Nephrology Journal Club
@nephjc.bsky.social
A twice monthly nephrology journal club that used to meet on Twitter. Hashtag #NephJC
www.nephjc.com
www.nephjc.com
November 20, 2025 at 12:35 AM
6/10
Give me something clever to say 🤓
IgAN is no longer one-size-fits-all.
Timing matters.
Excitingly, tailored treatment is slowly becoming a reality.
@doctorgates.bsky.social
Give me something clever to say 🤓
IgAN is no longer one-size-fits-all.
Timing matters.
Excitingly, tailored treatment is slowly becoming a reality.
@doctorgates.bsky.social
November 20, 2025 at 12:35 AM
6/10
Give me something clever to say 🤓
IgAN is no longer one-size-fits-all.
Timing matters.
Excitingly, tailored treatment is slowly becoming a reality.
@doctorgates.bsky.social
Give me something clever to say 🤓
IgAN is no longer one-size-fits-all.
Timing matters.
Excitingly, tailored treatment is slowly becoming a reality.
@doctorgates.bsky.social
5/10
A figure paints🖼️ a 1000 words!
Emerging evidence from APRIL/BAFF–axis trials underscores how central this pathway is to IgAN biology. Let’s put ORIGIN side by side with the others and see what we learn!
A figure paints🖼️ a 1000 words!
Emerging evidence from APRIL/BAFF–axis trials underscores how central this pathway is to IgAN biology. Let’s put ORIGIN side by side with the others and see what we learn!
November 20, 2025 at 12:35 AM
5/10
A figure paints🖼️ a 1000 words!
Emerging evidence from APRIL/BAFF–axis trials underscores how central this pathway is to IgAN biology. Let’s put ORIGIN side by side with the others and see what we learn!
A figure paints🖼️ a 1000 words!
Emerging evidence from APRIL/BAFF–axis trials underscores how central this pathway is to IgAN biology. Let’s put ORIGIN side by side with the others and see what we learn!
3/10 One post methods
🌍 Phase 3, multicenter, double-blind RCT
💉 IgAN pts randomized 1:1 → atacicept 150 mg SC weekly (self-admin) vs placebo
📉 Primary endpoint: % change in 24-hr UPCR at wk 36
🌍 Phase 3, multicenter, double-blind RCT
💉 IgAN pts randomized 1:1 → atacicept 150 mg SC weekly (self-admin) vs placebo
📉 Primary endpoint: % change in 24-hr UPCR at wk 36
November 20, 2025 at 12:35 AM
3/10 One post methods
🌍 Phase 3, multicenter, double-blind RCT
💉 IgAN pts randomized 1:1 → atacicept 150 mg SC weekly (self-admin) vs placebo
📉 Primary endpoint: % change in 24-hr UPCR at wk 36
🌍 Phase 3, multicenter, double-blind RCT
💉 IgAN pts randomized 1:1 → atacicept 150 mg SC weekly (self-admin) vs placebo
📉 Primary endpoint: % change in 24-hr UPCR at wk 36
2/10
What'd I miss?
Amazing how quickly IgAN guidelines have evolved – 2021 to 2025 has been a whirlwind! And what was once just a ‘future research direction’ is now front-and-center with real data. Feels like we’re witnessing the “ORIGIN” story of a new era in IgAN therapeutics!
What'd I miss?
Amazing how quickly IgAN guidelines have evolved – 2021 to 2025 has been a whirlwind! And what was once just a ‘future research direction’ is now front-and-center with real data. Feels like we’re witnessing the “ORIGIN” story of a new era in IgAN therapeutics!
November 20, 2025 at 12:35 AM
2/10
What'd I miss?
Amazing how quickly IgAN guidelines have evolved – 2021 to 2025 has been a whirlwind! And what was once just a ‘future research direction’ is now front-and-center with real data. Feels like we’re witnessing the “ORIGIN” story of a new era in IgAN therapeutics!
What'd I miss?
Amazing how quickly IgAN guidelines have evolved – 2021 to 2025 has been a whirlwind! And what was once just a ‘future research direction’ is now front-and-center with real data. Feels like we’re witnessing the “ORIGIN” story of a new era in IgAN therapeutics!
