Kidney Proteomics Maps New Targets for CKM health

A large kidney proteomics study links tissue proteins to cardio-kidney-metabolic traits and introduces a kidney pQTL map to guide future therapies.

Kidney Proteomics Reveals New Targets for Cardio-Kidney-Metabolic Health

Ndumele and colleagues analyzed 337 human kidney samples with whole-genome sequencing, RNA sequencing, and deep proteomics. They built a kidney protein quantitative trait loci (pQTL) resource and, together with 36 cardio-kidney-metabolic GWAS, used Bayesian co-localization and Mendelian randomization to prioritize 89 proteins for CKM traits. Among the standout signals are ANGPTL3, implicated in serum lipid levels and kidney function, and CHMP1A, linked to kidney function and hypertension.

The team also created a publicly accessible database that integrates genetic, transcript, and protein data. The study argues that kidney proteomics captures mechanisms not visible in gene expression profiles or blood proteomes, and that convergent signals across data layers point to actionable pathways. The authors say the work lays a foundation for targeted therapies but emphasize the need for functional validation and diverse cohorts before clinical use.

The work highlights how proteomics can fill gaps left by transcriptomics and plasma data. By mapping pQTLs in kidney tissue, scientists can connect genetic variation to protein abundance and disease traits in a tissue-specific way. The finding that ANGPTL3 in kidney might influence both lipids and kidney function points to a new cross-talk pathway. But the results are correlational and require lab experiments to test causality.

Yet translating such maps into therapies faces hurdles: replication in diverse populations, understanding tissue context, and moving from association to mechanism. The public database is a valuable resource, but clinicians need clear validation and safe, ethical deployment. The study nudges the field toward precision medicine for CKM health, but it also calls for careful, patient-centered development.

Highlights

Future studies will test whether these kidney signals translate into real patient benefits.