Across 98 unique CTIS-authorized European nephrology Phase II and Phase III trial codes, kidney function endpoints led the field: eGFR/creatinine appeared in 72 trials (73.5%), followed by safety/tolerability in 69 trials (70.4%) and proteinuria/albuminuria in 46 trials (46.9%). Primary endpoints were most often kidney-function driven, while secondary endpoints carried the wider safety, cardiovascular, PK, biomarker, and patient-reported endpoint burden.
The top three endpoint families were kidney function/eGFR/creatinine in 72 of 98 trials (73.5%), safety/tolerability in 69 of 98 (70.4%), and proteinuria/albuminuria in 46 of 98 (46.9%). Cardiovascular, blood-pressure, or mortality endpoints appeared in 44 of 98 trials (44.9%), showing that nephrology endpoint packages often extend beyond renal-only measures.
The dominant nephrology endpoint stack is renal function plus safety: eGFR/creatinine and safety each appeared in more than 70% of trials, while proteinuria/albuminuria was used in nearly half of the dataset. For CTIS/EU submissions, these three endpoint families are the most common benchmark package.
Primary endpoints were concentrated around kidney function/eGFR/creatinine in 48 of 98 trials (49.0%), proteinuria/albuminuria in 27 (27.6%), and safety in 26 (26.5%). Secondary endpoints were broader: kidney function appeared in 62 trials (63.3%), safety in 58 (59.2%), and cardiovascular/BP/mortality in 40 (40.8%). Explicit exploratory or other endpoints were uncommon, with biomarker/histology/imaging analyses in 3 trials (3.1%).
| Endpoint family | Primary | Secondary | Exploratory / other |
|---|---|---|---|
| Kidney function / eGFR / creatinine | 49.0% | 63.3% | 1.0% |
| Safety / tolerability | 26.5% | 59.2% | 1.0% |
| Proteinuria / albuminuria | 27.6% | 33.7% | 0.0% |
| Cardiovascular / BP / mortality | 11.2% | 40.8% | 0.0% |
| Composite kidney outcome / kidney failure | 10.2% | 33.7% | 0.0% |
| Biomarkers / histology / imaging | 9.2% | 29.6% | 3.1% |
Primary endpoints answer renal efficacy questions, while secondary endpoints carry the evidence-expansion load: safety appeared as a secondary endpoint in 58 trials and cardiovascular/BP/mortality in 40 trials. Exploratory endpoint labelling was rare at 3 of 98 trials, mainly biomarker-oriented.
The dataset included 45 Phase II trials, 50 Phase III trials, and 3 combined Phase II/III trials. Phase II trials emphasized safety/tolerability in 36 of 45 trials (80.0%) and biomarkers/histology/imaging in 22 of 45 (48.9%). Phase III trials shifted toward confirmatory renal and outcome endpoints: eGFR/creatinine in 37 of 50 (74.0%), cardiovascular/BP/mortality in 28 of 50 (56.0%), and composite kidney outcome/kidney failure in 23 of 50 (46.0%).
Phase II endpoint design is more exploratory and mechanism-heavy, with biomarkers/histology/imaging in 48.9% of trials. Phase III shifts toward registrational outcome structure, with composite kidney failure outcomes in 46.0% and cardiovascular/BP/mortality endpoints in 56.0%.
The largest disease group was glomerular/immune kidney disease with 30 of 98 trials (30.6%), followed by chronic kidney disease/proteinuria with 22 trials (22.4%) and kidney transplant/rejection with 15 trials (15.3%). IgA nephropathy/IgAN and kidney transplantation/graft-function subgroups were the largest recurring sub-disease clusters, each appearing in 14 of 98 trials (14.3%).
