title: Increased renal versican expression is associated with progression of chronic kidney disease.
abstract: Novel prognostic markers for progression of kidney disease are needed to distinguish patients who might benefit from a more aggressive nephroprotective therapy. Expression of the proteoglycan versican was evaluated in renal transcriptomics profiles and in an independent set of 74 renal biopsies. Versican levels were correlated to histologic damage scores and to renal outcome, and versican expression and regulation was evaluated in vitro. In transcriptomics profiles of renal tissue versican was positively correlated with (i) histological parameters in kidney biopsies, (ii) progressive decline of renal function in proteinuric kidney diseases, and (iii) impaired renal function and histology scores in diabetic nephropathy. In an independent cohort of 74 biopsies of glomerular diseases renal RNA levels of versican isoforms V0 and V1, but not V2 and V3 correlated significantly with creatinine after a mean follow up time of 53 months. Versican isoforms V0 and V1 together with serum creatinine at time of biopsy and the degree of glomerulosclerosis predicted 20% and 24% of the variability of creatinine at follow up, which was significantly more than serum creatinine and histological parameters alone (16%). However, when patients with acute kidney failure at time of biopsy (n = 5) were excluded, the additive predictive value of versican V1 was only marginally higher (35%) than creatinine and glomerulosclerosis alone (34%). Versican isoforms V0 and V1 were primarily expressed in vitro in proximal tubule cells and in fibroblasts. The results in humans were confirmed in three rodent models of kidney disease, in which renal versican expression was significantly upregulated as compared to corresponding controls. These data show for the first time an association of renal versican isoform V0 and V1 expression with progressive renal disease.
authors.affiliation: Medical University Innsbruck, Deptartment of Internal Medicine IV-Nephrology and Hypertension, Innsbruck, Austria. michael.rudnicki@i-med.ac.at
authors.forename: Michael
authors.initials: M
authors.lastname: Rudnicki
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.forename: Hannes
authors.initials: H
authors.lastname: Neuwirt
authors.forename: Susie-Jane
authors.initials: SJ
authors.lastname: Noppert
authors.forename: Johannes
authors.initials: J
authors.lastname: Leierer
authors.forename: Judith
authors.initials: J
authors.lastname: Sunzenauer
authors.forename: Susanne
authors.initials: S
authors.lastname: Eder
authors.forename: Carlamaria
authors.initials: C
authors.lastname: Zoja
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eller
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.forename: Gert
authors.initials: G
authors.lastname: Mayer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002460:Cell Line; D004195:Disease Models, Animal; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011379:Prognosis; D059368:RNA Isoforms / Q000378:metabolism; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053675:Versicans / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D059368:RNA Isoforms; D053773:Transforming Growth Factor beta1; D053675:Versicans