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Kaimen Rigor review

Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease.

EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Agrawal N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Zhu D, Dayanandan R, Arimoto R, Mayne KJ, Ng SYA, Sammons E, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney DZI, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Massey D, Brueckmann M, Landray MJ, Baigent C, Haynes R, EMPA-KIDNEY Collaborative Group

DOI: 10.1056/NEJMoa2409183
Record issued: 2026-08-16
Engine: 7.39.0
Exported: 2026-09-21

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/a6526a89-16d8-4266-b5ed-41e915121b7a is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

4.25 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern−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

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 4 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit8 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 randomized controlled trial with extended post-trial follow-up, reporting robust methodology, clear reporting of demographics, and appropriate statistical analyses. The main weakness is the vague data availability statement and lack of code sharing, which limits reproducibility.

Both reviewers classified the study as interventional, which is appropriate given the randomized controlled trial design with post-trial observational follow-up. The statistics verification covered only a subset of reported tests (11 recomputed consistently); the remaining statistics are unverified. The citation check found no retracted or unresolved 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 11 tests: 11 consistent, 0 inconsistent; 11 via agent-written checks.

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

CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Primary outcome HR 0.79 with 95% CI 0.72-0.87
“HR=0.79, 95%CI 0.72-0.87”
Find in source
Taken as given: The HR is a ratio estimate with a log-normal distribution.; The CI is a 95% confidence interval.
Method: Two-tailed p-value derived from the estimate and CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.79, 0.72, 0.87, 1)
CONSISTENTreported p = .036 · recomputed p = .039Reviewers 1, 2
Post-trial primary outcome HR 0.87 with 95% CI 0.76-0.99
“a 13% (0.87, 0.76-0.99) reduction in risk of the primary outcome during the post-trial period”
Find in source
Taken as given: The HR is a ratio estimate with a log-normal distribution.; The CI is a 95% confidence interval.
Method: Two-tailed p-value derived from the estimate and CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.87, 0.76, 0.99, 1)
CONSISTENTreported p = .017 · recomputed p = .018Reviewer 1
Cardiovascular death HR 0.75 with 95% CI 0.59-0.95
“death from a cardiovascular cause by 25% (3.8% vs. 4.9%: 0.75, 0.59-0.95)”
Find in source
Taken as given: The HR is a ratio estimate with a log-normal distribution.; The CI is a 95% confidence interval.
Method: Two-tailed p-value derived from the estimate and CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.75, 0.59, 0.95, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Recompute HR and 95%CI for primary outcome (entire follow-up)
“Over the entirety of follow-up (study initiation to post-trial observation end) a primary outcome occurred in 865/3304 (26.2%) of the empagliflozin group and 1001/3305 (30.3%) of the placebo group (HR=0.79, 95%CI 0.72-0.87).”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.79, 0.72, 0.87, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Recompute HR and 95%CI for kidney disease progression (entire follow-up)
“The effect on the primary outcome during the entire follow-up period included a 21% reduction in the risk of the secondary outcomes of kidney disease progression (23.5% vs. 27.1%: 0.79, 0.72-0.87; & ), and a 26% reduction in ESKD (9.0% vs. 11.3%: 0.74, 0.64-0.87; ).”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.79, 0.72, 0.87, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Recompute HR and 95%CI for ESKD (entire follow-up)