| Disease group | Trials | Most frequent endpoint pattern |
|---|---|---|
| Glomerular / immune kidney disease | 30 | Safety 25 / 30 (83.3%); proteinuria 24 / 30 (80.0%); eGFR 23 / 30 (76.7%) |
| CKD / proteinuria | 22 | eGFR 19 / 22 (86.4%); CV/BP/mortality 15 / 22 (68.2%); proteinuria 15 / 22 (68.2%) |
| Kidney transplant / rejection | 15 | Composite kidney outcome 13 / 15 (86.7%); eGFR 12 / 15 (80.0%); biomarkers 11 / 15 (73.3%) |
| Rare genetic / tubulopathy | 12 | eGFR 9 / 12 (75.0%); safety 8 / 12 (66.7%); PK and biomarkers each 5 / 12 (41.7%) |
| Dialysis / end-stage kidney disease | 9 | Safety 7 / 9 (77.8%); PK, dialysis/RRT, and composite outcomes each 4 / 9 (44.4%) |
| Acute kidney injury | 6 | eGFR/renal recovery 6 / 6 (100.0%); dialysis/RRT and CV/BP/mortality each 4 / 6 (66.7%) |
Disease drives endpoint choice strongly. Glomerular and immune kidney trials combine proteinuria, eGFR, and remission; transplant/rejection trials add composite graft outcomes and biomarkers; AKI trials are almost entirely renal-recovery and organ-support oriented, with eGFR/renal recovery in 100.0% of AKI trials.
Four modality groups had enough trials for comparison: small molecules in 59 of 98 trials (60.2%), peptide/protein/enzyme therapies in 14 (14.3%), monoclonal antibodies in 11 (11.2%), and cell therapies in 5 (5.1%). Small molecules were most renal-function heavy, monoclonal antibodies added remission/response endpoints, and cell therapies carried the strongest biomarker/histology signal.
| Modality | Trials | Endpoint signature |
|---|---|---|
| Small molecule | 59 | eGFR 46 / 59 (78.0%); safety 41 / 59 (69.5%); proteinuria 31 / 59 (52.5%) |
| Peptide / protein / enzyme | 14 | eGFR 9 / 14 (64.3%); safety 8 / 14 (57.1%); CV/BP and proteinuria each 7 / 14 (50.0%) |
| Monoclonal antibody | 11 | Safety and eGFR each 8 / 11 (72.7%); remission/response and proteinuria each 6 / 11 (54.5%) |
| Cell therapy | 5 | Biomarkers, composite kidney outcomes, and safety each 4 / 5 (80.0%) |
Small molecules dominate the nephrology Phase II–III landscape and use the broadest renal-function endpoint base. Monoclonal antibodies show a disease-control profile with remission/response in 54.5%, while cell therapies require more tissue, immune, or graft-related evidence, with biomarker/histology endpoints in 80.0%.
All 98 trials had CTIS initial submission and first authorization date fields. By first CTIS authorization year, 55 trials were authorized in 2024 (56.1%), 31 in 2025 (31.6%), and 12 in 2026 (12.2%). The endpoint families most relevant for CTIS/EU submission benchmarking were eGFR/creatinine in 72 trials, safety/tolerability in 69, and proteinuria/albuminuria in 46.
For EU submissions, the clearest CTIS benchmark is not a single endpoint but a recurring package: renal function, safety, and proteinuria. Together, these appear in 72, 69, and 46 of 98 trials respectively, making them the most defensible comparator set for protocol and endpoint benchmarking.
Three adjacent trial-design questions can be answered numerically from the same 98-trial dataset: which endpoint families are most CTIS-ready, which disease groups need disease-specific response measures, and which modalities require biomarker-heavy endpoint packages.
eGFR/creatinine in 72 / 98 trials, safety/tolerability in 69 / 98, and proteinuria/albuminuria in 46 / 98.
Glomerular / immune kidney disease: remission/response/relapse appeared in 18 / 30 trials (60.0%).
Cell therapy: biomarkers/histology/imaging appeared in 4 / 5 trials (80.0%), compared with 30 / 98 trials (30.6%) overall.
eGFR means estimated glomerular filtration rate. UACR means urine albumin-to-creatinine ratio. UPCR means urine protein-to-creatinine ratio. PK/PD means pharmacokinetics/pharmacodynamics. RRT means renal replacement therapy. CTIS means Clinical Trials Information System. Endpoint categories are trial-level and multi-label, so one trial can contribute to more than one endpoint family.