Time to Rethink the Current Paradigm for Assessing Kidney Function in Drug Development and Beyond

Area of Science:

• Nephrology
• Clinical Pharmacology
• Biomarker Development

Background:

• Chronic kidney disease (CKD) affects approximately 9.1% of the global adult population.
• Serum creatinine is a primary biomarker for kidney function, used in equations like Cockcroft-Gault and Schwartz.
• Traditional equations may not align with standardized creatinine assays, necessitating updated methods.

Purpose of the Study:

• To highlight advancements in kidney function assessment for chronic kidney disease (CKD) patients.
• To advocate for the adoption of newer, more accurate equations for estimating glomerular filtration rate (GFR).
• To call for a re-evaluation of kidney function assessment paradigms in clinical pharmacology for drug dosing.

Main Methods:

• Review of established and emerging equations for estimating GFR, including Cockcroft-Gault, Schwartz, and CKD-EPI.
• Discussion of standardized serum creatinine bioanalytical methodology and its impact on equation selection.
• Consideration of cystatin C as a biomarker alongside creatinine for improved GFR estimation.

Main Results:

• Introduction of more accurate GFR estimating equations like CKD-EPI and updated Schwartz equations.
• Validation of equations using standardized creatinine values and cystatin C.
• Development of a race-free CKD-EPI equation.

Conclusions:

• Clinical practice guidelines recommend shifting to newer GFR estimating equations for CKD diagnosis and management.
• Albuminuria is recommended alongside GFR for comprehensive CKD assessment.
• Further research is needed to evaluate the utility of these advancements in drug dose adjustments for CKD patients.