Clinical trials landscape¶
TL;DR — The CKD trial landscape has moved from albuminuria and short eGFR change toward sustained decline, kidney failure and cardiovascular death, but surrogate endpoints remain common in small or rare-disease studies. DAPA-CKD, EMPA-KIDNEY, CREDENCE, FIDELIO-DKD and FLOW provide completed outcome anchors (Heerspink 2020, PMID 32970396) (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190) (Perkovic 2019, PMID 30990260) (Bakris 2020, PMID 33264825) (Perkovic 2024, PMID 38785209). Live ClinicalTrials.gov queries on 2026-09-02 show current work on potassium-enabled RAS optimization, advanced-CKD SGLT2 inhibition, screening implementation, paediatric finerenone and cognition. The non-diabetic finerenone question has been answered rather than remaining open: FIND-CKD (NCT05047263) is complete and published (Heerspink 2026, PMID 42246672), as are CONFIDENCE (NCT05254002) and FINE-ONE (NCT05901831) (Agarwal 2025, PMID 40470996) (Heerspink 2026, PMID 41780000). Registry status is operational metadata, not proof of efficacy.
Completed outcome platform¶
DAPA-CKD and EMPA-KIDNEY broadened SGLT2 evidence beyond diabetes (Heerspink 2020, PMID 32970396) (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190). FIDELIO/FIGARO and FLOW were diabetic-CKD programs (Agarwal 2022, PMID 35023547) (Perkovic 2024, PMID 38785209); both classes have since reported beyond that population — finerenone in FIND-CKD and its glomerular-disease subgroup, and semaglutide in a pooled SELECT/FLOW/SOUL analysis that includes participants without diabetes (Heerspink 2026, PMID 42246672) (Neuen 2026, PMID 42246414) (Mann 2026, PMID 42567173).
Cause-specific platform¶
NefIgArd and PROTECT represent the shift to targeted IgA-nephropathy trials (Lafayette 2023, PMID 37591292) (Rovin 2023, PMID 37931634). FSGS shows why proteinuria and GFR endpoints can diverge (Rheault 2023, PMID 37921461).
Implementation trials¶
Screening and app-supported pathways test whether evidence reaches undiagnosed populations; their endpoints should include treatment initiation and equity, not testing yield alone.
Combination trials¶
The gap has narrowed but not closed. CONFIDENCE (NCT05254002) randomized 779 people with type 2 diabetes and CKD 1:1:1 to finerenone, empagliflozin or both, and combination therapy lowered uACR 29% more than finerenone alone and 32% more than empagliflozin alone at day 180 (Agarwal 2025, PMID 40470996). It is a phase 2 albuminuria trial covering two of four classes, so the missing design remains a strategy or factorial randomization across RAS, SGLT2, MRA and GLP-1 layers powered for kidney failure and death; current modelling cannot identify sequence (Neuen 2024, PMID 37952217).
Registry cautions¶
Recruiting status changes; eligibility and outcome definitions require record-level review. This page records a dated snapshot only.
Border¶
Dialysis-device and transplant-immunology pipelines are excluded unless they alter the decision, timing or patient-important outcome.
ClinicalTrials.gov snapshot¶
Every identifier and status below was returned by the ClinicalTrials.gov v2 API and re-verified during the independent audit on 2026-09-02.
