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Kaimen Rigor review

Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.

Diebold M, Gauthier PT, Mayer KA, Mackova M, Hinze C, Chang J, Patel UD, Schütz E, Jilma B, Schrezenmeier E, Budde K, Böhmig GA, Halloran PF

DOI: 10.1038/s41591-025-03653-3
Record issued: 2026-08-15
Engine: 7.39.0
Exported: 2026-09-22

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/d518462a-9a61-4f1f-9038-2e0c51d0f6b9 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

3 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingBiological variables partially met−0.25★
CitationsUnresolved reference−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

Statistics were not checked: no recomputable values were found in this text — no test statistic reported with its degrees of freedom, no effect estimate printed with both a 95% CI and a p-value, and no percentage printed with both its count and its denominator.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on molecular surrogate endpoints (ABMR activity scores, IFNγ-inducible and NK cell transcripts, injury scores) rather than hard clinical outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD or dose-exposure relationship) nor cite validated evidence linking these molecular surrogates to clinical outcomes such as graft survival or kidney failure. The abstract mentions a trend toward stabilizing eGFR, but this is not the primary basis and is not validated as a surrogate.
“Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts... suggesting that suppression of ABMR activity could potentially slow…”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The reported effect sizes are small fractions of baseline (e.g., IFNγ-inducible genes suppressed by 47%, NK cell genes by 28%) and are not anchored to a minimal clinically important difference or clinical meaningfulness. The paper acknowledges incomplete responses and recurrence, and the injury score slopes are suggestive but not statistically significant for all measures. No explicit clinical benefit threshold is provided.
“The therapeutic effect of felzartamab suppressed IFNγ-inducible ABMR activity genes by 47% compared with baseline, but by week 52 they increased back by 30% compared with week 24. Although still 17% below baseline at week 52, the difference was not…”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 105AvailabilityBroken references and links 06Copyedit4 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted and transparently reported molecular substudy of a randomized controlled trial, with strong ethics, data/code availability, and statistical methods. The main weaknesses are the lack of explicit randomization details and power analysis for the substudy, and the absence of age/sex-based analyses and main-text demographics.

Both reviewers classified the study as interventional, which is adopted. The evaluation covered all eight dimensions; several sub-criteria were marked not applicable (e.g., cell line authentication, housing conditions) due to the clinical nature of the study. The statistics verification component found no recomputable tests, so statistical correctness is not independently confirmed beyond the reported methods.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

lowinternal contradiction
The abstract states 'ten patients treated with felzartamab and ten patients in the placebo group', but the parent trial had 11 per group. The exclusion of two patients is explained, so this is not a contradiction.
“comparing pretreatment, end-of-treatment (week 24) and posttreatment (week 52) biopsies from ten patients treated with felzartamab and ten patients in the placebo group.”
AbstractFind in source

Overstated conclusions

3 findings · worst high

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions only partially backed by the presented evidenceAssessed

