Canagliflozin, dapagliflozin and empagliflozin in kidney disease

In this section: Registration and administrative information (PROSPERO field set) · What this object claims to contain

Registration and administrative information (PROSPERO field set)

Table 1. Registration and administrative information (PROSPERO field set)
Review title	Canagliflozin, dapagliflozin and empagliflozin in kidney disease
Review question (PICO)	In Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov \| Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD \| Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated'), what do the contributing trials show?
Population	Adults with chronic kidney disease (eGFR 25-75 mL/min/1.73m^2) with or without diabetes
Intervention	SGLT2 inhibitor (canagliflozin, dapagliflozin, empagliflozin)
Comparator	Placebo
Background / rationale	Not recorded — this object holds no background field, and an introduction generated without one would be argument that no source in this review supports
Eligibility criteria	not recorded on the page this object was extracted from
Information sources	0 source layers, listed on the Extraction tab
Search strategy	The executed strings, datetimes, filters and hit counts are on the Search tab
Study selection process	Not recorded — no screening record was recoverable from the page this object was extracted from, so who screened and how cannot be stated
Number of screeners	Not recorded — this object records no screener count
Data extraction items	Extracted per trial on this object: registry id; primary publication; arms; per-arm counts and the published effect; the randomised total, separately from the analysed denominator. Fields not listed here were not extracted.
Outcomes and prioritisation	Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov \| Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD \| Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')
Risk of bias method	Not recorded — no per-domain RoB-2 assessment exists yet
Synthesis methods	Not recorded — no outcome on this object carries a pooled estimate, so no synthesis method was applied
Subgroup analyses	Not recorded — this object records no subgroup-analysis field at all, so whether any were prespecified is UNKNOWN -- which is not the same as none having been
Meta-bias assessment	Not recorded — no funnel, Egger or Peters value is held on this object, so no meta-bias assessment is claimed
Certainty assessment	Not recorded — no GRADE record was recoverable from the page this object was extracted from
Funding	Not recorded — no funding statement is recorded for this review
Competing interests	Not recorded — no declaration is recorded
Built	2026-08-17T12:06Z
Schema	2-converted-from-extractor

What this object claims to contain

not recorded on the page this object was extracted from

Not held in this object. No search strategy was recoverable from the published page this object was extracted from, so no query, date or yield can be shown.

Not held in this object. No screening log was recoverable from the published page this object was extracted from, so no records-identified or excluded-with-reason counts exist here.

In this section: Extracted values, and where each came from · References · Included studies · Regulatory documents · Methods and guidance · Sources · Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated') · Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated') · What was measured · Pooled result · Contributing trials · Endpoint definitions, read from the registry

Extracted values, and where each came from

These values cannot be traced to a paper from this page. This object was RECOVERED from the published page itself rather than assembled from source documents. Each value below traces to the page it came from, but no verbatim source sentence and no resolvable link to a paper was recoverable, and the intervals are computed from a stored estimate and variance rather than read from anything a source printed. Treat every row as unverified against its source until it is checked against the trial report.

One row per extracted value. Every row carries the value, the verbatim sentence it was read from, a resolvable link to the source, and whether the number was read or derived. Where any of those is absent the row says so rather than omitting the value.

