition — same target, different exposure shape.
• Label lab tables show creatinine up 14% all-grade versus 8% on fulvestrant alone, with grade 3-4 essentially absent — drift, not injury.
• Sodium, potassium and magnesium each dip in roughly a fifth of patients; replete and move on — severe derangement is rare.
• Below eGFR 45 the pharmacokinetics are unstudied — that is an evidence gap, not a dose band.

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