If you’re interested in learning about all things genetic in nephrology, come to our Renal Genomics course in London, 5-6 March 2026!

This will be fantastic (not just because I am helping to organise it)! An amazing line up of speakers and topics. Hope to see you there!

Implications:
✅ Considering HLA context in research and clinical risk prediction
✅ A need for models integrating monogenic, APOL1, HLA, PRS, and environment

Paper link: www.ajkd.org/article/S027...

This work also won the @roysocmed.bsky.social Stewart Cameron Science Award 2025!

💡 Big picture:
Kidney failure risk can come from innate injury (APOL1) + adaptive immune predisposition (HLA).
The convergence of these pathways may explain why some patients progress rapidly to kidney failure without clear cause.
The genetic architecture of uKF is different to other CKD causes.

When we zoomed in on HLA in UK Biobank + 100KGP, we found:
👉 HLA-DQB1*03:19 strongly enriched in APOL1 carriers with early kidney failure (OR ~24, p=0.001) and West Africa!

Those with high-risk APOL1 also had:
🔹 Elevated steroid-sensitive nephrotic syndrome (SSNS) polygenic risk score
🔹 Signal driven by the HLA region

This suggested a second “immune hit.”

Among patients of African ancestry, high-risk APOL1 was hugely enriched:
📈 52% in uKF vs 8% in ancestry-matched controls.
Odds ratio ~9.

So APOL1 alone explains a lot. But we noticed something more…

Unexplained kidney failure (uKF) affects ~15% of patients needing dialysis/transplant.
We used whole-genome sequencing + large-scale case-control analyses (218 cases, >26k controls) to dissect the genetic architecture.

👉 17% of cases had a monogenic diagnosis (COL4A, NPHP1, etc).

🚨 New paper alert 🚨

Proud to share our work in AJKD: “Quantifying APOL1, HLA, and other genetic contributions to unexplained kidney failure”

What drives kidney failure when the cause is unknown? 🧵

www.ajkd.org/article/S027...

🫀 #Hypertension in autosomal dominant polycystic kidney disease: unique pathways, common consequences.
In #ADPKD, high blood pressure is often the first clinical sign and not just a complication of the kidney disease.
Actually its mechanisms differ markedly from other CKD-related hypertension... 🧵

A paper in Nature reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation. go.nature.com/415CMhr 🧬 🧪

📣 Latest from the lab: Performance of deep-learning-based approaches to improve polygenic scores www.nature.com/articles/s41...

Its thought deep learning will substantially improve PGS but the reality is MANY have tried but no/little gain has been seen so far. Here we report our negative results.

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👁️ The big picture
Nephrology is moving toward personalised, preventive, and sustainable care.
Proud to be an author on this piece — thanks to @melaniechan.bsky.social & the whole team.

📖 Read the full article: doi.org/10.1016/j.fh...

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🧬 WGS at birth
Whole genome sequencing of newborns enables early detection of Alport, ADPKD, IgA nephropathy + more.
Long-term, CRISPR could offer cures.

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📲 Remote, AI-powered follow-up
Wearables monitor cfDNA, proteinuria & other biomarkers at home. AI flags early signs of rejection before symptoms show.

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🧪 Immunosuppression reimagined
T cell therapies mean some patients won’t need lifelong drugs. Less toxicity, better graft survival.

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🐷 Xenotransplantation enters the chat
Gene-edited pig kidneys are being trialled in humans now. By 2050, they may help patients with no living/cadaveric match.

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🧬 Transplant demand skyrockets
We may need 200,000 kidney transplants a year in the UK by 2050. Transplant nephrology will be a specialty in its own right.

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🌍 Dialysis gets greener
Dialysis uses a lot of water and plastic. In 2050? Wearable, water-recycling, sorbent-based tech is mainstream. Less waste, more independence.

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👶 Prevention starts early
In 2050, obesity, diabetes and CKD prevention begin at school. National GLP-1 + lifestyle programmes are the new norm.

📘 What could nephrology look like in 2050?
This article for the Future Healthcare Journal was fun to write! — here’s a 🧵 of what might be coming next in kidney care:
shorturl.at/A18zK