| NCT ID | Study | Status at query | CKD question |
|---|---|---|---|
| NCT03036150 | DAPA-CKD | COMPLETED | Dapagliflozin kidney/CV outcomes |
| NCT03594110 | EMPA-KIDNEY | COMPLETED | Empagliflozin across broad CKD |
| NCT02065791 | CREDENCE | COMPLETED | Canagliflozin in diabetic nephropathy |
| NCT02540993 | FIDELIO-DKD | COMPLETED | Finerenone, kidney-primary diabetic CKD |
| NCT02545049 | FIGARO-DKD | COMPLETED | Finerenone, cardiovascular-primary diabetic CKD |
| NCT03819153 | FLOW | COMPLETED | Semaglutide kidney outcomes in T2D CKD |
| NCT03643965 | NefIgArd | COMPLETED | Targeted-release budesonide in IgA nephropathy |
| NCT03762850 | PROTECT | ACTIVE_NOT_RECRUITING | Sparsentan in IgA nephropathy |
| NCT03710291 | VALOR-CKD | TERMINATED | Veverimer and CKD progression |
| NCT05047263 | FIND-CKD | COMPLETED | Finerenone in non-diabetic CKD — primary results published (PMID 42246672); glomerular-disease subgroup (PMID 42246414) |
| NCT05254002 | CONFIDENCE | COMPLETED | Finerenone, empagliflozin or both; 180-day albuminuria (PMID 40470996) |
| NCT05901831 | FINE-ONE | COMPLETED | Finerenone in type 1 diabetes and CKD; 6-month albuminuria (PMID 41780000) |
| NCT05196035 | Finerenone paediatric CKD study | ACTIVE_NOT_RECRUITING | Proteinuric CKD in children |
| NCT06256991 | Potassium correction for RAS optimization | RECRUITING | Hyperkalaemia as a treatment barrier |
| NCT07027774 | HERO-aCKD | NOT_YET_RECRUITING | SGLT2 inhibition in advanced non-dialysis CKD |
| NCT06330480 | Check@Home | ENROLLING_BY_INVITATION | Population screening for CKD and atrial fibrillation |
| NCT06906640 | IRIS-CKD | RECRUITING | CKD screening/management implementation in diabetes |
| NCT05970341 | Kidney Health: Eat Well, Live Well | RECRUITING | Dietary implementation |
| NCT04975464 | BRINK Memory Study 2.0 | ACTIVE_NOT_RECRUITING | Cognitive phenotype in kidney disease |
The pipeline has moved to combination-on-background-SGLT2¶
The three largest general-CKD phase 3 programmes below share one design feature: SGLT2 inhibition is in both arms, and the question is what to add. This is a structural change from the 2019–2024 generation, in which SGLT2 inhibitors were the intervention. Smaller programmes still include SGLT2-versus-placebo and non-SGLT2 designs. All records below were retrieved live from the ClinicalTrials.gov API on 2026-09-02.
| Trial (NCT) | Intervention on background | n | Status | Primary outcome | Primary completion |
|---|---|---|---|---|---|
| EASi-KIDNEY (NCT06531824) | Aldosterone synthase inhibitor BI 690517 (vicadrostat) + empagliflozin vs placebo + empagliflozin | 11,000 | Recruiting | Time to first kidney disease progression, heart-failure hospitalisation, or cardiovascular death | 2028-08-30 |
| Baxdrostat + dapagliflozin (NCT06742723) | Aldosterone synthase inhibitor baxdrostat + dapagliflozin vs dapagliflozin | 5,000 | Recruiting | ≥50% sustained eGFR decline, kidney failure, heart-failure events, or CV death | 2029-12-18 |
| ZENITH High Proteinuria (NCT06087835) | Endothelin A antagonist zibotentan + dapagliflozin vs dapagliflozin | 1,835 | Active, not recruiting | Change in eGFR from baseline | 2027-02-18 |
| CKD adaptive platform trial (NCT06058585) | Finerenone vs placebo, platform architecture | 1,000 | Recruiting | eGFR slope | 2028-08-30 |
| Sotagliflozin in type 1 diabetes DKD (NCT06217302) | Sotagliflozin vs placebo | 150 | Recruiting | eGFR after wash-out following treatment period | 2028-12 |
Two aldosterone-synthase inhibitor outcome trials totalling 16,000 participants are the largest single bet in nephrology's current pipeline, and both are explicitly built on top of an SGLT2 inhibitor. They test a hypothesis the finerenone trials could not: whether suppressing aldosterone synthesis rather than blocking its receptor delivers the same or greater kidney protection with a different hyperkalaemia profile. EASi-KIDNEY at n = 11,000 is powered for a hard composite; the baxdrostat trial's inclusion of heart-failure events in the primary composite makes the two results non-interchangeable.
