Is kidney injury from Pralsetinib reversible?

Reversible. Typical onset: Hypertension within the first weeks to months..

How should kidney function be monitored during Pralsetinib therapy?

Blood pressure at baseline and regularly during therapy; CBC for neutropenia/anemia; liver enzymes per label; Serum creatinine periodically; cystatin C if a true GFR change is suspected.

Who is at higher risk of kidney injury from Pralsetinib?

Pre-existing hypertension; Cardiovascular disease; Concurrent nephrotoxins.

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Printable monograph

RET inhibitor

Pralsetinib

Gavreto · Pral

RET inhibitor · approved 2020 · 6 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
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 selective RET inhibitor — hypertension is its main vascular signal, with AKI rare.

MildRET inhibitor

RET fusion-positive NSCLCRET-altered thyroid cancer

§01

Signature kidney injury

Signature lesion

Hypertension

Representative grade ≥3 incidence11%

Hypertension is among the more common grade >=3 treatment-related adverse events (about 11% in the ARROW NSCLC cohort); clinically significant intrinsic AKI is rare.Source: Gainor et al., Lancet Oncol 2021

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Hypertension develops within the first weeks to months of treatment.

Distilled from: “Hypertension within the first weeks to 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 · Signature11%PMID 34118197 (opens PubMed in a new tab)
Grade >=3 hypertension in 11% (26/233) of RET fusion-positive NSCLC and 17% (24/142) of RET-altered thyroid cancer (ARROW); among the most common grade >=3 treatment-related events
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Pseudo-AKIRarequalitative — no citable incidence
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

11%grade ≥3 incidence

SeverityMild

ReversibilityReversible

Evidence6 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / EndotheliumGlomerular & peritubular capillaries

Proximal Tubule

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

Deep divePseudo-AKI: the creatinine rises and the kidney is fineCreatinine does not only filter — a fifth of it is pushed into the urine by tubular transporters, and a drug that blocks those transporters raises the number without touching the glomerulus, producing a rise that looks like acute kidney injury on every axis except the one that matters.

Mechanism of kidney injury

Hypertension reflects an on/near-target vascular effect of RET-pathway inhibition. Intrinsic nephrotoxicity is not characteristic; any creatinine rise may partly reflect hemodynamic effects (from hypertension) or tubular-secretion inhibition rather than true filtration loss.

Clinical presentation

New or worsened hypertension; AKI is uncommon. Cytopenias (neutropenia, anemia, lymphopenia) and transaminitis are prominent non-renal toxicities; pneumonitis is a notable class concern.

Management

Standard antihypertensives; dose-interrupt then reduce for medically uncontrolled BP. Supportive care and standard workup if AKI develops; confirm whether a creatinine rise is true injury or a transporter artifact.Lesion-level management framework

Risk factors

Pre-existing hypertension
Cardiovascular disease
Concurrent nephrotoxins

Prevention

Optimize antihypertensives

Anticancer mechanism· how it treats cancer

Highly potent, selective RET inhibitor targeting RET fusions and mutations; approved for RET fusion-positive NSCLC and thyroid cancers.

§04

Clinical depth

Renal dose adjustment

No dose adjustment for mild-moderate renal impairment; severe impairment is not well characterized and dialysis is not studied (use with caution). Modifications are driven by hypertension, pneumonitis, cytopenias, and hepatotoxicity.

Dialyzability & ESKD dosing

Highly protein-bound oral small molecule; not expected to be appreciably dialyzed. No validated ESKD dosing.

Differential diagnosis

Drug-induced hypertension vs other causes; uncommon true AKI vs transporter-mediated creatinine rise (stable cystatin C). If creatinine and cystatin C diverge, suspect the transporter effect rather than parenchymal injury.

Monitoring

Blood pressure at baseline and regularly during therapy
CBC for neutropenia/anemia; liver enzymes per label
Serum creatinine periodically; cystatin C if a true GFR change is suspected

Key trials & series

ARROW (RET fusion-positive NSCLC and RET-altered thyroid)
Hamidi 2024 hereditary-MTC RET-inhibitor safety series

Clinical pearls

Hypertension dominates the renal-relevant profile; significant intrinsic AKI is rare.
Newer agent — interpret the renal signal conservatively and lean on cystatin C for ambiguous creatinine changes.
Do not overlook pneumonitis and cytopenias, which more often drive dose modification than any renal event.

§05

References

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

Evidence accrual

6 references · 2021–2025 · 3 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.

FDA label — boxed warning & renal dosing· boxed warning

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

Boxed warning

WARNING: SERIOUS INFECTIONS, INCLUDING OPPORTUNISTIC INFECTIONS GAVRETO may increase the risk for serious infections, including bacterial, fungal, viral and opportunistic infections, which can lead to hospitalization or death. Withhold, reduce the dose or permanently discontinue GAVRETO based on severity [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] . WARNING: SERIOUS INFECTIONS, INCLUDING OPPORTUNISTIC INFECTIONS See full prescribing information for complete boxed warning. GAVRETO may increase the risk for serious infections, including bacterial, fungal, viral and opportunistic infections, which can lead to hospitalization or death. Withhold, reduce the dose or permanently discontinue GAVRETO based on severity. ( 2.3 , 5.1 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 1,788 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

Hypertensioncorroborated · ROR 6.13 — on the terms that name the lesion (ROR 5.39)
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Pseudo-AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Hypertension

ROR 6.1395% CI 5.26–7.14· 184 reports

SIADH / Hyponatremia

ROR 2.4995% CI 1.54–4.01· 17 reports

Electrolyte Disturbance

ROR 1.7995% CI 1.24–2.59· 29 reports

FAERS outcomes & reporting trend· 14.1% of reports w/ death · 29.1% w/ hospitalization

14.1%

Reported with a death outcome

252 of 1,788 reports

29.1%

Reported with hospitalization

520 of 1,788 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 1,788 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 0.3195% CI 0.12–0.82· 4 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue126Asthenia116Pyrexia79

Blood & lymphatic

Anaemia98White Blood Cell Count Decreased85Platelet Count Decreased56Myelosuppression38Haemoglobin Decreased37

Gastrointestinal

Diarrhoea93Constipation89Dry Mouth50Nausea50

Vascular

Hypertension96Blood Pressure Increased90

Respiratory

Dyspnoea52Cough49Pneumonitis44

Nervous system

Dizziness51Headache41

Immune / infection

Pneumonia75

Metabolic & electrolyte

Decreased Appetite42

Hepatobiliary

Hepatic Function Abnormal42

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 Pralsetinib 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

Brigatinib

Alunbrig · ALK TKI

Profile

Creatinine elevation; usually benign.

PSEUDOPREHTN

Mild#1 · 89% phenotype match

Momelotinib

Ojjaara · JAK/ACVR1 inhibitor

Profile

2023 myelofibrosis JAK inhibitor.

PSEUDOPRE

Mild#2 · 81% phenotype match

Vimseltinib

Romvimza · CSF1R tyrosine kinase inhibitor

Profile

A clean-kidney targeted TKI — watch the CPK, not the nephron.

PSEUDOPRE

Mild#3 · 81% phenotype match

Selpercatinib

Retevmo · RET inhibitor

Profile

Hypertension and creatinine rise.

HTNPREPSEUDO

Moderate#4 · 75% phenotype match

Alectinib

Alecensa · ALK TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDOPRE

Mild#5 · 73% phenotype match

Bosutinib

Bosulif · BCR-ABL TKI

Profile

Reversible eGFR decline.

PSEUDOPRE

Mild#6 · 73% phenotype match

Compare Pralsetinib 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 Other kinase 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.

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.