Albuminuria is a sensitive marker of kidney disease progression in the early stages of chronic kidney disease (CKD) and appears to be a cause of CKD progression in some diseases. Our initial publication in the general CKD population did not provide sufficient evidence to establish its validity in all settings. Indeed, in a subsequent publication on IgA nephropathy, we were able to demonstrate that there is a strong association between treatment effects on change in albuminuria and treatment effects on the clinical endpoint. In a subsequent larger meta-analysis in the general CKD population, we were able to provide data that support a role for change in albuminuria as a surrogate endpoint for CKD progression, particularly in patients with higher baseline albuminuria and where there are large treatment effects.
Overview
Proteinuria has been established as a marker of kidney damage in experimental studies, and clinicians consider an early reduction in albuminuria as indicative of a favorable response to treatment. Albuminuria is a sensitive marker of kidney disease progression in the early stages of CKD and appears to be a cause of CKD progression in some disease. Our initial publication in the general CKD population did not provide sufficient evidence to establish its validity in all settings. Indeed, in a subsequent publication on IgA nephropathy, we were able to demonstrate that there is a strong association between treatment effects on change in albuminuria and treatment effects on the clinical endpoint. In a subsequent larger meta-analysis in the general CKD population, we were able to provide data that support a role for change in albuminuria as a surrogate endpoint for CKD progression, particularly in patients with higher baseline albuminuria and where there are large treatment effects.
A decline in glomerular filtration rate (GFR) must occur prior to the development of kidney failure and is highly predictive of the development of kidney failure, and many have therefore asked whether smaller reductions in eGFR could be used in place of the doubling of serum creatinine or kidney failure as endpoints in RCT’s for treatments aimed at preventing progression of kidney disease. The use of alternative endpoints based on smaller eGFR reductions could reduce the length of trials, thereby increasing the feasibility of conducting RCTs and speeding the development of new treatments.
A technical report on timing strategies for estimating the acute GFR effect is available for your reference: