This Week in Nephrology — Oct 28, 2026
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The week's practice-changing Nephrology research, summarized for clinicians.
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Atacicept in IgA Nephropathy - Phase 3 Trial Final Efficacy Analysis.
Weekly atacicept kept eGFR essentially stable over two years in IgA nephropathy and cut composite kidney progression by about three quarters versus placebo, with fewer serious adverse events.
New England Journal of Medicine · 2026 · PubMed
This week’s papers
- 01
Atacicept in IgA Nephropathy - Phase 3 Trial Final Efficacy Analysis.
Weekly atacicept kept eGFR essentially stable over two years in IgA nephropathy and cut composite kidney progression by about three quarters versus placebo, with fewer serious adverse events.
Barratt J, Brenner RM, Barbour SJ, et al. · New England Journal of Medicine · 2026
From the briefingThe final efficacy analysis of ORIGIN 3, led by Barratt, randomized 428 adults with biopsy-confirmed IgA nephropathy to weekly subcutaneous atacicept, which blocks both BAFF and APRIL, or placebo [1]. At one year, kidney function in the atacicept group was essentially flat, while patients on placebo lost close to six units of eGFR. Over two years the annual decline was about five units per year slower with atacicept. Composite kidney progression occurred in about 5 percent of treated patients versus roughly 18 percent on placebo, a reduction in risk of about three quarters, and no atacicept patient progressed to dialysis, transplantation, or death, compared with seven patients on placebo. Serious adverse events were actually less frequent with atacicept.
If you only have time for one paper this week, make it the final ORIGIN 3 analysis of atacicept in the New England Journal [1]. It moves BAFF and APRIL inhibition beyond proteinuria to two-year eGFR preservation and fewer progression events, reopening the question of what first-line disease-modifying therapy in IgA nephropathy should look like.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 02
Sibeprenlimab in IgA Nephropathy - Final Phase 3 Trial Analysis.
The APRIL inhibitor sibeprenlimab stabilized eGFR over 24 months in IgA nephropathy, with one composite kidney event versus 28 on placebo and no excess serious infections.
Rizk DV, Barratt J, Suzuki Y, et al. · New England Journal of Medicine · 2026
From the briefingAlongside it, the final VISIONARY analysis from Rizk and colleagues tested sibeprenlimab, a monoclonal antibody that inhibits APRIL alone, given every four weeks to 510 patients [2]. The eGFR slope was essentially stable with sibeprenlimab against a loss of about four units per year on placebo, and by two years the gap in eGFR was about nine units. Only one patient on sibeprenlimab reached the composite kidney endpoint, compared with 28 patients on placebo, and serious infections were no more common, about 2 percent versus 4 percent. Taken together, these two trials provide placebo-controlled evidence that blocking APRIL, with or without BAFF, preserves kidney function over two years, not just proteinuria; they remain two-year follow-ups, so hard outcomes like kidney failure are still sparse events.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 03
Interim Analysis of a Phase 3 Trial of Povetacicept in IgA Nephropathy.
In an interim phase 3 analysis, dual BAFF and APRIL inhibitor povetacicept halved proteinuria at 36 weeks and resolved hematuria in most affected patients, though eGFR outcomes are pending.
Barratt J, Zhang H, Han SH, et al. · New England Journal of Medicine · 2026
From the briefingA third agent in the same class, povetacicept, a dual BAFF and APRIL inhibitor, reported a prespecified interim analysis of the RAINIER trial, also in the New England Journal, in another paper led by Barratt [3]. Among the first 199 of 557 participants, proteinuria fell by about half at 36 weeks versus almost no change on placebo, galactose-deficient IgA1 dropped by roughly three quarters, and hematuria resolved in 85 percent of treated patients with baseline hematuria versus 23 percent on placebo. Safety was similar to placebo. This is still a surrogate readout, and the eGFR data that atacicept and sibeprenlimab now have are not yet available for povetacicept. The complement pathway is the other major target.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 04
Ravulizumab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial.