6 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

partialReviewer 1
The main mechanism of action of felzartamab is on NK cells.
The paper provides indirect evidence (suppression of NK transcripts, reduction of blood NK cells) but acknowledges it cannot directly interrogate biopsy NK cells.
Evidence: Discussion: 'The decline in biopsy NK cell transcripts after felzartamab treatment, as well as the previously reported reduction of peripheral blood CD16 bright NK cell counts, suggests that the main mechanism of action of felzartamab is on NK cells.'
The decline in biopsy NK cell transcripts after felzartamab treatment, as well as the previously reported reduction of peripheral blood CD16 bright NK cell counts, suggests that the main mechanism of action of felzartamab is on NK cells.
Discussion ¶4reviewer’s wording
partialReviewer 2
Suppression of ABMR activity could potentially slow future progression to kidney failure.
The paper shows injury score improvements, but the link to kidney failure is speculative and based on surrogate markers.
Evidence: Discussion: 'suggesting that the course of felzartamab therapy reduced the risk of progression.'
“suggesting that the course of felzartamab therapy reduced the risk of progression.”
Discussion ¶6Find in source
supportedReviewers 1, 2
Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity.
The paper presents individual patient data showing suppression at week 24 in all nine patients.
Evidence: Figure 2a and text: 'ABMR Prob scores in all nine felzartamab-treated patients with elevated scores were suppressed at week 24.'
“ABMR Prob scores in all nine felzartamab-treated patients with elevated scores were suppressed at week 24.”
ResultsFind in source
supportedReviewers 1, 2
Felzartamab selectively suppressed IFNγ-inducible and NK cell transcripts, with minimal effect on ABMR stage-related endothelial transcripts.
The paper shows significant suppression of IFNγ and NK gene sets but no effect on endothelial genes, supported by figures and extended data.
Evidence: Figure 3d-f and Extended Data Tables 4-6.
Felzartamab suppressed the expression of IFNγ-inducible ABMR activity genes ... and NK expressed ABMR activity genes ... but had little effect on ABMR-associated endothelial genes.
Resultsreviewer’s wording
supportedReviewers 1, 2
Molecular recurrence was nearly universal by week 52.
The paper reports that 8 of 9 responders had increased ABMR scores by week 52.
Evidence: Results: 'Eight of the responders (all but patient 4) exhited an increase in the molecular ABMR Prob score by week 52.'
“Eight of the responders (all but patient 4) exhited an increase in the molecular ABMR Prob score by week 52.”
ResultsFind in source
supportedReviewers 1, 2
Felzartamab had parenchymal benefits at week 52, slowing the trajectories of molecular injury scores.
The paper shows negative slopes for injury scores in felzartamab-treated patients vs positive in placebo, with significant FDR for two of three scores.
Evidence: Figure 4d-f and text: 'The slopes of injury-repair response-associated transcripts ... were negative in patients treated with felzartamab and positive in patients treated with placebo.'
The slopes of injury-repair response-associated transcripts (IRRAT30), injury and repair induced transcripts, day 3 (IRITD3), and injury and repair induced transcripts, day 5 (IRITD5) scores in patients treated with felzartamab were negative in patients treated with felzartamab and positive in patients treated with placebo.
Resultsreviewer’s wording

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

INADEQUATESurrogate endpoint
The primary efficacy claim is based on molecular surrogate endpoints (ABMR activity scores, IFNγ-inducible and NK cell transcripts, injury scores) rather than hard clinical outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD or dose-exposure relationship) nor cite validated evidence linking these molecular surrogates to clinical outcomes such as graft survival or kidney failure. The abstract mentions a trend toward stabilizing eGFR, but this is not the primary basis and is not validated as a surrogate.
“Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts... suggesting that suppression of ABMR activity could potentially slow future progression to kidney failure.”
Find in source
INADEQUATEEffect size
The reported effect sizes are small fractions of baseline (e.g., IFNγ-inducible genes suppressed by 47%, NK cell genes by 28%) and are not anchored to a minimal clinically important difference or clinical meaningfulness. The paper acknowledges incomplete responses and recurrence, and the injury score slopes are suggestive but not statistically significant for all measures. No explicit clinical benefit threshold is provided.
“The therapeutic effect of felzartamab suppressed IFNγ-inducible ABMR activity genes by 47% compared with baseline, but by week 52 they increased back by 30% compared with week 24. Although still 17% below baseline at week 52, the difference was not statistically significant.”
Find in source

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Biological variables underreported (sex, age, strain)Assessed

Eight Dimensions7 pass · 1 warn

The introduction cites prior research on ABMR mechanisms, MMDx classification, and the prior felzartamab trial, acknowledging both the promise and limitations (e.g., recurrence after treatment). The rationale linking the need for molecular insights to the study objectives is explicit. Limitations of prior work are addressed by the design of this substudy, which provides comprehensive molecular characterization.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on ABMR pathogenesis, the MMDx system, and the prior clinical trial of felzartamab, and it articulates a logical rationale for the molecular analysis.