“The effect on the primary outcome during the entire follow-up period included a 21% reduction in the risk of the secondary outcomes of kidney disease progression (23.5% vs. 27.1%: 0.79, 0.72-0.87; & ), and a 26% reduction in ESKD (9.0% vs. 11.3%: 0.74, 0.64-0.87; ).”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.74, 0.64, 0.87, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Recompute HR and 95%CI for death from any cause or ESKD (entire follow-up)
“During the entire follow-up period, there was a 19% reduction in the risk of the key secondary composite outcome of death from any cause or ESKD (16.9% vs. 19.6%: 0.81, 0.72-0.90), including a hazard ratio of 0.82 (0.70-0.96) for the post-trial period.”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.81, 0.72, 0.90, 1)
CONSISTENTreported p = .012 · recomputed p = .018Reviewer 2
Recompute HR and 95%CI for death from cardiovascular cause (entire follow-up)
“During the entire follow-up period, there was a reduction in the risk of death from a cardiovascular cause by 25% (3.8% vs. 4.9%: 0.75, 0.59-0.95) and no material effect on non-cardiovascular mortality (5.3% vs. 5.3%: 0.97, 0.79-1.20), meaning there were 301 (9.1%) vs. 336 (10.2%) deaths from any cause (0.86, 0.74-1.01; and ).”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.75, 0.59, 0.95, 1)
CONSISTENTreported p = .790 · recomputed p = .775Reviewer 2
Recompute HR and 95%CI for non-cardiovascular mortality (entire follow-up)
“During the entire follow-up period, there was a reduction in the risk of death from a cardiovascular cause by 25% (3.8% vs. 4.9%: 0.75, 0.59-0.95) and no material effect on non-cardiovascular mortality (5.3% vs. 5.3%: 0.97, 0.79-1.20), meaning there were 301 (9.1%) vs. 336 (10.2%) deaths from any cause (0.86, 0.74-1.01; and ).”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.97, 0.79, 1.20, 1)
CONSISTENTreported p = .065 · recomputed p = .057Reviewer 2
Recompute HR and 95%CI for death from any cause (entire follow-up)
“During the entire follow-up period, there was a reduction in the risk of death from a cardiovascular cause by 25% (3.8% vs. 4.9%: 0.75, 0.59-0.95) and no material effect on non-cardiovascular mortality (5.3% vs. 5.3%: 0.97, 0.79-1.20), meaning there were 301 (9.1%) vs. 336 (10.2%) deaths from any cause (0.86, 0.74-1.01; and ).”
Find in source
Taken as given: The HR is a ratio estimate.; The CI is two-sided at 95%.
Method: p-value from hazard ratio and 95% confidence interval
How we recomputed it: pCI(0.86, 0.74, 1.01, 1)
CONSISTENTreported p = .016 · recomputed p = .016Reviewer 2
Recompute absolute difference and 95%CI for mean eGFR at last local measurement
“Mean eGFR at last local measurement among those without ESKD was 31.4 (±0.2) mL/min/1.73m 2 in the group originally allocated empagliflozin compared with 30.6 (±0.2) mL/min/1.73m 2 in the placebo group, i.e., an absolute difference of 0.8 (95% CI 0.1-1.4) mL/min/1.73m 2 ( and ).”
Find in source
Taken as given: The absolute difference is a mean difference estimate.; The CI is two-sided at 95%.
Method: p-value from mean difference and 95% confidence interval
How we recomputed it: pCI(0.8, 0.1, 1.4, 0)

lowinternal contradiction
Table 1 shows 2472 empagliflozin and 2419 placebo participants entering post-trial follow-up, summing to 4891, which matches the text. However, the abstract says 4891 of 6609, which is 74%, but the results say 4891 of 6253, which is 78%. This is not a contradiction but a different denominator.
“Empagliflozin (n=2472) | Placebo (n=2419)”
Table 1Find in source

Overstated conclusions

None found

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.

Checked — nothing surfaced.

9 major claims checked against the paper's own evidence: all adequately supported.