Table 2. Extracted values, and where each came from
Trial / outcome	Value as extracted	Verbatim source sentence	Source links	Read or derived
CREDENCE primary	OR 0.685 (95% CI 0.574 to 0.816)	no source sentence recorded — this value cannot be checked against a quoted line here	NCT02065791	DERIVED by us from extractor recovery from the published page The point estimate and interval shown here are DERIVED, not read: the extractor recovered an estimate and a variance on the analysis scale, and the interval is estimate +/- 1.96*sqrt(variance) back-transformed. No source document was consulted and no source sentence is recorded.
DAPA-CKD primary	OR 0.594 (95% CI 0.492 to 0.718)	no source sentence recorded — this value cannot be checked against a quoted line here	NCT03036150	DERIVED by us from extractor recovery from the published page The point estimate and interval shown here are DERIVED, not read: the extractor recovered an estimate and a variance on the analysis scale, and the interval is estimate +/- 1.96*sqrt(variance) back-transformed. No source document was consulted and no source sentence is recorded.
EMPA-KIDNEY primary	OR 0.74 (95% CI 0.646 to 0.848)	no source sentence recorded — this value cannot be checked against a quoted line here	NCT03594110	DERIVED by us from extractor recovery from the published page The point estimate and interval shown here are DERIVED, not read: the extractor recovered an estimate and a variance on the analysis scale, and the interval is estimate +/- 1.96*sqrt(variance) back-transformed. No source document was consulted and no source sentence is recorded.

References

Included studies

Regulatory documents

Methods and guidance

Sources

Table 3. Sources
Layer	Source	How it was obtained

Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')

What was measured

Table 4. What was measured
Comparator	not recorded on the page this object was extracted from
Estimand	not recorded on the page this object was extracted from — random-effects
Effect scale	reported on the log scale; nothing is pooled on this outcome

Pooled result

Estimate withdrawn. The three trials do not share one endpoint definition, and each registry record says so in its own words. All three composites count kidney-function decline, but at three different thresholds: CREDENCE counts a doubling of serum creatinine, DAPA-CKD counts a sustained decline of at least 50 per cent in eGFR, and EMPA-KIDNEY counts a sustained decline of at least 40 per cent in eGFR. Those are three different events, and the decline component is the largest contributor to each composite: a 40 per cent threshold admits strictly more patients than a 50 per cent threshold, which admits strictly more than a doubling of creatinine. The end-stage component differs too -- CREDENCE and DAPA-CKD floor it at an eGFR below 15, EMPA-KIDNEY at an eGFR below 10. Separately and sufficient on its own: every per-trial value this review held was an odds ratio derived by US from 2x2 counts, while all three trials analyse time to first occurrence -- DAPA-CKD's registry record states that 'the proportional hazards Cox regression model takes into account the time to the event'. The index card published that derived odds ratio under the label HR.

What is confirmed, stated as prominently as what is wrong. The component types agree across all three trials: every one counts kidney-function decline, end-stage kidney disease, renal death and cardiovascular death, and every one counts the first of them to occur. EMPA-KIDNEY's registry title names only 'kidney disease progression or cardiovascular death' and its description places renal death and the eGFR thresholds inside 'kidney disease progression' -- so reading the title alone would have made it look like a trial counting no renal death at all, which would have argued for splitting it from the other two for the wrong reason. The full description is quoted on every trial for exactly that reason. These three trials are close; they are not the same, and the difference is a threshold rather than a missing component. And the three results agree: crude risk ratios of 0.72, 0.63 and 0.77, all in the same direction. Agreement of results is not evidence of a common estimand. What is averaged is decided by what was counted, not by how the counts came out, and this withdrawal cannot be undone by observing that the numbers are close. The replacement question is identified and deliberately not taken: end-stage kidney disease as dialysis or transplant, and cardiovascular death, are each defined identically across all three and each is reported separately by all three. Taking it needs the trials' own reported hazard ratios for those components, from the registry results sections, and -- as recorded on ABLATION_AF -- a replacement question must be chosen before its answer is known. It is parked as a decision, not left as an oversight.

Previously displayed: OR 0.6793 (0.5996 to 0.7697); index card and table row: HR 0.68 (0.60-0.77), k=3 -- the DERIVED ODDS RATIO above, published under the label HR — superseded by this withdrawal.

