Michael S. Balzer

Bottom line: RAAS inhibition not just lowers pressure. It reshapes a pathological conversation btw/ distal nephron & inflammatory macs. And single-cell biology is no longer about making prettier atlases. It is about correcting assumptions we have been carrying for decades.

🧪Paper: t.ly/oNjkJ

The human data brought it home. Higher CTSD expr. in kidney tubules tracked w/ worse eGFR & more fibrosis. Patients on RAASi had lower CTSD. And a gene signature derived from enalapril-responsive cells stratified kidneys by outcomes, not diagnoses. Mechanism meeting prognosis is always satisfying.

Spatial transcriptomics sealed it. In human DKD kidneys, CTSD⁺ connecting tubules and TREM2⁺ macrophages sit next to each other. Not metaphorically. Physically. When disease is present, their neighborhood expands. When RAAS signaling is suppressed, that neighborhood quiets down. Context matters.

Then came the immune system. Those CTSD⁺ distal cells were talking — loudly — to a specific macrophage population: TREM2⁺ resident macrophages. These macrophages were inflammatory, expanded in DKD, and shrank with enalapril treatment. This was epithelial–immune crosstalk, not collateral damage.

Digging deeper, we found a distinct population of CTSD⁺ connecting tubule cells. They sit between healthy and injured states. Not fully broken, not fully normal. Transitional. Plastic. Vulnerable. And enalapril selectively depleted this population. That was the first “oh wow” moment.

One molecule kept showing up: cathepsin D (CTSD). Strongly induced in diabetic kidneys. Strongly suppressed by enalapril. And not everywhere — very specifically in a subset of distal nephron cells. This was not a generic injury marker. It looked like a state.

When we mapped the kidney cell by cell, the biggest enalapril “rescue” signal was not in proximal tubules. It was in the distal nephron. That alone made us stop and reread the plots twice.

Using long-term enalapril treatment in the ZSF1 rat DKD model, we confirmed the obvious first: blood pressure, albuminuria, fibrosis, injury markers all improved. So yes, the drug works. But where does it work? That question is where single-cell really earns its keep.

RAAS inhibitors have been used for decades. We all learned the story: glomeruli, proximal tubules, hemodynamics. But when we looked at this with single-cell resolution, the biology told a different story. Not louder. Just clearer. And it pointed us somewhere unexpected.

Excited to share our recent JASN paper on enalapril effects in #DKD using #single-cell approaches.🧪
Thanks to the whole team @nephrointberlin.bsky.social @PennKidney, and @Bayer.

Special 🙏 to my mentor @ksusztak.bsky.social. Her insightful X thread is copied below.

🔗 t.ly/oNjkJ #NephSky #MedSky

Check out a recent interesting case of C-H-BG syndrome from @nephrointberlin.bsky.social. A great example of how rare symptoms in a common disease can present with complex phenotypes.
#NephSky #MedSky 🧪
🔗 www.sciencedirect.com/science/arti...

A christmas tree ornament reading "He's making a lith and checking it twice", picturing a kidney with Santa's hat.

Merry Xmas! 🎄
Be kind to your kidneys this holiday season.
#NephSky #MedSky 🫘🧪

BigPAK or a bundle of balderdash? — NephJC We break down the latest salvo from Zarbock et al on a supposedly wonderful ‘bundle’

We really don’t think BigPAK makes sense

From our journal club at @uottawa.ca into a #NephJC shorts

www.nephjc.com/news/2025/12...

Keep Calm & Carry On
Inhibiting RAS 👑

#Kidneywk #Nephjc

👉 www.nephjc.com/news/stopacei
👉 www.nephjc.com/news/aceing-...

Well deserved, Rafael! Congrats!

👏Huge congratulations to my fantastic mentor @ksusztak.bsky.social for receiving the 2025 ASN Homer Smith award.

👏Fantastic to see @cetinsz.bsky.social from our team presenting insights into #single-cell transcriptomic patterns distinguishing recovery from non-recovery after #AKI. Exciting 🧪 at #KidneyWk Houston, TX! #MedSky #NephSky

❓Do we finally have a nodular sclerosis mouse model for DKD? 🔥Tour-de-force #kidneywk talk by @linkermannlab.bsky.social suggests so. 🧪 #NephSky #MedSky

Cell Decoder: decoding cell identity with multi-scale explainable deep learning. #SingleCellOmics #CellCharacterization #GenomeBiology 🧪🧬 🖥️
genomebiology.biomedcentral.com/articles/10....

spatial Omics in R/Bioconductor 18-20 May 2026 To foster international participation, this course will be held online

🚀 Curious about #SpatialOmics? Want to master spatial omics data analysis using #Rstats and @bioconductor.bsky.social ?

🔥 Registrations are now OPEN for the 3rd edition of our hands-on course with @stemang.bsky.social !

📅 Save the dates: 18–20 May 2026
www.physalia-courses.org/courses-work...

Thx, Rebecca!

Thanks, Tilo! 👍

💯👍

Thanks, Lennard! 🙏

The ERC awards €761m to the next generation of scientists in Europe The European Research Council (ERC) has selected 478 early-career researchers across Europe to receive this year’s Starting Grants. With a total funding of €761 million, these grants support excellent...

🚀Excited to announce that I’ve been awarded an @erc.europa.eu StG to advance research how kidneys heal themselves — a paradigm shift for understanding & treating #kidneydisease 🫘🩺🧬🧪
👉ERC press release: t.ly/CBxwB
👉Charité press release: t.ly/SR_Wn
#ERCStG #HorizonEU #KidneyResearch #NephSky #MedSky

Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules The interplay in expression of the stem cell markers THY1 and PROM1 in kidney proximal tubules marks the timeline of disease.

📑 Need something to read this weekend? If so, you're in luck!

"Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules" fueled by #KPMP investigators is hot off the press today @science.org

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

🔥 Huge congrats to @ksusztak.bsky.social & team on a landmark @natgenet.nature.com paper!
🚶‍♂️🐁🐀Cross-species 🫘kidney pathway dysregulation via #singlecell functional profiling of individual samples — opening new therapeutic avenues.
🔗 www.nature.com/articles/s41...
🧪 #NephSky #MedSky

🔥Paper alert @nature.com. Fantastic 🧪resource for the renal 🫘 community! #NephSky #MedSky

Congrats @puellesv.bsky.social lab and team!

Randomized, Double-Blind, Placebo-Controlled Phase 2a Study Assessing the Efficacy and Safety of Felzartamab for IgA Nephropathy

doi.org/10.1016/j.kint.2025.05.028

#OpenAccess #IgAN #felzartamab #IgANephropathy