Kidney function assessment and endpoint ascertainment in clinical trials

Area of Science:

• Nephrology
• Clinical Trials Methodology
• Cardiorenal Medicine

Background:

• Inconsistent reporting of kidney function and outcomes in clinical trials complicates result comparison.
• Standardized definitions for kidney endpoints are crucial for evaluating interventions across studies.

Purpose of the Study:

• To systematically review kidney function ascertainment, outcome reporting, and endpoint definitions in large trials for type 2 diabetes mellitus (T2DM), kidney disease, and heart failure (HF).

Main Methods:

• Systematic review of large (>1000 participants) T2DM, HF, and kidney disease trials published between January 2014 and January 2021.
• Data abstraction from trial publications and supplementary appendices for baseline kidney variables, outcome reporting, and endpoint definitions.
• Inclusion of 33 trials (16 T2DM, 10 HF, 7 kidney disease).

Main Results:

• Low reporting of baseline kidney function and albuminuria, particularly in HF trials.
• Significant variability in definitions for chronic kidney disease, eGFR decline, end-stage kidney disease, kidney death, and composite endpoints.
• Underrepresentation of patients with advanced kidney disease (eGFR <30 mL/min/1.73 m2) across included trials.

Conclusions:

• Heterogeneity in reporting kidney function and outcomes necessitates a consensus solution for future clinical trials.
• Standardizing definitions, improving baseline patient profiling, and increasing accrual of patients with advanced kidney disease are vital for enhanced trial comparability.