Contributing trials

Table 5. Contributing trials
Trial	Analysed treatment / control	OR (95% CI), or events	Source of this cell
CREDENCE NCT02065791	intervention: 2,202 control: 2,199	0.6845 (0.574 to 0.8163)	:
DAPA-CKD NCT03036150	intervention: 2,152 control: 2,152	0.5943 (0.4917 to 0.7182)	:
EMPA-KIDNEY NCT03594110	intervention: 3,304 control: 3,305	0.7405 (0.6463 to 0.8484)	:

not recorded on the page this object was extracted from

Endpoint definitions, read from the registry

What each trial COUNTED, in its own registry record's words, before anything here was pooled. A sentence saying what HAPPENED is not a sentence saying what was COUNTED, and only the second one licenses a pool. Read from the registry on 2026-08-18. Follow the registration link to disagree with any row.

Table 6. Endpoint definitions, read from the registry
Trial	Rank in its own trial	Registered outcome measure	Description, verbatim	Analysis set / window
CREDENCE NCT02065791	PRIMARY -- this trial's own primary outcome measure	Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiovascular (CV) Death	Primary composite endpoint is the composite of DoSC, eskd, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Eskd: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached eskd, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.	Up to 4.6 years
DAPA-CKD NCT03036150	PRIMARY -- this trial's own primary outcome measure	Time to the First Occurrence of Any of the Components of the Composite: >=50% Sustained Decline in eGFR or Reaching ESRD or CV Death or Renal Death.	End Stage Renal Disease (ESRD) is defined as: Sustained eGFR <15 mL/min/1.73m2 or, Chronic dialysis treatment or, Receiving a renal transplant. The proportional hazards Cox regression model takes into account the time to the event. Data is reported as the numbers of subjects with the event and the Hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table.	Up to 38.2 months
EMPA-KIDNEY NCT03594110	PRIMARY -- this trial's own primary outcome measure	Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')	Kidney disease progression was defined as: end stage kidney disease (defined as the initiation of maintenance dialysis or receipt of a kidney transplant) OR a sustained decline in estimated glomerular filtration rate (eGFR) to <10 mL/min/1.73m^2 OR renal death OR a sustained decline of >=40% in eGFR from randomisation.	From the day of randomisation to the day of the final follow-up visit in the interventional part of the trial, up to 1136 days.

In this section: Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated') · Forest plot · Risk of bias · GOSH · Trial-sequential analysis · Meta-regression

Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')

Forest plot

Drawn from the same stored estimates the table above lists. Box area is proportional to inverse-variance weight.

x-axis range

Fit to data 0.25 to 4

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 3d1bd09f1880a282), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — forest_fit.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — forest_fit.tiff, 12,129 KB.

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 3a2c7e3daa07bec2), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — forest_w2.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — forest_w2.tiff, 12,129 KB.

Changing the range moves the axis window only. The guides stay labelled with the null and the extremes of the plotted intervals, so no plotted value and no printed number differs between these views — and that is checked at build time, not asserted. Ranges not offered because they would crop the data: 0.5 to 2, 0.7 to 1.3.

Risk of bias

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Only the vector format is offered for this figure, by choice: it is line art — discrete marks, glyphs and labels — which SVG reproduces exactly at any size, so a raster would add weight without adding fidelity. The build was able to rasterise; it was asked not to.

Not drawn, because there is nothing to draw it from.

GOSH

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: dd33d4f986f7c7c5), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — gosh.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — gosh.tiff, 5,537 KB.

Deliberately not drawn. Every subset meta-analysis of 3 trials is 7 points; a cloud that small cannot show the multimodality GOSH exists to reveal, and a reader would take the picture as evidence of its absence.

Trial-sequential analysis

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 25ed9800fdf56614), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — tsa.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — tsa.tiff, 6,665 KB.

TSA boundaries depend entirely on a target information size that must be pre-specified. This review's protocol registers none, so any boundary drawn here would be a parameter chosen after seeing the data -- which is the practice TSA exists to protect against.

Meta-regression

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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 2316b730fa24744e), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.

Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — bubble.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — bubble.tiff, 5,537 KB.

The protocol pre-specifies no moderator, and at k = 3 a meta-regression would be fitted on 3 points. Not drawn rather than drawn with a caveat: a bubble plot invites reading a slope, and there is no slope here that any reader should read.

