Covering the world 🌐 @hswapnil.medsky.social @nephroseeker.medsky.social 🧑‍💻Reporting in from Yokohama, Japan #ISNWCN 🌸 📰Read all about the late breaking news #NephJC #NephSky www.nephjc.com/news/isnwcn-yokohama

The #ISNWCN has high trial impact clinical trials to celebrate latest and more successful results in our nephro world To celebrate the joy of getting together, and to #NephItForward, we officially opened up the #NephJC Editorial Internship application www.nephjc.com/news/nephjc-...

1/ Today’s #nephjc graduation was pure joy. Seeing mentors and interns from around the world come together reminded me why this community matters. ✨Thank you for making it extraordinary

1/10 Welcome to #TenPostNephJC Can we move beyond slowing CKD → to actually repairing the kidney? Last #NephJC we discussed Rilparencel, a renal autologous cell therapy (REACT) infusion and its effect on eGFR slope.

Up next, we are taking a break on 03/24/26. Don’t forget to play NephMadness! www. ajkdblog.org/2026/03/01/welcome-to-nephmadness-2026/ We will return in April with WCN late breaking news. #NephJC Good night!

This is Dr. Sai Vani. It has been an honor to be your host tonight. I think all of us are celebrating WKD on March 12 and advocating for the importance of preventing kidney diseases and protecting planet Mother Earth. Goodbye until next time!

I sincerely thank all my #NephJC 2025-2026 interns! This is our last discussion. They are #FOAMed heroes. We could not do what we do without them. ♥️

Please thank your #NephJC 2025-2026 interns! This is their last discussion. They are #FOAMed heroes. We could not do what we do without them. ♥️

Please vote for the #NephJC kidneys! 🏆 Sign up for the newsletter to get a ballot. 2026 #NephJCKidneys vote begins — NephJC

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A heartfelt thank you to Brian,Christina and Swapnil for helping me with this beautiful script and to all of our mentors for the ongoing guidance and support! Brian Rifkin, @christina@nephroseeker.medsky.social, #NephJC

A sincere thank you to my #NephJC interim team members. Akshaya Jayachandran Bogdan Agavriloaei#NephJC@nataliaroxona.bsky.social

T3q Great discussion! #NephJC Do you think we are entering the era of remission, and dare I say it, cures for chronic kidney disease. Slowing progression is great, but regenerative treatments are the future! #NephJC

T3p What is the impact in pts with T1DM vs T2DM? This study included T1D but did not report results separately. FINEONE (nsMRA) study suggests similar pathology and benefits. Should T1D get their own study? #NephJC

T3o REACT currently requires a kidney biopsy for harvesting. Normally we don’t do biopsies in obvious DKD. Do you think that your pts with DKD will experience more serious adverse events related to biopsy if the phase 3 trial of rilparencel is positive? #NephJC

T3n Limitations #NephJC ⬇️Small number of pts Exclusion pts with severe CKD Not blinded Still determining optimal dosing and timing

T3m Based on the available data, would you consider enrolling patients with DKD in the phase 3 trial of rilparencel? Are there any patients you would advise not to participate? Do you think REACT will be a viable option in 5-10 years? #NephJC

T3l Various studies are in the pipeline; some are completed, some are recruiting, and the majority of the studies are in the US. #NephJC

T3k There are many potential advantages of REACT over RRT & transplant. Many pts would like to be able to regenerate their own tissue to prevent organ failure, and/or exposure to lifelong immunosuppression. Pts who don’t qualify for transplant might still get rilparencel. #NephJC

T3j Current research is limited by a selection of pts at different CKD stages & different etiologies. Only a few trials, such as the REACT studies, specifically target DKD. Distinct types of kidney damage may affect the efficacy of the treatment. #NephJC

T3i Various studies done with different cell lines in patients with AKI and CKD have been attempted, including stem cells and progenitor cells. These studies are not without controversy, and unfortunately incorporate many elements that may lead to bias in observations. #NephJC

T3h The 2ary endpoints were less insightful due to the limited number of events, & short study. Most 2ary endpoints required a sig change in eGFR or UPCR. Notably, the probability of not meeting the end point was ≥80% for both cohorts through the 18-months. #NephJC

T3g In this small study that received 2 doses of REACT the effect was more impressive on GFR slope than SGLT2/GLP1 with only 1.16-1.24 ml/min/1.73m2/year reduction. If phase 3 trials show similar results, where do you see REACT being used (adjuvant or primary treatment)? #NephJC

T3f Do you think that if we implemented GDMT in a majority of DKD patients that we would even need/consider the use of REACT rilparencel infusions? Is there a high risk group that might benefit significantly from this treatment? Perhaps genetics will be the clue? #NephJC

T3e Pts received kidney protective medications: 💊80% ACEi 💊37% SGLT2i 💉39% GLP-1 RA SGLT2i and GLP-1 RA had less administration because of the lack of CKD guidelines during the period of the study, still these are higher than the general US population. #NephJC