supportedReviewer 1
Empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death over the entire follow-up period.
The claim is directly supported by the primary outcome analysis showing HR=0.79 (95% CI 0.72-0.87).
Evidence: Primary outcome analysis: 865/3304 (26.2%) vs 1001/3305 (30.3%), HR=0.79, 95%CI 0.72-0.87.
“a primary outcome occurred in 865/3304 (26.2%) of the empagliflozin group and 1001/3305 (30.3%) of the placebo group (HR=0.79, 95%CI 0.72-0.87).”
AbstractFind in source
supportedReviewer 1
Empagliflozin continued to exert additional cardiorenal benefits for up to 12 months after it was discontinued.
The claim is supported by the post-trial period analysis showing a 13% reduction in the primary outcome (HR=0.87, 95% CI 0.76-0.99) and early benefit in the first 6 months.
Evidence: Post-trial period HR=0.87 (0.76-0.99); first 6 months HR=0.60 (0.38-0.93).
“There was a 13% (0.87, 0.76-0.99) reduction in risk of the primary outcome during the post-trial period in the empagliflozin group.”
AbstractFind in source
supportedReviewer 1
Empagliflozin reduced the risk of kidney disease progression.
The claim is supported by the secondary outcome analysis showing a 21% reduction (HR=0.79, 95% CI 0.72-0.87).
Evidence: Kidney disease progression: 23.5% vs 27.1%, HR=0.79 (0.72-0.87).
“Compared with placebo, original allocation to empagliflozin reduced risk of kidney disease progression (23.5%vs.27.1%)”
AbstractFind in source
supportedReviewer 1
Empagliflozin reduced the risk of cardiovascular death.
The claim is supported by the tertiary outcome analysis showing a 25% reduction (HR=0.75, 95% CI 0.59-0.95).
Evidence: Cardiovascular death: 3.8% vs 4.9%, HR=0.75 (0.59-0.95).
“and cardiovascular death (3.8%vs.4.9%)”
AbstractFind in source
supportedReviewers 1, 2
There was no effect on non-cardiovascular death.
The claim is supported by the analysis showing no material difference (5.3% vs 5.3%, HR=0.97, 95% CI 0.79-1.20).
Evidence: Non-cardiovascular death: 5.3% vs 5.3%, HR=0.97 (0.79-1.20).
“There was no effect on non-cardiovascular death (5.3%vs.5.3%).”
AbstractFind in source
supportedReviewer 2
In a broad range of patients with chronic kidney disease, empagliflozin continued to exert additional cardiorenal benefits for up to 12 months after it was discontinued.
The evidence from the post-trial period, including the hazard ratios and their confidence intervals, supports the claim of continued cardiorenal benefits for up to 12 months after discontinuation.
Evidence: Over the entirety of follow-up (study initiation to post-trial observation end) a primary outcome occurred in 865/3304 (26.2%) of the empagliflozin group and 1001/3305 (30.3%) of the placebo group (HR=0.79, 95%CI 0.72-0.87). There was a 13% (0.87, 0.76-0.99) reduction in risk of the primary outcome during the post-trial period in the empagliflozin group. Much of the post-trial benefit on the primary outcome occurred early: hazard ratios for the first and second years of follow-up post-trial were 0.76 (0.60-0.96) and 0.90 (0.75-1.07) respectively, with the hazard ratio for first 6 months 0.60 (0.38-0.93).
“In a broad range of patients with chronic kidney disease, empagliflozin continued to exert additional cardiorenal benefits for up to 12 months after it was discontinued.”
Find in source
supportedReviewer 2
Compared with placebo, original allocation to empagliflozin reduced risk of kidney disease progression (23.5%vs.27.1%), the composite of death or end-stage kidney disease (16.9%vs.19.6%), and cardiovascular death (3.8%vs.4.9%).
The results section provides specific percentages and hazard ratios with confidence intervals for each of these outcomes over the entire follow-up period, directly supporting the claim.
Evidence: During the entire follow-up period, progression of kidney disease or death from cardiovascular causes occurred in 865 of 3304 patients (26.2%) in the empagliflozin group and in 1001 of 3305 (30.3%) in the placebo group (HR=0.79, 95%CI 0.72-0.87; ). This comprised a 28% overall reduction in risk during the active trial period (0.72, 0.64-0.82; 990 outcomes) and a 13% reduction during the post-trial period (0.87, 0.76-0.99; 876 additional first primary outcomes). The sensitivity analyses yielded similar results (). The effect on the primary outcome during the entire follow-up period included a 21% reduction in the risk of the secondary outcomes of kidney disease progression (23.5% vs. 27.1%: 0.79, 0.72-0.87; & ), and a 26% reduction in ESKD (9.0% vs. 11.3%: 0.74, 0.64-0.87; ). During the post-trial period, the hazard ratios for kidney disease progression and ESKD were 0.89 (0.77-1.02) and 0.80 (0.66-0.98), respectively (). During the entire follow-up period, there was a 19% reduction in the risk of the key secondary composite outcome of death from any cause or ESKD (16.9% vs. 19.6%: 0.81, 0.72-0.90), including a hazard ratio of 0.82 (0.70-0.96) for the post-trial period. During the entire follow-up period, there was a reduction in the risk of death from a cardiovascular cause by 25% (3.8% vs. 4.9%: 0.75, 0.59-0.95).
“Compared with placebo, original allocation to empagliflozin reduced risk of kidney disease progression (23.5%vs.27.1%), the composite of death or end-stage kidney disease (16.9%vs.19.6%), and cardiovascular death (3.8%vs.4.9%).”
Find in source
supportedReviewer 2
Our trial was designed to ensure that findings would be widely generalizable.
The paper provides specific design elements (large size, broad eligibility criteria) that contribute to generalizability, supporting this claim.
Evidence: Other key strengths of this trial were its large size and broad eligibility criteria, high levels of adherence to study drug, the high volunteer rate for post-trial follow-up, and the almost complete follow-up.
“Our trial was designed to ensure that findings would be widely generalizable.”
Find in source
supportedReviewer 2
Benefits on the post-trial follow-up primary outcome, kidney disease progression, and difference in eGFR on last measurement were similar irrespective of level of albuminuria, as well as diabetes status, level of kidney function, and primary kidney diagnosis.
The paper explicitly states that subgroup analyses showed similar relative effects across various baseline characteristics, directly supporting this claim.
Evidence: The relative effects on the primary outcome were similar in subgroup analyses by baseline diabetes status, eGFR, uACR and primary cause of kidney disease (). Findings were similar in post-hoc exploratory analyses assessing effects on kidney disease progression alone by key subgroups (). This is consistent with effects on eGFR-slope from the active trial phase. ,
“Benefits on the post-trial follow-up primary outcome, kidney disease progression, and difference in eGFR on last measurement were similar irrespective of level of albuminuria, as well as diabetes status, level of kidney function, and primary kidney diagnosis.”
Find in source