1/10
Last #NephJC we discussed the ORIGIN 3 trial which investigated the use of Atacicept in IgAN #TenPostNephJC
Read the article 👇
www.nejm.org/doi/10....
Last #NephJC we discussed the ORIGIN 3 trial which investigated the use of Atacicept in IgAN #TenPostNephJC
Read the article 👇
www.nejm.org/doi/10....
November 20, 2025 at 12:34 AM
1/10
Last #NephJC we discussed the ORIGIN 3 trial which investigated the use of Atacicept in IgAN #TenPostNephJC
Read the article 👇
www.nejm.org/doi/10....
Last #NephJC we discussed the ORIGIN 3 trial which investigated the use of Atacicept in IgAN #TenPostNephJC
Read the article 👇
www.nejm.org/doi/10....
This is @shelliefravel.bsky.social signing off with a 'Hawkeye Wave' - the tradition that has become the very best part of every home Iowa Hawkeye football game. hawkeyesports.com/wave
It has been an honor to be your host tonight, goodbye until next time!
It has been an honor to be your host tonight, goodbye until next time!
November 19, 2025 at 3:00 AM
This is @shelliefravel.bsky.social signing off with a 'Hawkeye Wave' - the tradition that has become the very best part of every home Iowa Hawkeye football game. hawkeyesports.com/wave
It has been an honor to be your host tonight, goodbye until next time!
It has been an honor to be your host tonight, goodbye until next time!
T3o: #NephJC
Although this is an exciting time with the FDA approving new therapies for IgAN rapidly - they are mostly not available or accessible outside a few select countries -especially in places like Asia where the bulk of IgAN patients live.
Implementation and equity have entered the chat.
Although this is an exciting time with the FDA approving new therapies for IgAN rapidly - they are mostly not available or accessible outside a few select countries -especially in places like Asia where the bulk of IgAN patients live.
Implementation and equity have entered the chat.
November 19, 2025 at 2:50 AM
T3o: #NephJC
Although this is an exciting time with the FDA approving new therapies for IgAN rapidly - they are mostly not available or accessible outside a few select countries -especially in places like Asia where the bulk of IgAN patients live.
Implementation and equity have entered the chat.
Although this is an exciting time with the FDA approving new therapies for IgAN rapidly - they are mostly not available or accessible outside a few select countries -especially in places like Asia where the bulk of IgAN patients live.
Implementation and equity have entered the chat.
T3n: #NephJC
Limitations
😭Lack of eGFR data. (I’m trying to be patient, I swear).
Because the blinded treatment period is ongoing, kidney function outcomes including the key measure of eGFR slope will only be available at a later date.
Limitations
😭Lack of eGFR data. (I’m trying to be patient, I swear).
Because the blinded treatment period is ongoing, kidney function outcomes including the key measure of eGFR slope will only be available at a later date.
November 19, 2025 at 2:49 AM
T3n: #NephJC
Limitations
😭Lack of eGFR data. (I’m trying to be patient, I swear).
Because the blinded treatment period is ongoing, kidney function outcomes including the key measure of eGFR slope will only be available at a later date.
Limitations
😭Lack of eGFR data. (I’m trying to be patient, I swear).
Because the blinded treatment period is ongoing, kidney function outcomes including the key measure of eGFR slope will only be available at a later date.
T3j: #NephJC
Overall, these interim results suggest that APRIL-based and BAFF/APRIL–based therapies may represent important future disease-modifying options in IgAN
A full throated, “Hallelujah” being reserved until eGFR data is finalized.
Overall, these interim results suggest that APRIL-based and BAFF/APRIL–based therapies may represent important future disease-modifying options in IgAN
A full throated, “Hallelujah” being reserved until eGFR data is finalized.
November 19, 2025 at 2:45 AM
T3j: #NephJC
Overall, these interim results suggest that APRIL-based and BAFF/APRIL–based therapies may represent important future disease-modifying options in IgAN
A full throated, “Hallelujah” being reserved until eGFR data is finalized.
