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
Pinned
Attacking the Origin of IgAN: ORIGIN3 and Atacicept — NephJC
This week, we will discuss the phase 3 ORIGIN3 trial of atacicept, an APRIL/BAFF inhibitor for use in IgAN.
www.nephjc.com
Tonite 11/18/25 on #Bluesky 9pm EST
We are discussing ORIGIN3 and atacicept in IgAN.
APRIL, BAFF and B-cells, Oh My! (🦁🐯🐻)
It's going to be Wicked good. 🧙♀️ #NephJC
Summary by @notjustdialysis.bsky.social
www.nephjc.com/news/atacicept-origin3-gtfb36
We are discussing ORIGIN3 and atacicept in IgAN.
APRIL, BAFF and B-cells, Oh My! (🦁🐯🐻)
It's going to be Wicked good. 🧙♀️ #NephJC
Summary by @notjustdialysis.bsky.social
www.nephjc.com/news/atacicept-origin3-gtfb36
Every year, #NephJC celebrates successful, practice-changing trials. ✨ Which trials do you think are deserving for #TopNephrology 2025? #nephsky
👇👇 Here's a throwback for 2024
www.nephjc.com/news/2024/1/...
👇👇 Here's a throwback for 2024
www.nephjc.com/news/2024/1/...
Top Stories in Nephrology 2024 — NephJC
Should we call 2024 the Renaissance of nephrology? It was probably the richest year in RCTs in the nephrology world, reflected in the higher number of Late-Breaking Clinical Trials sessions at every b...
www.nephjc.com
November 20, 2025 at 10:42 PM
Every year, #NephJC celebrates successful, practice-changing trials. ✨ Which trials do you think are deserving for #TopNephrology 2025? #nephsky
👇👇 Here's a throwback for 2024
www.nephjc.com/news/2024/1/...
👇👇 Here's a throwback for 2024
www.nephjc.com/news/2024/1/...
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!
A heartfelt thank you to Brian Rifkin and Christina Popa for writing this beautiful script and to all of our mentors for the ongoing guidance and support! @brianrifkin.bsky.social, @christina@nephroseeker.medsky.social, @hswapnil.medsky.social
November 19, 2025 at 2:59 AM
A heartfelt thank you to Brian Rifkin and Christina Popa for writing this beautiful script and to all of our mentors for the ongoing guidance and support! @brianrifkin.bsky.social, @christina@nephroseeker.medsky.social, @hswapnil.medsky.social
A sincere thank you to my NephJC intern team members @msocomd.bsky.social, @notjustdialysis.bsky.social, @salinesolut.bsky.social
November 19, 2025 at 2:59 AM
A sincere thank you to my NephJC intern team members @msocomd.bsky.social, @notjustdialysis.bsky.social, @salinesolut.bsky.social
Up next: It might seem a little fishy, but was a great catch 🎣 #NephJC
PISCES, the use of fish oil to decrease mortality in dialysis patients.
www.pubmed.ncbi.nlm....
PISCES, the use of fish oil to decrease mortality in dialysis patients.
www.pubmed.ncbi.nlm....
November 19, 2025 at 2:58 AM
Up next: It might seem a little fishy, but was a great catch 🎣 #NephJC
PISCES, the use of fish oil to decrease mortality in dialysis patients.
www.pubmed.ncbi.nlm....
PISCES, the use of fish oil to decrease mortality in dialysis patients.
www.pubmed.ncbi.nlm....
November 19, 2025 at 2:57 AM
Reposted by Nephrology Journal Club
It seems counterintuitive to give ACEi and SGLT2i which are just trying to decrease proteinuria (mask symptoms), rather than turning off the disease at the source.