In this section: Summary of findings · Reproducibility artifact · Other recorded qualifications

Summary of findings

Table 7. Summary of findings
Outcome	k	Pooled effect	Certainty
Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov \| Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD \| Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')	3	not pooled	See comment¹²

The pooled estimate for this outcome has been WITHDRAWN, so there is no estimate for a certainty rating to be about. Any rating this object still carries for this outcome was made about the withdrawn estimate and is not shown beside it.
Read this beside `whether the estimand was established`. That flag records that every contributing trial measures the same quantity. It records nothing about what that quantity was measured against -- whether the comparators are of one kind, whether each comparison was randomised, whether it was concurrent. The two questions were never separated. Named as P48 in PAGE-STANDARD.md v1.21.0 and swept by scripts/audit_mixed_contrast_pools.py.

Reproducibility artifact

Table 8. Reproducibility artifact
Canonical object	`—`
Registered at	`—` —
Schema	2-converted-from-extractor
Object last updated	2026-08-17T12:06Z
Source object SHA-256, first 16 hex characters	`ff1fb38e332203ac`
Page generated	2026-08-28 07:29 UTC
Generator build	`59b484ca7`. The standard this page was built to is NOT ESTABLISHED: this object carries no `build_stamp`, so the version above is the standard that exists now, not the one this page was built against.

This page CANNOT be rebuilt from what is recorded here: no canonical object is recorded and no registered commit is recorded. Each figure on the Analysis tab downloads as an SVG carrying exactly the values shown.

Other recorded qualifications

Statements this review records about the limits of what it establishes, which are not shown elsewhere on this page. They are reproduced from the object verbatim and are not summarised.

Table 9. Other recorded qualifications
Read from the protocol record not a result	Read from the protocol record's outcome-measure title and description. Not from a results table and not from an abstract sentence: a quote that says what happened is not a quote that says what was counted.
What is confirmed not only what is wrong	Stated as prominently as the problem, because a page that lists only what it found wrong misrepresents what it checked. The component types agree across all three trials. Every one counts kidney-function decline, end-stage kidney disease, renal death and cardiovascular death, and every one counts the first of them to occur. EMPA-KIDNEY's title names only 'kidney disease progression or cardiovascular death' and its description places renal death inside kidney disease progression -- so reading the title alone would have made it look like a trial that counts no renal death, and would have argued for splitting it from the other two. That is the bare-TITLE-with-components-in-the-DESCRIPTION trap already in the ledger, and it is why the description is quoted here in full for every trial. These trials are close. They are not identical, and the difference is a threshold rather than a missing component.
Withheld display	No pooled estimate is displayed. The value previously published on the index card, HR 0.68 (0.60-0.77) k=3, was a derived odds ratio labelled as a hazard ratio, over three composites with three different kidney-decline thresholds.
What this withdrawal does not establish	Not that the three trials disagree. Their crude risk ratios are 0.72, 0.63 and 0.77 and point the same way. Agreement of results is not evidence of a common estimand, and it is the reason this page cannot be rescued by observing that the numbers are close: what is being averaged is decided by what was counted, not by how the counts came out. Not that pooling these trials is wrong in principle -- syntheses that pool each trial's own primary composite exist and are defensible when they SAY that is what they are doing. What is not defensible is presenting the result as one endpoint under one measure label.

In this section: Paper · Title · Abstract · Introduction · Methods — search · Methods — eligibility criteria · Methods — outcomes sought at every registered rank · Results · Disagreements between sources · Limitations · Reporting guidelines · Note on registration · References · Figure legends · Figures · Trial characteristics · Not reported in this record

Paper

Each statement below cites the record it came from; those sources are listed at the end of every section. Where the record holds nothing, the section says so by name rather than being left out, so a procedure that was not carried out can be told from one that simply was never mentioned.

