Rajesh Mohandas

A psychedelic quickly reduced depression (in patients with major depression disorder) in a small, double-blind placebo randomized trial
www.nature.com/articles/s41...
Plus a new review on the science of psychedelic medicine
www.nature.com/articles/s41...

The New England Journal of Medicine Sibeprenlimab in IgA Nephropathy — Interim Analysis of a Phase 3 Trial A Research Summary based on Perkovic V et al. | 10.1056/NEJMoa2512133 | Published on November 8, 2025 Visual representations of the patients in the trial and the treatments they were assigned. Read the full Research Summary at NEJM.org.

In an interim analysis, sibeprenlimab, a humanized IgG2 monoclonal antibody that inhibits APRIL (the cytokine A proliferation-inducing ligand, a key driver of IgA nephropathy), reduced proteinuria as compared with placebo. Full phase 3 VISIONARY trial results and Research Summary: nej.md/493Xtza

Images and descriptions of what's available on NEJM.org this week

New in the February 6, 2025, issue of NEJM:

Iptacopan in IgA Nephropathy (APPLAUSE-IgAN phase 3 trial) nej.md/3UmrOkh

Atrasentan in Patients with IgA Nephropathy (ALIGN phase 3 trial) nej.md/3NzvISW

Liraglutide for Children with Obesity (SCALE Kids phase 3a trial) nej.md/3MBP1uc

#MedSky

The time of day for cancer immunotherapy is associated with major outcomes. Early is better. Results from a randomized trial of lung cancer, backs up the importance of our circadian rhythm and immune system
www.nature.com/articles/s41...

Teens may have come up with a new way to detect, treat Lyme disease using CRISPR gene editing To compete at iGEM, a sort of science Olympics, teens at a Georgia high school set their sights on finding a better way to detect and treat Lyme disease. Their approach uses CRISPR gene editing.

Remarkable story of a Georgia high school team who used CRISPR to make a rapid diagnostic test strip for Lyme disease, speeding dx from 2 weeks to days
www.cbsnews.com/news/teens-m...

50% risk reduction and curves separating in just a few months ? Insane!

Figure 2. Change in bodyweight (A) Mean percent change in bodyweight from baseline to week 48, shown as observed means and bars indicating SEs. The model-based estimates of the mean percent change in bodyweight and differences among treatment groups at week 48 with the corresponding p values (efficacy estimand only) and 95% CIs are shown in (B) (efficacy estimand) and (D) (treatment-regimen estimand); bars indicate SEs. Multiplicity adjustment was not performed, and p values should be interpreted as exploratory. (C) shows the percentage of participants with bodyweight reductions of at least 5%, 10%, 15%, 20%, 25%, and 30% from baseline to week 48. The percentage of participants is annotated above each bar, calculated with the use of Rubin's rules by combining the percentages of participants who met the thresholds in imputed datasets. *The model-based estimates and 95% CIs from a mixed model repeated measures analysis for the efficacy estimand are shown on the right, denoted by 48.

Eli Lilly continuing to hit it out the park

Selective amylin agonist as an alternative to GLP1RAs? #eloralintide

www.thelancet.com/journals/lan... in @thelancet.com

(Yeah I know it’s #KidneyWk but what do we do till Houston wakes up!)

cc @rnflex.bsky.social

The mechanical response of vinculin Vinculin buffers force via dynamic domain unfolding/refolding under physiological load and lacks a stable head-tail lock.

Vinculin is a simple adapter protein right? Wrong!

That’s been the prevailing view for the 46 years since it was discovered.

Here we provide a new paradigm and show that vinculin is a complex mechanosensor itself, containing 6 binary switch domains.

www.science.org/doi/10.1126/...

This #ASNCJASN article finds physical exercise prior to hemodialysis provides cardioprotective effects in a randomized controlled trial. kidney.pub/CJASN0767

Orfoglipron in @nejm.org

www.nejm.org/doi/full/10....

See discussion below for why this is significant!

#MedSky #NephSky

Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial Among patients receiving maintenance dialysis, spironolactone 25 mg daily orally did not reduce the composite outcome of cardiovascular mortality and hospitalisation due to heart failure compared with...

Spironolactone does not work for dialysis

ACHIEVE published in @thelancet.com

@lastwalsh.bsky.social and colleagues

www.thelancet.com/journals/lan...

Coming soon to a #NephJC near you

This is figure 5, which shows the therapeutic efficacy of a plaque-evading lithium salt.

Lithium has an essential role in the brain and is deficient early in Alzheimer’s disease, which can be recapitulated in mice and treated with a novel lithium salt that restores the physiological level, according to a paper in Nature. go.nature.com/47mxemu #medsky 🧪

Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression | NEJM The need to suppress a patient’s immune system after the transplantation of allogeneic cells is associated with wide-ranging side effects. We report the outcomes of transplantation of genetically m...