Evidence

paraphrase[Introduction, paragraph 1-3]

“Until recently, no therapy had been proven effective in suppressing ABMR activity or halting progression. However, a recent phase 2 trial of human IgG1 monoclonal anti-CD38 antibody felzartamab in kidney allograft recipients with active or chronic active ABMR has shown promise.”

paraphrase[Introduction, paragraph 4]

“Molecular analysis of ABMR biopsies can provide insights into the mode of action of interventions targeting CD38 in ABMR.”

paraphrase[Introduction, paragraph 4]

“While the previous study focused on clinical outcomes, the present study provides a comprehensive examination of the molecular features of the response...”

PASSReviewer 2· 90% conf

Evidence

paraphrase[Introduction, paragraph 1-3]

paraphrase[Introduction, paragraph 4]

“Molecular analysis of ABMR biopsies can provide insights into the mode of action of interventions targeting CD38 in ABMR.”

“However, in the biopsy 32 weeks after the last treatment, there was histological recurrence in three patients.”

Introduction ¶3Find in source

Randomization method and unit are not detailed in this paper but are referenced to the parent trial; blinding is stated (double-blind). Power analysis is not reported for this substudy, but the parent trial's design is referenced. Inclusion/exclusion criteria are described. Outlier handling is addressed through the exclusion of two patients with missing data and the use of robust statistical methods. Controls are inherent in the placebo group. Independent replication is not applicable for a single trial, but the paper discusses validation in future trials.

Sub-criteria

controlsADEQUATE

power analysisNOT REPORTED

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitINADEQUATE

inclusion exclusionADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The study design is rigorous: it is a prespecified endpoint of a randomized, double-blind, placebo-controlled trial with clear inclusion/exclusion criteria, a defined analysis population, and appropriate statistical methods.

Evidence

paraphrase[Methods, Trial design]

“This analysis was a prespecified endpoint of an investigator-driven, randomized, double-blind, placebo-controlled phase 2 trial...”

paraphrase[Methods, Trial design]

“Patients were eligible if they had a functioning kidney allograft ≥180 days after transplantation with an eGFR ≥20 ml min−1 1.73 m−2. ... Major exclusion criteria included the presence of TCMR Banff grade ≥1, de novo or recurrent severe thrombotic microangiopathy, polyoma virus nephropathy or de novo or recurrent glomerulonephritis.”

“One patient in the placebo group lost his graft after 14 weeks owing to ABMR, and no 24- and 52-week follow-up biopsies were performed; for one patient in the felzartamab group, no molecular analysis at week 24 was available.”

MethodsFind in source

PASSReviewer 2· 85% conf

The study design is rigorous: it is a prespecified analysis of a randomized, double-blind, placebo-controlled trial with clear inclusion/exclusion criteria, a defined analysis population, and appropriate statistical methods.

Evidence

“This analysis was a prespecified endpoint of an investigator-driven, randomized, double-blind, placebo-controlled phase 2 trial”

MethodsFind in source

“Patients were eligible if they had a functioning kidney allograft ≥180 days after transplantation with an eGFR ≥20 ml min −1 1.73 m −2 . ABMR diagnosis was based on the Banff 2019 schema and presence of HLA class I and/or II antigen-specific antibodies (preformed and/or de novo). Major exclusion criteria included the presence of TCMR Banff grade ≥1, de novo or recurrent severe thrombotic microangiopathy, polyoma virus nephropathy or de novo or recurrent glomerulonephritis.”

MethodsFind in source

“For the present study, which focused on the molecular results of study biopsies, we excluded two patients because of missing biopsy results. One patient in the placebo group lost his graft after 14 weeks owing to ABMR, and no 24- and 52-week follow-up biopsies were performed; for one patient in the felzartamab group, no molecular analysis at week 24 was available.”

MethodsFind in source

The paper states that patient age and sex were collected and reported, but no age- or sex-based analyses were carried out due to insufficient sample sizes. Demographics are reproduced in Supplementary Table, but not in the main text. Health status is implied by inclusion criteria (e.g., eGFR threshold). Species/strain and housing are not applicable for human subjects.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthINADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

Sex and age are reported, but no age- or sex-based analyses were performed, and detailed demographic characteristics are only in supplementary tables.