Terminal complement inhibitor ravulizumab lowered proteinuria about 43 percent more than placebo at week 34 in IgA nephropathy, without meningococcal infections, pending kidney function outcomes.
Barratt J, Farag YMK, Rice K, et al. · New England Journal of Medicine · 2026
From the briefingIn the I CAN trial, again in the New England Journal, Barratt and colleagues gave intravenous ravulizumab, a terminal complement inhibitor, every eight weeks to adults with persistent proteinuria despite standard therapy [4]. At week 34, proteinuria was about 43 percent lower than with placebo, with fewer serious adverse events and no meningococcal infections. Again, this is an interim proteinuria result, and kidney function outcomes are pending.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 05
Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy.
In an open-label extension, iptacopan sustained proteinuria reduction to 48 months and slowed eGFR decline in placebo switchers, although ongoing kidney function loss persisted without a control group.
Rovin BH, Trimarchi H, Maes B, et al. · Kidney International · 2026
From the briefingFrom Kidney International, Rovin and colleagues report the open-label extension of APPLAUSE-IgAN with the oral factor B inhibitor iptacopan [5]. Proteinuria reduction was sustained to 48 months, and patients who switched from placebo saw their annual eGFR decline improve from about five units per year to about two. However, patients on iptacopan throughout still lost roughly three and a half units per year, and without a concurrent control group these long-term figures are descriptive. One emerging contrast is worth flagging: in the trials reporting eGFR slopes this week, the B-cell-directed agents appeared to nearly flatten decline over two years, whereas the iptacopan extension shows ongoing loss; these were different populations and designs, so this is not a head-to-head comparison, and the question of sequencing or combining these mechanisms is unanswered.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 06
Efficacy and safety of eculizumab in patients with anti-glomerular basement membrane disease: an investigator-initiated, open-label, phase II clinical trial.
In 16 patients with anti-GBM disease, adding eculizumab was associated with fewer end-stage kidney events than historical controls, but the small open-label design makes findings exploratory.
Kuang H, Yu Jia X, Chen P, et al. · Nephrology Dialysis Transplantation · 2026
From the briefingComplement inhibition also appeared in a much rarer and more aggressive disease. In Nephrology Dialysis Transplantation, Kuang and colleagues report an investigator-initiated, open-label phase 2 study of eculizumab added to standard care in anti-glomerular basement membrane disease [6]. Among 16 treated patients, a quarter reached end-stage kidney disease by six months, compared with about half of 40 retrospectively identified controls, and three of seven patients needing dialysis recovered kidney function. Urinary and plasma markers confirmed complement blockade. With a single centre, a tiny sample, and historical controls, the authors themselves describe this as exploratory and call for adequately powered trials.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 07
Initiation of Apixaban Versus Warfarin in Patients With Kidney Failure on Hemodialysis With Newly Diagnosed Atrial Fibrillation: A Target Trial Emulation.
Among hemodialysis patients with new atrial fibrillation, starting apixaban rather than warfarin was associated with about a third less ischemic stroke and a quarter less bleeding, with residual confounding possible.
Winkelmayer WC, Montez-Rath ME, He M, et al. · American Journal of Kidney Diseases · 2026
From the briefingIn the American Journal of Kidney Diseases, Winkelmayer and colleagues emulated a target trial using the United States Renal Data System, comparing apixaban with warfarin started within 30 days of newly diagnosed atrial fibrillation in patients on hemodialysis [7]. Among nearly 4,000 matched pairs with a median CHA2DS2-VASc score of 4, apixaban initiation was associated with about a third lower rate of ischemic stroke and about a quarter lower rate of clinically important bleeding, with no difference in mortality and no signal in negative control outcomes such as hip fracture. Treatment durations were short in both groups, and residual confounding remains possible, but this adds observational support for apixaban over warfarin when anticoagulation is chosen in this population; it does not settle whether to anticoagulate at all.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 08
Efficacy and Safety of Upacicalcet in Hemodialysis Patients with Secondary Hyperparathyroidism: Two Randomized Clinical Trials.
