Kidney Week 2025 Annual Meeting-Integrative Omics Approaches for Proactive and Precision CKD Treatment: From Genotype to Phenotype

Video Transcription

Video Summary

The transcript covers a conference session on how “exposomics” and multi-omics tools can clarify causes, mechanisms, biomarkers, and prediction in chronic kidney disease (CKD), including environmentally and socially mediated risk.<br /><br />Nate Rains defines the exposome (lifetime external exposures and internal biological states) and describes exposome-wide association approaches. Using CKD of nontraditional cause (CKDnt/Mesoamerican nephropathy) as a model, he shows how exposomics can: (1) generate mechanistic hypotheses (e.g., urinary proteomics suggesting tubular dysfunction, complement activation, mitochondrial changes); (2) connect specific exposures to pathology (survey-linked paraquat exposure supported by biopsy and mouse-model similarities); (3) leverage genomics as an “exposomics” tool (a protective variant associated with better volume/heat resilience in mice). He also distinguishes direct exposure measures (metals/pesticides) from indirect signatures (metabolomics suggesting gut permeability/inflammation; mitochondrial mutation burden as a marker of prior AKI). Therapeutic implications include targeting NAD+ pathway derangements related to heat stress and kidney injury. Key challenges: exposure timing, measurement precision, causality/reverse causality, confounding, ethics, and translating findings into action.<br /><br />Insa Schmidt focuses on integrating omics with social determinants of health to study “biological embedding” of adversity. She reviews evidence linking adversity to epigenetic changes, epigenetic age acceleration (partly mediating SES associations with hypertension and kidney decline), and proteomic signatures of disadvantage and aging (notably immune and kidney aging). Her group’s CRIC analyses link SES to specific proteins/metabolites and to CKD outcomes.<br /><br />Ruth Dubin presents large-scale SomaScan proteomics in CRIC/ARIC to identify proteins associated with CKD progression and to build multi-protein risk prediction models that match or exceed clinical models (e.g., KFRE) and highlight druggable targets. Additional models predict heart failure in CKD and mortality in dialysis patients.<br /><br />Casey Greene discusses “prime-time” implementation of pharmacogenomics with EHR decision support (high alert compliance) and research on foundation-model-style data integration linking genetics, transcriptomics (TWAS), and learned expression patterns to identify drug targets, validated with CRISPR screens.

Asset Subtitle

Moderator(s): Morgan Grams, Dong Zhou

Presentation(s):

Exposomics and Environmental Determinants in CKD - Nathan Raines
Unraveling the Biology of Adversity: Integrating Omics with Social Determinants of Health in CKD - Insa Schmidt
Omics in CKD: Prognosis and Prediction - Ruth Dubin
Applications of Omics Technologies in Clinical Practice: What's Ready for Prime Time? - Casey Greene

Meta Tag

Date 11/6/2025

Pathway 1 CKD Non-Dialysis

Pathway 2 Pathology

Session ID 505374

Keywords

exposomics

exposome-wide association study (ExWAS)

multi-omics integration

chronic kidney disease (CKD)

CKD of nontraditional cause (CKDnt)

Mesoamerican nephropathy

environmental exposures (metals/pesticides)

paraquat exposure

urinary proteomics biomarkers

tubular dysfunction and complement activation

metabolomics and gut permeability/inflammation

mitochondrial mutation burden (AKI signature)

social determinants of health (SES) and biological embedding

epigenetic age acceleration

SomaScan proteomics risk prediction (CRIC/ARIC)