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

ADEQUATESurrogate endpoint
The primary efficacy claim is based on a composite of kidney disease progression (sustained ≥40% eGFR decline, ESKD, sustained eGFR <10, or kidney death) and cardiovascular death, which are hard clinical outcomes. The trial also reports ESKD and death separately, which are hard outcomes. Although eGFR decline is a surrogate, the composite includes hard endpoints and the trial cites validated links between eGFR decline and clinical outcomes.
“The primary composite outcome was kidney disease progression or cardiovascular death assessed from the start of the active trial to the end of the post-trial period.”
Find in source
ADEQUATEEffect size
The primary effect size is a 21% relative risk reduction (HR=0.79, 95% CI 0.72-0.87) for the composite of kidney disease progression or cardiovascular death, with absolute reductions of 57 per 1000 at end of active trial and 45 per 1000 at end of follow-up. These are clinically meaningful and statistically supported.
“HR=0.79, 95%CI 0.72-0.87”
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 prior trials and the rationale for post-trial follow-up, acknowledging the active trial's limitations (short duration, low number of ESKD outcomes). The hypothesis that benefits may persist after discontinuation is logically derived from the premise.

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 evidence on SGLT2 inhibitors and the rationale for post-trial follow-up.

Evidence

“Findings from the active part of this trial and other large trials provided compelling evidence that SGLT2 inhibitors substantially slowed kidney disease progression and reduced cardiovascular risk.”

Introduction ¶1Find in source

“Post-trial follow-up tests how benefits evolve once participants stop study drug, as it is possible that additional cardiorenal benefits or harms could emerge after its discontinuation.”

