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
A VALIANT effort to combat complement disorders with pegcetacoplan — NephJC
This week, we will discuss the VALIANT study, pegcetacoplan in C3G and IC MPGN.
www.nephjc.com
Wilst thou join us here, where the Sky is Blue? #NephJC
On 1/13/26 at 9pm EST 'tis true
We shall converse of the great knight's quest,
a VALIANT effort from Sir Pegcetacoplan vs complement! ⚔️
www.nephjc.com/news/valiant-c3g
On 1/13/26 at 9pm EST 'tis true
We shall converse of the great knight's quest,
a VALIANT effort from Sir Pegcetacoplan vs complement! ⚔️
www.nephjc.com/news/valiant-c3g
1/10 Last #NephJC we discussed Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN #TenPostNephJC
Given the central role of complement dysregulation in C3 glomerulonephritis, we assessed whether complement-targeted therapies confer therapeutic benefit.
www.nejm.org/doi/full/10....
Given the central role of complement dysregulation in C3 glomerulonephritis, we assessed whether complement-targeted therapies confer therapeutic benefit.
www.nejm.org/doi/full/10....
January 16, 2026 at 9:16 PM
1/10 Last #NephJC we discussed Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN #TenPostNephJC
Given the central role of complement dysregulation in C3 glomerulonephritis, we assessed whether complement-targeted therapies confer therapeutic benefit.
www.nejm.org/doi/full/10....
Given the central role of complement dysregulation in C3 glomerulonephritis, we assessed whether complement-targeted therapies confer therapeutic benefit.
www.nejm.org/doi/full/10....
Look out for a Vote for #NephJCKidneys 2026 !!
Nominations are OPEN for the 2026 NephJC Kidneys — NephJC
The NephJC Kidneys are back for the eighth year! Nominate you favorites of
2025- 2026!
www.nephjc.com
January 14, 2026 at 2:57 AM
Look out for a Vote for #NephJCKidneys 2026 !!
Up next 1/27/25
POTCAST, Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias
www.nejm.org/doi/ful...
POTCAST, Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias
www.nejm.org/doi/ful...
January 14, 2026 at 2:56 AM
Up next 1/27/25
POTCAST, Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias
www.nejm.org/doi/ful...
POTCAST, Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias
www.nejm.org/doi/ful...
January 14, 2026 at 2:55 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...
January 14, 2026 at 2:53 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...
Great discussion! This has been Janany S
A sincere thank you to my #NephJC intern team members.
Natalia Nombera Aznaran @drsaivani.bksy.social Akshaya Jayachandran
A sincere thank you to my #NephJC intern team members.
Natalia Nombera Aznaran @drsaivani.bksy.social Akshaya Jayachandran
January 14, 2026 at 2:51 AM
Great discussion! This has been Janany S
A sincere thank you to my #NephJC intern team members.
Natalia Nombera Aznaran @drsaivani.bksy.social Akshaya Jayachandran
A sincere thank you to my #NephJC intern team members.
Natalia Nombera Aznaran @drsaivani.bksy.social Akshaya Jayachandran
T3o #NephJC
🧑⚕️ At what threshold (proteinuria and/or activity?) or timepoint (post transplant vs recurrence?) would you actually use pegcetacoplan?
Will pegcetacoplan be a first line agent with confirmed C3GN?
🧑⚕️ At what threshold (proteinuria and/or activity?) or timepoint (post transplant vs recurrence?) would you actually use pegcetacoplan?
Will pegcetacoplan be a first line agent with confirmed C3GN?
January 14, 2026 at 2:50 AM
T3o #NephJC
🧑⚕️ At what threshold (proteinuria and/or activity?) or timepoint (post transplant vs recurrence?) would you actually use pegcetacoplan?
Will pegcetacoplan be a first line agent with confirmed C3GN?
🧑⚕️ At what threshold (proteinuria and/or activity?) or timepoint (post transplant vs recurrence?) would you actually use pegcetacoplan?
Will pegcetacoplan be a first line agent with confirmed C3GN?
T3n #NephJC
⚖️ Enough to change practice now or do we need the results from the follow up?
C3GN is very rare, will you have enough experience or will you refer to a GN specialist for treatment?
⚖️ Enough to change practice now or do we need the results from the follow up?
