Great discussion! INFINITI shows SGLT2 inhibitors behave differently—but plausibly beneficially—in transplanted kidneys. What more trial evidence would you like to have before implementing in your practice? #NephJC

T3i 📌 Bottom line: INFINITI shows that SGLT2 inhibitors “work differently”but plausibly beneficially in KTRs. The field now needs long-term outcome trials to answer the real question: do they improve graft and patient survival? #NephJC

T3h: ⚠️ Limitations ⏳ Short follow-up duration 🛡️ Low-risk, stable transplant population ⚖️ Underrepresentation of women and minorities 🎯 ❌ No hard clinical outcomes (graft failure, CV events) #NephJC

T3g 💪 Strengths: ✔️ Measured GFR with iohexol ✔️ Lithium clearance for tubular physiology ✔️ Rigorous mechanistic design #NephJC

T3e Despite small MAP reductions, there was no improvement in arterial stiffness, SVR, or sympathetic tone. This suggests transplant-specific vascular and tubular physiology may blunt traditional SGLT2i BP mechanisms. Perhaps a longer study may have shown different results?⚠️ #NephJC

T3d 👉 Strong glucosuria without natriuresis. This challenges the classic SGLT2i narrative. Possible explanations: • Calcineurin-inhibitor–mediated sodium retention • Rapid distal sodium reabsorption • Altered tubular signaling in denervated grafts #NephJC

T3c Notably, this occurred without meaningful albuminuria reduction, aligning with growing evidence that SGLT2i benefits go beyond proteinuria. Were you surprised there wasn’t lowering (of already low) albuminuria? #NephJC

T3b 📉The preserved acute GFR dip strongly suggests that intraglomerular pressure unloading still occurs in transplanted kidneys. The magnitude of the dip mirrors non-transplant SGLT2i trials — reinforcing that this is likely a hemodynamic, not toxic, effect. #NephJC

T2k Safety outcomes were reassuring: 🦠 ❌ No UTIs 🍄 ❌ No genital infections 💊 🔒 Tacrolimus levels remained stable 🚑 ❌ No excess AKI 🍬 ⚖️ Low rates of hypoglycemia 💧 ⚖️ Minimal volume depletion #NephJC

T2i Vascular & hemodynamic findings: 🫀 No significant change in arterial stiffness (augmentation index, PWV) at 12 weeks. 📊 Cardiac output measures unchanged. ⚡ Renin, aldosterone, catecholamines, HR, and HRV showed no differences vs placebo at 1 or 12 weeks. #NephJC

T2h 🔍🧠📊 Tubular sodium handling was… unexpected. Despite robust glucosuria, FENa, FELi, and distal sodium reabsorption did NOT differ vs placebo. Volume effects were present: ✔️ Increased 24-h urine volume ✔️ Sustained glucosuria at both 1 and 12 weeks. #NephJC

T2g Proteinuria At baseline, participants had low-grade proteinuria -UACR ~2–3 mg/mmol- very low After SGLT2i → NO significant reduction in UACR at 1 or 12 weeks UACR and 24-hour urine protein excretion remained unchanged across timepoints, despite the clear mGFR dip. #NephJC

T2f Creatinine-based eGFR showed directionally similar changes, closely mirroring the early hemodynamic dip seen in native-kidney SGLT2i trials. Crucially, this GFR dip was not accompanied by harm: ❌ No excess AKI ❌ No biochemical instability ❌ No signal for acute rejection #NephJC

T2d 📉 At 1 week, dapagliflozin led to a placebo-adjusted MAP reduction of ~3.9 mmHg. However, this BP effect was modest and transient. By 12 weeks, MAP and DBP differences were attenuated and not consistently sustained. #NephJC

T2c The primary endpoint was seated systolic BP. 👉 Dapagliflozin did NOT reduce SBP at either 1 week or 12 weeks vs placebo. Is this unexpected? #NephJC

T2b 👥Baseline characteristics: 🗓️Mean age 53 yrs; 🧁 57% diabetes, 💊62% hypertension; 🫘mean eGFR ~68 ml/min/1.73 m². Baseline characteristics were well balanced. #NephJC

Hmm... mechanistic and safety studies tend to be short. CONFIDENCE trial had about 24 weeks, MIRO-CKD also 12 weeks #NephJC

T2a ♾️ INFINITI randomized 52 stable kidney transplant recipients, >6 months post-KT. #NephJC

T1l Understanding how a drug works in Kidney transplant recipients (KTRs) is a prerequisite to asking whether it improves outcomes—INFINITI sets the stage for that next step. #NephJC