Title

Canagliflozin, dapagliflozin and empagliflozin in kidney disease¹

Sources for this section (1)

title

Abstract

Question. In Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated'), what do the contributing trials show?¹

Sources for this section (1)

question

Introduction

Background. This review asks: In Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated'), what do the contributing trials show? It examines 3 randomised trials and does not pool them. The outcome sought is Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated').¹

Sources for this section (1)

manuscript.introduction

Methods — search

Primary trials. No bibliographic search for primary trials was run. The 3 included trials were identified by reading named registrations on the dates recorded on each entry. The basis on which this object was verified is not recorded. What this object does not claim is not recorded. The bar this object had to clear is not recorded.¹

Sources for this section (1)

bookkeeping_2026_08_21.the_search_its_date_and_its_databases

Methods — eligibility criteria

not recorded on the page this object was extracted from¹

Sources for this section (1)

screening.eligibility

Methods — outcomes sought at every registered rank

Every registered rank -- primary, secondary and other -- was read for 3 of 3 contributing trials before any decision about which outcomes could be combined; each records the time it was read.¹

Sources for this section (1)

inputs.trials[].all_ranks_read_utc

Results

Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated'). These 3 trials are not pooled, and the reason is stated rather than the outcome being quietly omitted: Withheld on two independent grounds, each established from a source and each sufficient on its own. (1) the three trials do not share one endpoint definition. All three composites count kidney-function decline, but at three different thresholds, and all three registry records say so in their own words: Credence counts doubling of serum creatinine, dapa-ckd counts a sustained decline of at least 50% IN eGFR, and EMPA-KIDNEY counts a sustained decline of at least 40% IN eGFR. Those are three different events. A 40% threshold admits strictly more patients than a 50% threshold, which admits strictly more than a doubling of creatinine, and the decline component is the largest contributor to each composite. The eskd component differs too: Credence and DAPA-CKD floor it at eGFR below 15, EMPA-KIDNEY at eGFR below 10. (2) the stored effect measure is not the measure the trials report. Every per-trial value in this object is an odds ratio this project derived from 2x2 counts, while all three trials analyse time to first occurrence -- DAPA-CKD's registry record states outright that 'the proportional hazards Cox regression model takes into account the time to the event', and the other two describe time-to-first-occurrence analyses. The index card published the derived odds ratio under the label HR. Neither ground can be repaired by re-pooling; both need the trials' own reported hazard ratios and a common endpoint. And, recorded separately on the withdrawal itself: the three trials do not share one endpoint definition, and each registry record says so in its own words. All three composites count kidney-function decline, but at three different thresholds: Credence counts a doubling of serum creatinine, dapa-ckd counts a sustained decline of at least 50 per cent in eGFR, and EMPA-KIDNEY counts a sustained decline of at least 40 per cent in eGFR. Those are three different events, and the decline component is the largest contributor to each composite: a 40 per cent threshold admits strictly more patients than a 50 per cent threshold, which admits strictly more than a doubling of creatinine. The end-stage component differs too -- credence and DAPA-CKD floor it at an eGFR below 15, EMPA-KIDNEY at an eGFR below 10. Separately and sufficient on its own: every per-trial value this review held was an odds ratio derived by US from 2x2 counts, while all three trials analyse time to first occurrence -- DAPA-CKD's registry record states that 'the proportional hazards Cox regression model takes into account the time to the event'. The index card published that derived odds ratio under the label HR.¹

Sources for this section (1)

outcomes[id=primary].name, results.by_outcome.primary.poolable_reason, results.by_outcome.primary.pooled.withdrawn_reason

Disagreements between sources

not recorded on the page this object was extracted from¹

not recorded on the page this object was extracted from²

Sources for this section (2)

reconciliation.why_this_step_exists
reconciliation.clean_because

Limitations

What this review does not give a clinician: the number of events in each arm, any absolute effect or number needed to treat and any measure of harm. A relative effect cannot be turned into the benefit or the risk facing one patient without them, so this review can support a judgement about what these trials found and not a judgement about what to do.¹

