Loss of FERM domain-containing protein 3 (FRMD3) is associated with severity of chronic kidney disease. Loss of FERM domain-containing protein 3 (FRMD3) is associated with severity of chronic kidney disease

Purpose: Transcriptiome profiling of chronic kidney disease Methods: Transcriptome profiling was performed in human renal biopsy tissue and correlated with parameters of kidney function, including estimated glomerular filtration rate (eGFR), degree of renal tubulointerstitial fibrosis (%TIF), as well as CKD progression over a median follow-up period of 60 months. Results: Transcriptome analysis performed in two independent cohorts of patients with CKD (n=24 and n=17, respectively) identified a cluster of genes (n=93) significantly correlated (FDR P35%) in NAD(P)H-dependent oxidoreductase activity, and a corresponding increase in caspase activity (50%). Conclusions: Using global transcriptome profiling we define a cluster of transcripts associated with severity of CKD and identify loss of FRMD3 expression as a potential molecular driver. Loss of FRMD3 expression may contribute to mitochondrial function and TIF. Overall design: We examined the transcriptional profile of human kidney biopsies, aiming to provide insight into the mechanisms of progressive CKD. This approach led to the identification of FERM domain protein 3, (FRMD3) as a molecular driver of disease.