Integrated serum and urine-omics analyses in ADPKD as a source of biomarkers and mechanistic insight

Project title:

Integrated serum and urine-omics analyses in autosomal dominant polycystic kidney disease (ADPKD) as a source of biomarkers and mechanistic insight

Objectives:

• Analyze the urinary proteome using mass spectrometry (MS) from the German AD(H)PKD cohort, which includes approximately 2,100 samples. Perform data cleaning, normalization, imputation, and batch effect correction.
• Identify urinary proteins associated with eGFR decline using wLASSO and LIMMA, the
  computational methods, and explore associated biomolecular functions implicated in
  ADPKD progression.
• Determine the predictive capacity of the eGFR slope-associated proteins and establish their added value in multivariate models integrating state-of-the-art clinical variables and
  prediction tools (i.e., eGFR, age, sex, MIC, genotype, PRO-PKD score).

Results:

• More than two thousand proteins were detected in urine samples from patients with ADPKD, and after normalization, over fifteen hundred proteins remained for further analysis.
• Twenty proteins were most strongly associated with eGFR decline, and their molecular functions primarily indicate renal epithelial adhesion and the breakdown of structural integrity.
• The urinary proteome-based multivariate model shows superior performance compared to the clinical model (r²=0.32 vs r²=0.22). Furthermore, integrating current ADPKD progression methods with urinary proteins enhances predictive capacity (r²=0.37 vs r²=0.32).