Afamitresgene autoleucel (Afami-cel)
Tecelra · MAGE-A4 TCR-T cell therapy
First TCR-T cell therapy for a solid tumor; CRS-associated hemodynamic AKI.
PRELYTE
Moderate#1 · 89% phenotype match
Capivasertib
Truqap · Capi
AKT inhibitor · approved 2023 · 8 citations
Up to date· through 2026
Deeply sourced7/9 · 6 signals
- Met: 8 citations
- Not met: 12+ references
- Met: Accrued over 10+ years (span: 12y)
- Met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Met: Current through 2026
- 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.
An AKT inhibitor for breast cancer — AKI tends to ride on its diarrhea and hyperglycemia.
ModerateAKT inhibitor
HR-positive HER2-negative advanced breast cancer (PIK3CA/AKT1/PTEN-altered)
§01
Signature kidney injury
Signature lesion
Diarrhea and hyperglycemia are the characteristic on-target toxicities (diarrhea very common; hyperglycemia frequent, occasionally severe). AKI, when it occurs, is largely a downstream pre-renal consequence of diarrhea-related volume loss and osmotic/metabolic disturbance; direct renal incidence is not well quantified. Rash is common but not nephrotoxic.Source: Turner et al., N Engl J Med 2023 (CAPItello-291)
Onset & rechallenge
Time to injuryAcute (~1–7 days)
Early in therapy, tracking diarrhea/hyperglycemia (first cycles).
Distilled from: “Early in therapy, tracking diarrhea/hyperglycemia (first cycles).”
§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.
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
§03
Kidney injury
Mechanism of kidney injury
AKT inhibition has two on-target effects with renal consequences. (1) Loss of AKT-dependent insulin signaling causes hyperglycemia (occasionally severe, with osmotic diuresis, dehydration and rarely DKA-like states), driving pre-renal volume depletion and electrolyte loss. (2) AKT blockade in gut epithelium produces secretory diarrhea; the resulting hypovolemia leads to pre-renal azotemia that can progress to ischemic tubular injury if severe. The kidney is injured indirectly via GI and metabolic toxicity rather than by a direct tubular toxin.
Clinical presentation
Rising creatinine in the context of diarrhea and hyperglycemia, with pre-renal indices (low FeNa, concentrated urine) early; hyperglycemia and electrolyte shifts (hypokalemia, hyponatremia) on labs. Resolves with rehydration and metabolic control.
Management
Aggressive supportive care for diarrhea and hyperglycemia with volume and electrolyte repletion; hold/dose-reduce per label for grade ≥3 toxicity. Treat hyperglycemia (hydration, antihyperglycemics, insulin if severe). Supportive AKI care; renal function recovers with restoration of volume and glycemic control.Lesion-level management framework
Risk factors
- Severe diarrhea / volume depletion
- Diabetes or baseline hyperglycemia
- Pre-existing CKD
- Concurrent nephrotoxins or diuretics
Prevention
- Prompt antidiarrheal therapy (loperamide) and aggressive oral/IV rehydration
- Manage hyperglycemia early, before osmotic diuresis drives volume depletion
- Patient education to report diarrhea early
Anticancer mechanism· how it treats cancer
Potent pan-AKT (AKT1/2/3) ATP-competitive serine/threonine kinase inhibitor that blocks PI3K–AKT–mTOR signaling downstream of common oncogenic alterations. Approved with fulvestrant for HR-positive HER2-negative advanced breast cancer harboring PIK3CA, AKT1 or PTEN alterations.
§04
Clinical depth
Renal dose adjustment
No dedicated renal dose adjustment for mild–moderate impairment; severe impairment/ESKD not well studied. Dose modification is driven by GI/metabolic toxicity grade. Capivasertib is given on an intermittent (4-days-on/3-days-off) schedule.
Dialyzability & ESKD dosing
Hepatically metabolized small molecule (CYP3A4); dialyzability not well characterized and unlikely to be the management lever. In advanced CKD, focus on volume/glucose management.
Differential diagnosis
Pre-renal AKI from diarrhea/hyperglycemic osmotic diuresis vs intrinsic tubular injury (the former corrects rapidly with volume) vs concurrent nephrotoxin; check glucose and volume status before attributing AKI to a direct renal lesion.
