Assay heterogeneity further limits translation: Klotho measurements show poor inter-assay agreement and non-linear relationships across CKD stages [147], ApoM/S1P signaling demonstrates context-dependent effects without validated clinical thresholds [147], and NGAL/LCN2 shows context-dependent effects and links mineralocorticoid signaling to vascular fibrosis, further reducing specificity in multimorbidity [27]. This evidence concerns the gene APOM and chronic kidney disease.