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Kaimen Rigor review

A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

Landoni G, Monaco F, Ti LK, Baiardo Redaelli M, Bradic N, Comis M, Kotani Y, Brambillasca C, Garofalo E, Scandroglio AM, Viscido C, Paternoster G, Franco A, Porta S, Ferrod F, Calabrò MG, Pisano A, Vendramin I, Barucco G, Federici F, Severi L, Belletti A, Cortegiani A, Bruni A, Galbiati C, Covino A, Baryshnikova E, Giardina G, Venditto M, Kroeller D, Nakhnoukh C, Mantovani L, Silvetti S, Licheri M, Guarracino F, Lobreglio R, Di Prima AL, Fresilli S, Labanca R, Mucchetti M, Lembo R, Losiggio R, Bove T, Ranucci M, Fominskiy E, Longhini F, Zangrillo A, Bellomo R, PROTECTION Study Group

DOI: 10.1056/NEJMoa2403769
Record issued: 2026-08-16
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/033a9db9-d3cb-424a-b6d8-673243b89e00 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

2.75 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ClaimsOverstated claim−0.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingData & code availability partially met−0.25★

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

Not verified in this report

No data or code availability links were detected to verify.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary outcome is AKI defined by serum creatinine criteria (KDIGO), which is a surrogate biomarker for clinical outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD or dose-exposure relationship) nor does it cite validated evidence linking this surrogate to hard clinical outcomes in this context.
“The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary effect is a reduction in AKI incidence from 31.7% to 26.9% (relative risk 0.85). While statistically significant, the absolute reduction is 4.8 percentage points, and the clinical meaningfulness is not anchored to a minimal clinically important difference or a hard outcome improvement. The paper does not provide an explicit anchor for clinical meaningfulness.
“AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002).”
Find in source
03Conclusion reaches beyond the evidence
mediumOverreachreviewer-assessedFull detail
The findings may apply to more than two million patients who undergo heart surgery worldwide every year.
the trial population differed substantially from patients in low- and middle-income countries and from patients in geographic regions with an ethnic distribution that differed from that in our trial population
Discussion ¶4reviewer’s wording

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit2 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 rigorously designed and reported randomized controlled trial with strong internal validity, clear ethics documentation, and appropriate statistical methods. The main weakness is the vague data sharing statement, which lacks concrete access details. Minor copyedit issues and an overstated generalizability claim are also noted.

Both reviewers agreed on study type (interventional) and on all dimension statuses. The only divergence was minor (regulatory compliance and limitations addressed), which did not affect statuses. The statistics verification covered only 3 tests; the rest are unverified. The citation check found no retracted or missing references.

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

Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .002 · recomputed p = .002Reviewer 1
Primary outcome relative risk p-value from reported counts
“AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002).”
Find in source
Taken as given: The counts 474 and 555 are the number of AKI events in each group.; The denominators are the group sizes 1759 and 1752.; The test used is a two-tailed chi-square test without continuity correction.
Method: Pearson chi-square test on the 2x2 table of AKI events vs non-events.
How we recomputed it: pChi2x2(474, 1759-474, 555, 1752-555)
CONSISTENTreported p = .002 · recomputed p = .001Reviewer 2
Primary outcome relative risk p-value from reported RR and 95% CI
“AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002).”
Find in source
Taken as given: The relative risk is 0.85 with 95% CI 0.77 to 0.94.; The CI is two-sided at 95%.; The p-value is two-tailed.
Method: Used pCI function to derive p-value from RR and CI assuming log-normal distribution.
How we recomputed it: pCI(0.85, 0.77, 0.94, 1)
CONSISTENTreported p = .010 · recomputed p = .013Reviewer 2
Stage 3 AKI relative risk p-value from reported RR and 95% CI
“Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87).”
Find in source
Taken as given: The relative risk is 0.56 with 95% CI 0.35 to 0.87.; The CI is two-sided at 95%.; The p-value is two-tailed.
Method: Used pCI function to derive p-value from RR and CI assuming log-normal distribution.
How we recomputed it: pCI(0.56, 0.35, 0.87, 1)

lowinternal contradiction
The sample size calculation states 3066 patients would provide 90% power and was rounded to 3500, but 3066 rounded to the nearest hundred is 3100, not 3500. This may be a typographical or rounding explanation issue.
“a sample size of 3066 patients would have provided 90% power with a significance level of 0.05 and was rounded to 3500 patients”
Statistical analysisFind 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 overstated beyond the evidenceAssessed