T1f The 1° endpoint was seated systolic blood pressure—chosen as a surrogate of vascular and volume effects. Is this a good endpoint given the short length of the study? Do you usually see ⬇️ in BP in patients on #flozins? Do you frequently stop BP meds? #NephJC

T1e ⚔️ Participants were randomized 1:1 to 💊 Dapagliflozin 10 mg daily vs 💊 Placebo Physiologic assessments were performed at baseline, 1 week (acute effects), and 12 weeks (chronic exposure). #NephJC

🔍 Inclusion criteria. Any surprises here? #NephJC

T1b Participants were stable kidney transplant recipients, ≥6 months post-transplant. Initially restricted to patients with diabetes, eligibility was later expanded to non-diabetic recipients after publication of DAPA-CKD. #NephJC

honestly not sure! remember RASi effect in transplant is not as impressive (ahem pubmed.ncbi.nlm.nih.gov/27712852/ in @ajkd.bsky.social ) despite @kdigo.org guidelines #NephJC

Markers of endothelial and podocyte stress in structurally normal kidney transplants! pubmed.ncbi.nlm.nih.gov/34952098/ #NephJC

🎨 No olviden revisar la versión en español traducir por Milagros Flores #NephJC

🎨Beautiful visual abstract by Janany Sabescumar Janany Sabes #NephJC

moving on from IgAN to FSGS: BI 764198 a TRPC6 inhibitor reduces proteinuria in an N = 67 phase 2 RCT www.thelancet.com/journals/lan... in @thelancet.com #NephSky

Even the NEJM editorial comment on RALES argued that spiro reduced sudden cardiac death by arrhythmia by blocking urinary K loss (MRA), this being a superior way to maintain total body stores of an intracellular ion than replacing losses. #NephJC

T3l POTCAST interventions are widely available 🍌 diet 💊 MRAs 🧂 KCl supplements 💧 reducing K⁺-losing diuretics <50% hit the target but ~75% stayed on therapy… enough to improve outcomes #NephJC

T3i It seems like nephrologists are somehow quietly saving cardiology And yes, I’m talking about the pillars of HF management 😏👀#NephJC

Agree 100% These findings do not necessarily mean the increase in K of 0.3 has direct electrophysiology implications, It could have other mediators #NephJC

eg #NephJC

T3f In the landmark MRA trials (RALES, EPHESUS, EMPHASIS-HF, FINEARTS-HF), patients taking MRAs for HF had improved survival, including fewer sudden cardiac deaths #NephJC

T3c Most of the benefit came from fewer ICD therapies (shocks or pacing) and documented ventricular tachycardia. Effects were consistent across subgroups & independent of the drug used #NephJC

increased potassium intake causes natriuresis (the K-switch) described by Paul Welling, Ellison et al www.ahajournals.org/doi/10.1161/... maybe natriuresis is helpful here too for some outcomes? #NephJC

T2k Discontinuations: 67 participants stopped meds due to side effects: ⚠️ 27% MRA ⚠️ 34% K⁺ supplements ⚠️ 39% both Although, the side effects were manageable #NephJC

¿Elevar el K⁺ al rango alto-normal puede reducir las descargas del DAI y las hospitalizaciones? 🎨Resumen visual por @jeyakumarmeyyappan.bsky.social ✍️Traducido por @dramiliflores.bsky.social www.nephjc.com/news/2026/1/...

T2h Hospitalizations: 🏥Unplanned hospitalization for arrhythmias: 6.7% vs 10.7%, HR 0.63 🏥Unplanned HF hospitalization: 3.5% vs 5.5%, HR 0.64 High-normal K⁺ seems protective #NephJC

T2g Secondary outcomes (Appropriate ICD therapy/VT) 👉15.3% high-normal K 👉 20.3% standard care 🎯HR 0.75 (95% CI 0.57–0.98) a clear reduction in dangerous arrhythmias #NephJC

T2f 🔍 Benefit of high-normal K⁺ was consistent across subgroups Is this enough to rewrite your K goals? 👀 #NephJC

T2e Primary endpoint results 👉An event occurred in 22.7% of the high-normal K group vs 29.2% with standard care 📉High-normal K reduced risk by 24%; at 5 years the absolute risk difference was 7.7% #NephJC

ChatGPT? i raise you to Open Evidence #NephJC

do not worry too much about balance in RCTs eg www.linkedin.com/pulse/stop-o... from @stephensenn.bsky.social #NephJC

T0h 📌 Let’s break down the Methods, OK? #NephJC

relevant curve from pmc.ncbi.nlm.nih.gov/articles/PMC... #NephJC

Check the insightful #NephJC summary by Shellie Fravel, PharmD and Clemens Weber

IF telling us what is deposited, not why 🫠 #nephjc

Some strong complement pathway dysregulation #nephjc