The zibotentan phase 3 is worth flagging for its endpoint choice: change in eGFR from baseline, not a clinical composite (NCT06087835). Given that the ALIGN experience in IgA nephropathy showed the same drug class producing a significant on-treatment eGFR difference and a non-significant one after off-treatment follow-up (PMID 42242268), the specification of the eGFR endpoint will determine what this trial can claim.
Adaptive platform architecture arrives in nephrology¶
The CKD adaptive platform trial (NCT06058585), sponsored by The George Institute, runs finerenone against placebo within a platform designed to add and drop arms, with eGFR slope as the primary outcome and 1,000 participants. Platform designs have transformed evidence generation in oncology and critical care and have been essentially absent from nephrology, where each drug class has required its own multi-thousand-participant standalone trial. Whether an eGFR-slope-primary platform is accepted by regulators for approval, rather than only for prioritisation, is the open question that determines its impact — and it depends directly on the surrogate-validity literature discussed in definition, staging and measurement.
Questions the pipeline is not asking¶
Three gaps are visible from the register itself.
- No head-to-head comparisons of the established classes. CONFIDENCE (PMID 40470996) randomized finerenone and empagliflozin against each of them alone on 180-day albuminuria; nothing in the current phase 3 landscape compares an SGLT2 inhibitor against a GLP-1 receptor agonist or a non-steroidal MRA on hard kidney endpoints.
- Kidney transplant evidence remains surrogate-based. A 208-person, 12-month randomized trial in chronic allograft dysfunction found no eGFR benefit from dapagliflozin, although proteinuria, blood pressure and weight fell (David-Neto 2026, PMID 42102257). DEAK is recruiting 330 de novo transplant recipients for a three-year chronic-eGFR-slope primary endpoint, with ten-year registry follow-up for cardiovascular events and graft and patient survival (Kongerud 2026, PMID 42315275; NCT05788276). Neither study is powered for graft failure, cardiovascular events or mortality.
- Non-drug interventions are almost absent at scale. Against 16,000 participants in two aldosterone-synthase trials, the largest recruiting non-pharmacological CKD trials are an order of magnitude smaller, despite intradialytic exercise producing one of the largest functional effect sizes in the literature (PMID 38320198).
Mechanistic trials that explain the outcome trials¶
Smaller trials now routinely carry the mechanistic load. The renal mode-of-action study of semaglutide in type 2 diabetes and CKD (NCT04865770, n = 106, completed 2024-11-21) used BOLD MRI change in cortical kidney oxygenation (R2*) as its primary outcome — an attempt to test the hypoxia mechanism (see pathophysiology and progression) directly rather than inferring it from eGFR. Pairing an 11,000-patient outcome trial with a 106-patient imaging study is the current template for connecting a clinical effect to a mechanism.
The glomerular-disease pipeline is now larger than the general-CKD pipeline¶
Where the general-CKD trials (above) test combinations on background SGLT2 inhibition, the glomerular-disease pipeline is testing mechanistically distinct single agents, overwhelmingly against a proteinuria primary endpoint. All records retrieved live from the ClinicalTrials.gov API on 2026-09-02.
| Trial (NCT) | Target / agent | n | Condition | Primary endpoint | Primary completion |
|---|---|---|---|---|---|
| NCT06935357 | Felzartamab (anti-CD38) | 454 | IgA nephropathy | % change in UPCR from baseline | 2027-05-31 |
| NCT07014826 | HRS-5965 | 378 | Primary IgA nephropathy | Ratio of 24-h UPCR to baseline | 2027-10 |
| NCT07390123 | HSK39297 | 370 | Primary IgA nephropathy | Ratio to baseline in 24-h UPCR at 36 weeks | 2027-12 |
| NCT06819826 | SC0062 | 360 | IgA nephropathy with proteinuria | Change in 24-h UPCR at 36 weeks | 2026-12-31 |
| NCT06963827 | Mezagitamab | 347 | IgA nephropathy | Change in proteinuria at week 36 | 2028-09-07 |
| NCT06858319 | Zigakibart, open-label extension | 220 | IgA nephropathy | Adverse events | 2031-06-25 |
| NCT07220083 | BI 764198 | 286 | Focal segmental glomerulosclerosis | Relative change in 24-h UPCR at week 104 | 2028-12-27 |
| NCT05183646 | DMX-200 on background ARB | 286 | FSGS | Urine protein/creatinine ratio | 2029-12 |
| NCT07213960 | APL2 (pegcetacoplan), sequential phase 2/3 | 270 | FSGS | Change in log-transformed UPCR | 2029-10 |
| NCT04939935 (IMPEDE-PKD) | Metformin XR | 1,174 | ADPKD | Change in eGFR | 2030-12 |
| NCT07280585 (STOP-PKD) | Dapagliflozin | 420 | ADPKD | Chronic eGFR slope | 2030-05-15 |
| NCT05373264 | Hydrochlorothiazide | 300 | ADPKD | Change in kidney function decline | 2030-07 |
Three observations follow from the register itself.