Monitoring
- Fasting glucose/HbA1c at baseline and periodically
- Stool frequency and hydration status
- Serum creatinine and electrolytes (K, Na) each cycle
Key trials & series
- CAPItello-291 (Turner NEJM 2023) phase III with fulvestrant
- CAPItello-290/-281 program (broader development)
Clinical pearls
- Protect the kidney by treating the diarrhea and hyperglycemia fast — the AKI is downstream volume/metabolic, not a tubular toxin.
- Severe hyperglycemia from AKT inhibition can cause osmotic diuresis and pre-renal AKI; monitor glucose proactively.
- The intermittent 4-on/3-off schedule helps mitigate cumulative GI toxicity.
- Rehydration and glycemic control reverse the creatinine rise in most cases.
Where it strikes· nephron segments & injury signatures
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
§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 · 2014–2025 · 3 since 2023Primary (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.
- 1.LandmarkCapivasertib in Hormone Receptor-Positive Advanced Breast Cancer.Turner NC et al. · N Engl J Med · 2023 · PMID 37256976Pivotal CAPItello-291 trial detailing rash and diarrhea as the principal grade >=3 toxicities.
- 2.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107Onconephrology reference for pre-renal/volume-depletion AKI mechanisms.
- 3.Renal Side Effects of Novel Molecular Targeted Oncologic Agents.Fenoglio R et al. · G Ital Nefrol · 2023 · PMID 38007829Onconephrology overview of renal effects of novel targeted agents, supporting that AKT-inhibitor AKI is largely secondary rather than a direct lesion.
- 4.Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch · 2021 · PMID 34840210Histologic survey of targeted-therapy renal complications giving context to the absence of a defined AKT-inhibitor lesion.
- 5.Drug-induced rise in serum creatinine: cystatin C to the rescue? Evidence, pitfalls and knowledge gaps.Van Regemorter E et al. · Eur J Intern Med · 2025 · PMID 41224604Reviews drug-related creatinine rises across targeted agents and the cystatin-C approach to distinguish true from apparent AKI.
- 6.Management of euvolemic hyponatremia attributed to SIADH in the hospital setting.Peri A et al. · Minerva Endocrinol · 2014 · PMID 24513602Approach to drug- and illness-related hyponatremia, relevant to the electrolyte shifts (hyponatremia/hypokalemia) accompanying capivasertib diarrhea.
Case reports — ranked by strength· 2
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 · LimitedCapivasertib-Induced Refractory Hyperglycemia in a Nondiabetic Patient With Metastatic Breast Cancer.Darapu H et al. · AACE Endocrinol Diabetes 2026 · PMID 41938274Case report of capivasertib-induced refractory hyperglycemia with mixed DKA/HHS leading to acute renal failure and hemodynamic instability requiring continuous renal replacement therapy.CaseC · Limited[A Case of Drug‒Induced Tubulointerstitial Nephritis Caused by Capivasertib Therapy].Takemae M et al. · Gan To Kagaku Ryoho 2025 · PMID 41047780Case report of a 79-year-old woman who developed drug-induced tubulointerstitial nephritis with proteinuria and renal dysfunction during capivasertib plus fulvestrant therapy, treated with steroid pulse therapy.
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 Capivasertib 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Loncastuximab tesirine
Zynlonta · Antibody-drug conjugate (CD19/PBD)
Capillary-leak-type edema, effusions and AKI.
PRELYTE
Moderate#2 · 89% phenotype match
Ziftomenib
Komzifti · Menin inhibitor
2025 NPM1-mutated AML menin inhibitor; differentiation syndrome and tumor lysis.
PRELYTE
Moderate#3 · 89% phenotype match
Catumaxomab
Removab · Trifunctional bispecific (EpCAM×CD3)
Intraperitoneal; cytokine-release- and ascites/paracentesis-driven prerenal AKI; withdrawn (EU) 2017.
PRELYTE
Moderate#4 · 88% phenotype match
Quizartinib
Vanflyta · FLT3 inhibitor
2023 AML FLT3 inhibitor; tumor lysis and QT.
PRELYTE
Mild#5 · 84% phenotype match
Imetelstat
Rytelo · Telomerase inhibitor
2024 MDS agent; tumor lysis risk.
PRELYTE
Mild#6 · 83% phenotype match
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
- 5Capivasertib· this agentPRE — 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.