C3GN is very rare, will you have enough experience or will you refer to a GN specialist for treatment?
January 14, 2026 at 2:49 AM
T3n #NephJC
⚖️ Enough to change practice now or do we need the results from the follow up?
C3GN is very rare, will you have enough experience or will you refer to a GN specialist for treatment?
⚖️ Enough to change practice now or do we need the results from the follow up?
C3GN is very rare, will you have enough experience or will you refer to a GN specialist for treatment?
T3m
Limitations #NephJC
🔬 The renal histologic activity index is not yet validated.
🧑⚕️ Post-transplant subgroup was small (supportive signals from NOBLE help). We need caution before generalizing these findings.
Limitations #NephJC
🔬 The renal histologic activity index is not yet validated.
🧑⚕️ Post-transplant subgroup was small (supportive signals from NOBLE help). We need caution before generalizing these findings.
January 14, 2026 at 2:48 AM
T3m
Limitations #NephJC
🔬 The renal histologic activity index is not yet validated.
🧑⚕️ Post-transplant subgroup was small (supportive signals from NOBLE help). We need caution before generalizing these findings.
Limitations #NephJC
🔬 The renal histologic activity index is not yet validated.
🧑⚕️ Post-transplant subgroup was small (supportive signals from NOBLE help). We need caution before generalizing these findings.
T3l
Limitations #NephJC
⏳ No long-term safety or efficacy data yet: open label follow-up and the VALE extension will be key.
🧒 No follow-up biopsies in adolescents, reducing interpretation in this high-risk population.
Limitations #NephJC
⏳ No long-term safety or efficacy data yet: open label follow-up and the VALE extension will be key.
🧒 No follow-up biopsies in adolescents, reducing interpretation in this high-risk population.
January 14, 2026 at 2:47 AM
T3l
Limitations #NephJC
⏳ No long-term safety or efficacy data yet: open label follow-up and the VALE extension will be key.
🧒 No follow-up biopsies in adolescents, reducing interpretation in this high-risk population.
Limitations #NephJC
⏳ No long-term safety or efficacy data yet: open label follow-up and the VALE extension will be key.
🧒 No follow-up biopsies in adolescents, reducing interpretation in this high-risk population.
T3k
🛡️ Safety profile was similar to previous studies.
🦠 Absence of encapsulated infections is reassuring.
🧑⚕️ Graft loss or rejection was not reported.
👀 Anything else we should have been watching for? #NephJC
🛡️ Safety profile was similar to previous studies.
🦠 Absence of encapsulated infections is reassuring.
🧑⚕️ Graft loss or rejection was not reported.
👀 Anything else we should have been watching for? #NephJC
January 14, 2026 at 2:46 AM
T3k
🛡️ Safety profile was similar to previous studies.
🦠 Absence of encapsulated infections is reassuring.
🧑⚕️ Graft loss or rejection was not reported.
👀 Anything else we should have been watching for? #NephJC
🛡️ Safety profile was similar to previous studies.
🦠 Absence of encapsulated infections is reassuring.
🧑⚕️ Graft loss or rejection was not reported.
👀 Anything else we should have been watching for? #NephJC
T3j
🧪 Glomerular C3 staining ↓ and complement biomarkers support a disease-modifying signal.
📊 But, activity score change was not significant and formal testing was limited by hierarchical design
🤔 So… is the issue finally being addressed with pegcetacoplan?
#NephJC
🧪 Glomerular C3 staining ↓ and complement biomarkers support a disease-modifying signal.
📊 But, activity score change was not significant and formal testing was limited by hierarchical design
🤔 So… is the issue finally being addressed with pegcetacoplan?
#NephJC
January 14, 2026 at 2:45 AM
T3j
🧪 Glomerular C3 staining ↓ and complement biomarkers support a disease-modifying signal.
📊 But, activity score change was not significant and formal testing was limited by hierarchical design
🤔 So… is the issue finally being addressed with pegcetacoplan?
#NephJC
🧪 Glomerular C3 staining ↓ and complement biomarkers support a disease-modifying signal.
📊 But, activity score change was not significant and formal testing was limited by hierarchical design
🤔 So… is the issue finally being addressed with pegcetacoplan?
#NephJC
T3i
Why proximal complement inhibition matters #NephJC
🧠 C3G and IC-MPGN are driven by uncontrolled complement activation.