Sources for this section (1)

results.by_outcome

Reporting guidelines

This review reports against PRISMA 2020. A screening record is held on this object and the flow it supports is shown in the Methods. The completed PRISMA checklist and FLOW diagram are not held here: the venue requires them deposited in an approved repository with a DOI cited in the Data Availability Statement, and minting that DOI is an author action rather than a build step.¹

Sources for this section (1)

screening

Note on registration

No PROSPERO registration or protocol record is held on this object. That is not the same as knowing this review was not registered, and neither claim is made. It is recorded here as an absence so that a reader does not have to infer it from silence.¹

Sources for this section (1)

bookkeeping_2026_08_21.whether_this_review_was_prospectively_registered

References

Included studies, by registration¹
Trial	Registration	Registry	Read
	NCT02065791	ClinicalTrials.gov
	NCT03036150	ClinicalTrials.gov
	NCT03594110	ClinicalTrials.gov

Methods guidance and software, with what each is cited for²
Cited for	Reference
the reporting guideline this manuscript is written against	Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71

Sources for this section (2)

manuscript.references
manuscript.references

Figure legends

Figures, and what each one shows¹
Outcome	Figure	What it shows
Multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov \| Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD \| Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')	Forest plot	not pooled; the reason is given in Results

Sources for this section (1)

results.by_outcome

Figures

Figure 1 not drawn. this pool was withdrawn, and the reason is given in Results. A forest plot is the pooled claim in picture form, so drawing one here would restate the very combination this review retracted.

Figure 1. Forest plot -- multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated'). k = 3.¹

Figure 2 not drawn. this pool was withdrawn. The funnel's bounds are drawn from the pooled estimate, so there is no pooled value left for it to be drawn around.

Figure 2. Funnel plot -- multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiov | Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD | Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated'). k = 3.²

Sources for this section (2)

results.by_outcome.primary.per_trial, results.by_outcome.primary.pooled
results.by_outcome.primary.per_trial, results.by_outcome.primary.pooled

Trial characteristics

Characteristics of every trial contributing to this review¹
Registration	Trial	Participants	Randomised	Primary outcome measured over	Design
NCT02065791	CREDENCE	not recorded on the page this object was extracted from	4401	Up to 4.6 years	Canagliflozin 100 mg (treatment, n=2202) vs Placebo (control, n=2199) [+2 further fields recorded on the object]
NCT03036150	DAPA-CKD	not recorded on the page this object was extracted from	4304	Up to 38.2 months	Dapagliflozin (treatment, n=2152) vs Placebo (control, n=2152) [+2 further fields recorded on the object]
NCT03594110	EMPA-KIDNEY	not recorded on the page this object was extracted from	6609	From the day of randomisation to the day of the final follow-up visit in the interventional part of the trial, up to 1136 days.; From the day of randomization in the interventional part of the trial until the individual day of end of study in the non-interventional part of the trial. Up to 1869 days.	Empagliflozin 10 mg (treatment, n=3304) vs Placebo (control, n=3305) [+2 further fields recorded on the object]

Sources for this section (1)

inputs.trials

Not reported in this record

The items below were not written because the record does not hold what they would be composed from. They are named here so that an absence is not mistaken for an omission.