4 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

overstatedReviewer 2
The findings may apply to more than two million patients who undergo heart surgery worldwide every year.
The trial population was predominantly White and from high-income countries, and the authors acknowledge limited generalizability to low- and middle-income countries, so the claim of broad applicability is somewhat overstated.
Evidence: The paper states the trial population differed substantially from patients in low- and middle-income countries.
the trial population differed substantially from patients in low- and middle-income countries and from patients in geographic regions with an ethnic distribution that differed from that in our trial population
Discussion ¶4reviewer’s wording
supportedReviewers 1, 2
Infusion of amino acids reduced the occurrence of AKI after cardiac surgery.
The primary outcome shows a statistically significant reduction in AKI with a relative risk of 0.85 and P=0.002, directly supporting the claim.
Evidence: Primary outcome: AKI occurred in 474/1759 (26.9%) vs 555/1752 (31.7%), RR 0.85 (95% CI 0.77-0.94), P=0.002.
“AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002).”
AbstractFind in source
supportedReviewers 1, 2
Amino acid infusion reduced the severity of AKI, specifically stage 3 AKI.
Stage 3 AKI was significantly lower in the amino acid group (1.6% vs 3.0%, RR 0.56, 95% CI 0.35-0.87), supporting the claim.
Evidence: Stage 3 AKI occurred in 29 (1.6%) vs 52 (3.0%), RR 0.56 (95% CI 0.35-0.87).
“Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87).”
AbstractFind in source
supportedReviewers 1, 2
Amino acid infusion did not increase adverse events.
No significant differences in prespecified adverse events were observed, and no adverse drug reactions were reported, supporting the claim.
Evidence: Table 4 shows no significant differences in adverse events; no adverse drug reactions reported.
“We observed no significant differences between the two groups in the numbers of patients with prespecified adverse events (Table 4).”
ResultsFind in source

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

INADEQUATESurrogate endpoint
The primary outcome is AKI defined by serum creatinine criteria (KDIGO), which is a surrogate biomarker for clinical outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD or dose-exposure relationship) nor does it cite validated evidence linking this surrogate to hard clinical outcomes in this context.
“The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria.”
Find in source
INADEQUATEEffect size
The primary effect is a reduction in AKI incidence from 31.7% to 26.9% (relative risk 0.85). While statistically significant, the absolute reduction is 4.8 percentage points, and the clinical meaningfulness is not anchored to a minimal clinically important difference or a hard outcome improvement. The paper does not provide an explicit anchor for clinical meaningfulness.
“AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002).”
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.

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

The introduction cites numerous animal and human studies supporting the biological plausibility (renal hypoperfusion, amino acids recruiting renal functional reserve). The rationale directly leads to the trial hypothesis. Limitations of prior research are implicitly addressed by the need for a large definitive trial, though not explicitly framed as addressing prior limitations.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale linking amino acid infusion to kidney protection.

Evidence

paraphrase[Introduction, paragraph 2]

“Previous studies have shown that infusion of amino acids increases nephron plasma flow by means of decreased afferent arteriolar resistance, decreased tubuloglomerular feedback activation, and increased cortical nitric oxide synthase activity.”

“to test the hypothesis that intravenous amino acid therapy would lead to a lower occurrence of postoperative AKI than placebo.”

Introduction ¶3Find in source

absence[Introduction]

Limitations of prior research are not explicitly discussed as such.

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale linking amino acid infusion to kidney protection.

Evidence

paraphrase[Introduction, paragraph 2]

“Studies in animals have shown that cardiopulmonary bypass decreases renal blood flow by more than 50% and induces renal medullary tissue hypoxia, which is followed by decreased GFR.”

paraphrase[Introduction, paragraph 3]

“Accordingly, we performed the Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery (PROTECTION) trial ... to test the hypothesis that intravenous amino acid therapy would lead to a lower occurrence of postoperative AKI than placebo.”