🚫 Prior C5-targeted approaches showed limited benefit → ongoing C3 activation was likely the issue.
Why proximal complement inhibition matters #NephJC
🧠 C3G and IC-MPGN are driven by uncontrolled complement activation.
🚫 Prior C5-targeted approaches showed limited benefit → ongoing C3 activation was likely the issue.
January 14, 2026 at 2:44 AM
T3i
Why proximal complement inhibition matters #NephJC
🧠 C3G and IC-MPGN are driven by uncontrolled complement activation.
🚫 Prior C5-targeted approaches showed limited benefit → ongoing C3 activation was likely the issue.
Why proximal complement inhibition matters #NephJC
🧠 C3G and IC-MPGN are driven by uncontrolled complement activation.
🚫 Prior C5-targeted approaches showed limited benefit → ongoing C3 activation was likely the issue.
T3h
The efficacy signal was broad! #NephJC
🧒🧑 Pegcetacoplan showed efficacy across subgroups, including adolescents and patients on immunosuppression.
🔁 In a disease with high post-transplant recurrence, especially in the young population, how should this shape our practice?
The efficacy signal was broad! #NephJC
🧒🧑 Pegcetacoplan showed efficacy across subgroups, including adolescents and patients on immunosuppression.
🔁 In a disease with high post-transplant recurrence, especially in the young population, how should this shape our practice?
January 14, 2026 at 2:43 AM
T3h
The efficacy signal was broad! #NephJC
🧒🧑 Pegcetacoplan showed efficacy across subgroups, including adolescents and patients on immunosuppression.
🔁 In a disease with high post-transplant recurrence, especially in the young population, how should this shape our practice?
The efficacy signal was broad! #NephJC
🧒🧑 Pegcetacoplan showed efficacy across subgroups, including adolescents and patients on immunosuppression.
🔁 In a disease with high post-transplant recurrence, especially in the young population, how should this shape our practice?
T3g
According to a study by Fontan et al, in C3 glomerulopathy proteinuria is the predicting factor for ESRD; even a 50% reduction in proteinuria will improve survival. If proteinuria further decreases to <300 mg/day, 85% won’t reach end-stage kidney failure. #NephJC
According to a study by Fontan et al, in C3 glomerulopathy proteinuria is the predicting factor for ESRD; even a 50% reduction in proteinuria will improve survival. If proteinuria further decreases to <300 mg/day, 85% won’t reach end-stage kidney failure. #NephJC
January 14, 2026 at 2:42 AM
T3g
According to a study by Fontan et al, in C3 glomerulopathy proteinuria is the predicting factor for ESRD; even a 50% reduction in proteinuria will improve survival. If proteinuria further decreases to <300 mg/day, 85% won’t reach end-stage kidney failure. #NephJC
According to a study by Fontan et al, in C3 glomerulopathy proteinuria is the predicting factor for ESRD; even a 50% reduction in proteinuria will improve survival. If proteinuria further decreases to <300 mg/day, 85% won’t reach end-stage kidney failure. #NephJC
T3f
It is worth repeating that in the VALIANT study, 68.1% of participants experienced a reduction in proteinuria and stabilization of GFR; additionally, the histological index for C3 staining reached 0 in 71% of patients. #NephJC
It is worth repeating that in the VALIANT study, 68.1% of participants experienced a reduction in proteinuria and stabilization of GFR; additionally, the histological index for C3 staining reached 0 in 71% of patients. #NephJC
January 14, 2026 at 2:41 AM
T3f
It is worth repeating that in the VALIANT study, 68.1% of participants experienced a reduction in proteinuria and stabilization of GFR; additionally, the histological index for C3 staining reached 0 in 71% of patients. #NephJC
It is worth repeating that in the VALIANT study, 68.1% of participants experienced a reduction in proteinuria and stabilization of GFR; additionally, the histological index for C3 staining reached 0 in 71% of patients. #NephJC
T3e
This study addressed all three requirements (proteinuria, stabilization of eGFR, and changes in histology index) needed by the C3G trial endpoints workgroup to label the pegcetacoplan as effective in the treatment of C3 glomerulopathy #NephJC
This study addressed all three requirements (proteinuria, stabilization of eGFR, and changes in histology index) needed by the C3G trial endpoints workgroup to label the pegcetacoplan as effective in the treatment of C3 glomerulopathy #NephJC
January 14, 2026 at 2:40 AM
T3e
This study addressed all three requirements (proteinuria, stabilization of eGFR, and changes in histology index) needed by the C3G trial endpoints workgroup to label the pegcetacoplan as effective in the treatment of C3 glomerulopathy #NephJC
This study addressed all three requirements (proteinuria, stabilization of eGFR, and changes in histology index) needed by the C3G trial endpoints workgroup to label the pegcetacoplan as effective in the treatment of C3 glomerulopathy #NephJC
T3d
Was PEG effective? #NephJC
📉 Proteinuria went down
📊 eGFR stabilized
🧪 Histology improved
What else would you want to see?
