The #NephJC crew landed on #KidneyWk, and the team is back to bring you the science behind the headlines! From Thursday through Saturday, we’ll be sharing selected highlights, focusing on late-breaking clinical trials and simultaneous publications.
For each study, we’ll unpack the findings, limitations, and consider what they could mean for kidney care. Whether you’re joining the meeting or following along online, pull up a chair and join the discussion.
We did this last year (link) with excellent feedback, so we are bringing it back. Swap and Cristina talked about the rationale (mostly FOMO!) and how this was done here.
Day 1 Studies:
VISIONARY: Sibeprenlimab in IgAN, Rizk et al, NEJM 2026
ORIGIN: Atacicept in IgAN, Barratt et al, NEJM 2026
VIDEO-KD: Video Decision aids in CKD, Volandes et al, JAMA IM 2026
Pregnancy in kidney donors; Wang et al, JAMA 2026
Protein restriction in CKD is worse, Suh et al, JAMA Network Open 2026
Vascular Access outcomes over time, Roetker et al, JASN 2026
A couple of other studies were published which are not getting into:
Longer term data from APPLAUSE-IgAN (iptacopan) Rovin et al, Kidney Int 2026. After VISIONARY and ORIGIN, these look pretty tame results. They are important nevertheless as access to these drugs varies. Read the studies - it does suggest ongoing benefit.
Urinary biomarkers from the SANCTUARY trial (Ravulizumab in IgA) Cammett et al CJASN 2026 - and it seems this molecule was approved by the FDA today.
Double bonanza for IgAN therapeutics today: atacicept and sibeprenlimab both report their final phase 3 results in NEJM.
We’ve spent a lot of time on both of these trials. We covered the proteinuria interims (ORIGIN Interim, NephJC summary) and (VISIONARY Interim, NephJC summary), and both times we said the same thing: lovely proteinuria data, but we’ll hold the Hallelujah until the eGFR slope arrives. Well, the slopes are here.
Sibeprenlimab: and the kidneys followed
Sibeprenlimab in IgA Nephropathy — Final Phase 3 Trial Analysis
Authors: Dana V. Rizk, M.D., Jonathan Barratt, Ph.D., Yusuke Suzuki, M.D., Ph.D., Hong Zhang, M.D., Ph.D., Muh Geot Wong, M.B., B.S., Ph.D., Adrian Liew, M.B., B.S., M.R.C.P., Richard Lafayette, M.D., Vladimír Tesař, M.D., Ph.D., Hernán Trimarchi, M.D., Ph.D., Kevin Carroll, Ph.D., Ian S.D. Roberts, M.B., Ch.B., Vivekanand Jha, M.D. https://orcid.org/0000-0002-8015-9470, Alejandra Quevedo, M.D., Seung Hyeok Han, M.D., Ph.D., Rosnawati Yahya, M.B., B.Ch., M.R.C.P., Chee Kay Cheung, M.B., Ch.B., Ph.D., Raja Ramachandran, D.M., M.D., Michael Walsh, Ph.D., Bobby Chacko, M.D., D.M., Manuel Praga, Ph.D., Jin-Bor Chen, M.D., José Suassuna, M.D., Ph.D., Jing Xia, Ph.D., Lokesh Shah, M.D., and Vlado Perkovic, M.B., B.S., Ph.D., for the VISIONARY Trial Investigators Group*
Why was the study done?
We all know Sibe! Sibeprenlimab is a monoclonal antibody that neutralizes APRIL selectively. In the interim analysis, 24-hr UPCR at 9 months was reduced by 51.2% Vs placebo, which supported accelerated approval. When we covered it, our question was whether the kidneys would follow, and whether blocking APRIL alone is enough.
How was it done?
This is the same double-blind VISIONARY design: sibeprenlimab 400 mg subcutaneously every 4 weeks vs placebo for 100 weeks. Like all IGAN trials, these are biopsy proven IGAN, with proteinuria > 1g, eGFR > 30, and excluding sedonary IgAN. Everyone got RASi, flozins were allowed, not mandated. Patients with T2 or C2 on MEST-C, nephrotic syndrome, or heavy fibrosis were excluded. The key secondary endpoint was the annualized eGFR slope over 24 months.
Figure S1: VISIONARY Trial design from Rizk et al, NEJM 2026
What did it show?
The cohort was 510 adults (259 vs 251) with biopsy-proven IgAN, proteinuria ≥0.75 g/g (or ≥1 g/day), and stable maximal RAS blockade, with a mean eGFR of 64 and 45% on SGLT2i. The slope was +0.3 with sibeprenlimab vs −4.2 with placebo (difference 4.5; 95% CI 3.6 to 5.4), with consistent results across sensitivity analyses and subgroups. The 24-month eGFR change was +1.3 vs −7.9 (difference 9.2; 95% CI 7.1 to 11.4). The composite of sustained 40% eGFR decline, creatinine doubling, eGFR <15, or kidney replacement therapy occurred in 1 patient (0.4%) vs 28 (11.2%) (HR 0.029; 95% CI 0.004 to 0.214), with KRT in 5 placebo patients and none on sibeprenlimab. The antiproteinuric effect held at 24 months, with UPCR down 61.3% vs 1.3%. Proteinuria below 0.5 g/day was reached by 36.7% vs 9.1%, and hematuria resolved in 78.6% vs 20.2%. IgA fell about 75%, IgM 77%, and IgG 37%. The subgroup analysis (not shown here) is pretty impressive for consistent effect.
Adverse events were similar (90.7% vs 90.0%). Serious adverse events were 8.1% vs 12.7%, and serious infections 1.9% vs 4.0%. Twenty-four patients dropped below an IgG of 400 mg/dl, but none had a serious or severe infection. There were no deaths.
Figure 1: Composite Kidney End Point (Full Analysis Population) from Rizk et al, NEJM 2026
Table 2: Efficacy Outcomes from Rizk et al, NEJM 2026
What does it mean?
The kidneys followed. An APRIL-only strategy can flatten the slope, and the Gd-IgA1 and hematuria result fits a real change in disease activity. A few methodological notes of caution, the striking hazard ratio (0.029) rests on a single event in the treated arm, so the absolute difference (0.4% vs 11.2%) is the better number to quote. They back it up with logistic and other sensitivity analyses that don’t rely on that assumption. The slope was estimated from week 4 onward, and set aside data after rescue therapy but a post hoc analysis from baseline agreed (difference 4.7). It’s another sponsor-run trial (Otsuka), and follow-up ends at 24 months, with the open-label extension ongoing.
Atacicept: the slope we were waiting for…
Atacicept in IgA Nephropathy — Phase 3 Trial Final Efficacy Analysis
Authors: Jonathan Barratt, Ph.D., Robert M. Brenner, M.D., Sean J. Barbour, M.D., Kirk N. Campbell, M.D., Tom Doan, Necmi Eren, M.D., Jürgen Floege, M.D., Marshall W. Fordyce, M.D., Vivekanand Jha, Zeeshan Khawaja, M.D., Beom Seok Kim, M.D., Ph.D. https://orcid.org/0000-0002-5732-2583, Adrian Liew, M.D., Bart Maes, M.D., Ph.D., Atanu Pal, M.D., D.M., Roberto Pecoits-Filho, M.D., Ph.D., Richard K.S. Phoon, M.D., Dana V. Rizk, M.D., Hitoshi Suzuki, M.D., Ph.D., Vladimír Tesař, M.D., Ph.D., Hernán Trimarchi, M.D., Ph.D., Xuelian Wei, Ph.D., Lixi Yu, Ph.D., Hong Zhang, M.D., Ph.D., and Richard Lafayette, M.D., for the ORIGIN Phase 3 Trial Investigators
Why was the study done?
IgA nephropathy is the most common primary glomerular disease (yes we all know that, but it seems disrespectful to not state this crowdpleaser cliche at least once). Atacicept is a TACI-Fc fusion protein that blocks both BAFF and APRIL. The ORIGIN 3 interim (NephJC summary | Podcast) showed a 45.7% vs 6.8% proteinuria reduction at 36 weeks, which led to FDA accelerated approval in July 2026. Approval on a surrogate endpoint comes with a promise to show the hard eGFR data will follow, so this is that report.
How was it done?
We’ve discussed this many times before - the IgAN trials follow a cookie cutter established design. It is the same double-blind, placebo-controlled design: adults with biopsy-proven IgAN on maximal supportive care, randomized 1:1 to atacicept 150 mg weekly subcutaneously or placebo. Proteinuria > 1g/day and eGFR > 30 with a BP < 150/90 and excluding secondary IgA, nephrotic syndrome or RPGN. Everyone gets background RASi, flozin use is measured, not mandated. Finerenone is not even mentioned (since FIND-CKD [Heerspink et al NEJM 2026 | NephJC summary | podcast] was still ongoing at the time this was designed).
