Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases.
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-beta (TGF-beta), monocyte chemotactic protein-1 (MCP-1) and collagen IV between disease groups and controls. Urinary TGF-beta 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-beta expression did not correlate with its ELISA level. Urinary TGF-beta 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-beta or MCP-1.


CONCLUSIONS
Amongst the target genes examined, the mRNA expression of TGF-beta 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-beta mRNA expression in urine may be a useful non-invasive tool for assessing the severity of renal damage in patients with chronic kidney diseases.
Szeto
Cheuk-Chun
CC
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. ccszeto@cuhk.edu.hk
Chan
Rebecca Wing-Yan
RW
Lai
Ka-Bik
KB
Szeto
Carol Yi-Ki
CY
Chow
Kai-Ming
KM
Li
Philip Kam-Tao
PK
Lai
Fernand Mac-Moune
FM
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011336:Probability; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000652:urine*
D015415:Biomarkers; D018932:Chemokine CCL2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta