Collagen type III and VI remodeling biomarkers are associated with kidney fibrosis in lupus nephritis
Background: Lupus nephritis (LN) occurs in up to 40% of patients with systemic lupus erythematosus (SLE). Reliable biomarkers of kidney damage are needed to identify SLE patients at risk to develop LN in order to improve screening, treat earlier, and halt progression to kidney failure. Novel biomarkers of extracellular matrix remodeling were evaluated as markers of kidney fibrosis and disease activity in LN patients. Methods: Biomarkers of the interstitial collagen type III (PRO-C3) and type VI (PRO-C6) formation as well as of collagen type III (C3M) degradation were evaluated in the serum and urine of 40 patients with LN, 20 SLE patients without LN, 20 healthy controls and 10 biopsy controls (histological kidney inflammation/damage without SLE). Their association with histological markers of interstitial fibrosis and tubular atrophy, with inflammatory cell infiltration and with disease activity and chronicity in the LN patients was assessed. Results: Despite PRO-C3 (serum) and PRO-C6 (serum and urine) were significantly elevated in LN patients compared to healthy controls, they were not able to separate the LN from the SLE patients. C3M (urine) levels were not different in the LN group compared to the others. C3M (urine) strongly correlated and PRO-C6 (serum and urine) inversely correlated with kidney function (eGFR). The biomarkers of interstitial collagen turnover PRO-C6 (serum) and C3M (urine) correlated with histological markers of interstitial fibrosis, tubular atrophy, and monocyte infiltration. Conclusions: Non-invasive collagen turnover biomarkers are promising tools to identify SLE patients with kidney histological modifications.