Unfortunately in the real world, cost does matter. #NephJC
Unfortunately in the real world, cost does matter. #NephJC
a man is yawning while talking on a cell phone with the word show written above him
ALT: a man is yawning while talking on a cell phone with the word show written above him
media.tenor.com
November 19, 2025 at 2:54 AM
It seems counterintuitive to give ACEi and SGLT2i which are just trying to decrease proteinuria (mask symptoms), rather than turning off the disease at the source.
Unfortunately in the real world, cost does matter. #NephJC
Unfortunately in the real world, cost does matter. #NephJC
If you want to stay on top of #NephJC happenings, sign up for our once a week newsletter
www.nephjc.com/newsl...
www.nephjc.com/newsl...
November 19, 2025 at 2:56 AM
If you want to stay on top of #NephJC happenings, sign up for our once a week newsletter
www.nephjc.com/newsl...
www.nephjc.com/newsl...
T4a: #NephJC
We recently got to hear the patient voice from @jonathanpollack.bsk.social
About his journey with IgAN and his excitement for a future of precision medicine while also calling for greater worldwide equity.
We recently got to hear the patient voice from @jonathanpollack.bsk.social
About his journey with IgAN and his excitement for a future of precision medicine while also calling for greater worldwide equity.
KDIGO IgA Guidelines: A Patient Voice — NephJC
We have a patient perspective on the new IgA Guidelines and what it means
to live with IgA in these times.
www.nephjc.com
November 19, 2025 at 2:52 AM
T4a: #NephJC
We recently got to hear the patient voice from @jonathanpollack.bsk.social
About his journey with IgAN and his excitement for a future of precision medicine while also calling for greater worldwide equity.
We recently got to hear the patient voice from @jonathanpollack.bsk.social
About his journey with IgAN and his excitement for a future of precision medicine while also calling for greater worldwide equity.
T3p: #NephJC
Outside of cost/coverage…
Will you be likely to recommend APRIL/BAFF therapy to your patients with IgAN?
Since it gets to the mechanisms of IgAN, should it be first line in mild/moderate disease?
Outside of cost/coverage…
Will you be likely to recommend APRIL/BAFF therapy to your patients with IgAN?
Since it gets to the mechanisms of IgAN, should it be first line in mild/moderate disease?
November 19, 2025 at 2:51 AM
T3p: #NephJC
Outside of cost/coverage…
Will you be likely to recommend APRIL/BAFF therapy to your patients with IgAN?
Since it gets to the mechanisms of IgAN, should it be first line in mild/moderate disease?
Outside of cost/coverage…
Will you be likely to recommend APRIL/BAFF therapy to your patients with IgAN?
Since it gets to the mechanisms of IgAN, should it be first line in mild/moderate disease?
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.
T3m: #NephJC
Safety
Although immunoglobulin levels decreased as expected with BAFF/APRIL inhibition, no cases of hypogammaglobulinemia or opportunistic infections were reported. This aligns with prior data showing that atacicept modulates B-cell survival without causing broad immunosuppression.
Safety
Although immunoglobulin levels decreased as expected with BAFF/APRIL inhibition, no cases of hypogammaglobulinemia or opportunistic infections were reported. This aligns with prior data showing that atacicept modulates B-cell survival without causing broad immunosuppression.
November 19, 2025 at 2:48 AM
T3m: #NephJC
Safety
Although immunoglobulin levels decreased as expected with BAFF/APRIL inhibition, no cases of hypogammaglobulinemia or opportunistic infections were reported. This aligns with prior data showing that atacicept modulates B-cell survival without causing broad immunosuppression.
Safety
Although immunoglobulin levels decreased as expected with BAFF/APRIL inhibition, no cases of hypogammaglobulinemia or opportunistic infections were reported. This aligns with prior data showing that atacicept modulates B-cell survival without causing broad immunosuppression.
T3l: #NephJC
The fact that atacicept still produced benefits with optimized background treatment makes the findings highly relevant to clinical practice.
The consistent effect across subgroups: eGFR, geographic regions,& SGLT2i use, adds confidence in the robustness of the proteinuria effect.