Proteinuria is carrying almost the entire IgA nephropathy pipeline. Every recruiting phase 3 IgA nephropathy trial listed above has UPCR as its primary endpoint. Given that iptacopan's proteinuria signal did convert to an eGFR slope difference and a kidney-failure hazard ratio of 0.57 (PMID 41910396), while the same class of endpoint in FSGS did not convert (PMID 37921461), the field is placing a large collective bet that the IgA nephropathy translation generalises to other mechanisms within the same disease.
Paediatric extension is now routine and early. Iptacopan (NCT06994845, n=31), ravulizumab (NCT07024563, n=36) and atrasentan (NCT07498335, n=28) all have dedicated paediatric IgA nephropathy studies recruiting — a marked change from a field in which children historically received adult drugs years later without dedicated data.
ADPKD has become a repurposing field. Its three largest recruiting trials test metformin, dapagliflozin and hydrochlorothiazide — none developed for cystic disease — with eGFR-based primary endpoints and completion dates in 2030. After tolvaptan, the pipeline is not novel-mechanism but existing-drug.
Decision and interpretation matrix¶
| Dimension | Question | Guardrail |
|---|---|---|
| Diagnostic axis | Cause + G category + A category | Avoid treating eGFR as the diagnosis |
| Time axis | Chronicity and trajectory | Separate acute change from persistent disease |
| Risk axis | Kidney failure + cardiovascular events + death | Show competing events |
| Treatment axis | Eligibility, absolute benefit, harm, burden | Do not rank drugs by relative effect alone |
| Measurement axis | Assay, equation, repeatability | State what was actually measured |
| Equity axis | Testing, referral, access, affordability | Audit downstream care, not labels only |
| Patient axis | Symptoms, function, life participation | Include outcomes patients prioritize |
| Evidence axis | RCT, cohort, model, guideline | Do not collapse designs |
Evidence ledger¶
This ledger makes the page’s evidentiary mix inspectable. It does not imply that every source answers every question.
| PMID | Record used | Role and boundary |
|---|---|---|
| 32970396 | Dapagliflozin in Patients with Chronic Kidney Disease. (Heerspink 2020, PMID 32970396) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 36331190 | Empagliflozin in Patients with Chronic Kidney Disease. (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 30990260 | Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. (Perkovic 2019, PMID 30990260) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 33264825 | Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. (Bakris 2020, PMID 33264825) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 38785209 | Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. (Perkovic 2024, PMID 38785209) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 35023547 | Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. (Agarwal 2022, PMID 35023547) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 37591292 | Targeted-release budesonide in primary IgA nephropathy: NefIgArd 2-year results. (Lafayette 2023, PMID 37591292) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 37931634 | Sparsentan versus irbesartan in IgA nephropathy: PROTECT 2-year results. (Rovin 2023, PMID 37931634) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 37921461 | Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. (Rheault 2023, PMID 37921461) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 37952217 | Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. (Neuen 2024, PMID 37952217) | Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up. |
| 38490803 | KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. (KDIGO CKD Work Group 2024, PMID 38490803) | Guideline or commentary; recommendation evidence depends on its review. |
| 38519239 | Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. (Levin 2024, PMID 38519239) | Guideline or commentary; recommendation evidence depends on its review. |