Is 26 wks long enough for safety?
Should multiple complement blocker be used sequentially?
Was PEG effective? #NephJC
📉 Proteinuria went down
📊 eGFR stabilized
🧪 Histology improved
What else would you want to see?
Is 26 wks long enough for safety?
Should multiple complement blocker be used sequentially?
January 14, 2026 at 2:39 AM
T3d
Was PEG effective? #NephJC
📉 Proteinuria went down
📊 eGFR stabilized
🧪 Histology improved
What else would you want to see?
Is 26 wks long enough for safety?
Should multiple complement blocker be used sequentially?
Was PEG effective? #NephJC
📉 Proteinuria went down
📊 eGFR stabilized
🧪 Histology improved
What else would you want to see?
Is 26 wks long enough for safety?
Should multiple complement blocker be used sequentially?
T3c
Iptacopan, a Factor B inhibitor, only decreased proteinuria 35-40% at 12 months.
Changes in eGFR were not significant and C3 IF staining was only modestly decreased (0.8 on a 12 point scale).
🤔Something better needed to be discovered. #NephJC
Iptacopan, a Factor B inhibitor, only decreased proteinuria 35-40% at 12 months.
Changes in eGFR were not significant and C3 IF staining was only modestly decreased (0.8 on a 12 point scale).
🤔Something better needed to be discovered. #NephJC
January 14, 2026 at 2:38 AM
T3c
Iptacopan, a Factor B inhibitor, only decreased proteinuria 35-40% at 12 months.
Changes in eGFR were not significant and C3 IF staining was only modestly decreased (0.8 on a 12 point scale).
🤔Something better needed to be discovered. #NephJC
Iptacopan, a Factor B inhibitor, only decreased proteinuria 35-40% at 12 months.
Changes in eGFR were not significant and C3 IF staining was only modestly decreased (0.8 on a 12 point scale).
🤔Something better needed to be discovered. #NephJC
T3b
Because increased complement activation causes C3GN and IC-MPGN, complement inhibition is a logical target with an increasing list of efficacious meds.
However, previous complement inhibitors eculizumab/avacopan (C5/C5a inhibitors) showed limited effects due to ongoing C3 activation. #NephJC
Because increased complement activation causes C3GN and IC-MPGN, complement inhibition is a logical target with an increasing list of efficacious meds.
However, previous complement inhibitors eculizumab/avacopan (C5/C5a inhibitors) showed limited effects due to ongoing C3 activation. #NephJC
January 14, 2026 at 2:37 AM
T3b
Because increased complement activation causes C3GN and IC-MPGN, complement inhibition is a logical target with an increasing list of efficacious meds.
However, previous complement inhibitors eculizumab/avacopan (C5/C5a inhibitors) showed limited effects due to ongoing C3 activation. #NephJC
Because increased complement activation causes C3GN and IC-MPGN, complement inhibition is a logical target with an increasing list of efficacious meds.
However, previous complement inhibitors eculizumab/avacopan (C5/C5a inhibitors) showed limited effects due to ongoing C3 activation. #NephJC
T3a
Precision medicine is needed for complement mediated kidney diseases.
The more we know about underlying pathophysiology, the more we want to specifically target the abnormality to halt disease progression (while ideally limiting side-effects). #NephJC
Precision medicine is needed for complement mediated kidney diseases.
The more we know about underlying pathophysiology, the more we want to specifically target the abnormality to halt disease progression (while ideally limiting side-effects). #NephJC
January 14, 2026 at 2:36 AM
T3a
Precision medicine is needed for complement mediated kidney diseases.