The fact that atacicept still produced benefits with optimized background treatment makes the findings highly relevant to clinical practice.
The consistent effect across subgroups: eGFR, geographic regions,& SGLT2i use, adds confidence in the robustness of the proteinuria effect.
November 19, 2025 at 2:47 AM
T3l: #NephJC
The fact that atacicept still produced benefits with optimized background treatment makes the findings highly relevant to clinical practice.
The consistent effect across subgroups: eGFR, geographic regions,& SGLT2i use, adds confidence in the robustness of the proteinuria effect.
The fact that atacicept still produced benefits with optimized background treatment makes the findings highly relevant to clinical practice.
The consistent effect across subgroups: eGFR, geographic regions,& SGLT2i use, adds confidence in the robustness of the proteinuria effect.
T3k: #NephJC
Strengths
Patients were already receiving standard of care treatment: nearly all were on maximal RAS blockade & more than 1/2 were on an SGLT2i.
This is in contrast to NEFIGARD where almost no one was #flozinated - likely reflecting the evolution of evidence & growing access.
Strengths
Patients were already receiving standard of care treatment: nearly all were on maximal RAS blockade & more than 1/2 were on an SGLT2i.
This is in contrast to NEFIGARD where almost no one was #flozinated - likely reflecting the evolution of evidence & growing access.
November 19, 2025 at 2:46 AM
T3k: #NephJC
Strengths
Patients were already receiving standard of care treatment: nearly all were on maximal RAS blockade & more than 1/2 were on an SGLT2i.
This is in contrast to NEFIGARD where almost no one was #flozinated - likely reflecting the evolution of evidence & growing access.
Strengths
Patients were already receiving standard of care treatment: nearly all were on maximal RAS blockade & more than 1/2 were on an SGLT2i.
This is in contrast to NEFIGARD where almost no one was #flozinated - likely reflecting the evolution of evidence & growing access.
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.
T3i: #NephJC
The major limitation shared by both studies is the absence of eGFR slope data.
While the early surrogate endpoints are promising, the long-term renal benefits remain unknown (though the phase 2b results are promising).
If atacicept does get early approval will you wait on GFR data?
The major limitation shared by both studies is the absence of eGFR slope data.
While the early surrogate endpoints are promising, the long-term renal benefits remain unknown (though the phase 2b results are promising).
If atacicept does get early approval will you wait on GFR data?
November 19, 2025 at 2:44 AM
T3i: #NephJC
The major limitation shared by both studies is the absence of eGFR slope data.
While the early surrogate endpoints are promising, the long-term renal benefits remain unknown (though the phase 2b results are promising).
If atacicept does get early approval will you wait on GFR data?
The major limitation shared by both studies is the absence of eGFR slope data.
While the early surrogate endpoints are promising, the long-term renal benefits remain unknown (though the phase 2b results are promising).
If atacicept does get early approval will you wait on GFR data?
T3h: #NephJC
Both treatments were well tolerated, with low rates of serious adverse events & predictable immunoglobulin reductions that stabilized without causing hypogammaglobulinemia or opportunistic infections.
Do you think dose optimization might change safety in clinical practice?
Both treatments were well tolerated, with low rates of serious adverse events & predictable immunoglobulin reductions that stabilized without causing hypogammaglobulinemia or opportunistic infections.
Do you think dose optimization might change safety in clinical practice?
November 19, 2025 at 2:43 AM
T3h: #NephJC
Both treatments were well tolerated, with low rates of serious adverse events & predictable immunoglobulin reductions that stabilized without causing hypogammaglobulinemia or opportunistic infections.
Do you think dose optimization might change safety in clinical practice?
Both treatments were well tolerated, with low rates of serious adverse events & predictable immunoglobulin reductions that stabilized without causing hypogammaglobulinemia or opportunistic infections.
Do you think dose optimization might change safety in clinical practice?
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?