Items not reported, and why
Article area	Item not reported	Reason
Abstract	The Background sentence of the abstract	Background is argument -- why this question matters -- and no arrangement of the quantities this object holds yields it. It is emitted only from an authored field and there is no composition path for it here
Abstract	The Methods sentence of the abstract	None of the method facts this would be composed from -- databases searched, eligibility, pooling model, risk-of-bias tool, certainty approach -- is recorded on this object
Abstract	The Results sentence of the abstract -- no outcome on this object carries a pooled point estimate, so there is nothing to report and none is manufactured here	The reason each pool is declined is given in Results
Abstract	The Conclusions sentence of the abstract	A conclusion is argument -- what a reader should now believe -- and it is emitted only from an authored field. Composing one from the estimate would be this renderer telling the reader what to conclude, which no field supports
Keywords	The keyword list	A content gap; no keywords are recorded and inventing them would be indexing this review under terms nobody chose
Methods — search	A database search for primary trials, which was not carried out for this review; the included trials were identified from named registrations	No further reason is recorded.
Methods — how many studies at each stage	The k cascade	No further reason is recorded.
Methods — synthesis	The model/estimator sentence for multiple trial-declared outcomes: Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (eskd), and Renal or Cardiov \| Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD \| Interventional Part: Time to First Occurrence of Kidney Disease Progression or Cardiovascular Death ('as Adjudicated')	No pooled estimate was produced for this outcome, so no model was fitted and none is described
Methods — synthesis	The claim that records were screened in duplicate by two independent reviewers	No further reason is recorded.
Methods — synthesis	The claim that risk of bias was assessed with a named tool	No further reason is recorded.
Methods — synthesis	The claim that certainty of evidence was graded	No further reason is recorded.
Methods — synthesis	The claim that the review methods were prespecified before data collection	No further reason is recorded.
Risk of bias in the included results	The risk-of-bias assessment	No further reason is recorded.
Risk of bias in the included results	The risk-of-bias distribution	No further reason is recorded.
Certainty of the evidence	Certainty of the evidence, by outcome, with every rating step	No further reason is recorded.
Certainty of the evidence	The certainty assessment	No GRADE record is held, so the certainty column elsewhere on this page is an em dash rather than a guess
Discussion	The Discussion -- this is a content gap	The object records no interpretive text, and none is generated here: text written by the renderer would be an argument no field supports
Comparison with published syntheses	The comparison with published syntheses	No published synthesis is recorded for this topic, so no denominator can be given
Conclusions	The Conclusions -- this is a content gap	The object records no interpretive text, and none is generated here: text written by the renderer would be an argument no field supports
Data availability	The data availability statement	No further reason is recorded.
Software availability	The software and environment statement	No further reason is recorded.
Author contributions	The author-contributions statement	Who did what is a fact about people, and this object records none
Competing interests	The competing-interests declaration	F1000Research requires this section on every article, and requires explicit text where there is nothing to declare. It is a statement about the author and not about the evidence: no field of this object implies it and none is invented here
Grant information	The grant information	The venue requires each funder's name, the grant number where applicable, and the person the grant was assigned . None of that is derivable from a synthesis
Funding and conflicts of interest	The funding and conflict-of-interest statement -- a content gap	A submission requires it and this object does not carry it; it is not inferable from anything held here
Note on registration	The registration note	No further reason is recorded.
Registration	A registration statement: no prospective registration is recorded for this review, and whether one exists elsewhere has not been established	No further reason is recorded.
Extended data: statistical output, quoted verbatim	The verbatim model output	No analysis output is stored on this object, so nothing can be quoted and nothing is paraphrased in its place
Submission conformance	The submission conformance statement	No further reason is recorded.

Not held in this object. No statistical panel set was recoverable from the published page this object was extracted from.

Submission readiness: NOT READY

Canagliflozin, dapagliflozin and empagliflozin in kidney disease

Registration and administrative information (PROSPERO field set)

What this object claims to contain

Extracted values, and where each came from

References

Included studies

Regulatory documents

Methods and guidance

Sources

What was measured

Pooled result

Contributing trials

Endpoint definitions, read from the registry

Forest plot

Risk of bias

GOSH

Trial-sequential analysis

Meta-regression

Summary of findings

Reproducibility artifact

Other recorded qualifications

Paper

Title

Abstract

Introduction

Methods — search

Methods — eligibility criteria

Methods — outcomes sought at every registered rank

Results

Disagreements between sources

Limitations

Reporting guidelines

Note on registration

References

Figure legends

Figures

Trial characteristics

Not reported in this record

Page standard