Value of urinary noninvasive markers in patients with IgA nephropathy

doi:10.3877/cma.j.issn.2095-3216.2012.01.008

Abstract

Abstract:

Objective

To investigate the levels of noninvasive urinary biomarkers interleukin-6 (IL-6), interleukin-18 (IL-18), transforming growth factor-β1 (TGF-β1), kidney injury molecule -1 (Kim-1) in the IgA nephropathy patients, and to demonstrate the correlation between noninvasive urinary biomarkers and clinical and histological damages in IgA nephropathy, and to evaluate the clinical application value of these urinary biomarkers.

Methods

One hundred and fifteen patients were prospectivly observed in the nephropathy department of Chinese People's Liberation Army General Hospital from 2007 December to 2008 April, who were diagnosed as IgA nephropathy firstly through renal biopsy. All the patients with IgA nephropathy were included into IgA nephropathy group and classified according to Lee's histological classification. Thirty patients with non-IgA nephropathy (minor glomerular abnormalities 8 cases, minimal change disease 11 cases, membranous nephropathy 11 cases) entered the disease control group, and 30 healthy adults entered the healthy control group. IL-6, IL-18, TGF-β1 and Kim-1 were detected with enzyme-linked immuno sorbent assay (ELISA). The SPSS 13.0 statistical software was used for statistical analysis. Count data were analyzed with χ² test,and measurement data were compared using the analysis of variance, while the correlation were analyzed with the linear correlation and Spearman rank correlation method.

Results

Compared with the healthy control group, the disease control group and the IgA nephropathy group had significant differences in hypertensive proportion, serum urea nitrogen level, serum creatinine level, and serum albumin level (P ＜ 0.05). According to the Lee's pathological grading, the patients of the IgA nephropathy group were divided into mild group (15 cases), moderate group (63 cases), and severe group (37 cases). The levels of urinary IL-6, IL-18, TGF-β1 and Kim-1 in IgA nephropathy group were higher than those of the healthy control group (P ＜ 0.05). With the pathological grade increasing, the urinary levels of IL-6, IL-18, TGF-β1 and Kim-1 increased in the patients with IgA nephropathy. The levels of urinary IL-6, IL-18, TGF-β1 and Kim-1 in severe sub-group were higher than those of the mild sub-group or moderate sub-group (P ＜ 0.05). The urinary levels of IL-6, IL-18, TGF-β1 and Kim-1 were correlated with glomerular filtration rate, the degree of glomerulosclerosiss,degree of renal tubular atrophy, fibrosis, and infiltration of inflammatory cells in the renal interstitium. In combining the urinary IL-6 and urinary KIM-1, or urinary TGF-β1 and urinary IL-6 for diagnosis of the pathological grade of IgA nephropathy, the sensitivity reached respectively 82.6% and 78.3%, and the specificity 88.9% and 92.2%, respectively. In combining the urinary IL-6 and urinary TGF- β1 for diagnosis of the renal chronic degree, the sensitivity and specificity reached 81.5% and 82.6%, respectively.

Conclusions

The urinary levels of IL-6, IL-18, TGF-β1 and Kim-1 can reflect clinical and pathological lesions of IgA nephropathy patients. Two urinary biomarkers combination for diagnose of the pathological characters have clinical practicability. IL-6 and KIM-1 or TGF- β1 and IL-6 combination for diagnose of the pathological classification, and IL-6 and TGF- β1 combination for diagnosis of the chronic degree, showed higher sensitivity and specificity.

Key words: Glomerulonephritis, IgA nephropathy, Interleukin-6, Interleukin-18, Transforming growth factor beta-1, Kidney injure molecule-1

Zhuo GAO, Ri-bao WEI, Jie, WU, Cai-hua LIE, Yuan-sheng XIE, Xiang-mei CHEN. Value of urinary noninvasive markers in patients with IgA nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2012, 01(01): 31-36.