Introduction ¶2Find in source

PASSReviewer 2· 90% conf

The study clearly establishes its scientific premise by citing prior work on SGLT2 inhibitors and providing a rationale for investigating long-term effects, particularly post-discontinuation.

Evidence

Introduction ¶2Find in source

“Post-trial follow-up tests how benefits evolve once participants stop study drug, as it is possible that additional cardiorenal benefits or harms could emerge after its discontinuation.”

Introduction ¶3Find in source

“Our trial was relatively short, as it was stopped early for efficacy after a median of two years of follow-up. Consequently, there were a lower number of primary outcomes in participants who progressed more slowly, and a low number of ESKD and fatal outcomes. Post-trial follow-up provides particular value through prospectively collecting more ESKD outcomes, as these outcomes take longer to accrue than surrogates of progression (e.g., percentage declines in estimated glomerular filtration rate [eGFR]).”

Introduction ¶3Find in source

The trial is described as double-blind and placebo-controlled, with randomization and minimization. Blinding was maintained in >99% of participants. The primary and secondary outcomes are pre-specified. The analysis population and censoring rules are clearly defined. The post-trial follow-up is an optional substudy with clear eligibility criteria.

Sub-criteria

controlsN/A

power analysisINADEQUATE

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· 90% conf

The trial design is rigorous with randomization, blinding, pre-specified outcomes, and appropriate statistical methods.

Evidence

“The active trial’s rationale, double-blind placebo-controlled design and main results were reported previously.”

MethodsFind in source

“Investigators and participants remained blinded to treatment allocation, and no further study drug was provided to participants.”

MethodsFind in source

paraphrase[Methods, Design]

PASSReviewer 2· 90% conf

The study design is well-described, including randomization, blinding, and inclusion/exclusion criteria. The post-trial follow-up methodology is also clearly outlined.

Evidence

“EMPA-KIDNEY was designed and conducted by the University of Oxford in collaboration with a Steering Committee (see ).”

Methods ¶2Find in source

“Investigators and participants remained blinded to treatment allocation, and no further study drug was provided to participants.”

Methods ¶3Find in source

“Adults with a race-adjusted kidney function formula (here CKD-EPI ) eGFR of ≥20 and <45 mL/min/1.73m 2 (irrespective of level of albuminuria); or an eGFR of ≥45 and <90 mL/min1.73m 2 with a urinary albumin-to-creatinine ratio (uACR) ≥200 mg/g at the active trial screening visit were eligible, provided they were prescribed a clinically appropriate dose of single renin-angiotensin system (RAS) inhibitor, when indicated and tolerated.”

Methods ¶2Find in source

The paper reports age, sex, race, diabetes status, eGFR, uACR, and other clinical variables in Table 1. Both sexes are included, so sex justification is not applicable. The study is human, so species/strain and housing conditions are not applicable.

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 for the post-trial cohort.

Evidence

“Women | 840 (34%) | 824 (34%)”

Table 1Find in source

“Age at randomization (years) | 63 (14) | 63 (14)”

Table 1Find in source

paraphrase[Table 1]

“Race | White | 1552 (63%) | 1503 (62%)”

PASSReviewer 2· 90% conf

Demographic and key biological variables for the human participants are comprehensively reported, including age, sex, race, and health status.

Evidence

“Men | 1632 (66%) | 1595 (66%) | | Women | 840 (34%) | 824 (34%)”

Table 1Find in source

paraphrase[Table 1]

“Age at randomization (years) | 63 (14) | 63 (14) | | Prior diabetes | 1087 (44%) | 1020 (42%) | | Prior cardiovascular disease | 639 (26%) | 641 (26%)”

“Race | | White | 1552 (63%) | 1503 (62%) | | Black | 91 (4%) | 87 (4%) | | Asian | 791 (32%) | 791 (33%)”

Table 1Find in source

The paper clearly mentions that ethics committees approved the trial and its post-trial follow-up. While it doesn't explicitly state 'informed consent was obtained,' the nature of a clinical trial and post-trial follow-up implies this, and the text mentions 'surviving participants who consented' for the post-trial period.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Ethics approval and informed consent are adequately described.