“However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain.”

Introduction ¶1Find in source

Randomization used a web-based system with permuted-block sequences stratified by site. Blinding was comprehensive (patients, physicians, investigators, data collectors, outcome assessors, statisticians). Power analysis was pre-specified with 90% power to detect a 20% relative risk reduction. Inclusion/exclusion criteria were clearly defined. Outlier handling is addressed through ITT, per-protocol, and as-treated analyses with multiple imputation for missing data. Controls are the placebo group. Independent replication is not applicable for a single pivotal trial.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Randomization and Blinding]

“Randomization was performed by means of a Web-based system with the use of computer-generated, permuted-block sequences with stratification according to site.”

paraphrase[Methods, Randomization and Blinding]

“Patients, physicians, investigators, data collectors, and outcome assessors were unaware of the group assignments.”

paraphrase[Methods, Statistical Analysis]

“We estimated that a sample size of 1750 patients in each group (a total of 3500 patients) would give the trial 90% power to detect a 20% lower risk of AKI in the amino acid infusion group than in the placebo group at a two-sided alpha level of 0.05”

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Randomization and Blinding]

“Randomization was performed by means of a Web-based system with the use of computer-generated, permuted-block sequences with stratification according to site.”

paraphrase[Methods, Randomization and Blinding]

“Patients, physicians, investigators, data collectors, and outcome assessors were unaware of the group assignments.”

paraphrase[Methods, Statistical Analysis]

The trial reports age, sex, body-mass index, and various comorbidities in Table 1. Both sexes are enrolled, so sex justification is not applicable. Age and health status are reported. Species/strain and housing conditions are not applicable for a human trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and clinical characteristics are well reported, including age, sex, and comorbidities.

Evidence

“Median age (IQR) — yr 66 (57–73) 0 67 (58–73) 0 Female sex — no. (%) 530 (30.1) 0 527 (30.1) 0”

Table 1Find in source

“Medical condition — no. (%) Arterial hypertension while receiving medical treatment 1090 (62.0) 1 1083 (61.8) 0”

Table 1Find in source

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, and comorbidities.

Evidence

“Female sex — no. (%) 530 (30.1) 0 527 (30.1) 0”

Table 1Find in source

“Median age (IQR) — yr 66 (57–73) 0 67 (58–73) 0”

Table 1Find in source

“Medical condition — no. (%) Arterial hypertension while receiving medical treatment 1090 (62.0) 1 1083 (61.8) 0”

Table 1Find in source

The paper states that the ethics committee at each participating center approved the trial protocol and that all patients provided written informed consent. This satisfies both irb_ethics_statement and informed_consent. Regulatory compliance is implied by the trial being registered and conducted in accordance with standard guidelines, though not explicitly named.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval and informed consent are clearly documented.

Evidence

paraphrase[Methods, Trial Design]

“The ethics committee at each participating center approved the trial protocol”

“All patients provided written informed consent.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethics approval and informed consent are clearly documented.

Evidence

paraphrase[Methods, Trial Design]

“The ethics committee at each participating center approved the trial protocol”

“All patients provided written informed consent.”

MethodsFind in source

The amino acid treatment (Isopuramin 10%, Baxter) and placebo (Ringer's solution, Baxter) are identified with manufacturer. Dose and regimen are specified. Statistical software (Stata version 18) is identified. No antibodies, cell lines, or mycoplasma testing are applicable.

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· 90% conf

The investigational product and placebo are identified with manufacturer and dose, and statistical software is named.

Evidence

paraphrase[Methods, Trial Design]

“The amino acid treatment (Isopuramin 10%, Baxter) and placebo (Ringer’s solution, Baxter) were provided by the manufacturer”

“Data were stored in an electronic case-report form and analyzed with the use of Stata software, version 18 (StataCorp).”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

The investigational product (amino acids and placebo) is adequately identified, and statistical software is named.