T3d 23/24 pts received 2 injections - cohort 1 15/25 pts received 2 injections - cohort 2 ⬇️ time between injections in Cohort 1 - another possible explanation for differences in eGFR slope between this 2 cohorts The best timing and dose has yet to be determined. #NephJC

T3c Are you not impressed?! #NephJC The findings of the study were significant, and the effect size was substantially larger than the approximately 1.2 mL/min/1.73 m² per year benefit observed with established therapies like SGLT2 inhibitors and GLP-1 RAs in large-scale trials. 🤯

T3b The difference in eGFR slope⬇️ - 4.6 ml/min/1,73m2 in cohort 1 The difference in eGFR slope⬇️ - 1.7 ml/min/1,73m2 in cohort 2 - likely because of the different exposure to rilparencel. #NephJC

T3a The study demonstrated a clinically meaningful difference in CKD progression, measured by change in eGFR slope before and after treatment with rilparencel. Take another look. #NephJC

Let’s inject some energy into the discussion. #NephJC

T2g 🩸Safety profile #NephJC Adverse effects after injection occurred in 16 participants (33%) Three participants experienced six biopsy-related serious adverse events No biopsy-related & no product related death was reported Any other complications you expected?

T2f AND..Reduced 5 yr KFRE risk. #NephJC At mo 18 after the first injection was: Cohort 1: ⬇️29% Cohort 2: ⬇️28% Have you seen this trend with other GDMTs?

T2e Reduced 2 yr KFRE risk. #NephJC At 12 months after the first injection was: Cohort 1: ⬇️29% Cohort 2: ⬇️16%

T2d Change in slope of eGFR from first injection to end of study #NephJC ⬇️Cohort 1: -2.85 ml/min/1,73m2 ⬇️Cohort 2: -2.19 ml/min/1.73m2 The differences are at least partially due to difference in 2nd injections: 24 in 1 vs 15 in 2

T2c Primary outcome #NephJC Cohort 1: ⬇️difference in slope of eGFR after treatment was 4.57 ml/min/1.73m2 Cohort 2: ⬇️ difference in slope of eGFR after treatment was 1.7 ml/min/1.73m2 Are these results surprising to you?

T2b Baseline characteristics Mean age: 60 yo Mean eGFR: 33 ml/min per 1.73 m2 80% of pts on ACE inhibitors 90% Caucasian 78% T2DM, 22% T1DM Does this population seem similar to yours? #NephJC

T2a 🏥 5 sites in the United States 🎲 Screened from July 2021 to March 2023 49 pts treated with rilparencel #NephJC

Let’s move onto the results. To inject or not to inject ? This is the questions #NephJC

T1g Hard endpoints and surrogate end points. The study was only 18 months, do the secondary endpoints seem likely in the study? Many GDMT studies stopped around 24 mo due to efficacy. Can this be possible in the ERA of GDMT in DKD? #NephJC

T1f Secondary outcomes - time from first injection to the following: #NephJC a) ⬇️ 40% reduction in eGFR b) ⬇️ eGFR ,15 ml/min per 1.73 m 2 sustained from 30 days c) ⬇️ 30% and 30 mg/g increase in UACR sustained for 90 days d) kidney or cardiovascular death

T1e Primary Outcome Change in slope of eGFR in the preinjection period and after the last injection. The change in trajectory and change in KFRE prediction were used to show efficacy of rilprancel. #NephJC

T1d Inclusion and exclusion criteria #NephJC Anything else you’d want?

T1c Pts were randomized 1:1, no control (sham) pts #NephJC Cohort 1 - 2 rilparencel injections into the kidney, 3 months apart, 1 in each kidney Cohort 2 - 1 rilparencel injection & 2nd only upon a sustained ⬇️ in eGFR or an⬆️ in UACR

T1b Rilparencel- an autologous cell therapy that is composed of cells obtained by kidney biopsy. The harvested tissue undergoes enzymatic digestion & density gradient separation to isolate a heterogeneous population of renal epithelial lineage cells. #NephJC

T1a 📋 This was a phase 2, multicenter, randomized, open-label trial designed to evaluate the safety and efficacy of rilparencel in adults with type 1 or type 2 diabetes mellitus and advanced CKD. #NephJC

Let’s move on to the methods of this liquid regenerative therapy for DKD #NephJC

T0j A previous study that used rilparencel (a locoregional autologous cell therapy derived from renal biopsy samples) in moderate DKD was conducted in 2019. Rilparencel was well tolerated, and adverse events were consistent with those expected from a kidney biopsy. #NephJC

T0i So, if we dip into our Sci-Fi bag (I’m still waiting on a tricorder), we would develop a way to harvest specific lineages of renal cells, grow them in cultures outside the body and reinject them to damaged kidneys…and that is the idea behind rilparencel. #NephJC

T0h The problem with dialysis is that it can handle the filtration of fluid and waste, but it does not replicate the paracrine/endocrine function of the kidney. This is why the replacement of renal parenchymal cells is an attractive therapy at many CKD stages. #NephJC