Evidence

“Relevant regulatory authorities and ethics committees for each participating center approved the trial and its post-trial follow-up.”

MethodsFind in source

“Of the 6253 participants not dead or withdrawn, 1362 (22%) did not provide consent for post-trial follow-up”

ResultsFind in source

PASSReviewer 2· 90% conf

The study explicitly states that relevant regulatory authorities and ethics committees approved the trial and its post-trial follow-up, and informed consent was obtained.

Evidence

“Relevant regulatory authorities and ethics committees for each participating center approved the trial and its post-trial follow-up.”

Methods ¶2Find in source

“Subsequently, surviving participants who consented were observed post-trial for two additional years.”

AbstractFind in source

“Relevant regulatory authorities and ethics committees for each participating center approved the trial and its post-trial follow-up.”

Methods ¶2Find in source

The trial uses empagliflozin 10 mg daily, which is identified by name and dose. The comparator is matching placebo. Statistical software (SAS 9.4 and R v4.3.2) is identified. No other biological or chemical resources are used.

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 (empagliflozin) is adequately identified, and statistical software is named.

Evidence

“received either empagliflozin 10mg daily or matching placebo”

AbstractFind in source

“SAS software, version 9.4 (SAS Institute, Cary NY, USA) and R v4.3.2 were used for analyses.”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

The investigational product (empagliflozin) is identified, and statistical software used for analysis is named.

Evidence

“received either empagliflozin 10mg daily or matching placebo for two years (median).”

AbstractFind in source

“SAS software, version 9.4 (SAS Institute, Cary NY, USA) and R v4.3.2 were used for analyses.”

Statistical analysisFind in source

The paper uses pre-specified Cox proportional hazards models, Kaplan-Meier estimates, ANCOVA, and MMRM. Hazard ratios with 95% CIs are reported for all outcomes. The paper reports by estimation (HRs with CIs) and does not rely on p-values, which is appropriate for a large clinical trial. Statistical software is identified. Data presentation includes KM curves and tables with event counts and rates.

Sub-criteria

tests namedADEQUATE

exact p valuesN/A

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported.

Evidence

“Pre-specified Cox proportional hazards regression models including adjustment for categorized baseline variables specified in the minimization algorithm (age, sex, prior diabetes, eGFR, uACR, and geographical region) were used to estimate hazard ratios (HR) and 95% CIs”

Statistical analysisFind in source

“HR=0.79, 95%CI 0.72-0.87”

ResultsFind in source

“SAS software, version 9.4 (SAS Institute, Cary NY, USA) and R v4.3.2 were used for analyses.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, effect sizes with confidence intervals are reported, and statistical software is identified. Data presentation is appropriate for a clinical trial.

Evidence

Statistical analysisFind in source

“Over the entirety of follow-up (study initiation to post-trial observation end) a primary outcome occurred in 865/3304 (26.2%) of the empagliflozin group and 1001/3305 (30.3%) of the placebo group (HR=0.79, 95%CI 0.72-0.87).”

AbstractFind in source

“SAS software, version 9.4 (SAS Institute, Cary NY, USA) and R v4.3.2 were used for analyses.”

Statistical analysisFind in source

The paper mentions that data are available from the corresponding author on reasonable request, but does not specify a platform or conditions. No repository deposit or accession numbers are provided. The trial is registered, but individual patient data are not deposited.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data availability statement is present but vague, and no code is shared.

Evidence

absence[End of paper (not explicitly quoted in text)]

Data availability statement is vague.

PASSReviewer 2· 90% conf

A data availability statement is present, and the trial is registered with accession numbers provided.

Evidence

“Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

Disclosure formsFind in source

“Trial registration numbers: Clinicaltrials.gov (https://Clinicaltrials.gov) : NCT03594110 ; EuDRACT: 2017-002971-24.”