Overall, these interim results suggest that APRIL-based and BAFF/APRIL–based therapies may represent important future disease-modifying options in IgAN
A full throated, “Hallelujah” being reserved until eGFR data is finalized.
T3g: #NephJC
Although sibeprenlimab targets APRIL alone while atacicept blocks both BAFF and APRIL, the two trials showed broadly similar clinical effects: meaningful reductions in proteinuria, strong improvements in key biomarkers, and high rates of hematuria resolution.
Although sibeprenlimab targets APRIL alone while atacicept blocks both BAFF and APRIL, the two trials showed broadly similar clinical effects: meaningful reductions in proteinuria, strong improvements in key biomarkers, and high rates of hematuria resolution.
November 19, 2025 at 2:42 AM
T3g: #NephJC
Although sibeprenlimab targets APRIL alone while atacicept blocks both BAFF and APRIL, the two trials showed broadly similar clinical effects: meaningful reductions in proteinuria, strong improvements in key biomarkers, and high rates of hematuria resolution.
Although sibeprenlimab targets APRIL alone while atacicept blocks both BAFF and APRIL, the two trials showed broadly similar clinical effects: meaningful reductions in proteinuria, strong improvements in key biomarkers, and high rates of hematuria resolution.
T3f: #NephJC
Whether dual inhibition APRIL/BAFF offers a longer-term advantage over APRIL-selective therapy remains a key question that only eGFR slope data will answer. APRIL-selective therapy also prevents its action at other receptors (BCMA).
Do you think either has the advantage?
Whether dual inhibition APRIL/BAFF offers a longer-term advantage over APRIL-selective therapy remains a key question that only eGFR slope data will answer. APRIL-selective therapy also prevents its action at other receptors (BCMA).
Do you think either has the advantage?
November 19, 2025 at 2:41 AM
T3f: #NephJC
Whether dual inhibition APRIL/BAFF offers a longer-term advantage over APRIL-selective therapy remains a key question that only eGFR slope data will answer. APRIL-selective therapy also prevents its action at other receptors (BCMA).
Do you think either has the advantage?
Whether dual inhibition APRIL/BAFF offers a longer-term advantage over APRIL-selective therapy remains a key question that only eGFR slope data will answer. APRIL-selective therapy also prevents its action at other receptors (BCMA).
Do you think either has the advantage?
T3e: #NephJC
As newer trials such as APPLAUSE-IgAN (iptacopan) & NEFIGARD (budesonide) continue to illuminate parts of the cascade, the APRIL–BAFF pathway stands out as the most direct attempt to target the source of pathogenic IgA production.
Will this class of meds become foundational in IgAN?
As newer trials such as APPLAUSE-IgAN (iptacopan) & NEFIGARD (budesonide) continue to illuminate parts of the cascade, the APRIL–BAFF pathway stands out as the most direct attempt to target the source of pathogenic IgA production.
Will this class of meds become foundational in IgAN?
November 19, 2025 at 2:40 AM
T3e: #NephJC
As newer trials such as APPLAUSE-IgAN (iptacopan) & NEFIGARD (budesonide) continue to illuminate parts of the cascade, the APRIL–BAFF pathway stands out as the most direct attempt to target the source of pathogenic IgA production.
Will this class of meds become foundational in IgAN?
As newer trials such as APPLAUSE-IgAN (iptacopan) & NEFIGARD (budesonide) continue to illuminate parts of the cascade, the APRIL–BAFF pathway stands out as the most direct attempt to target the source of pathogenic IgA production.
Will this class of meds become foundational in IgAN?
T3d: #NephJC
In VISIONARY, APRIL-selective B-cell inhibition ⬇️proteinuria & IgA-related biomarkers, confirming APRIL’s key pathogenic role.
In ORIGIN-3, atacicept’s BAFF + APRIL blockade targets earlier B-cell checkpoints, dismantling both the production & maintenance of aberrant IgA response.
In VISIONARY, APRIL-selective B-cell inhibition ⬇️proteinuria & IgA-related biomarkers, confirming APRIL’s key pathogenic role.
In ORIGIN-3, atacicept’s BAFF + APRIL blockade targets earlier B-cell checkpoints, dismantling both the production & maintenance of aberrant IgA response.
