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.

ABSTRACT:Objective To observe the effects of late Na current (INa‐L ) and rapidly activating delayed rectifier K current (IKr ) on ventricular heterogeneity and frequency dependency by using high resolution voltage sensitive optical mapping technology .Methods The model of 12 isolated hearts was constructed in rabbits . Voltage sensitive dye Di‐4‐ANEPPS were perfused into the isolated hearts by Langendorff method .LED source with the wave length of 532 nm was used to record APD80 and APD50 of the left and right ventricles .Experimental groups were divided into 3 groups by perfusion drugs dofetillide (30 nmol/L) ,dofetillide+ATX‐Ⅱ(1 nmol/L) ,and dofetillide +ATX‐Ⅱ +mexiletine (10μmol/L) .The subjects were intervened by the above drugs in order ,and they were self‐compared before dosing .After each drug administration ,the hearts were stimulated respectively with the BCL of 2 000 ms ,1 000 ms ,500 ms ,and 300 ms .Then we observed the changes of APD80 and APD50 in the left and right ventricles before and after the interventions .Results ① In the control group ,APD80 and APD50 of the right ventricle were longer than those of the left ventricle in response to different stimulation , and the differences increased with the decrease of stimulating frequency .② When BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles were prolonged respectively after administration of dofetillide , but the differences in APD80 and APD50 were insignificant between the left and right ventricles (P>0 .05) .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency . ③ After administration of ATX‐Ⅱ , when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles increased significantly compared with those in the control group and dofetillide intervention group (P<0 .05) .And the increase of APD in the left ventricle was greater than that of the right ventricle .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency .④ After administration of mexiletine ,when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the primary state (P<0 .05) .APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the control group (P< 0 .05) and ATX‐Ⅱ group (P>0 .05) .The increase of ΔAPD80 of the two ventricles became milder when the stimulating frequency decreased . Conclusion ① IKr blocked by dofetillide did not affect the heterogeneity between the two ventricles , which showed reverse‐frequency dependence . ② In the context of blocking IKr , ATX‐Ⅱ increased the heterogeneity between the left and right ventricles and enhanced the reverse‐frequency dependence .In contrast ,mexiletine ,the blocker of INa‐L ,decreased the heterogeneity between the two ventricles and reverse‐frequency dependence .