Evidence

paraphrase[Methods, Trial Design]

“The amino acid treatment (Isopuramin 10%, Baxter) and placebo (Ringer’s solution, Baxter) were provided by the manufacturer”

“Data were stored in an electronic case-report form and analyzed with the use of Stata software, version 18 (StataCorp).”

Statistical analysisFind in source

Tests are named (chi-square, Fisher's exact, Kaplan-Meier). Exact p-values are reported for the primary outcome (P=0.002). Effect sizes with 95% CIs are reported. Software is identified. Data presentation includes per-group n and appropriate figures. Mathematical plausibility checks: the primary outcome counts (474/1759=26.9%, 555/1752=31.7%) are plausible; stage 1+2+3 counts sum to 474 and 555 respectively (430+15+29=474, 492+11+52=555). No arithmetic errors detected.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-reported, with exact p-values and confidence intervals.

Evidence

“relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002”

AbstractFind in source

“Dichotomous data were compared with the use of the two-tailed chi-square test or Fisher’s exact test when appropriate”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals for the primary outcome.

Evidence

“AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002).”

AbstractFind in source

“Dichotomous data were compared with the use of the two-tailed chi-square test or Fisher’s exact test when appropriate”

Statistical analysisFind in source

“0.85 (0.77 to 0.94)”

Table 3Find in source

The paper mentions 'A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.' This is vague and does not specify the access mechanism. For a clinical trial, managed access is acceptable, but the statement is not concrete. No code sharing is mentioned.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the provided text; no repository or accession numbers are given.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

FundingFind in source

WARNReviewer 2· 80% conf

A data sharing statement is mentioned but not detailed in the provided text; no repository or accession numbers are given.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

Data availabilityFind in source

Trial registration number is provided (NCT03709264). Methods are detailed enough for replication. Limitations are explicitly discussed in the Discussion. Conclusions are proportional to the results. Funding and COI are disclosed. Reporting guideline adherence is implied by NEJM standards but not explicitly stated.

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· 95% conf

The trial is registered, methods are complete, limitations are discussed, and conclusions are proportional.

Evidence

“PROTECTION ClinicalTrials.gov number, NCT03709264”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

“Our trial has several limitations. First, we used serum creatinine level alone to diagnose AKI...”

PASSReviewer 2· 95% conf

The trial is registered, methods are complete, limitations are discussed, and conclusions are proportional.

Evidence

“PROTECTION ClinicalTrials.gov number, NCT03709264.”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

“Our trial has several limitations. First, we used serum creatinine level alone to diagnose AKI...”

“Supported by a grant (RF-2016-02363260) from the Italian Ministry of Health. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

FundingFind in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

NCT03709264

Broken references and links

None found · partly checked

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.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 44 references by DOI: 2 verified — 42 no DOI (shown, not verified).

