Length of proteinuria remission helps predict ESKD progression in IgA nephropathy
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Including the duration of proteinuria remission may better predict which patients with IgA nephropathy will progress to end-stage kidney disease vs. considering proteinuria reduction alone, according to study findings.
“There are significant challenges unique to IgA nephropathy that have substantially hampered the design of clinical trials capable of evaluating new therapies, the most important of which is the considerable variation in the time lag between diagnosis and the development of a hard clinical endpoint such as ESKD, or a 50% reduction in kidney function,” Mark Canney, PhD, of the University of British Columbia the Ottawa Hospital Research Institute, and colleagues wrote. “As a result, clinical trials require long follow-up over many years to observe a treatment effect on cost and complexity of clinical trials in IgA nephropathy, thereby severely limiting the evaluation of new therapies.”
Due to this, the researchers contended it was important to investigate “earlier surrogate measures” to predict outcomes.
For the study, 1,864 patients with biopsy-proven IgA nephropathy were followed for a median of 3.9 years.
Proteinuria remission was defined as at least a 25% reduction in proteinuria from the highest value after biopsy, as well as an absolute reduction in proteinuria to less than 1 gram per day.
“The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements,” the researchers wrote. “We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR).”
In total, 14.7% of the study population experienced the primary outcome, with findings suggesting each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression and that each additional 3 months in remission was associated with a “smaller, nonsignificant risk reduction.”
Canney and colleagues noted the relationship between duration of proteinuria remission and outcome was nonlinear.
“This study provides new data to support the use of proteinuria as a surrogate outcome measure in IgA nephropathy by demonstrating the duration of proteinuria remission needs to be considered when evaluating proteinuria reduction as a surrogate measure for the long-term benefit on kidney outcomes,” the researchers concluded.
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