Is kidney injury from Acalabrutinib reversible?

Variable. Typical onset: Tumor lysis early (first cycle); hypertension over weeks–months..

How should kidney function be monitored during Acalabrutinib therapy?

Blood pressure periodically (lower but real hypertension risk); Tumor-lysis labs during early cytoreduction of bulky disease.

How can kidney injury from Acalabrutinib be prevented?

TLS risk stratification with hydration and urate-lowering therapy Blood-pressure monitoring and control

Who is at higher risk of kidney injury from Acalabrutinib?

High tumor burden / bulky disease; Pre-existing hypertension or CKD; Volume depletion; Prior arrhythmia, Black ancestry (for BTKi hypertension).

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Printable monograph

BTK inhibitor

Acalabrutinib

Calquence · Acala

BTK inhibitor · approved 2017 · 8 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 8 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
Met: Current through 2025
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.

A more selective second-generation BTK inhibitor — less hypertension than ibrutinib, with tumor lysis the main renal risk.

MildBTK inhibitor (2nd generation)

CLL/SLLMantle-cell lymphoma

§01

Signature kidney injury

Signature lesion

Hypertension

Representative incidence15%

Hypertension occurs but is less frequent than with ibrutinib (~15% vs ~26% in a matched real-world cohort; ELEVATE-RR confirmed lower hypertension and atrial fibrillation head-to-head). One single-center cardio-oncology cohort still found ~49% new/worsened hypertension by sensitive criteria. Tumor lysis is the principal route to AKI; direct nephrotoxicity is case-level.Source: Majrashi et al., Pharmacol Res Perspect 2025 (HTN 15%)

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Tumor lysis early (first cycle); hypertension over weeks to months.

Distilled from: “Tumor lysis early (first cycle); hypertension over weeks–months.”

§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.

Hypertension#1 · Signatureno population incidence denominator
In ELEVATE-RR (head-to-head vs ibrutinib in relapsed/refractory CLL, n=533), any-grade hypertension was markedly less frequent with acalabrutinib, with a ~2.8-fold lower exposure-adjusted incidence than ibrutinib — a milder BTK-inhibitor vascular signal. PMID 37390310 (opens PubMed in a new tab)
Prerenal / Hemodynamic AKIRarequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Crystal / Obstructive NephropathyRarequalitative — no citable incidence
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

15%incidence

SeverityMild

ReversibilityVariable

Evidence8 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / EndotheliumGlomerular & peritubular capillaries

Tubular Lumen

Hypertension

Raised blood pressure — archetypally on-target loss of endothelial nitric oxide from VEGF-pathway blockade, studied as a pharmacodynamic marker of drug exposure. Other agents raise it too: vascular effects of BCR-ABL, BTK and RET inhibitors and of copanlisib; abiraterone's mineralocorticoid excess; androgen suppression or blockade.

§03

Kidney injury

Mechanism of kidney injury

Greater BTK selectivity reduces the off-target kinase/endothelial effects that drive ibrutinib's hypertension and presumed glomerular endothelial injury, so the hypertension burden is lower. AKI is mainly hemodynamic or from tumor lysis on rapid cytoreduction of bulky CLL/lymphoma (urate/phosphate release with intratubular crystal injury).

Clinical presentation

Generally stable renal function; a blood-pressure rise that is usually milder than ibrutinib; tumor-lysis labs when high-burden disease responds rapidly. Headache (early, self-limited) is a characteristic non-renal effect.

Management

Manage tumor lysis (hydration, rasburicase/allopurinol, electrolyte correction) and hypertension; dose-modify (from 100 mg twice daily) for severe events.Lesion-level management framework

Risk factors

High tumor burden / bulky disease
Pre-existing hypertension or CKD
Volume depletion
Prior arrhythmia, Black ancestry (for BTKi hypertension)

Prevention

TLS risk stratification with hydration and urate-lowering therapy
Blood-pressure monitoring and control

Anticancer mechanism· how it treats cancer

More selective covalent BTK inhibitor (binds cysteine-481) with substantially fewer off-target kinase effects than ibrutinib, used in CLL/SLL and mantle-cell lymphoma.

Note · Cardiovascular/renal tolerability is more favorable than ibrutinib, validating ELEVATE-RR in the real world — but hypertension remains a BTKi class effect, so it should still be monitored.

§04

Clinical depth

Renal dose adjustment

No dose adjustment for mild-to-moderate renal impairment (CrCl ≥30 mL/min); severe impairment (CrCl <30) and dialysis are not well studied. <2% renal excretion; hepatic (CYP3A) clearance dominates. Acid-reducing agents alter absorption of the original capsule (a key non-renal interaction).

Dialyzability & ESKD dosing

Not meaningfully dialyzable — highly protein-bound, hepatically cleared small molecule. No post-HD supplemental dosing needed.

Differential diagnosis

As with ibrutinib, separate drug-related effects from CLL-intrinsic kidney disease and tumor lysis. Lower hypertension than ibrutinib helps, but a new BP rise should still be recognized as a likely BTKi class effect rather than dismissed.

Monitoring

Blood pressure periodically (lower but real hypertension risk)
Tumor-lysis labs during early cytoreduction of bulky disease

Key trials & series

Byrd et al., JCO 2021 — ELEVATE-RR, first randomized phase 3 head-to-head vs ibrutinib (lower hypertension and atrial fibrillation)
Ghia et al., JCO 2020 — ASCEND registrational R/R CLL trial
Majrashi et al., Pharmacol Res Perspect 2025 — real-world acalabrutinib 15% vs ibrutinib 26.3% hypertension

Clinical pearls

Acalabrutinib's renal-relevant advantage over ibrutinib is real-world lower hypertension and atrial fibrillation (ELEVATE-RR) — but hypertension is still a class effect.
The principal route to AKI is tumor lysis during rapid CLL/lymphoma debulking, not direct tubulotoxicity.
Acid-reducing drugs blunt absorption of the original capsule formulation — an efficacy, not renal, pitfall worth remembering.

Beyond the kidney — non-renal toxicities· 2 organ systems

Class-level context for the major non-renal toxicities of the BTK inhibitor class.

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

Atrial fibrillation, ventricular arrhythmia

Vascular

Hypertension, VTE/ATE, bleeding, aneurysm

Bleeding, hypertension

§05

References

7 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

7 references · 2018–2025 · 2 since 2023

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 Triggered by Acalabrutinib in Chronic Lymphocytic Leukemia (CLL): Diagnostic and Therapeutic Implications.Fadi M et al. · Cureus 2025 · PMID 41141198Case report of acalabrutinib-triggered tumor lysis syndrome in CLL causing acute kidney injury with severe hyperuricemia, hyperphosphatemia, hyperkalemia, and worsening renal function.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 12,049 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· 3 signals

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

Crystal / Obstructive Nephropathycorroborated · ROR 3.72
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
HypertensionNo 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.

Crystal / Obstructive Nephropathy

ROR 3.7295% CI 3.10–4.46· 118 reports

SIADH / Hyponatremia

ROR 1.8495% CI 1.49–2.28· 85 reports

Electrolyte Disturbance

ROR 1.2295% CI 1.03–1.45· 134 reports

FAERS outcomes & reporting trend· 21.5% of reports w/ death · 26.8% w/ hospitalization

21.5%

Reported with a death outcome

2,592 of 12,049 reports

26.8%

Reported with hospitalization

3,233 of 12,049 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 12,049 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 0.7395% CI 0.57–0.93· 64 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue677Fall363Asthenia299Pain286Pyrexia230

Nervous system

Headache623Dizziness259

Gastrointestinal

Diarrhoea409Nausea259

Blood & lymphatic

Anaemia221White Blood Cell Count Increased185Platelet Count Decreased175

Immune / infection

Pneumonia320Covid-19241

Musculoskeletal

Arthralgia250Myalgia181

Respiratory

Dyspnoea327

Cardiac

Atrial Fibrillation280

Skin

Rash240

Vascular

Haemorrhage176

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 Acalabrutinib 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

Zanubrutinib

Brukinsa · BTK inhibitor

Profile

Tumor lysis in CLL/lymphoma.

PRELYTEXTAL

Mild#1 · 76% phenotype match

Asciminib

Scemblix · BCR-ABL STAMP inhibitor

Profile

Hypertension and pancreatitis; allosteric BCR-ABL inhibitor.

HTNPRE

Mild#2 · 70% phenotype match

Brentuximab vedotin

Adcetris · Antibody-drug conjugate (CD30/MMAE)

Profile

Tumor lysis in lymphoma.

PRELYTEXTAL

Mild#3 · 65% phenotype match

Polatuzumab vedotin

Polivy · Antibody-drug conjugate (CD79b/MMAE)

Profile

Tumor lysis; emerging renal data.

PRELYTEXTAL

Mild#4 · 65% phenotype match

Pirtobrutinib

Jaypirca · Non-covalent BTK inhibitor

Profile

2023 BTK inhibitor; tumor lysis risk.

XTALPRELYTE

Mild#5 · 61% phenotype match

Epcoritamab

Epkinly · Bispecific (CD20×CD3)

Profile

CRS and tumor lysis — emerging.

PRELYTEXTAL

Moderate#6 · 60% phenotype match

Compare Acalabrutinib 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 BTK 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.

1Acalabrutinib· this agentHTN — HypertensionMild
2ZanubrutinibPRE — Prerenal / Hemodynamic AKIMild
3PirtobrutinibXTAL — Crystal / Obstructive NephropathyFAERS AKIMild
4IbrutinibHTN — HypertensionModerate

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.