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).

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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.