Evidence

“Patient age and sex was collected and reported in the study, but no age- or sex-based analyses were carried out in the study, in part because of insufficient sample sizes (Supplementary Table ).”

MethodsFind in source

“Demographics of all 22 patients were published previously and are reproduced in Supplementary Table for convenience.”

Results ¶1Find in source

WARNReviewer 2· 80% conf

Sex and age are reported in aggregate, but no age- or sex-based analyses are performed, and detailed demographics are only in supplementary tables.

Evidence

MethodsFind in source

“Demographics of all 22 patients were published previously and are reproduced in Supplementary Table for convenience.”

Results ¶1Find in source

The paper names the institutional ethics committees (Medical University of Vienna and Vienna General Hospital, Charité Universitätsmedizin Berlin) with protocol numbers, states informed consent was obtained, and mentions adherence to Good Clinical Practice, Declaration of Helsinki, and Declaration of Istanbul. This satisfies all applicable criteria.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval from named committees, informed consent, and regulatory compliance are all explicitly reported.

Evidence

“Ethics approval was obtained from the institutional ethics committees of the Medical University of Vienna and Vienna General Hospital (EK1161/2021) and Charité Universitätsmedizin Berlin (EUDRACT identifier 2021-000545-40, code FELZ01).”

EthicsFind in source

paraphrase[Methods, Ethics approval]

“Informed consent was obtained from all patients before enrollment as approved by the local center institutional review board...”

“The trial adhered to the principles of Good Clinical Practice, Good Laboratory Practice, the Declaration of Helsinki and the Declaration of Istanbul.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethics approval from named committees, informed consent, and regulatory compliance are all clearly reported.

Evidence

EthicsFind in source

“Informed consent was obtained from all patients before enrollment as approved by the local center institutional review board”

EthicsFind in source

“The trial adhered to the principles of Good Clinical Practice, Good Laboratory Practice, the Declaration of Helsinki and the Declaration of Istanbul.”

EthicsFind in source

Felzartamab is named with manufacturer (Hi-Bio) and dose (16 mg/kg). The microarray platform (GeneChip PrimeView U219) and software (Affymetrix GeneChip Command Console, R packages) are identified. Antibodies, cell lines, and mycoplasma testing are not applicable as this is a clinical trial with no wet-lab assays.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (felzartamab) is identified with dose and regimen, and the microarray platform and software are specified.

Evidence

paraphrase[Methods, Trial design]

“patients received a total of nine doses of intravenous felzartamab (16 mg kg−1 per dose) or matching placebo over the course of 20 weeks.”

“gene expression was measured using GeneChip, PrimeView U219 arrays (Applied Biosystems, Thermo Fisher Scientific). All gene expression data were collected using Affymetrix GeneChip Command Console Scan Control v.4.0.0.1567 and processed in R using the BioBase v.2.64.0 library.”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational product (felzartamab) is identified with dose and regimen, and the microarray platform and software are specified.

Evidence

“patients received a total of nine doses of intravenous felzartamab (16 mg kg −1 per dose) or matching placebo over the course of 20 weeks.”

MethodsFind in source

“gene expression was measured using GeneChip, PrimeView U219 arrays (Applied Biosystems, Thermo Fisher Scientific).”

MethodsFind in source

“Statistical analyses were performed using R software, v.R 4.3.3.”

Statistical analysisFind in source

Tests are named (ART-ANOVA, linear mixed-effects, limma empirical Bayes). Assumptions for mixed models were checked. Exact p-values are reported for some analyses (e.g., FDR values for injury scores), but many results are presented as effect sizes with confidence intervals. Software is identified (R v4.3.3, packages). Data presentation includes individual patient points and density plots. Mathematical plausibility is not applicable due to continuous outcomes and small sample size.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical methods are well-described, including ART-ANOVA, linear mixed-effects models, and limma, with FDR correction. Exact p-values are not always reported, but effect sizes and confidence intervals are provided for key analyses.