| 11565518 | Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. (Brenner 2001, PMID 11565518) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 11565517 | Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. (Lewis 2001, PMID 11565517) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 11565519 | The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. (Parving 2001, PMID 11565519) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 18707986 | Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. (Mann 2008, PMID 18707986) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 24206457 | Combined angiotensin inhibition for the treatment of diabetic nephropathy. (Fried 2013, PMID 24206457) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 34619108 | Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. (Heerspink 2021, PMID 34619108) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 38061371 | Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the EMPA-KIDNEY trial. (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 38914124 | Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. (Mann 2024, PMID 38914124) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 30697905 | SGLT2 inhibitors and cardiovascular, renal and safety outcomes in T2D and CKD: meta-analysis. (Toyama 2019, PMID 30697905) | Synthesis; heterogeneity and included-study definitions constrain transport. |
| 36316605 | SGLT2 inhibitors in advanced CKD: systematic review and meta-analysis. (Cao 2023, PMID 36316605) | Synthesis; heterogeneity and included-study definitions constrain transport. |
| 36927680 | Finerenone outcomes in stage 4 CKD and type 2 diabetes. (Sarafidis 2023, PMID 36927680) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 36272755 | Executive summary of KDIGO 2022 Diabetes Management in CKD guideline. (Rossing 2022, PMID 36272755) | Guideline or commentary; recommendation evidence depends on its review. |
| 33637203 | Executive summary of KDIGO 2021 Blood Pressure in CKD guideline. (Cheung 2021, PMID 33637203) | Guideline or commentary; recommendation evidence depends on its review. |
| 31533906 | Patiromer to enable spironolactone in resistant hypertension and CKD: AMBER. (Agarwal 2019, PMID 31533906) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 40542996 | Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. (Huang 2025, PMID 40542996) | Synthesis; heterogeneity and included-study definitions constrain transport. |
| 40470996 | Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes (CONFIDENCE). (Agarwal 2025, PMID 40470996) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 42246672 | Finerenone in Persons with Chronic Kidney Disease without Diabetes (FIND-CKD). (Heerspink 2026, PMID 42246672) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 41780000 | Finerenone in Type 1 Diabetes and Chronic Kidney Disease (FINE-ONE). (Heerspink 2026, PMID 41780000) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 42246414 | Finerenone in CKD due to glomerular diseases: prespecified FIND-CKD subgroup analysis. (Neuen 2026, PMID 42246414) | Intervention study; eligibility, comparator, endpoint and follow-up bound inference. |
| 42567173 | Semaglutide kidney outcomes pooled across SELECT, FLOW and SOUL. (Mann 2026, PMID 42567173) | Synthesis; heterogeneity and included-study definitions constrain transport. |
What can and cannot be concluded¶
- Risk associations do not by themselves establish that changing the marker changes risk.
- A relative effect must be paired with baseline risk, follow-up and the exact endpoint.
- Albuminuria, acute eGFR change, chronic eGFR slope and kidney failure are not interchangeable.
- Subgroup consistency is not evidence that every subgroup had adequate power.
- Guideline recommendations combine evidence with values, feasibility, cost and service capacity.
- Older adults require competing-mortality and treatment-burden framing.
- Dialysis and transplantation comparisons are vulnerable to eligibility and immortal-time bias.
- Modelled lifetime benefit is not a randomized observed benefit.
- A biochemical response without a patient-important outcome remains a surrogate result.
- This page is research synthesis, not individualized medical advice.
Research-design checklist¶
- Define CKD cause, G category, A category and chronicity at baseline.
- Report the creatinine or cystatin C equation and laboratory calibration.
- Prespecify acute and chronic eGFR slopes when haemodynamic effects are expected.
- Keep sustained GFR decline, kidney failure and replacement therapy separable.
- Report absolute event risks, follow-up and confidence intervals with relative effects.
- Treat death as a competing event where it can preclude kidney failure.
- Measure hyperkalaemia, acute kidney injury and treatment discontinuation consistently.
- Include symptoms, function, life participation and treatment burden.
- Describe background RAS, SGLT2, MRA and GLP-1 therapy explicitly.
- Prespecify albuminuria and cause strata without over-reading underpowered interactions.
- Record screening, prescribing, persistence and monitoring as separate implementation steps.
