Across 54 European CTIS-authorized Phase II and Phase III chronic kidney disease and kidney-failure trials, kidney function endpoints led the landscape: estimated glomerular filtration rate, kidney-function decline, or kidney-failure progression appeared in 29 trials (53.7%). Safety/tolerability followed in 23 trials (42.6%), dialysis or renal replacement therapy endpoints in 22 trials (40.7%), cardiovascular or mortality endpoints in 21 trials (38.9%), and albuminuria/proteinuria endpoints in 19 trials (35.2%).
The most frequently measured endpoint family was eGFR or kidney-function decline, used in 29 of 54 trials (53.7%). The next tier was safety/tolerability in 23 trials (42.6%), dialysis or renal replacement therapy (RRT) adequacy/progression in 22 trials (40.7%), cardiovascular events or mortality in 21 trials (38.9%), and albuminuria/proteinuria in 19 trials (35.2%).
European CKD development still centers on renal-function preservation, but the endpoint mix is not purely nephrology-driven: safety, dialysis/RRT, and cardiovascular outcomes together show that many CTIS submissions position CKD as a multi-system risk condition rather than a single biomarker disease.
eGFR/kidney-function endpoints were primary in 19 of 54 trials (35.2%) and secondary in 25 of 54 (46.3%). Cardiovascular/mortality endpoints were primary in 12 trials (22.2%) and secondary in 18 (33.3%), while exploratory/other endpoint reporting was rare, appearing in 1 trial (1.9%).
| Endpoint family | Primary | Secondary | Exploratory |
|---|---|---|---|
| eGFR / kidney function decline | 19 | 25 | 0 |
| Safety / tolerability / AEs | 11 | 17 | 0 |
| Dialysis / RRT adequacy or clearance | 9 | 21 | 0 |
| Cardiovascular events / mortality | 12 | 18 | 0 |
| Albuminuria / proteinuria | 8 | 14 | 0 |
| Quality of life / PROs | 0 | 11 | 0 |
The primary endpoint hierarchy is renal-function first, but secondary endpoints carry much of the clinical and operational complexity: dialysis/RRT appears secondary in 21 trials, cardiovascular outcomes in 18, safety in 17, and PRO/QoL only as secondary in 11.
Among 21 Phase II trials, primary endpoints most often measured eGFR/kidney function (8 trials; 38.1%), safety/tolerability (7; 33.3%), and albuminuria/proteinuria (6; 28.6%). Among 33 Phase III trials, eGFR/kidney function remained first (11; 33.3%), but cardiovascular/mortality endpoints were nearly as common as primary endpoints (10; 30.3%).
Phase II trials use shorter mechanistic or biomarker endpoints such as UACR, eGFR change, PK, and safety. Phase III trials retain eGFR but more often add hard cardiovascular or mortality outcomes, reflecting broader outcome claims and larger risk-reduction programs.
In general CKD trials (15 trials), eGFR/kidney-function endpoints appeared in 11 (73.3%). In kidney failure/dialysis/ESRD trials (14), dialysis/RRT endpoints appeared in 10 (71.4%) and safety in 9 (64.3%). In CKD with cardiovascular comorbidity (10), cardiovascular/mortality endpoints appeared in 7 (70.0%) and eGFR in 6 (60.0%).
| Disease cluster | n | eGFR | UACR/UPCR | Safety | Dialysis/RRT | CV/mortality |
|---|---|---|---|---|---|---|
| General CKD | 15 | 11 | 7 | 4 | 5 | 7 |
| Kidney failure / dialysis / ESRD | 14 | 5 | 2 | 9 | 10 | 4 |
| CKD with cardiovascular comorbidity | 10 | 6 | 3 | 2 | 5 | 7 |
| Renal anaemia / CKD anaemia | 5 | 0 | 0 | 1 | 1 | 1 |
| Diabetic CKD / T1D-T2D CKD | 3 | 2 | 2 | 2 | 0 | 1 |
Disease context strongly predicts endpoint choice: general CKD programs prioritize renal function, dialysis/ESRD programs prioritize dialysis adequacy and safety, while cardio-renal CKD trials use cardiovascular and mortality outcomes almost as often as kidney-function outcomes.
Small molecules appeared in 33 trials and were associated with eGFR/kidney-function endpoints in 21 (63.6%) and cardiovascular/mortality endpoints in 15 (45.5%). Peptide/protein/enzyme interventions appeared in 15 trials and used eGFR endpoints in 8 (53.3%), while “Other” modalities appeared in 6 trials and concentrated around dialysis/RRT endpoints in 5 (83.3%).
Small molecules are the main modality class supporting broad renal, albuminuria, dialysis, and cardiovascular endpoint strategies. Non-small-molecule groups are smaller and more specialized, often tied to dialysis, anaemia, immune, or procedural contexts.
Using first CTIS authorization year, the CKD/kidney-failure cohort included 31 trials in 2024, 12 in 2025, and 11 in 2026. eGFR/kidney-function was the leading primary endpoint family in 2024 (11/31; 35.5%) and 2025 (6/12; 50.0%), while albuminuria/proteinuria led the 2026 primary endpoint mix (3/11; 27.3%).
For CTIS/EU submission planning, eGFR remains the most stable anchor endpoint across years, but 2026 records show albuminuria/proteinuria gaining prominence as a primary endpoint in smaller, biomarker-led CKD programs.
Renal biomarker overlap was common: 18 of 54 trials (33.3%) measured both eGFR/kidney-function and albuminuria/proteinuria endpoints. Cardiovascular and kidney-function endpoints overlapped in 15 trials (27.8%), and dialysis/RRT plus safety endpoints overlapped in 13 (24.1%).
The strongest adjacent insight is that CKD endpoint packages often combine renal-function and albuminuria measures, while PROs remain supportive rather than claim-defining. Pediatric CKD trials are visible but still a minority of the CTIS endpoint cohort.
eGFR means estimated glomerular filtration rate. UACR means urine albumin-to-creatinine ratio. UPCR means urine protein-to-creatinine ratio. RRT means renal replacement therapy. AEs means adverse events. PROs means patient-reported outcomes. CV means cardiovascular. CTIS refers to the Clinical Trials Information System used for EU clinical trial submissions and authorizations.