Important first-in-human report today for donor pancreatic islet beta-cell transplant to an individual w/Type 1 diabetes. With genome editing, there was no immune response induced or need for immunosuppression. Major implications for transplantation in general @nejm.org
www.nejm.org/doi/pdf/10.1...

Could gene-targeted therapy be coming for autosomal dominant polycystic kidney disease? Farabursen, a new medication acquired by Novartis offers to potentially impact cyst formation and even regression. kidney.pub/KN1707-07 #ASNKidneyNews

@nephrosparks.bsky.social

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk | NEJM Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib have not been fu...

Our means for lowering LDL cholesterol keeps expanding. A new CETP inhibitor adds to the mix of drug options New RCT @nejm.org
(And Lp(a) drugs are not far behind)
www.nejm.org/doi/full/10....

Diet outperforms microbial transplant to drive microbiome recovery in mice - Nature Experiments in mouse models show that proper recovery of the intestinal microbiota following depletion, with or without faecal microbiota transplant therapy, is dependent on syntrophic interactions th...

To restore the gut microbiome after antibiotics, the right diet (rich in carbohydrates, low in fat) was a better approach than fecal microbial transplants (in the experimental model)
www.nature.com/articles/s41...
www.nature.com/articles/d41...

Lorundrostat - an aldosterone synthase inhibitor.
Lorundrostat was associated with greater reductions in 24-hr average BP than placebo in pts with uncontrolled & treatment-resistant hypertension.
K level >6.0 occurred in 5 pts (5%) in the stable-dose group.
www.nejm.org/doi/full/10....
@nejm.org

ExerGeneDB
A physical exercise-regulated differential gene expression database

Human/mouse/rat >6k samples microarray/bulk/scRNAseq
+ncRNA

+Genes related to interactions b/w Exercise & gender/age/BMI

exergenedb.com

#JSHS_MedHealth 2025
www.sciencedirect.com/science/arti...

Suppression of the inflammation that occurs with aging ("inflammaging") by blocking thrombospondin-1 (Thbs1), prevented age-related blood stem cell defects and expanded lifespan in the mouse model (KO-knockout)
www.science.org/doi/10.1126/...

As promised, @asnpublications.bsky.social is on the platform. Four publications, one account. Please follow for the best in scientific publishing in nephrology!

The nitroplast: A nitrogen-fixing organelle A bacterial endosymbiont of marine algae evolved to an organelle

Move over mitochondria, a new organelle called the nitroplast is here.

In a Science study from earlier this year, researchers report that a nitrogen-fixing organelle has been identified in a marine alga. Learn more in this #SciencePerspective:

The Anatomical Quirk That Saved Dr. No A wild tale of how scientists unraveled embryology's most fascinating mystery.

Looking for something fun to read? Here’s a #popsci piece I did on the crazy history of cilia and left/right patterning in embryos. Remember #devbiolwriteclub Bluesky Boot Camp starts Monday Dec. 2! Please RS (re-skeet?)

nautil.us/the-anatomic...

Blood pressure of 142/80 in red. with an exclamation point.

All modern inpatient hypertension research:

"Whatever you do, don't treat inpatient hypertension"

Current EHRs

Blood pressure of 142/80 in red. With an exclamation point.

🤦🏻‍♂️

U.S. okays organ transplants between people with HIV, expanding donor pool The landmark move is expected to shorten wait times for organs for all patients and reduce hurdles to life-saving care for those with HIV.

People with HIV will be able to receive kidney or liver transplants from donors who also have HIV, federal health officials announced Tuesday.

The landmark move, which takes effect Wednesday, is expected to shorten wait times for organs for all patients.

"Drink more water!" It's the easiest health advice around. Tired? Headache? Trying to be like Tom Brady? Just drink more water. But as a nephrologist, I get asked all the time: How much is the right amount? And the truth is... we don't really know. 🧵

Kaplan Meier curve showing the cumulative incidence of type 2 diabetes in people given tirzepatide vs placebo

This month, a phase 3 trial of tirzepatide (a GLP-1 drug) found that it reduced the chances of developing type 2 diabetes by around 90% (!), among people with obesity and pre-diabetes.

That's a reduction if I ever saw one.
www.nejm.org/doi/full/10....

Down goes daprodustat.

The HIF-PHI drugs for CKD anemia will go down as the drug class with the greatest hype that utterly failed in delivering anything of note for patients. Just an epic decades long drama for nothing.

I sometimes forget how flexible proteins are. It becomes really apparent when you use NMR states for an animation. That poor cofactor is getting pushed around a lot 😅

#sciart #blender3d #biocatalysis

Is there clinical equipoise? If I was a patient with hyponatremia I would want slow correction. No RCT for me!