NDT Advance Access originally published online on November 23, 2004
Nephrology Dialysis Transplantation 2005 20(1):105-113; doi:10.1093/ndt/gfh574
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Nephrol Dial Transplant Vol. 20 No. 1 © ERA-EDTA 2004; all rights reserved
Original Article
Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases
1 Department of Medicine and Therapeutics and 2 Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China
Correspondence and offprint requests to: Dr C.C. Szeto, Department of Medicine & Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. Email: ccszeto{at}cuhk.edu.hk
Background. The degree of renal scarring in kidney biopsy is an important prognostic factor in patients with chronic kidney diseases. We hypothesize that gene expression in the urinary sediment reflects the degree of renal damage.
Methods. We studied 29 patients with chronic kidney disease who underwent kidney biopsy (12 immunoglobulin-A nephropathy and 17 glomerulosclerosis) and 10 healthy controls. The mRNA expressions of a panel of target genes in urinary sediment were measured by real-time quantitative polymerase chain reaction. The results were compared with the degree of histological damage and renal function decline.
Results. There were significant differences in the urinary expression of transforming growth factor-ß (TGF-ß), monocyte chemotactic protein-1 (MCP-1) and collagen IV between disease groups and controls. Urinary TGF-ß mRNA expression correlated significantly with estimated glomerular filtration rate (r = –0.412, P = 0.029) and the degree of tubulointerstitial scarring (r = 0.418, P = 0.024). Urinary MCP-1 expression correlated with the degree of glomerulosclerosis (r = 0.450, P = 0.014), but not tubulointerstitial scarring. Urinary MCP-1 expression correlated with its corresponding level by enzyme-linked immunosorbent assay (ELISA) (r = 0.650, P<0.001), but TGF-ß expression did not correlate with its ELISA level. Urinary TGF-ß gene expression correlated with its intra-renal expression in glomeruli (r = 0.701, P<0.001) and tubulointerstitium (r = 0.573, P = 0.001) by immunohistochemistry, while urinary MCP-1 gene expression correlated with its staining in glomeruli (r = 0.576, P = 0.001) but not tubulointerstitium. After 12 months, there was a significant inverse correlation between the rate of renal function decline and urinary expression of connective tissue growth factor (r = –0.471, P = 0.010) and collagen I (r = –0.399, P = 0.032), but not TGF-ß or MCP-1.
Conclusions. Amongst the target genes examined, the mRNA expression of TGF-ß in urinary sediment correlated with renal function, the degree of histological damage and intra-renal level in patients with chronic kidney diseases. Measurement of TGF-ß mRNA expression in urine may be a useful non-invasive tool for assessing the severity of renal damage in patients with chronic kidney diseases.
Keywords: monocyte chemotactic protein; renal failure; transforming growth factor
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