Biomarkers of glomerular inflammation and fibrosis

Abstract

Progression of glomerular diseases to chronic kidney disease or renal failure is a major diagnostic and therapeutic problem. In addition to finding new treatment, more reliable biomarkers, using near patient technology, are needed to improve early detection of patients at risk of progressive renal injury. To achieve this aim, two approaches were applied to study novel biomarkers of glomerular inflammation and fibrosis. Firstly, expression of specific inflammatory cytokines and growth factors, including two members of the CCN protein family which are connective tissue growth factor (CTGF)/CCN2 and nephroblastoma overexpressed gene (NOV)/CCN3, were studied in a rat model of crescentic glomerulonephritis (GN). CCN2/CTGF is now regarded as a major profibrotic growth factor of chronic renal inflammation and fibrosis. On the other hand, recently, emerging evidence suggests that CCN3/NOV acts as an endogenous negative regulator of extracellular matrix accumulation and is capable of counteracting the fibrogenic effect of CCN2/CTGF. This targeted approach may be helpful in providing a novel insight into the pathophysiological activities of these two CCN proteins involved in progressive kidney disease and development of novel therapy. With regard to Fourier transform infrared (FTIR) spectroscopy, it has been increasingly used in biomedical research but so far it has not been investigated for diagnosing and/or screening progressive kidney disease. Thus, the second approach was aimed to investigate whether FTIR technique could be employed as an unbiased method of detecting sensitive renal biomarkers. Using FTIR spectroscopy, several characteristic urinary and plasma spectral markers related to renal inflammation and chronic fibrosis were identified from the rat model of crescentic GN. In particular the urinary 1545 cm-1 spectral marker was also reliable in assessing therapeutic responses in corticosteroid-treated rats with GN and severe lupus nephritis in mice. In addition, this urinary spectral marker was translatable in assessment of crescentic GN in patients. In conclusion, analysis of specific cytokines/growth factors and FTIR spectroscopic technology are likely to improve or assist diagnosis and evaluate progression of glomerulonephritis.