Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

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

Name: Kaimen Rigor review — Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.
Item: Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.
Rating: 96
Author: Alpha1

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

Paper source

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Kaimen Rigor review — 3★ (Adequate), 0 critical, 5 high issues for “Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.”

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

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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

Read full text (PMC)

DOI

10.1038/s41591-025-03653-3

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

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

Paper source

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

Read full text (PMC)

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

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

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.

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

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.

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).

9 data/code links checked; 9 live.

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.

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

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Read alongside

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

Read full text (PMC)

DOI

10.1038/s41591-025-03653-3

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Record fingerprint

9dec2c8fa801d10fcb06065f682a2957956c16e6e7a96f3118749b5384c141ba

Verify via API

Issued Aug 15, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

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

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Overstated conclusions

3 findings · worst high

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.

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

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Biological variables underreported (sex, age, strain)Assessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 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.”

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

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

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]

MethodsFind in source

PASSReviewer 2· 85% conf

Evidence

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

MethodsFind in source

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

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

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

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

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.”

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

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

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

Sub-criteria

code sharingADEQUATE

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

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

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

Evidence

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

MethodsFind in source

paraphrase[Discussion, paragraph 8]

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.

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).

9 data/code links checked; 9 live.

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.

Kaimen Rigor Action ItemsFinal pass before journal submission

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