Figure S1, Trial design, from Barratt J et al, NEJM 2026,
The analysis plan changed in May 2026, after alignment after the sponsor agreed this with the FDA, so the final analysis looks at eGFR at week 52 (instead of week 104) plus the annualized slope through week 104. That lets patients move to open-label drug sooner, again, a sign of how hard a prolonged placebo is becoming to justify in this rapidly changing times.
What did it show?
Of 431 randomized, 428 were treated (214 per arm), with a median age of 41, about 55% Asian, and an impressive 61% on flozins at baseline. Mean eGFR was 64 ml/min/1.73 m2 and UPCR was about 1.6 g/g.
At week 52 the eGFR change was −0.11 with atacicept vs −5.69 with placebo (difference 5.58; 95% CI 3.68 to 7.48). The annualized slope through week 104 was −0.60 vs −5.60 (difference 5.00; 95% CI 3.55 to 6.45). That atacicept slope sits under the KDIGO 2025 target of losing less than 1 ml/min/yr - and practically implies hardly any loss of GFR at all. The composite of a sustained 30% eGFR decline, eGFR <15, dialysis, transplant, or death occurred in 11 patients (5.1%) vs 38 (17.8%) (HR 0.24; 95% CI 0.12 to 0.48). Nobody on atacicept reached dialysis, transplant or death, compared with 7 patients on placebo. The rest of the hierarchy fell in line too: UPCR down 53% vs 5%, Gd-IgA1 down 66%, and hematuria resolved in 81% vs 21%. Subgroups, including by baseline eGFR and flozin use, pointed the same way.
Figure 1, Mean Change in Estimated GFR, Annualized Estimated GFR Slope, and Composite Kidney-Disease Progression, from Barratt J et al, NEJM 2026,
Adverse events were similar (74.8% vs 78.0%), and serious events were fewer with atacicept (7.0% vs 15.4%). Infections were balanced, and there were no opportunistic infections or clinically relevant hypogammaglobulinemia, despite the expected drop in immunoglobulins. Injection-site reactions were more common (30.4% vs 7.5%). Antidrug antibodies appeared in nearly half of atacicept patients, with no apparent effect on efficacy or safety.
Table 2. Key Secondary Efficacy End Points from Barratt J et al, NEJM 2026
What does it mean?
This is the confirmation we asked for. Atacicept stabilized eGFR on top of contemporary care, and the proteinuria signal was based on actual biology, not just a surrogate. Some caution still applies. The composite was driven entirely by the 30% eGFR decline, and hard outcomes were few. The placebo slope (−5.6) is steep, and 21% of placebo patients discontinued vs 7% on atacicept, though the post hoc ITT analysis still held (slope difference 4.15). The composite was driven entirely by a sustained ≥30% eGFR decline, a lower bar than the 40% decline used in VISIONARY. Only 7 patients (all on placebo) reached dialysis, transplant, or death, so the hard-outcome data are still sparse. Only 50 atacicept and 37 placebo patients contributed at week 104, because of open-label crossover and the June 2026 data cutoff. The slope through 104 is therefore largely extrapolated from earlier follow-up. It’s a sponsor-run trial with no active comparator, and newer IgAN drugs were barred during the blinded period. Two years of follow-up won’t tell us about durability, so we’ll watch the open-label extension. Even with the caveats, the eGFR slope on atacicept is the one we’ve been waiting for, so a restrained “Hallelujah” feels earned.
So who wins: dual BAFF/APRIL or APRIL alone?
We asked this in the interim blogs, and these papers give the first answer on eGFR. Atacicept’s slope difference was 5.0 and sibeprenlimab’s was 4.5, with hematuria resolution at about 80% for both and similar safety. Honestly, it’s a draw. Cross-trial comparisons are risky: the composite endpoints differ (30% vs 40% decline, plus creatinine doubling or KRT), the placebo slopes differ (−5.6 vs −4.2), and the follow-up timepoints differ. Only a head-to-head trial or longer follow-up will separate them. For now, upstream B-cell and plasma cell modulation holds up as a real disease modifying strategy in IgAN, and that is real good news for us. Whether it is APRIL alone or BAFF/APRIL combined as a mechanism doesn’t seem to matter with these empiric data.