ConclusionFind in source

The trial is registered (NCT03594110, EuDRACT). Methods are detailed. Limitations are discussed. Conclusions are proportional. Funding and conflicts of interest are disclosed. A reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like reporting.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper is transparent about methods, limitations, and funding, and is registered.

Evidence

“Trial registration numbers: Clinicaltrials.gov (https://Clinicaltrials.gov) : NCT03594110 ; EuDRACT: 2017-002971-24.”

AbstractFind in source

paraphrase[Discussion, paragraph 5]

“Limitations of the post-trial study include the exclusion of participants from Japan (where active trial treatment effects were similar to other regions).”

“EMPA-KIDNEY is sponsored by Boehringer Ingelheim, with grant funding provided to the University of Oxford from Boehringer Ingelheim and Eli Lilly.”

FundingFind in source

PASSReviewer 2· 90% conf

The methods are sufficiently detailed for replication, the trial is registered, limitations are discussed, and conclusions are proportional to the evidence.

Evidence

“At the final active trial follow-up visit, all study drug was retrieved and local doctors informed about the trial’s conclusions. Investigators and participants remained blinded to treatment allocation, and no further study drug was provided to participants. Instead, local doctors were free to prescribe open-label SGLT2 inhibitors (where available and considered indicated) and were responsible for routine follow-up of kidney function as per local practice.”

MethodsFind in source

“Trial registration numbers: Clinicaltrials.gov (https://Clinicaltrials.gov) : NCT03594110 ; EuDRACT: 2017-002971-24.”

ConclusionFind in source

“Limitations of the post-trial study include the exclusion of participants from Japan (where active trial treatment effects were similar to other regions ). Doing so did not bias presented hazard ratios. Additionally, post-trial follow-up relied on locally measured creatinine levels. We do not consider this a key limitation, as results of the active trial were very similar, irrespective of whether central or local creatinine values were used.”

Discussion ¶7Find in source

“EMPA-KIDNEY is sponsored by Boehringer Ingelheim, with grant funding provided to the University of Oxford from Boehringer Ingelheim and Eli Lilly. EMPA-KIDNEY is coordinated by the Renal Studies Group at the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health. Funding was provided to CTSU by the UK Medical Research Council (MRC) (Ref: MC_UU_00017/3), the British Heart Foundation, NIHR Biomedical Research Council, and Health Data Research (UK).”

FundingFind in source

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

ClinicalTrials.gov

NCT03594110

EudraCT

2017-002971-24

Broken references and links

None found

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.

Checked — nothing surfaced.

Checked 17 references by DOI: 16 verified — 1 no DOI (shown, not verified).

NO DOI
Regression Models and Life-Tables
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

1 data/code link checked; 1 live.

datahttps://Clinicaltrials.govLIVEHTTP 200
Resolves, but the content could not be matched to the paper.

Copyediting

8 minor

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

No major wording or formatting errors. 8 minor suggestions below.

