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A brief thread on why we undertook this study looking at duration of proteinuria remission and clinical outcome in IgA nephropathy, published in this month’s issue of @JASN_News https://jasn.asnjournals.org/content/32/2/436 (1/10)
In 2019 the Kidney Health Initiative and the FDA published an important paper that proposed proteinuria reduction as a surrogate endpoint for therapeutic interventions in IgAN https://cjasn.asnjournals.org/content/14/3/469 (2/10)
As a result, the FDA now accepts proteinuria reduction as a short-term outcome in clinical trials (e.g. NEFIGAN study of budesonide) and this can be used to apply for accelerated drug approval (3/10)
However, the KHI publication also recognized a major knowledge deficit in the use of proteinuria as a surrogate outcome in clinical trials:
“…the minimal magnitude and duration of proteinuria reduction that confers a protective effect is currently unknown” (4/10)
“…the minimal magnitude and duration of proteinuria reduction that confers a protective effect is currently unknown” (4/10)
To address this question, we examined the association between the *duration* of proteinuria remission and the risk of disease progression in 1864 patients with biopsy-proven IgAN from 6 international cohorts (5/10)
We defined remission as:
A 25% reduction in proteinuria
From a peak of >1g/day
To an absolute value of <1g/day
We chose a 25% reduction based on this meta-analysis of clinical trials https://www.sciencedirect.com/science/article/pii/S0272638616002146?via%3Dihub (6/10)
A 25% reduction in proteinuria
From a peak of >1g/day
To an absolute value of <1g/day
We chose a 25% reduction based on this meta-analysis of clinical trials https://www.sciencedirect.com/science/article/pii/S0272638616002146?via%3Dihub (6/10)
Each 3 months in remission was associated with a 9% reduction in the risk of ESKD or a 50% decline in eGFR (HR 0.91, 95% CI 0.89-0.93)
Benefit was less evident after 4 years in remission, however patients in remission for this long had an excellent prognosis (7/10)
Benefit was less evident after 4 years in remission, however patients in remission for this long had an excellent prognosis (7/10)
Importantly, we did not observe a minimum duration of remission that conferred a long-term benefit
The longer you stay in proteinuria remission, the lower your risk of kidney failure (8/10)
The longer you stay in proteinuria remission, the lower your risk of kidney failure (8/10)
By quantitating this effect (both magnitude and duration), these findings can inform clinical trial programs that rely on short-term proteinuria reduction by providing a more accurate assessment of a therapy’s anticipated impact on long-term kidney outcomes in IgAN (9/10)
Sincere thanks to all of the investigators from the International IgA Nephropathy Network, especially co-authors Dan Cattran and @SeanJBarbour
Here’s a link to the paper and the #VisualAbstract again
https://jasn.asnjournals.org/content/32/2/436 (10/10)
Here’s a link to the paper and the #VisualAbstract again
https://jasn.asnjournals.org/content/32/2/436 (10/10)