What about access and cost?
Sibeprenlimab (Voyxact) was approved by the FDA under accelerated approval on November 25, 2025, with an estimated annual net price of $292,500. Atacicept (Trutakna) followed on July 7, 2026, with a list price (wholesale acquisition cost) of $32,700 for a 28-day supply, roughly $425,000 a year. Net and list prices aren’t comparable, so the real gap is smaller than it looks. There are also telitacicept (China) and povetacicept on the way, so this space is likely to get crowded, though unlikely any cheaper.
Neither drug is cheap, and both are weekly or monthly injectables that need specialist prescribing and payer approval. As NephJC noted last year, most IgAN patients live in Asia, where access to these agents is far more limited than in the US. The data on palliativbe therapies (aka supportive management) has also improved with data on flozins (DAPA-CKD), finerenone (FIND-CKD). Perhaps atrsentan and sparsentan also belong here? There are also other intermediate agents with effect sizews in between, such as iptacopan, and ravulizumab. And let’s not forget good old steroids - and fancier steroids (targeted release budesonide) as well.
JAMA | Original Investigation
Video Decision Support and Advance Care Planning in Older Adults With Advanced Kidney Disease
The VIDEO-KD Randomized Clinical Trial
Angelo E. Volandes; Joshua R. Lakin; Yuchiao Chang; Charlotta Lindvall, MD; Lisa M. Quintiliani; Andrew L. Lundquist; Annie Liu, MD; Manjula Kurella Tamura; Mark Unruh, MD; Susan P.Y. Wong; Aretha Delight Davis,; Cynthia Garde; Lori Henault,; Upeka Samarakoon; Amresh Hanchate; Ernest Mandel; Jamie A. Green; Kyla Lawson; Seth N. Randa; Michael K. Paasche-Orlow.
Published Online: October 22, 2026 doi: 10.1001/jamainternmed.2026.5989
Why was the study done?
VIDEO-KD was done to address a gap of older adults facing kidney failure: dialysis vs conservative kidney management. The authors describe a practical problem on advanced CKD care: conservative management is not consistently discussed, goals and preferences often remain undocumented, and dialysis can become the default during an acute illness rather than an informed choice.
So far, previous kidney decision-support trials have shown promising but varied results. Education improved knowledge, but video was not significantly better than the verbal script, and treatment preferences did not differ between groups (Eneanya et al, Am J Nephrol 2020). Other interventions improved decision quality (Landin et al, Ann Intern Med 2023) and advance care planning (ACP) engagement and increased advance directive documentation , Lupu et al, AJKD 2022). Thus, earlier trials had demonstrated improvements in decision quality and formal ACP documentation, while VIDEO-KD extends this evidence to documentation of kidney-treatment discussions.
The intervention therefore targeted two steps: understanding the options, through a video decision aid, and communicating preferences, through a patient-created video, audio, or written declaration shared with the clinician.
How was the study done, and what did it show?
This was a randomized trial at 12 outpatient clinics including 453 adults > 65 years or older with advanced CKD (eGFR ≤30 mL/min/1.73 m²) who were not yet receiving dialysis.
Intervention participants combined a 12-minute video explaining HD, PD, and conservative kidney management. They then created a video, audio, or written statement describing their values and treatment preferences, which was sent to their treating clinician. Controls received usual care.
The primary outcome was ACP documentation within 12 months, or before death, whichever came first. Outcome reviewers were masked to treatment assignment.
Figure1, flowchart of the study population, from Volandes, JAMA, 2026
ACP documentation was higher in the intervention: 56.6% versus 40.0%, an absolute increase of 16.6 percentage points (95% CI, 7.5-25.7; p<0.001). Documented discussions of kidney-treatment options also increased: 46.1% versus 31.6%.
Immediately after the video, the proportion of intervention participants who were undecided fell from 39.6% before the video to 13.2%. Conservative management was preferred by 50.7%, compared with 31.8% of controls at enrollment. These were stated preferences, not treatment subsequently received.
Table 2, primary and secondary outcomes at 12 months, from Volandes, JAMA, 2026
How should we interpret it?
The design: randomization, multicenter recruitment and masked outcome, strengthen the primary finding. However, the trial tested the whole package: education, plus a personal statement shared with the clinician, so the contribution of each cannot be separated.