Evidence

paraphrase[Methods, Statistical analyses]

“The effect of felzartamab treatment on classifier and PBT scores was assessed by an aligned-rank transformed analysis of variance (ART-ANOVA).”

paraphrase[Methods, Statistical analyses]

“The assumptions of the linear mixed-effects model were confirmed using diagnostic plots and statistical tests provided by the 'performance' package 0.12.3 in R.”

“The shaded regions depict 95% confidence intervals for predicted scores.”

Figure 4Find in source

PASSReviewer 2· 80% conf

Statistical methods are well-described, including tests, software, and handling of multiple testing; effect sizes are reported with confidence intervals for key analyses.

Evidence

“The effect of felzartamab treatment on classifier and PBT scores was assessed by an aligned-rank transformed analysis of variance (ART-ANOVA)”

Statistical analysisFind in source

“The assumptions of the linear mixed-effects model were confirmed using diagnostic plots and statistical tests provided by the ‘performance’ package 0.12.3 in R.”

Statistical analysisFind in source

“The shaded regions depict 95% confidence intervals for predicted scores.”

Figure 4Find in source

The data availability statement provides a concrete route for the deidentified patient dataset (via Dr. Böhmig after marketing authorization) and names the GEO accession for microarray data. Code is shared in a public GitHub repository with a step-by-step guide. This satisfies all applicable criteria.

Sub-criteria

code sharingADEQUATE

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data and code are available: microarray data deposited in GEO with accession, code in a public GitHub repository, and a data availability statement with a concrete access route for the deidentified patient dataset.

Evidence

paraphrase[Data availability]

“All .CEL files from microarrays are available at Gene Expression Omnibus GSE275824 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275824).”

paraphrase[Code availability]

“All R code used for these analyses is available via GitHub at https://github.com/TSI-PTG/CD38-effect-of-treatment/.”

“The deidentified patient dataset can be obtained via Dr. Georg Böhmig (georg.boehmig@meduniwien.ac.at) 1 year after marketing authorization of felzartamab.”

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data and code availability are well-documented: microarray data deposited in GEO, code on GitHub, and a data access procedure for the deidentified patient dataset.

Evidence

“All .CEL files from microarrays are available at Gene Expression Omnibus GSE275824 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275824) .”

Data availabilityFind in source

“All R code used for these analyses is available via GitHub at https://github.com/TSI-PTG/CD38-effect-of-treatment/ .”

Data availabilityFind in source

“The deidentified patient dataset can be obtained via Dr. Georg Böhmig (georg.boehmig@meduniwien.ac.at) 1 year after marketing authorization of felzartamab.”

Data availabilityFind in source

Trial registration numbers (EudraCT, ClinicalTrials.gov) are provided. Limitations are thoroughly discussed (small sample, multiple testing, lack of single-cell data). Conclusions are appropriately cautious. Funding and competing interests are disclosed. A reporting guideline (e.g., CONSORT) is not explicitly referenced, but the paper includes a reporting summary.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The paper is transparent: trial registration is provided, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. A reporting guideline is not explicitly mentioned but the paper follows a structured format.

Evidence

“EudraCT number 2021-000545-40, NCT05021484 (https://clinicaltrials.gov/ct2/show/NCT05021484)”

MethodsFind in source

paraphrase[Discussion, paragraph 8]

“This phase 2 clinical trial has a number of limitations. The study population was small, and validation of these findings in ensuing larger clinical trials for felzartamab will be anticipated with interest...”

paraphrase[Competing interests]

“Data for this study were generated in an investigator-initiated trial supported by Hi-Bio. ... G.A.B. is supported by a research grant from Human Immunology Biosciences, Inc. (HI-Bio)...”

PASSReviewer 2· 85% conf

The manuscript is transparent: trial registration is provided, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

“EudraCT number 2021-000545-40, NCT05021484 (https://clinicaltrials.gov/ct2/show/NCT05021484)”

MethodsFind in source

Discussion ¶8Find in source

paraphrase[Competing interests]

“Data for this study were generated in an investigator-initiated trial supported by Hi-Bio. P.F.H. holds shares in Transcriptome Sciences Inc. (TSI)...”