November 19, 2025 at 2:39 AM
T3d: #NephJC
In VISIONARY, APRIL-selective B-cell inhibition ⬇️proteinuria & IgA-related biomarkers, confirming APRIL’s key pathogenic role.
In ORIGIN-3, atacicept’s BAFF + APRIL blockade targets earlier B-cell checkpoints, dismantling both the production & maintenance of aberrant IgA response.
In VISIONARY, APRIL-selective B-cell inhibition ⬇️proteinuria & IgA-related biomarkers, confirming APRIL’s key pathogenic role.
In ORIGIN-3, atacicept’s BAFF + APRIL blockade targets earlier B-cell checkpoints, dismantling both the production & maintenance of aberrant IgA response.
T3c: #NephJC
The emerging evidence from APRIL/BAFF–axis trials (including VISIONARY (sibeprenlimab) & ORIGIN-3 (atacicept)) highlight how central this pathway is to the mechanisms of IgAN.
The emerging evidence from APRIL/BAFF–axis trials (including VISIONARY (sibeprenlimab) & ORIGIN-3 (atacicept)) highlight how central this pathway is to the mechanisms of IgAN.
November 19, 2025 at 2:38 AM
T3c: #NephJC
The emerging evidence from APRIL/BAFF–axis trials (including VISIONARY (sibeprenlimab) & ORIGIN-3 (atacicept)) highlight how central this pathway is to the mechanisms of IgAN.
The emerging evidence from APRIL/BAFF–axis trials (including VISIONARY (sibeprenlimab) & ORIGIN-3 (atacicept)) highlight how central this pathway is to the mechanisms of IgAN.
T3b: #NephJC
This interim analysis produced clear improvements in key biomarkers of IgAN.
The magnitude of the proteinuria reduction & parallel drop in Gd-IgA1 support the idea that atacicept is acting directly on the drivers of disease, rather than through non-specific hemodynamic effects.
This interim analysis produced clear improvements in key biomarkers of IgAN.
The magnitude of the proteinuria reduction & parallel drop in Gd-IgA1 support the idea that atacicept is acting directly on the drivers of disease, rather than through non-specific hemodynamic effects.
November 19, 2025 at 2:37 AM
T3b: #NephJC
This interim analysis produced clear improvements in key biomarkers of IgAN.
The magnitude of the proteinuria reduction & parallel drop in Gd-IgA1 support the idea that atacicept is acting directly on the drivers of disease, rather than through non-specific hemodynamic effects.
This interim analysis produced clear improvements in key biomarkers of IgAN.
The magnitude of the proteinuria reduction & parallel drop in Gd-IgA1 support the idea that atacicept is acting directly on the drivers of disease, rather than through non-specific hemodynamic effects.
T2e: #NephJC
2° Endpoints
📉Atacicept reduced Gd-IgA1 by 68.3% at week 36 vs 2.9% with placebo, as early as week 4
🩸Among patients with baseline ≥1+ hematuria, 81% in the atacicept group achieved resolution vs 21% with placebo arm
🥤UACR ratio fell by 47.3% in atacicept vs 8.8% with placebo
2° Endpoints
📉Atacicept reduced Gd-IgA1 by 68.3% at week 36 vs 2.9% with placebo, as early as week 4
🩸Among patients with baseline ≥1+ hematuria, 81% in the atacicept group achieved resolution vs 21% with placebo arm
🥤UACR ratio fell by 47.3% in atacicept vs 8.8% with placebo
November 19, 2025 at 2:33 AM
T2e: #NephJC
2° Endpoints
📉Atacicept reduced Gd-IgA1 by 68.3% at week 36 vs 2.9% with placebo, as early as week 4
🩸Among patients with baseline ≥1+ hematuria, 81% in the atacicept group achieved resolution vs 21% with placebo arm
🥤UACR ratio fell by 47.3% in atacicept vs 8.8% with placebo
2° Endpoints
📉Atacicept reduced Gd-IgA1 by 68.3% at week 36 vs 2.9% with placebo, as early as week 4
🩸Among patients with baseline ≥1+ hematuria, 81% in the atacicept group achieved resolution vs 21% with placebo arm