- Report representation, access and affordability variables needed for equity analysis.
Open questions¶
- What trial design can test combination and sequence across four classes and still be affordable and powered for kidney failure? CONFIDENCE randomized two classes on albuminuria over 180 days (Agarwal 2025, PMID 40470996); the lifetime four-class estimate is actuarial (Neuen 2024, PMID 37952217). → OQ-1
- Should implementation and screening trials be required to report treatment initiation and equity, rather than testing yield alone?
- Which surrogate endpoints have been validated for which disease and drug class? Chronic eGFR slope performed well for SGLT2 inhibitors but proteinuria response failed in FSGS (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371) (Rheault 2023, PMID 37921461). → OQ-19
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How should registry snapshots be maintained so that a “recruiting” or “no published result” claim does not silently go stale? This audit found FIND-CKD, CONFIDENCE and FINE-ONE published after the page was drafted.
-
Will aldosterone synthase inhibition improve on mineralocorticoid receptor blockade? Two trials totalling 16,000 participants on background SGLT2 inhibition (NCT06531824, NCT06742723) test this, with non-interchangeable primary composites.
- Will regulators accept eGFR slope from an adaptive platform trial (NCT06058585) as a basis for approval, or only for prioritisation?
- Why is no phase 3 trial comparing the established kidney-protective classes head to head on hard endpoints, when combination sequencing is the daily clinical question?
-
Why are kidney transplant recipients still absent from outcome trials when physiology studies show the expected drug effects (PMID 41385300)?
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Does the iptacopan proteinuria-to-outcome translation in IgA nephropathy generalise to the other mechanisms now in phase 3 with UPCR primary endpoints (NCT06935357, NCT07014826, NCT07390123, NCT06819826, NCT06963827)?
- Will the ADPKD repurposing trials (metformin NCT04939935, dapagliflozin NCT07280585, hydrochlorothiazide NCT05373264) succeed where novel-mechanism development stalled after tolvaptan?
- Given the number of agents entering IgA nephropathy simultaneously, what trial design would establish sequencing or combination on clinical outcomes? A 65-person randomized crossover study has compared an endothelin antagonist, an SGLT2 inhibitor and their combination on four-week proteinuria (Chen 2026, PMID 41949916), but the phase 3 programmes remain placebo-controlled and non-comparative.
Related pages¶
- diabetic kidney disease — complementary CKD evidence and decision context.
- glp1 and emerging therapy — complementary CKD evidence and decision context.
- mineralocorticoid receptor antagonists — complementary CKD evidence and decision context.
- ras blockade and blood pressure — complementary CKD evidence and decision context.
- sglt2 inhibitors — complementary CKD evidence and decision context.
- inherited and glomerular disease — complementary CKD evidence and decision context.
References¶
- Heerspink et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. PMID 32970396
- EMPA-KIDNEY Collaborative Group et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. PMID 36331190
- Perkovic et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. PMID 30990260
- Bakris et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383(23):2219-2229. PMID 33264825
- Perkovic et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. PMID 38785209
- Agarwal et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484. PMID 35023547
- Lafayette et al. Targeted-release budesonide in primary IgA nephropathy: NefIgArd 2-year results. Lancet. 2023;402(10405):859-870. PMID 37591292
- Rovin et al. Sparsentan versus irbesartan in IgA nephropathy: PROTECT 2-year results. Lancet. 2023;402(10417):2077-2090. PMID 37931634
- Rheault et al. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023;389(26):2436-2445. PMID 37921461
- Neuen et al. Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. Circulation. 2024;149(6):450-462. PMID 37952217
- KDIGO CKD Work Group et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. PMID 38490803
- Levin et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684-701. PMID 38519239
- Brenner et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. PMID 11565518
- Lewis et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851-860. PMID 11565517
- Parving et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870-878. PMID 11565519
- Mann et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. Lancet. 2008;372(9638):547-553. PMID 18707986
- Fried et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892-1903. PMID 24206457
- Heerspink et al. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9(11):743-754. PMID 34619108
- EMPA-KIDNEY Collaborative Group et al. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol. 2024;12(1):39-50. PMID 38061371
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