The more we know about underlying pathophysiology, the more we want to specifically target the abnormality to halt disease progression (while ideally limiting side-effects). #NephJC
Precision medicine is needed for complement mediated kidney diseases.
The more we know about underlying pathophysiology, the more we want to specifically target the abnormality to halt disease progression (while ideally limiting side-effects). #NephJC
T2j
Safety #NephJC
🛡️ Overall AE rates looked similar between arms
🦠 Serious infections were uncommon, with no encapsulated bacteria signals
⚠️ The only death was in the pegcetacoplan arm due to COVID-19
🧠 Reassuring enough? What other concern would limit PEG use?
Safety #NephJC
🛡️ Overall AE rates looked similar between arms
🦠 Serious infections were uncommon, with no encapsulated bacteria signals
⚠️ The only death was in the pegcetacoplan arm due to COVID-19
🧠 Reassuring enough? What other concern would limit PEG use?
January 14, 2026 at 2:34 AM
T2j
Safety #NephJC
🛡️ Overall AE rates looked similar between arms
🦠 Serious infections were uncommon, with no encapsulated bacteria signals
⚠️ The only death was in the pegcetacoplan arm due to COVID-19
🧠 Reassuring enough? What other concern would limit PEG use?
Safety #NephJC
🛡️ Overall AE rates looked similar between arms
🦠 Serious infections were uncommon, with no encapsulated bacteria signals
⚠️ The only death was in the pegcetacoplan arm due to COVID-19
🧠 Reassuring enough? What other concern would limit PEG use?
T2i
🧬But do the tissue and biology align? #NephJC
🧪 C3 staining decreased in 74% PEG vs 12% placebo
🔬Zero C3 intensity: 71% PEG vs 9% placebo
🔬 Activity score trended lower but was not statistically significant at 26 wks
🎯 Serum C3 ↑ and soluble C5b-9 ↓ after PEG; C4 unchanged.
🧬But do the tissue and biology align? #NephJC
🧪 C3 staining decreased in 74% PEG vs 12% placebo
🔬Zero C3 intensity: 71% PEG vs 9% placebo
🔬 Activity score trended lower but was not statistically significant at 26 wks
🎯 Serum C3 ↑ and soluble C5b-9 ↓ after PEG; C4 unchanged.
January 14, 2026 at 2:33 AM
T2i
🧬But do the tissue and biology align? #NephJC
🧪 C3 staining decreased in 74% PEG vs 12% placebo
🔬Zero C3 intensity: 71% PEG vs 9% placebo
🔬 Activity score trended lower but was not statistically significant at 26 wks
🎯 Serum C3 ↑ and soluble C5b-9 ↓ after PEG; C4 unchanged.
🧬But do the tissue and biology align? #NephJC
🧪 C3 staining decreased in 74% PEG vs 12% placebo
🔬Zero C3 intensity: 71% PEG vs 9% placebo
🔬 Activity score trended lower but was not statistically significant at 26 wks
🎯 Serum C3 ↑ and soluble C5b-9 ↓ after PEG; C4 unchanged.
T2h
🟢 Don't forget the eGFR. Stable or improved eGFR (≤15% decline): 68% pegcetacoplan vs 59% placebo.
📈 Mean eGFR difference at 26 weeks: +6.3 ml/min/1.73m² favoring pegcetacoplan.
#NephJC
🟢 Don't forget the eGFR. Stable or improved eGFR (≤15% decline): 68% pegcetacoplan vs 59% placebo.
📈 Mean eGFR difference at 26 weeks: +6.3 ml/min/1.73m² favoring pegcetacoplan.
#NephJC
January 14, 2026 at 2:32 AM
T2h
🟢 Don't forget the eGFR. Stable or improved eGFR (≤15% decline): 68% pegcetacoplan vs 59% placebo.
📈 Mean eGFR difference at 26 weeks: +6.3 ml/min/1.73m² favoring pegcetacoplan.
#NephJC
🟢 Don't forget the eGFR. Stable or improved eGFR (≤15% decline): 68% pegcetacoplan vs 59% placebo.
📈 Mean eGFR difference at 26 weeks: +6.3 ml/min/1.73m² favoring pegcetacoplan.
#NephJC