Intravenous calcimimetic upacicalcet more than doubled the proportion of hemodialysis patients achieving a 30 percent parathyroid hormone reduction, but asymptomatic hypocalcemia and dose interruptions were common.
Kendrick J, Ketteler M, Wolf M, et al. · Journal of the American Society of Nephrology · 2026
From the briefingIn the Journal of the American Society of Nephrology, Kendrick and colleagues report the twin PATH trials of upacicalcet, an intravenous calcimimetic given after dialysis, in 768 patients with secondary hyperparathyroidism [8]. In both trials, roughly 43 percent of patients on upacicalcet achieved at least a 30 percent fall in parathyroid hormone, versus about 17 percent on placebo. Gastrointestinal effects matched placebo, but corrected calcium below 7.5 occurred in between a third and close to half of treated patients, roughly double the placebo rate, and dose interruptions were common, though symptomatic hypocalcemia was rare. These are 27-week biochemical results without a comparison to existing calcimimetics or any hard outcome data.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 09
KDOQI Commentary on the 2025 AHA/ACC Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.
A KDOQI work group endorses most of the 2025 hypertension guideline for non-dialysis chronic kidney disease, including the below 130 over 80 target and PREVENT risk calculator, while noting evidence gaps.
Chang TI, Cluett JL, Cohen DL, et al. · American Journal of Kidney Diseases · 2026
From the briefingIn the American Journal of Kidney Diseases, a KDOQI work group led by Chang reviews the 2025 American Heart Association and American College of Cardiology hypertension guideline for people with non-dialysis chronic kidney disease [9]. The work group supports most recommendations, including the general target below 130 over 80, and highlights that the guideline formally adopts the PREVENT calculator, which incorporates kidney and metabolic parameters into cardiovascular risk estimation. The group adds expert commentary on medication interactions, electrolytes, and kidney injury, and notes areas where evidence in chronic kidney disease remains thin.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
- 10
Video Decision Support and Advance Care Planning in Older Adults With Advanced Kidney Disease: The VIDEO-KD Randomized Clinical Trial.
A video decision aid with patient-recorded preferences raised advance care planning documentation from 40 to about 57 percent in older adults with advanced kidney disease and reduced treatment indecision.
Volandes AE, Lakin JR, Chang Y, et al. · JAMA Internal Medicine · 2026
From the briefingFinally, in JAMA Internal Medicine, Volandes and colleagues report VIDEO-KD, a randomized trial at 12 clinics enrolling 453 adults aged 65 or older with advanced chronic kidney disease [10]. Patients who watched a video decision aid covering hemodialysis, peritoneal dialysis, and conservative management, then recorded their own goals for their clinician, had advance care planning documented in about 57 percent of cases versus 40 percent with usual care. After the video, the share of patients undecided about treatment fell from about four in ten to about one in eight, and about half of intervention patients preferred conservative kidney management, compared with about a third of controls. The trial measured documentation and stated preference rather than actual treatment received, but it provides randomized evidence that a scalable tool can shift these conversations.
Written by AI from the published abstract, for healthcare professionals. Not medical advice; check the paper before acting on it.
The full briefing
This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.
Welcome to This Week in Nephrology. This week we're covering 10 notable papers spanning a wave of targeted therapies for IgA nephropathy and complement-mediated disease, new evidence for anticoagulation and mineral bone management in dialysis, and the way we frame blood pressure and end-of-life decisions in chronic kidney disease. Let's dive in.