🥤UACR ratio fell by 47.3% in atacicept vs 8.8% with placebo
T2d: #NephJC
📉The decline in proteinuria was already evident by week 12 & continued thru week 36
🚨Prespecified subgroup analyses showed that this benefit was consistent across all categories, including age, sex, region, race, baseline UPCR/ eGFR & SGLT2i use
📉The decline in proteinuria was already evident by week 12 & continued thru week 36
🚨Prespecified subgroup analyses showed that this benefit was consistent across all categories, including age, sex, region, race, baseline UPCR/ eGFR & SGLT2i use
November 19, 2025 at 2:32 AM
T2d: #NephJC
📉The decline in proteinuria was already evident by week 12 & continued thru week 36
🚨Prespecified subgroup analyses showed that this benefit was consistent across all categories, including age, sex, region, race, baseline UPCR/ eGFR & SGLT2i use
📉The decline in proteinuria was already evident by week 12 & continued thru week 36
🚨Prespecified subgroup analyses showed that this benefit was consistent across all categories, including age, sex, region, race, baseline UPCR/ eGFR & SGLT2i use
T2c: #NephJC
1° Endpoint
At week 36- 🗓️
📉Atacicept: 24-hour urinary protein-to-creatinine ratio decreased by 45.7%
🔻Placebo: 24-hour urinary protein-to-creatinine ratio decreased by 6.8%
1° Endpoint
At week 36- 🗓️
📉Atacicept: 24-hour urinary protein-to-creatinine ratio decreased by 45.7%
🔻Placebo: 24-hour urinary protein-to-creatinine ratio decreased by 6.8%
November 19, 2025 at 2:31 AM
T2c: #NephJC
1° Endpoint
At week 36- 🗓️
📉Atacicept: 24-hour urinary protein-to-creatinine ratio decreased by 45.7%
🔻Placebo: 24-hour urinary protein-to-creatinine ratio decreased by 6.8%
1° Endpoint
At week 36- 🗓️
📉Atacicept: 24-hour urinary protein-to-creatinine ratio decreased by 45.7%
🔻Placebo: 24-hour urinary protein-to-creatinine ratio decreased by 6.8%
T2b: #NephJC
99.5% of patients were already receiving the max tolerated dose of a RASi at baseline, & just over half (53.2%) were #flozinated
About 60% had 1+ or more hematuria, with proteinuria 2 g/day & preserved GFR (60 ml/min).
Are these the patients you most often encounter with IgAN?
99.5% of patients were already receiving the max tolerated dose of a RASi at baseline, & just over half (53.2%) were #flozinated
About 60% had 1+ or more hematuria, with proteinuria 2 g/day & preserved GFR (60 ml/min).
Are these the patients you most often encounter with IgAN?
November 19, 2025 at 2:30 AM
T2b: #NephJC
99.5% of patients were already receiving the max tolerated dose of a RASi at baseline, & just over half (53.2%) were #flozinated
About 60% had 1+ or more hematuria, with proteinuria 2 g/day & preserved GFR (60 ml/min).
Are these the patients you most often encounter with IgAN?
99.5% of patients were already receiving the max tolerated dose of a RASi at baseline, & just over half (53.2%) were #flozinated
About 60% had 1+ or more hematuria, with proteinuria 2 g/day & preserved GFR (60 ml/min).
Are these the patients you most often encounter with IgAN?
T2a: #NephJC
A total of 203 participants were included in the 36-week interim efficacy analysis, with 106 patients receiving atacicept and 97 patients receiving placebo.
A total of 203 participants were included in the 36-week interim efficacy analysis, with 106 patients receiving atacicept and 97 patients receiving placebo.
November 19, 2025 at 2:29 AM
T2a: #NephJC
A total of 203 participants were included in the 36-week interim efficacy analysis, with 106 patients receiving atacicept and 97 patients receiving placebo.
A total of 203 participants were included in the 36-week interim efficacy analysis, with 106 patients receiving atacicept and 97 patients receiving placebo.