Registered (2 IDs: ClinicalTrials.gov, EudraCT). No reporting guideline cited.

ClinicalTrials.gov

NCT05021484

EudraCT

2021-000545-40

Broken references and links

1 finding · worst low

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

References not resolvable to a published paperRecomputed

Checked 39 references by DOI: 2 verified — 1 DOI unresolved, 36 no DOI (shown, not verified).

UNRESOLVED10.5281/zenodo.594511
ARTool: aligned rank transform for nonparametric factorial ANOVAs
Cited DOI does not resolve to any Crossref record.
NO DOI
Exploring the complexity of death-censored kidney allograft failure
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The molecular phenotype of kidney transplants: insights from the MMDx Project
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Subthreshold rejection activity in many kidney transplants currently classified as having no rejection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Molecular diagnosis of ABMR with or without donor-specific antibody in kidney transplant biopsies: differences in timing and intensity but similar mechanisms and outcomes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 Expert Consensus from the Transplantion Society Working Group
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Emerging drugs for antibody-mediated rejection after kidney transplantation: a focus on phase II & III trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Trifecta Study: comparing plasma levels of donor-derived cell-free DNA with the molecular phenotype of kidney transplant biopsies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Distinct molecular processes mediate donor-derived cell-free DNA release from kidney transplants in different disease states
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Building a tissue-based molecular diagnostic system in heart transplant rejection: the heart Molecular Microscope Diagnostic (MMDx) system
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Factors associated with kidney graft survival in pure antibody-mediated rejection at the time of indication biopsy: Importance of parenchymal injury but not disease activity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Morphologic and molecular features of antibody-mediated transplant rejection: pivotal role of molecular injury as an independent predictor of renal allograft functional decline
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A randomized phase 2 trial of felzartamab in antibody-mediated rejection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
CD38 antibody daratumumab for the treatment of chronic active antibody-mediated kidney allograft rejection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Daratumumab use prior to kidney transplant and T cell-mediated rejection: a case report
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Translating B cell immunology to the treatment of antibody-mediated allograft rejection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
An atlas of healthy and injured cell states and niches in the human kidney
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Epithelial cell states associated with kidney and allograft injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Discrepancy analysis comparing molecular and histology diagnoses in kidney transplant biopsies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Isatuximab monotherapy for desensitization in highly sensitized patients awaiting kidney transplant
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
HLA desensitization in solid organ transplantation: anti-CD38 to across the immunological barriers
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Banff 2019 Kidney Meeting Report (I): updates on and clarification of criteria for T cell- and antibody-mediated rejection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The molecular phenotypes of rejection in kidney transplant biopsies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: new insights from the Genome Canada studies of kidney transplant biopsies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Common errors in the implementation and interpretation of microarray studies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Molecular assessment of disease states in kidney transplant biopsy samples
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
An aligned rank transform procedure for multifactor contrast tests
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mixed-effects models for slope-based endpoints in clinical trials of chronic kidney disease
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
limma powers differential expression analyses for RNA-sequencing and microarray studies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Bioinformatics and Computational Biology Solutions using R and Bioconductor
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
clusterProfiler: an R package for comparing biological themes among gene clusters
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
clusterProfiler 4.0: a universal enrichment tool for interpreting omics data
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

9 data/code links checked; 9 live.

dataGEOLIVEHTTP 200
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275824
Resolves to GEO (data repository).
datahttps://www.geneontology.org/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://bioconductor.org/packages/release/bioc/html/DOSE.htmlLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://www.genome.jp/kegg/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://curator.reactome.org/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://www.gsea-msigdb.org/gsea/msigdbLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://www.wikipathways.org/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
codeGitHubLIVEHTTP 200
https://github.com/TSI-PTG/CD38-effect-of-treatment/
Resolves to GitHub (code repository).
codehttps://tsi-ptg.github.io/CD38-effect-of-treatment/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.