The preference findings deserve more caution: intervention patients were reassessed immediately after the video, whereas controls were assessed only at enrollment. The study therefore did not establish whether preferences remained stable over time. It also did not measure whether clinicians viewed the declarations, whether documentation was comprehensive, or whether subsequent care matched patients’ wishes.
The practical takeaway: this approach improved the recording of treatment conversations and helped patients articulate an immediate preference. Whether it leads to better real-world treatment decisions remains unanswered.
Renal reserve, or reserved judgement? Preeclampsia after kidney donation
Pregnancy Outcomes After Living Kidney Donation
Carol Wang; Kyla L. Naylor; Eric McArthur; James A. King; Jessica M. Sontrop; Joseph Beyene; Dervla Connaughton; Elizabeth Hendren; Michelle Hladunewich; Ngan N. Lam; Krista L. Lentine; Rhiannon Lyons; Sarah D. McDonald; Pavel S. Roshanov; Erik Youngson; Amit X. Garg.
JAMA Published Online: October 22, 2026
doi: 10.1001/jama.2026.21737
Why was the study done?
About two-thirds of living kidney donors are female, and most are of childbearing age. That makes "Can I still have a baby?” a standard question at donor evaluation. The 2004 Amsterdam forum said yes, with no expected penalty (Delmonico F, Transplantation, 2005). Three later studies disagreed. One compared pregnancies before and after donation in Minnesota (Ibrahim NH et al, Am J Transplant, 2009). One used Norwegian registry data (Reisaeter AV et al, Am J Transplant, 2009). The third was an Ontario-matched cohort of 131 donor pregnancies (Garg AX, NEJM, 2015). All three suggested more gestational hypertension or preeclampsia after donation.
KDIGO’s 2017 donor guideline responded by recommending that candidates be counseled about the risk (Lentine KL et al, Transplantation, 2017). Systematic reviews still graded the evidence as low to moderate certainty, because the studies had few postdonation pregnancies and wide CIs (Pippias M et al, Am J Transplant, 2022; Bellos and Pergialitois, Eur J Obstet Gynecol Reprod Biol, 2022).
The biology is plausible. Pregnancy requires a large rise in renal blood flow and GFR and a solitary kidney has already used much of its reserve. In uninephrectomized mice, pregnancy produced impaired renal adaptation, placental hypoperfusion, and an angiogenic state (Dupont V et al, JCI, 2022).
The question was this: in a larger cohort drawn from three Canadian provinces, after donation, more often complicated by hypertensive disorders than pregnancies in matched healthy donors?
How was the study done, and what did it show?
This was a matched cohort study using link administrative data from Ontario, British Columbia, and Alberta, with a protocol published in advance (Wang C et al, CJKHD, 2021). Donors were females who donated between July 1992 and August 2021 at 10 centers and later had a singleton pregnancy of at least 20 weeks. Each donor pregnancy was matched 1:4 to nondonor pregnancies on delivery date, maternal age, time from cohort entry to delivery, parity, and neighborhood income quintile. The authors excluded anyone with any of 35 conditions that would preclude donation, required recent primary care contact, and assigned each non-donor a simulated nephrectomy date. Estimates were calculated within each province and pooled by fixed-effect meta-analysis. Follow-up ran to March 2023, and the unit of analysis was the pregnancy, not the person.
The final sample was 385 pregnancies in 353 donors and 1540 pregnancies in 1535 non-donors. Mean age at delivery was 32.7 vs 32.6 years, and about a third of mothers were 35 or older. Delivery came a mean of 5.6 years after donation. Roughly a third of the donor pregnancies were already in the 2015 NEJM report (Garg AX, NEJM, 2015).
Figure- flowchart of inclusion and exclusion criteria for selecting donors and non-donors, from Wang C, JAMA, 2026
Gestational hypertension (RR 1.51, 95% CI 1.10 to 2.08) was again significantly higher in pregnancies after kidney donation. So was preclampsia or eclampsia (RR 1.52, 95% CI 1.10 to 2.29). More striking was small for gestational age (SGA, below 1oth percentile) which stood out: 13.8% vs 7.9% (RR 1.86; 1.37-2.52, risk difference 5.4 points). The post hoc cutoffs pointed the same way, with RR 1.84 below the 5th percentile and 2.47 below the 3rd. Early onset disease before 34 weeks was rare (1.6% vs 1.3%). Preterm birth, low birth weight, NICU admission, and cesarean delivery did not differ significantly, severe maternal morbidity was 4.4% vs 6.5%, and there were no stillbirths in either group.