IgA nephropathy had a remarkable week, with four phase 3 trials in the New England Journal of Medicine and long-term data in Kidney International, and the headline is that the field is moving from proteinuria surrogates toward kidney function itself. The final efficacy analysis of ORIGIN 3, led by Barratt, randomized 428 adults with biopsy-confirmed IgA nephropathy to weekly subcutaneous atacicept, which blocks both BAFF and APRIL, or placebo [1]. At one year, kidney function in the atacicept group was essentially flat, while patients on placebo lost close to six units of eGFR. Over two years the annual decline was about five units per year slower with atacicept. Composite kidney progression occurred in about 5 percent of treated patients versus roughly 18 percent on placebo, a reduction in risk of about three quarters, and no atacicept patient progressed to dialysis, transplantation, or death, compared with seven patients on placebo. Serious adverse events were actually less frequent with atacicept. Alongside it, the final VISIONARY analysis from Rizk and colleagues tested sibeprenlimab, a monoclonal antibody that inhibits APRIL alone, given every four weeks to 510 patients [2]. The eGFR slope was essentially stable with sibeprenlimab against a loss of about four units per year on placebo, and by two years the gap in eGFR was about nine units. Only one patient on sibeprenlimab reached the composite kidney endpoint, compared with 28 patients on placebo, and serious infections were no more common, about 2 percent versus 4 percent. Taken together, these two trials provide placebo-controlled evidence that blocking APRIL, with or without BAFF, preserves kidney function over two years, not just proteinuria; they remain two-year follow-ups, so hard outcomes like kidney failure are still sparse events.
A third agent in the same class, povetacicept, a dual BAFF and APRIL inhibitor, reported a prespecified interim analysis of the RAINIER trial, also in the New England Journal, in another paper led by Barratt [3]. Among the first 199 of 557 participants, proteinuria fell by about half at 36 weeks versus almost no change on placebo, galactose-deficient IgA1 dropped by roughly three quarters, and hematuria resolved in 85 percent of treated patients with baseline hematuria versus 23 percent on placebo. Safety was similar to placebo. This is still a surrogate readout, and the eGFR data that atacicept and sibeprenlimab now have are not yet available for povetacicept. The complement pathway is the other major target. In the I CAN trial, again in the New England Journal, Barratt and colleagues gave intravenous ravulizumab, a terminal complement inhibitor, every eight weeks to adults with persistent proteinuria despite standard therapy [4]. At week 34, proteinuria was about 43 percent lower than with placebo, with fewer serious adverse events and no meningococcal infections. Again, this is an interim proteinuria result, and kidney function outcomes are pending. From Kidney International, Rovin and colleagues report the open-label extension of APPLAUSE-IgAN with the oral factor B inhibitor iptacopan [5]. Proteinuria reduction was sustained to 48 months, and patients who switched from placebo saw their annual eGFR decline improve from about five units per year to about two. However, patients on iptacopan throughout still lost roughly three and a half units per year, and without a concurrent control group these long-term figures are descriptive. One emerging contrast is worth flagging: in the trials reporting eGFR slopes this week, the B-cell-directed agents appeared to nearly flatten decline over two years, whereas the iptacopan extension shows ongoing loss; these were different populations and designs, so this is not a head-to-head comparison, and the question of sequencing or combining these mechanisms is unanswered.
Complement inhibition also appeared in a much rarer and more aggressive disease. In Nephrology Dialysis Transplantation, Kuang and colleagues report an investigator-initiated, open-label phase 2 study of eculizumab added to standard care in anti-glomerular basement membrane disease [6]. Among 16 treated patients, a quarter reached end-stage kidney disease by six months, compared with about half of 40 retrospectively identified controls, and three of seven patients needing dialysis recovered kidney function. Urinary and plasma markers confirmed complement blockade. With a single centre, a tiny sample, and historical controls, the authors themselves describe this as exploratory and call for adequately powered trials.
