Szeto Cheuk-Chun, Chan Rebecca Wing-Yan, Lai Ka-Bik, Szeto Carol Yi-Ki, Chow Kai-Ming, Li Philip Kam-Tao, Lai Fernand Mac-Moune
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Nephrol Dial Transplant. 2005 Jan;20(1):105-13. doi: 10.1093/ndt/gfh574. Epub 2004 Nov 23.
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.
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.
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.
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.
肾活检中肾瘢痕形成的程度是慢性肾脏病患者的一个重要预后因素。我们推测尿沉渣中的基因表达反映了肾损伤的程度。
我们研究了29例接受肾活检的慢性肾脏病患者（12例免疫球蛋白A肾病和17例肾小球硬化症）以及10名健康对照者。通过实时定量聚合酶链反应测量尿沉渣中一组靶基因的mRNA表达。将结果与组织学损伤程度和肾功能下降情况进行比较。
疾病组与对照组之间转化生长因子-β（TGF-β）、单核细胞趋化蛋白-1（MCP-1）和IV型胶原的尿表达存在显著差异。尿TGF-β mRNA表达与估计肾小球滤过率显著相关（r = -0.412，P = 0.029）以及肾小管间质瘢痕形成程度相关（r = 0.418，P = 0.024）。尿MCP-1表达与肾小球硬化程度相关（r = 0.4５0，P = 0.014），但与肾小管间质瘢痕形成无关。尿MCP-1表达与其酶联免疫吸附测定（ELISA）相应水平相关（r = 0.650，P<0.001），但TGF-β表达与其ELISA水平不相关。通过免疫组织化学，尿TGF-β基因表达与其在肾小球（r = 0.701，P<0.001）和肾小管间质（r = 0.573，P = 0.001）中的肾内表达相关，而尿MCP-1基因表达与其在肾小球中的染色相关（r = 0.576，P = 0.001）但与肾小管间质无关。12个月后，肾功能下降率与结缔组织生长因子（r = -0.471，P = 0.010）和I型胶原（r = -0.399，P = 0.032）的尿表达之间存在显著负相关，但与TGF-β或MCP-1无关。
在所检测的靶基因中，慢性肾脏病患者尿沉渣中TGF-β的mRNA表达与肾功能、组织学损伤程度和肾内水平相关。检测尿中TGF-β mRNA表达可能是评估慢性肾脏病患者肾损伤严重程度的一种有用的非侵入性工具。
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