Table 3. Maternal and fetal outcomes of kidney donor and nondonor pregnancies, from Wang C, JAMA, 2026
The primary result held when pregnancies from the 2015 study (Ontario deliveries before April 2013) were excluded (RR 1.58; 1.05-2.36). It was similar in nulliparous and parous pregnancies. It was larger at maternal age 35 or older (RR 1.99, 1.18-3.33) than under 35 (RR 1.41; 0.93-2.15). The E-value for the lower bound of the primary CI was 1.40 (VandeWeele and Ding, Ann Intern Med, 2017).
What does it mean?
Hypertensive disorders of pregnancy appear modestly more common after donation. The crude difference is 3.6 percentage points, about one extra hospitalized case per 28 donor pregnancies. The modelled difference is 2.7 points, about one per 37, and its CI includes zero. Most donor pregnancies (88%) were unaffected, and early-onset disease was not increased.
The data cannot tell us why. An RR of 1.51 on a code-based composite, with an E value of only 1.40, supports counseling but does not prove the nephrectomy causes preeclampsia. Start with what’s missing: there is no blood pressure, BMI, aspirin use, or postdonation eGFR. The “renal reserve” mechanism is therefore never measured. The outcome itself is blunt, putting gestational hypertension and severe preeclampsia in the same bin.
Ascertainment bias is possible. Donors have slightly more surveillance than non-donors in Ontario, with a median of 4 vs 3 ultrasounds, 11 vs 10 prenatal visits, and 12 vs 11 urinalyses. The difference is small, but it runs in the direction that would inflate a coded diagnosis. Unmeasured confounding is plausible. In Ontario, 64% of donors were first-degree relatives of their recipients. A shared hereditary tendency to vascular or kidney disease could easily produce an association of 1.4, and the relatedness analysis was too small to settle the question. Multiplicity is another concern. With 12 secondary and 8 post hoc outcomes, the SGA signal could be chance, as the authors acknowledge, although its consistency across percentile cutoffs is hard to dismiss.
Finally, generalizability is limited. Race and ancestry were not available, most donors were White, and care was delivered in publicly funded systems. Donors of African ancestry, including APOL1 high-risk carriers, remained unstudied (Hsu et al, JAMA Internal Med, 2026).
Fou counseling, this is now the most precise estimate available, and it moves the field from “maybe” to “modest but real”. Whether donors should be managed as a high-risk group, for example with aspirin prophylaxis and closer blood pressure follow-up, is a question this dataset cannot answer. Has nephrectomy dented the placenta’s supply line, or are we seeing the family history that the donor shares with the recipient?
Nevertheless - while we do not want to dissuade living kidney donation, these are potential future risks (and notably absolute risks remain small despite the significant relative risks) that should be discussed with potential donors, particularly if pregnancy is in their future. There was a similar notable finding in male kidney donors (Garg et al, Annals IM 2025; a RR of about 39 for hydrocele and scrotal surgery on the side of the laparoscopic kidney donation) which is again worth discussing with male donors as well.
Low Daily Protein Intake and Risk of Kidney Failure and Mortality in Chronic Kidney Disease
Sang Heon Suh, MD, PhD1,2; Hong Sang Choi, MD, PhD1,2; Chang Seong Kim, MD, PhD1,2
Eun Hui Bae, MD, PhD1,2; Jayoun Kim, PhD3; Ji Yong Jung, MD, PhD4,5; Jong Cheol Jeong, MD, PhD6; Kyu-Beck Lee, MD, PhD7; Kook-Hwan Oh, MD, PhD8,9; Seong Kwon Ma, MD, PhD1,2; Soo Wan Kim, MD, PhD1,2; for the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) Investigators
JAMA Netw Open Published Online: October 22, 2026 2026;9;(10):e2634568. doi:10.1001/jamanetworkopen.2026.34568
Why was the study done?