Copyediting

4 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly clarity, typo, consistency.

MINORtypoResults, Individual patient responses
“exhited”
→ exhibited
Typographical error.
MINORconsistencyAbstract vs. Results
“ten patients treated with felzartamab and ten patients in the placebo group”
→ Ensure consistent use of 'felzartamab-treated' vs 'felzartamab' throughout.
Minor wording inconsistency.
MINORclarityMethods, Statistical analyses
“The assumptions of the linear mixed-effects model were confirmed using diagnostic plots and statistical tests provided by the 'performance' package 0.12.3 in R.”
→ Specify which diagnostic plots and tests were used.
Could be more specific for reproducibility.
MINORclarityMethods, Statistical analyses
“The effect of treatment was assessed as the interaction term between treatment group and follow-up visit.”
→ Clarify that this is the treatment-by-time interaction.
Could be clearer for readers unfamiliar with the design.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported; an informed reader should weigh the small sample size and the lack of explicit randomization/power details for the substudy, but these do not undermine the main conclusions. No erratum is warranted based on the identified issues, though the authors could consider a correction to clarify the randomization method and power analysis.

1.
HIGHreporting
In the Methods (Trial design), explicitly state the randomization method (e.g., computer-generated random sequence) and randomization unit (patient), even if inherited from the parent trial.
The randomization sub-criteria are currently reported_but_inadequate; specifying them improves transparency and reproducibility.
2.
HIGHstatistics
In the Methods (Statistical analyses), add a statement about the a priori power/sample size calculation for the molecular endpoints, or clarify that the substudy was exploratory and not powered.
Power analysis is not reported, which is a common reviewer concern for substudies.
3.
HIGHreporting
In the Results or Methods, provide a table of baseline demographics (age, sex, eGFR, etc.) in the main text rather than only in supplementary material.
Demographics are only in supplementary tables, which is a reporting gap for biological variables.
4.
HIGHstatistics
In the Results, report exact p-values for all key comparisons (e.g., ABMR activity scores) instead of only effect sizes and confidence intervals.
Exact p-values are reported_but_inadequate; providing them facilitates meta-analysis and reader verification.
5.
HIGHother
Verify the reference 'ARTool: aligned rank transform for nonparametric factorial ANOVAs' (DOI 10.5281/zenodo.594511) as it was not found in the registry; correct or replace if necessary.
A not-found reference may be a fabrication signal and should be verified.
6.
MEDIUMreporting
In the Methods or Reporting Summary, explicitly reference the CONSORT or STROBE reporting guideline followed.
A reporting guideline is not explicitly named, which is a minor transparency gap.
7.
MEDIUMreporting
In the Discussion, add a note on the generalizability of findings given the small sample size and single-center nature.
This would further temper conclusions and address potential overgeneralization.
8.
MEDIUMreporting
In the Methods (Statistical analyses), specify which diagnostic plots and statistical tests were used to confirm the linear mixed-effects model assumptions.
The copyedit flagged this as unclear; more specificity improves reproducibility.
9.
MEDIUMreporting
In the Methods (Statistical analyses), clarify that the treatment effect is the treatment-by-time interaction term.
The copyedit noted this could be clearer for readers unfamiliar with the design.
10.
MEDIUMdata code
In the Data availability statement, provide a timeline for when the deidentified patient dataset will be available, rather than only conditional on marketing authorization.
A concrete timeline improves data accessibility and transparency.
11.
LOWcopyedit
Fix the typo 'exhited' to 'exhibited' in the Results, Individual patient responses section.
Typographical error that should be corrected.
12.
LOWcopyedit
Ensure consistent use of 'felzartamab-treated' vs 'felzartamab' throughout the abstract and results.
Minor wording inconsistency flagged by copyedit.

Full text (51,860 chars)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.

Diebold M, Gauthier PT, Mayer KA, Mackova M, Hinze C, Chang J, Patel UD, Schütz E, Jilma B, Schrezenmeier E, Budde K, Böhmig GA, Halloran PF

DOI

10.1038/s41591-025-03653-3

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-22