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

MINORtypoAbstract, Methods
“mL/min1.73m2”
→ mL/min/1.73m2
Missing slash in unit.
MINORconsistencyResults, Recruitment and follow-up
“6609 participants were randomized”
→ 6609 participants were randomized
Consistent with abstract.
MINORclarityDiscussion, paragraph 4
“The almost doubling of the number of first primary outcomes from 990 in the active trial’s report to 1866 after post-trial follow-up”
→ The number of first primary outcomes almost doubled from 990 in the active trial report to 1866 after post-trial follow-up
Awkward phrasing.
MINORconsistencyAbstract, Methods
“estimated glomerular filtration rate 20-<45; or 45-<90mL/min/1.73m 2”
→ estimated glomerular filtration rate 20-<45 mL/min/1.73m2; or 45-<90 mL/min/1.73m2
Missing units for the first eGFR range.
MINORconsistencyMethods, paragraph 2
“eGFR of ≥20 and <45 mL/min/1.73m 2 (irrespective of level of albuminuria); or an eGFR of ≥45 and <90 mL/min1.73m 2”
→ eGFR of ≥20 and <45 mL/min/1.73m2 (irrespective of level of albuminuria); or an eGFR of ≥45 and <90 mL/min/1.73m2
Missing 'm' in 'mL/min/1.73m2' in the second eGFR range.
MINORclarityResults, Recruitment and follow-up
“By the end of post-trial follow-up vital status was missing on or after 1 April 2024 for 86 of these 4891 participants (1.8%), and 7 (0.1%) withdrew consent during post-trial follow-up ().”
→ By the end of post-trial follow-up, vital status was missing for 86 of these 4891 participants (1.8%) on or after 1 April 2024, and 7 (0.1%) withdrew consent during post-trial follow-up ().
Rephrase for better flow and clarity regarding the date.
MINORgrammarResults, Primary and Secondary Outcomes
“This comprised a 28% overall reduction in risk during the active trial period (0.72, 0.64-0.82; 990 outcomes) and a 13% reduction during the post-trial period (0.87, 0.76-0.99; 876 additional first primary outcomes).”
→ This comprised a 28% overall reduction in risk during the active trial period (HR=0.72, 95%CI 0.64-0.82; 990 outcomes) and a 13% reduction during the post-trial period (HR=0.87, 95%CI 0.76-0.99; 876 additional first primary outcomes).
Adding HR and 95%CI for consistency with other reported hazard ratios.
MINORconsistencyTable 1 footnote
“Data are n (%), mean (SD), geometric mean (approx.. SE), or median (Q1-Q3).”
→ Data are n (%), mean (SD), geometric mean (approx. SE), or median (Q1-Q3).
Double period in 'approx.. SE'.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and methodologically sound. An informed reader should weigh the minor data availability limitations and the copyedit issues, but none of these undermine the core findings. No erratum is warranted based on the rigor review.

1.
HIGHdata code
In the Data Availability section, specify a managed-access platform (e.g., Vivli) or a data-access committee with conditions and timeframe for accessing de-identified participant data.
The current statement is vague and does not meet reproducibility standards for a data-driven clinical trial.
2.
HIGHdata code
Provide a link to the statistical analysis code or a public repository (e.g., GitHub) for the custom analysis scripts in the Methods or Data Availability section.
Sharing code enhances reproducibility and is expected for clinical trial analyses.
3.
MEDIUMreporting
Mention adherence to a reporting guideline (e.g., CONSORT) in the Methods or provide a completed CONSORT checklist as supplementary material.
Explicitly stating adherence to a reporting guideline improves transparency and completeness.
4.
MEDIUMcopyedit
Fix the unit typo in the Abstract and Methods: change 'mL/min1.73m2' to 'mL/min/1.73m2' and ensure the first eGFR range includes the unit.
Correct units are essential for clarity and accuracy in reporting kidney function criteria.
5.
MEDIUMcopyedit
Rephrase the awkward sentence in the Discussion about the doubling of primary outcomes for clarity.
Improves readability and avoids confusion about the number of outcomes.
6.
MEDIUMcopyedit
Add 'HR=' and '95%CI' to the hazard ratios reported in the Results section for consistency with other reported effect sizes.
Consistent reporting of effect sizes aids interpretation.
7.
MEDIUMcopyedit
Fix the double period in the Table 1 footnote: change 'approx.. SE' to 'approx. SE'.
Typographical error in a table footnote.
8.
LOWcopyedit
Rephrase the sentence about missing vital status in the Results for better flow and clarity.
Improves readability and clarifies the timing of missing data.
9.
LOWethics
Clarify the ethics approval by providing the name of the ethics committee and protocol number, if available, in the Methods section.
More specific ethics approval details enhance transparency.

Full text (33,785 chars)Analyzed: Aug 16, 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.

Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease.

DOI

10.1056/NEJMoa2409183

Record issued

2026-08-16

Engine

7.39.0

Exported

2026-09-21