Low protein diet was the OG intervention for CKD, to slow down the inexorable decline….predating RAS inhibition. And an ancient intervention like that should remain there, in the cobwebs of nephrology history. After all, the large, randomized trials were emphatically negative (eg MDRD, Klahr et al NEJM). However, the KDOQI guidelines gave low protein diets a grade 1A recommendation - and KDIGO still has it in there, though significantly downgraded as a practice recommendation in select patients - and the main recommendation (2C) is for a higher protein intake of 0.8-1 g/kg/day. But this topic - though entirely non-controversial, remains something that is practiced in parts of the world (coupled with the $$$ ketoanalogues - despite this negative trial: Bellizzi et al, Am J Clin Nutr 2022) based on biased and poorly conducted and analysed observational studies. On NephJC we have discussed this issue tangentially (NephJC short on cost analysis; NephJC summary on protein supplements). The major issue here of course is that a low protein diet will lower the serum creatinine - by causing muscle wasting and malnutrition. This is how the MDRD formula was derived in the first place from the MDRD trial - all patients underwent nuclear GFR estimation and not serum creatinine based measurements. Practitioners still prescribing and using low protein diets are thus either ignorant, illinformed, or charlatans (or some combination). Nevertheless - changing diet is always a popular method which patients invariably ask us about diet as an intervention (see this entertaining blog about one such story from the Last Month team). Possibly this is still prevalent in Korea - hence the relevance of this study.
How was the study done, and what did it show?
This was an observational study using the KNOW-CKD cohort, which included patients ranging from CKD stage 1 (!) to advanced CKD stage 5 not on dialysis, from 2011 to 2016. The study observation ended 2024. In this analysis, they used 5 groups of dietary protein intake (DPI) - calculated from everyone having 24 hour urines and nitrogen measurement - at baseline, and not with poor quality food diaries or food frequency questionnaires, or unreliable diet recalls. The 5 groups were DPI of less than 0.6, 0.6 to less than 0.8, 0.8 to less than 1.0, 1.0 to less than 1.2, or at least 1.2 g/kg/day. Over the period of follow up, they noted the occurrence of kidney failure (aka dialysis or kidney transplant). All cause mortality and MACE were secondary outcomes, ascertained from medical records. Subgroup and sensitivity analysis including a propensity score matched analysis was done - more on that with results.
Overall, from 2238 participants in KNOW-CKD, 1861 were included (figure 1) with a median follow up of 9.3 years. Table 1 below shows the baseline characteristics - and several features jump out. An impressive 80+ % were on RASi. Low protein intake was more common in females, with higher Charlson score (aka more comorbidities), diabetes, worse CKD status, and higher SBP. Though median ACR was lower in this group, the proportion with ACR > 300 mg/g was similar. Thus overall slightly higher risk of CKD even at baseline in the low protein diet group.
Table 1 from Suh et al, JAMA NO, 2026
After a median of 9.3 years follow up, 345 ended up with kidney failure, and there was a gradient of higher risk with lower DPI (see table 2 and figure 2). This was after adjustment for the covariates mentioned in table 1 above. All cause mortality (but not MACE) were also higher in the low DPI group.
Figure 2 from Suh et al, JAMA NO, 2026
Table 2 from Suh et al, JAMA NO, 2026
The results were robust in all analysis, including restriction to those with normal serum albumin, diabetes status, sx, and after propensity score matching.
What does it mean?
Low protein diets should be dead, but like zombies they remain practiced in many places. This is another stake in their body (but not a decapitation which is what zombies deserve). The main limitation is that table 1 gives us a lot of concern. The association of worse CKD status with low protein intake might mean someone may have recognized them as higher risk and advised low protein intake. That is a form of selection bias which we cannot adjust away. The higher mortality is a slightly more robust signal - and the authors talk a low about protein energy wasting in the discussion as a cause despite not showing any data to support that in their study. Malnutrition does occur - famously in the long term outcomes of MDRD too higher mortality was noted, presumably from similar mechanisms. We have written about these topics as well in the past for unconvinced readers (Bawazir et al, J Bras Nefrol 2025 and Obeid et al Kidney360 2022).
Trends in Mortality of Patients with Central Venous Catheters versus Arteriovenous Accesses for Hemodialysis
Nicholas S. Roetker, James B. Wetmore, Jiannong Liu, David T. Gilbertson, Kirsten L. Johansen
Journal of the American Society of Nephrology Publish Ahead of Print, October 22, 2026. | DOI: 10.1681/ASN.0000001293
Why was the study done?
Another comparative vascular access study! The fistula first zealots believe in every hemodialysis patient getting an arteriovenous fistula aka AVF (or AV Graft) and the infidel non-believers do not (and even dare to attempt doing a clinical trial comparing the two; Quinn et al, JASN 2026). A central venous catheter (CVC) aka the line of death - are associated with higher infection rates, and many observational studies suggest a significantly higher mortality rate (eg Xue et al AJKD 2003). OTOH, the heretic Canadians point out that such comparisons are inherently biased, as sicker patients, those who are not good AVF surgical candidates, and those whose AVFs fail get into the CVC control group which represents a huge selection bias. See figure below from Quinn and Ravani, NDT 2014. To belabor this point, in this prospective observational study, they demonstrated that even an attempt to create a fistula predialysis (regardless if that attempt was successful)l was associated with a lower mortality - however only 2.3% of the deaths were access related. Hence the vast majority of this ‘excess’ mortality probably captures underlying higher risk features not related to CVC or AVF interventions.
Figure from Quinn and Ravani, NDT 2014.
Since the pilot AVF vs CVC trial (Quinn et al, JASN 2026) was unable to recruit successfully, this observational trial takes a similar approach in a much larger number of patients.
How was the study done, and what did it show?
This study was done with USRDS data - and the figure below shows the methods in more detail. The patient population was incident kidney failure from 2013 to 2022. Notable aspects are:
Patients with an AVF (or maturing AV access) at dialysis initiation were excluded, which removes some of the immortal time bias that would be accrued by these patients.
a clone-censor-weighting approachwas used to evaluate two treatment patterns
beginning at hemodialysis initiation: continuous CVC use versus successful transition to an AV access
inverse-probability-of-censoring weighting was then used to account for selection bias from artificial censoring and maintain the covariate balance over follow-up. This approach
Figure 2 from Roetker et al, JASN 2026
The base cohort was followed until the earliest occurrence of death, treatment modality change, a 3-month EQRS data gap, loss to follow-up, or 18 months of follow-up.The primary outcome was all-cause death, and the secondary outcome was bloodstream infection (BSI) related death.Specifically, the authors wanted to measure the difference between CVCs and AVF, but also evaluate the change over time.
Figure 1 from Roetker et al, JASN 2026
The overall study included ~ half a million dialysis patients, as shown in figure 1. This excludes about 350,000 with functioning or mature AV accesses. The median age was 63 years, with 47% non-Hispanic Whites, representing the usual mix of the US dialysis population. At hemodialysis initiation, 46% of patients had received no prior nephrology care (reflecting this select group with CVCs).
Table 2 from Roetker et al, JASN 2026
Among patients initiating HD with a CVC in 2013 and remaining on a CVC, the 18-month cumulative risk of death was 26.8%, ~ 5.9% absolute risk higher than in those with AVF. By 2022, this absolute risk had decreased to 4.2%, as seen in table 2. The BSI-related eaths were a much smaller component of this, at 2.19 versus 1.49, and demonstrate a similar shrinkage of differences over time (from 0.72 to 0.37) over time as shown in figure 3.
Table 3 from Roetker et al, JASN 2026
Figure 3 from Roetker et al, JASN 2026
What does it mean?
Things are getting better - which is a hopeful note regardless of the CVC/AVF fights. Notable this is despite including the 2020-22 pandemic years in the analysis. A lot has been done to prevent blood stream infections (with CDC-led initiatives and tracking and measurement) along with the underlying secular improvement over time. Secondly, the difference in outcomes between AVF and CVC mortality is clearly decreasing, especially more marked in the absolute scale. Lastly, though the same also applies not just to all-cause mortality but to blood stream infection related mortality - the absolute numbers here are about a tenth of the all-cause mortality. Unless one believes that CVC kills dialysis patients by another mechanism such as inflammation (and we ignore the Zeus non-effect) - this just demonstrates the sheer magnitude of underlying bias that cannot be adjusted away despite the sophisticated methodology. Patients who get AVF surgery are inherently different. Databases may also under-ascertain underlying comorbid conditions as the authors point out, which limits the ability to adjust for these confounders.
Overall this is a good news story, with greater methodological strength - albeit not perfection - than the average observational study in this area. Though another AVF vs CVC trial may drop soon, (the OASIS trial of ~ 150 patients from Netherlands was presented today showing no difference between randomization to CVC vs AVF, final publication awaited) - this is high quality data that we have now on the relative outcomes and change over time.
Summaries by Cristina Popa, Akshaya Jayachandran ,
Brian Rifkin, Milagros Flores, Swapnil Hiremath