1.Association of urinary kidney injury molecu le-1 with renal tubulointerstitial lesions and its clinical significance in lupus nephritis patients
Zongfa YIN ; Yongrong ZHAO ; Yan ZHUANG ; Yunqiu GAO ; Zuolin LI ; Yingying GAO ; Lijuan TAN
Chinese Journal of Rheumatology 2017;21(7):461-465,后插1
Objective To explore the association of urinary level of kidney injury molecule-1 (KIM-1) with renal tubulointerstitial lesions in patients with lupus nephritis (LN). And to find a potential clinical biomarker, which could reflect the specific tubulointerstitial lesions of LN. Methods Sixty cases of biopsy proven new-onset LN patients were enrolled into the study. And 10 normal kidney tissues were collected, which came from 10 patients with kidney trauma or renal tumor nephrectomy. Sixty patients with LN were divided into mild disease group, moderate disease group, severe disease group and the extremely severe disease group according to the criteria of 2000 Hill's morphologic index for the evaluation of renal pathology. Urine and renal tissues specimen were collected. The clinical and pathological data were analyzed retrospectively. Urine level of KIM-1 was detected by enzyme linked immunosorbent assay (-). Immunohistochemical staining was used to observe the expression of KIM-1 in the renal tissue. T-test, One-Way analysis of variance(ANOVA) test or rank sum test and Pearson or Spearman correlation analysis were used for statistical analysis. Results ①With the aggravation of tubulointerstitial lesions, the urinary level of KIM-1 was increased gradually, which was shown in the control group [(0.32 ±0.03) ng/ml], mild group [(2.31 ±0.30) ng/ml], moderate group [(6.12 ±0.51) ng/ml], severe group [(12.51 ±1.83) ng/ml] and the extremely severe group [(15.30 ±2.11) ng/ml] (all P<0.05); ② With the aggravation of tubulointerstitial lesions, the expression of KIM-1 in the renal tissue was increased gradually which was shown in the control group [(2.13±0.12)%], mild group [(35.01±0.33)%], moderate group [(51.12± 2.11)%], severe group [(63.50 ±1.80)%] and the extremely severe group [(75.31 ±3.22)%] (all P<0.05);③ Urinary KIM-1 level in LN patients was positively correlated with the expression of KIM-1 in the renal tissue (r=0.870, P<0.01);④Urinary KIM-1 level in LN patients was positively correlated with 24 hUP, systemic lupus erythematosus disease activity index (SLEDAI), renol (R)-SLEDAI, glomerular activity index (GAI), tubulointerstitial ativity imdex (TLAI), chronicity (AI) (r=0.826, 0.741, 0.824, 0.743, 0.871, 0.741, P<0.05), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r=-0.726, P<0.05), while was not correlated with CI (r=0.532, P>0.05). The expression of KIM-1 in the renal tissue was positively correlated with serum creatinine (SCr), quantity of 24 h UP, SLEDAI, R-SLEDAI, GAI, TLAI and AI (r=0.780, 0.780, 0.812, 0.727, 0.735, 0.910, 0.701, P<0.05), and was negatively correlated with eGFR (r=-0.727, P<0.05), while it was no correlated with CI (r=0.543, P>0.05). Conclusion Urinary KIM-1 enables to assess the tubulointerstitial lesion in LN patients, and it can be a sensitive biomarker to predict the tubulointerstitial damage and to evaluate the degree of tubulointerstitial lesions.