Turning to the dialysis unit, two papers address long-standing management questions. In the American Journal of Kidney Diseases, Winkelmayer and colleagues emulated a target trial using the United States Renal Data System, comparing apixaban with warfarin started within 30 days of newly diagnosed atrial fibrillation in patients on hemodialysis [7]. Among nearly 4,000 matched pairs with a median CHA2DS2-VASc score of 4, apixaban initiation was associated with about a third lower rate of ischemic stroke and about a quarter lower rate of clinically important bleeding, with no difference in mortality and no signal in negative control outcomes such as hip fracture. Treatment durations were short in both groups, and residual confounding remains possible, but this adds observational support for apixaban over warfarin when anticoagulation is chosen in this population; it does not settle whether to anticoagulate at all. In the Journal of the American Society of Nephrology, Kendrick and colleagues report the twin PATH trials of upacicalcet, an intravenous calcimimetic given after dialysis, in 768 patients with secondary hyperparathyroidism [8]. In both trials, roughly 43 percent of patients on upacicalcet achieved at least a 30 percent fall in parathyroid hormone, versus about 17 percent on placebo. Gastrointestinal effects matched placebo, but corrected calcium below 7.5 occurred in between a third and close to half of treated patients, roughly double the placebo rate, and dose interruptions were common, though symptomatic hypocalcemia was rare. These are 27-week biochemical results without a comparison to existing calcimimetics or any hard outcome data.
Our final theme is how we assess risk and support decisions in chronic kidney disease outside dialysis. In the American Journal of Kidney Diseases, a KDOQI work group led by Chang reviews the 2025 American Heart Association and American College of Cardiology hypertension guideline for people with non-dialysis chronic kidney disease [9]. The work group supports most recommendations, including the general target below 130 over 80, and highlights that the guideline formally adopts the PREVENT calculator, which incorporates kidney and metabolic parameters into cardiovascular risk estimation. The group adds expert commentary on medication interactions, electrolytes, and kidney injury, and notes areas where evidence in chronic kidney disease remains thin. Finally, in JAMA Internal Medicine, Volandes and colleagues report VIDEO-KD, a randomized trial at 12 clinics enrolling 453 adults aged 65 or older with advanced chronic kidney disease [10]. Patients who watched a video decision aid covering hemodialysis, peritoneal dialysis, and conservative management, then recorded their own goals for their clinician, had advance care planning documented in about 57 percent of cases versus 40 percent with usual care. After the video, the share of patients undecided about treatment fell from about four in ten to about one in eight, and about half of intervention patients preferred conservative kidney management, compared with about a third of controls. The trial measured documentation and stated preference rather than actual treatment received, but it provides randomized evidence that a scalable tool can shift these conversations.
If you only have time for one paper this week, make it the final ORIGIN 3 analysis of atacicept in the New England Journal [1]. It moves BAFF and APRIL inhibition beyond proteinuria to two-year eGFR preservation and fewer progression events, reopening the question of what first-line disease-modifying therapy in IgA nephropathy should look like.
Here is what this week's evidence adds up to in Nephrology. First, two randomized trials now show that inhibiting APRIL, alone or with BAFF, nearly halts eGFR decline in IgA nephropathy over two years, while povetacicept and ravulizumab have so far shown only proteinuria benefit, and longer follow-up on kidney failure is still needed for all of them. Second, complement inhibition shows durable but incomplete benefit with iptacopan in IgA nephropathy and only early, uncontrolled promise in anti-GBM disease. Third, for patients on hemodialysis with new atrial fibrillation, observational data favour apixaban over warfarin for both stroke and bleeding, though the broader question of anticoagulation in this group remains open. Fourth, upacicalcet lowers parathyroid hormone more than placebo at the cost of frequent asymptomatic hypocalcemia, with no outcome or comparative data yet. And fifth, randomized evidence shows that video decision support increases advance care planning in older adults with advanced kidney disease, and that many of these patients lean toward conservative management once informed.
That's your roundup for This Week in Nephrology. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.
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