NO DOI
The Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists/American Society for Extracorporeal Technology clinical practice guidelines for the prevention of adult cardiac surgery-associated acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Postoperative acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Epidemiology and pathophysiology of cardiac surgery-associated acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Global incidence and outcomes of adult patients with acute kidney injury after cardiac surgery: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prevention of cardiac surgery-associated acute kidney injury by implementing the KDIGO guidelines in high-risk patients identified by biomarkers: the PrevAKI-Multicenter Randomized Controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prevention of acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Bedside tool for predicting the risk of postoperative dialysis in patients undergoing cardiac surgery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Renal hemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep under total intravenous anesthesia
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dynamic responses of renal oxygenation at the onset of cardiopulmonary bypass in sheep and man
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Strategies that improve renal medullary oxygenation during experimental cardiopulmonary bypass may mitigate postoperative acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effects of cardiopulmonary bypass on renal perfusion, filtration, and oxygenation in patients undergoing cardiac surgery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Intraoperative renal hypoxia and risk of cardiac surgery-associated acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The renal hemodynamic response to amino acid infusion in the rat
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mechanisms of renal hemodynamic regulation in response to protein feeding
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Modification of tubuloglomerular feedback signal by dietary protein
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Kidney function in early diabetes: the tubular hypothesis of glomerular filtration
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Renal hemodynamic effects of dietary protein in the rat: role of nitric oxide
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The effects of recruitment of renal functional reserve on renal cortical and medullary oxygenation in non-anesthetized sheep
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The effect of IV amino acid supplementation on mortality in ICU patients may be dependent on kidney function: post hoc subgroup analyses of a multicenter randomized trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Intravenous amino acid therapy for kidney protection in cardiac surgery patients: a pilot randomized controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial: the PROTECTION trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
KDIGO clinical practice guideline for acute kidney injury
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Validation of a classification system for causes of death in critical care: an assessment of inter-rater reliability
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Acute kidney injury after cardiac surgery according to Risk/Injury/Failure/Loss/End-stage, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes classifications
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A multiple testing procedure for clinical trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Renal functional reserve: from physiological phenomenon to clinical biomarker and beyond
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Renal effects of amino acid infusion in cardiac surgery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Enteral feeding improves outcome and protects against glycerol-induced acute renal failure in the rat
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cardiac and vascular surgery-associated acute kidney injury: the 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
High protein-induced glomerular hypertrophy is vascular endothelial growth factor-dependent
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Perioperative intravenous amino acid infusion in major urologic surgery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
High-dose amino acid infusion preserves diuresis and improves nitrogen balance in non-oliguric acute renal failure
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Preoperative renal functional reserve predicts risk of acute kidney injury after cardiac operation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Utility of biomarkers for sepsis-associated acute kidney injury staging
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

Copyediting

2 minor

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

No major wording or formatting errors. 2 minor suggestions below.

2 copyedit issues flagged: mostly typo, consistency.

MINORtypoAbstract
“A cute kidney injury”
→ Acute kidney injury
Spacing error in the extracted text.
MINORconsistencyMethods, Statistical Analysis
“a sample size of 3066 patients would have provided 90% power with a significance level of 0.05 and was rounded to 3500 patients”
→ Clarify the rounding logic; 3066 rounded to 3500 is not standard rounding.
Potential inconsistency in sample size calculation description.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and generally well-reported, but an informed reader should weigh the vague data sharing statement and the overstated generalizability claim. No erratum is warranted for the minor copyedit issues, but the authors should consider clarifying the data sharing mechanism and tempering the generalizability claim in any correction or correspondence.

1.
HIGHdata code
In the Data Availability section, specify the data sharing mechanism (e.g., data access committee, platform like Vivli, conditions, and timeframe) instead of the vague reference to a statement at NEJM.org.
A concrete data sharing statement is expected for clinical trials and improves transparency and reproducibility.
2.
HIGHreporting
Temper the claim that the findings may apply to more than two million patients worldwide, given the predominantly White, high-income-country population and acknowledged limited generalizability to low- and middle-income countries.
The claim is overstated relative to the evidence and could mislead readers about the applicability of the results.
3.
MEDIUMreporting
Explicitly state adherence to CONSORT reporting guidelines in the Methods or a separate section.
Explicit guideline adherence is a standard expectation for trial reporting and was noted as inadequate by both reviewers.
4.
MEDIUMstatistics
Clarify the sample size calculation rounding: 3066 patients rounded to 3500 is not standard; explain the rationale or correct the number.
The current description is internally inconsistent and may confuse readers about the power calculation.
5.
MEDIUMdata code
Consider depositing de-identified aggregate data or statistical analysis code in a public repository (e.g., Zenodo) with a DOI.
Enhances reproducibility and aligns with open science expectations, though not mandatory for a clinical trial.
6.
LOWcopyedit
Fix the typo in the Abstract: change 'A cute kidney injury' to 'Acute kidney injury'.
Corrects a spacing error that could be distracting to readers.
7.
LOWreporting
Clarify regulatory compliance by naming the ethical framework (e.g., Declaration of Helsinki) in the Methods.
Adds explicit detail to the ethics statement, addressing a minor gap noted by one reviewer.

Full text (39,555 chars)Analyzed: Aug 16, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

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.

A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

DOI

10.1056/NEJMoa2403769

Record issued

2026-08-16

Engine

7.39.0

Exported

2026-09-22