A healthy donor kidney aging signature estimable from PAS histology and its association with progression of diabetic kidney disease

Higher healthy-donor kidney tissue-aging scores in diabetic kidney disease are linked to faster eGFR decline, with overall partial ρ = -0.61 after biopsy in 24 patients.

• Why it matters: It is unclear whether normal aging-like cellular organization and stress programs appear in DKD and whether they track the speed of kidney function loss.
• What they did: Single-cell spatial transcriptomics using a 5,101-gene panel profiled zero-time donor biopsies (n=24; ages 36–66) and DKD biopsies (n=28), then applied unchanged tissue-aging scores to DKD and tested association with post-biopsy eGFR decline in 24 patients.
• The result: In DKD, higher transcriptomic aging scores predicted faster eGFR loss independently of age, sex, baseline eGFR, and proteinuria, and PAS-estimated scores correlated with transcriptomic scores (mean ρ = 0.62) and were also linked to faster loss (partial ρ = -0.44 to -0.56).

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