High collagen I gene expression as an independent predictor of adverse renal outcomes in lupus nephritis patients with preserved renal function

Abstract

Context. - The deposition of extracellular matrix is a major pathogenic mechanism leading to fibrosis and progressive decline in renal function in patients with lupus nephritis (LN). Currently, available clinicopathologic features cannot predict renal outcome consistently. Objective. - To test that the expression of renal fibrogenic genes correlates with renal fibrosis at the time of biopsy and is predictive of renal outcomes. Design. - Renal gene expression levels of transforming growth factor β-1 (TGFB1), and collagen I (COL1) were studied by real-time multiplex quantitative polymerase chain reaction in a prospective cohort of patients with LN (n = 39). Extracellular matrix index (ECMI) and collagen I/ III matrix index were measured from Picro-Sirius Red- stained slides under normal and polarized light, respectively. Results. - After follow-up (median, 43.9 months), renal failure (50% reduction in glomerular filtration rate [GFR] or dialysis) had developed in 13 subjects. The expression levels of renal fibrogenic genes were increased as compared to controls without LN. COL1 correlated with collagen I/III matrix index at baseline. Both high expression of TGFB1 or COL1 tended to predict renal failure by univariate analysis. By multivariate analysis, high ECMI and low GFR were predictive of renal failure. In patients with baseline GFR of 60 mL/min/1.73 m2or greater, high renal COL1 expression was an independent (hazard ratio = 4.4, P = .04) predictor of renal failure. Conclusions. - High renal COL1 expression is a strong predictor of adverse renal outcome in patients with LN and preserved baseline GFR. These findings support larger prospective studies to confirm the benefits of COL1 in identifying patients at high risk of progression to renal disease.