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Figures/Tables 5

References 11

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项目	例数	平均年龄（岁）	性别比（男/女）	身体质量指数（kg/m²)	伴高血压病[例(%)]	血尿素氮（mmol/L)	血肌酐（μmol/L)	血清白蛋白（g/L）	尿蛋白定量（g/24h）
健康对照组	30	32.07±8.49	1∶1	23.06±3.30	0（0）	4.34±0.79	66.80±9.57	44.46±3.03	-
疾病对照组	30	36.43±13.33	1∶1	25.56±5.22	7（23.3%）^a	7.11±4.47^a	4.17±35.35^a	32.86±12.83^a	3.57±3.46
IgA肾病组	115	34.50±11.82	1∶1.3	24.16±3.50	40（34.8%）^ab	6.38±3.77^a	111.33±131.24^ab	37.27±6.07^a	1.68±1.44^b

项目	例数	平均年龄（岁）	性别比（男/女）	身体质量指数（kg/m²)	伴高血压病[例(%)]	血尿素氮（mmol/L)	血肌酐（μmol/L)	血清白蛋白（g/L）	尿蛋白定量（g/24h）
健康对照组	30	32.07±8.49	1∶1	23.06±3.30	0（0）	4.34±0.79	66.80±9.57	44.46±3.03	-
疾病对照组	30	36.43±13.33	1∶1	25.56±5.22	7（23.3%）^a	7.11±4.47^a	4.17±35.35^a	32.86±12.83^a	3.57±3.46
IgA肾病组	115	34.50±11.82	1∶1.3	24.16±3.50	40（34.8%）^ab	6.38±3.77^a	111.33±131.24^ab	37.27±6.07^a	1.68±1.44^b

组别	例数	IL-6(pg/mg.cr)	IL-18(pg/mg.cr)	Kim-1(ng/mg.cr)	TGF-β1(ng/mg.cr)
健康对照组	30	9.77±2.42	30.78±12.12	3.75±1.87	35.50±12.13
疾病对照组	30	12.03±3.82^a	47.10±26.69^a	5.21±2.10^a	38.47±14.85^a
IgA肾病组	115	19.61±11.84^ab	62.41±46.61^ab	9.46±6.42^ab	58.59±37.42^ab
轻度组	15	12.13±5.41	41.36±27.50	6.40±3.05	39.40±23.21
中度组	63	15.38±7.10	52.12±32.82^c	6.66±4.23	51.36±33.86^c
重度组	37	29.84±13.55^cd	89.74±60.66^cd	15.38±6.47^cd	84.62±38.57^cd

组别	例数	IL-6(pg/mg.cr)	IL-18(pg/mg.cr)	Kim-1(ng/mg.cr)	TGF-β1(ng/mg.cr)
健康对照组	30	9.77±2.42	30.78±12.12	3.75±1.87	35.50±12.13
疾病对照组	30	12.03±3.82^a	47.10±26.69^a	5.21±2.10^a	38.47±14.85^a
IgA肾病组	115	19.61±11.84^ab	62.41±46.61^ab	9.46±6.42^ab	58.59±37.42^ab
轻度组	15	12.13±5.41	41.36±27.50	6.40±3.05	39.40±23.21
中度组	63	15.38±7.10	52.12±32.82^c	6.66±4.23	51.36±33.86^c
重度组	37	29.84±13.55^cd	89.74±60.66^cd	15.38±6.47^cd	84.62±38.57^cd

临床及病理指标	尿IL-6	尿IL-18	尿TGF-β1	尿Kim-1
年龄	0.099	0.121	0.238	0.126
高血压病史	0.279^a	0.193	0.331^a	0.257^a
24h尿蛋白定量	0.037	0.402^a	0.015	0.238^a
血尿素氮	0.278^a	0.345^a	0.159	0.288^a
血肌酐	0.474^a	0.472^a	0.357^a	0.393^a
肾小球滤过率	-0.497^a	-0.491^a	-0.407^a	-0.452^a
病理分级	0.654^a	0.443^a	0.369^a	0.532^a
肾小球病理改变
系膜增生积分	0.397^b	0.128	0.142	0.363^b
新月体百分数	0.019	0.243^b	0.112	0.106
球性硬化百分数	0.573^a	0.380	0.413^a	0.411^a
节段损害积分	0.314	0.312	0.166	0.331
肾小管间质病理改变
间质炎细胞浸润积分	0.587^a	0.467^a	0.340^a	0.500^a
间质纤维化积分	0.620^a	0.535^a	0.376^a	0.591^a
肾小管萎缩积分	0.624^a	0.520^a	0.412^a	0.556^a
肾脏慢性化积分	0.583^a	0.371^a	0.424^a	0.427^a

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