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The Decade Ahead: Predicting Long-Term Proteinuria Risk in SLE

Sheila Reyes, MD Oct 28, 2025

The ACR Convergence 2025 in Chicago opens with engaging topics curated for the global rheumatologist. As a clinician, I always look forward to sessions that provide updates and practical key points that I can bring home and apply to my practice.

Abstract 2360: Single-center lupus pregnancy cohort found that: 🔹 Absence of DORIS remission associated w/ adverse pregnancy outcomes (Pre-term, Pre-eclampsia) 🔹 This is along with known risk factors: antihypertensive use, prior nephritis, active disease @RheumNow #ACR25 https://t.co/STg1NBeFPo

https://x.com/AkhilSoodMD/status/1983276334278386022/photo/1

Reaadmissions in sle pregnancies from 66k patients Insurance and economics seem to be very important in predictions using machine learning. Abst#2629 #ACR25 @RheumNow https://t.co/x2oo9TOxoh

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#ACR25 Abstr#2601 At single cell level using CyTOF, metabolic activity varied btw HC & autoimmune groups but clusters in At-Risk ANA+ve appeared closer to #SLE. ANA+ve who progressed to AI-CTD showed Plasmablast expansion & enhanced glycolysis. Could be used as target @RheumNow https://t.co/jtrM1wvQLk

https://x.com/Yuz6Yusof/status/1983253903673012604/photo/1

@RheumNow Obinutuzumab for lupus nephritis was a very recent FDA addition two weeks ago, and we’ll play catch-up with the hematologists to get familiar with it, including its safety profile #ACR25 FDA Update @RheumNow https://t.co/h6bf4roGzB

#IL2 #Rx in active #SLE? Maybe 🤔 IL2 is tricky - low dose May help #SLE but too much of a good thing may have a neg impact. RCT of IL2i in #SLE gave a good dose response and improved TRegs. #ACRBest #ACR25 @RheumNow @ACRheum #LB01 https://t.co/F61qz5x5We

#ACR25 Abstr#LB10 Promising 4-Year data of Deucravacitinib in blinded phase 2 RCT +LTE study showed efficacy inc. LLDAS and CLASI-50 response were maintained/improved over time in #SLE No concerning safety signal. Looking forward to Phase 3 results next year @RheumNow https://t.co/fZv82zJ6Q4

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#ACR25 How hard will you go & at what cost? A study in China using CD20/BCMA Bispecific autologous CAR-T showed profound depletion, normalisation of abs and good response in #SLE (10/11 had LN). But 2 had G3 infections & cytopenia. Presenters said some had IVIG @RheumNow #ACRBest https://t.co/TF0wpib5rr

Data from this retrospective cohort study by Alomari et al show that SLE pts on SGLT2is ⬇️rates of PulHPN (OR 0.79) ⬇️all-cause mortality (0.49) ⬇️hospitalizations (OR 0.56) ⬇️LN (OR 0.4) vs non-SGLT2i users(p<0.001) Impt role of SGLT2i as adjunct tx #ACR25 @RheumNow Abs2438 https://t.co/NQJTzQwRCt

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#ACR25 Abstr#LB01 After several smaller studies, a Multicentre, Phase 2b RCT of 152 #SLE pts in China. SRI-4 was met in IL-2 as s/c every other day for 12 wks, followed by weekly for another 12 wks vs PBO. Efficacy & T-regs expansion were dose dependent. On to Phase 3 @RheumNow https://t.co/L0rYr5D1R1

https://x.com/Yuz6Yusof/status/1983210295192375678/photo/1

Late Breaker: Phase 2 RCT of low dose IL2 in SLE Dose dependent response in SRI4 over 12 weeks & surprisingly high rates of LLDAS Too early to know if useful, but worth evaluating in a phase 3 #ACR25 @RheumNow Abstr#LB01 https://t.co/oPOLG82nwi

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The CAR T engine doesn’t stop! LB04: Phase 1 bispecific CD19/BCMA CAR T in refractory autoimmune disease 🚗💥 ✅ Low AEs (mostly Gr 1–2 CRS, hematologic) 💪 Robust efficacy in lupus nephritis 🔄 Deep B-cell depletion → naïve B-cell repopulation @RheumNow #ACR25

HCQ weight-based dosing: out HCQ whole blood monitoring: in Whole blood levels more precisely balance risks of SLE flare (under-dosing) vs. toxicitiy (over-dosing) Many pt on <5 mg/kg had supra-therapeutic blood levels with risk for toxicity @RheumNow #ACR25 #ACRBest Abst 1722 https://t.co/qIbACxAW39

https://x.com/Dr_Brian_MD/status/1983186074932482553/photo/1

Pooled data fr diff SLE cohorts by Dr SGarg et al were evaluated to determine an upper threshold tx range of HCQ 750-1150 ng/mL: safe & effective HCQ levels >1150ng/mL-supratx, no added tx benefit CKD st >/=3: 2x ⬆️odds of toxic hcq levels #ACR25 @RheumNow Abs1722 #ACRBest https://t.co/RFx1VO0bov

#1723 Why is systemic autoimmunity more common in females? Loss of X-chromosome inactivation maintenance in B cells (not T cells) amplifies interferon-driven disease, with increased autoantibodies, inflammation and renal injury. Key mechanistic advance. @RheumNow #ACR25

3rd plenary session! #1722 Defining safe HCQ levels in SLE: whole-blood 750-1150ng/mL= therapeutic range; >1150ng/mL ➡️ ~2× toxicity risk; <750ng/mL ➡️ higher flare risk CKD ≥3 increases odds of supratherapeutic levels New era of precision monitoring in SLE? @RheumNow #ACR25

Plenary 3, HCQ blood levels in SLE HCQ level > 1150: 1.9x risk of HCQ toxicity HCQ level < 750: 1.4x risk of active SLE HCQ dose < 5mg/kg: 1.9x risk active SLE My take home? Blindly reducing dose to <5mg/kg is BAD; use levels instead! @RheumNow #ACRBest #ACR25 Abstr1722 https://t.co/UCBPAKAyon

#ACR25 Please find my video interview with Prof Edward Vital @edvital on their work on International Consensus of Glucocorticoid Tapering Guideline in #SLE #lupus Abstr#1526 @RheumNow https://t.co/MnQdcdASkG https://t.co/b7GMcnFU2m

#ACR25 Please find my video and take on Abstr#0646. Promising new Bi-specific T-cell engager (BiTE) other than Blinatumomab in #SLE @RheumNow https://t.co/5JrLG41nsD https://t.co/KeY6AkHUNK

#ACR25 Please find my video and take on Abstr#0803. Should we use Belimumab before- or after a trial of concentional immunosuppressant in #SLE? @RheumNow https://t.co/ExIvrdJXw5 https://t.co/AVb5ohWwXZ

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The Decade Ahead: Predicting Long-Term Proteinuria Risk in SLE

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