The renal function trajectory in clinical trial design: challenges and opportunities

Area of Science:

• Nephrology
• Clinical Pharmacology

Background:

• Assessing renal function changes in drug trials is complex.
• An initial decrease in estimated glomerular filtration rate (eGFR) is common when starting new medications.
• Surrogate endpoints in renal drug development require careful interpretation.

Purpose of the Study:

• To address the challenges of using renal function changes as surrogate endpoints in new drug trials.
• To discuss strategies for optimizing the use of novel renoprotective therapies.
• To identify patient populations most likely to benefit from interventions that slow kidney function decline.

Main Methods:

• Commentary and analysis of existing literature on renal function endpoints.
• Discussion of factors complicating the interpretation of eGFR changes.
• Review of criteria for patient selection in clinical trials for kidney disease.

Main Results:

• The interpretation of renal function changes over time is complicated by various factors.
• Initial decreases in eGFR are expected and do not necessarily indicate treatment failure.
• Effective use of new drugs requires targeting patients with a high likelihood of rapid kidney function loss.

Conclusions:

• Careful consideration of confounding factors is essential when evaluating renal function in drug trials.
• New drugs that slow kidney function decline should be reserved for high-risk patients.
• Optimizing drug benefits necessitates precise patient selection based on predicted disease progression.