Kidney Injury Molecule-1in Patients With Nephropathy Syndrome Complicated With Acute Kindney Injury

Objective:Primary nephrotic syndrome（PNS） is a common clinical renaldisease,acute kindney injury（AKI） is the most common and criticalcomplication,AKI seriously impact on the prognosis. Clinical observation onrenal pathological AKI usually manifests as acute tubular necrosis（ATN）.Renal biopsy is the clinical gold standard to diagnose the ATN,but renalbiopsy is of destructiveness and chanciness.Therefore,a early, sensitive,noninvasive and specific marker is necessary to diagnose the AKI. In recentyears through genomics and proteomics in human and animal model studieshave found that cystatin C （Cys）, interleukin-18（IL-18）, and neutrophilgelatinase associated lipocalin （NGAL） may be the early diagonosis mark ofAKI. Kidney injury molecule-1（KIM-1） is a marker for proximal tubularinjury, the hallmark of virtually all proteinuric, toxic and ischaemic renaldiseases. Recently, much attention has been paid to its possiblepathophysiological role in modulating tubular damage and repair. Our study isto investigate the level of urine KIM-1（by enzyme linked immunosorbentassay） and tissue KIM-1（by immunohistochemical method） in the PNS, andto carry out the relative researches with trial index commonly used in clinicalmedicine, so as to discuss the possible effect of KIM-1in the primarynephrotic syndrome.Methods:Step1:We selected72patients as the cases（45male,27female）, whoconformed to the criterion of primary nephrotic syndrome（24h urineprotein>3.5g, plasma albumin<30g/L）.They were divided into different groupsdepend on pathology：1.PNS with non ATN group （37male and20female）:（1）. Minimal change disease （MCD）（16male and8female）;（2）.Membranous nephropathy （MN）（15male and8female）;（3）. Mesangial proliferative glomerulonephritis（MsPGN）（6male and4female）.2. PNS withATN group（8male and7female）: MCD with ATN10;MPGN with ATN5.Step2:15cases （8male and7female） were collected from the patientswho were performed normal urine analysis in the health examination.Moreover, the kidney tissue were obtained from5patients （3male and2female） who had nephrectomy because of renal duplication, tumor and soon.Step3: Enzyme linked immunosorbent assay （ELISA） was applied todetect the urinary level of KIM-1in PNS patients and the control group. Alsocomparations were made between those groups and the control group.Immunohistochemistry was used to detect kidney tissue level of KIM-1inpatients complicated with ATN and other groups.KIM-1expression index （EI）were detected by IMS-2000image analysis system. Also comparations weremade between those groups and the control group.Step4: Determine the clinical index （such as β₂MG,24h urine protein,serum creatinine）, correlation analysis was processed between ELISA,immunohistochemical result and clinical index.Step5: Differences among groups were evaluated by one-way analysis ofvariance test or nonparametric test. To determine the significance betweengroup means in the analysis of variance, the nearest significant difference test（SNK-q test） was used as the multiple comparison test.Step6: SPSS13.0statistical software was used to analyze the above mentioned data, P <0.05wasconsidered as significant.Results:1. Compared with normal controls and other PNS groups, the urinarylevel of KIM-1were significantly increased in patients with ATN. Also theurinary level of KIM-1in PNS without ATN groups were significantlyincreased compared with that of normal controls （P <0.05）. The urinary levelof KIM-1in the MCD group, MN group, MPGN group control group were（2.41±0.58、2.54±0.67、2.87±0.50、0.73±0.35）ng/ml. The urinary level ofKIM-1in PNS with ATN with was significantly higher compared with the other PNS without ATN group （P <0.05）. The urinary level of KIM-1inMCD with ATN and MPGN with ATN were significantly higher comparedwith other two non ATN groups （P <0.05）. The level of KIM-1in MCD withnon ATN group, MCD with ATN group, MPGN with non ATN group,MPGN with ATN group respectively were（2.41±0.58、3.30±0.62、2.87±0.50、4.21±1.00）ng/ml.2. The expression of KIM-1in tubule：It was shown that the positivestaining for KIM-1was observed in the proximal tubule epithelium in the PNSand control groups. The EI of KIM-1in MCD Group, MN group, MPGNgroup and control group respectively were （5.52±0.72、6.00±1.23、6.39±0.76、2.57±1.22）. The EI of KIM-1in PNS with ATN was significantly highercompared with the other PNS without ATN group （P <0.05）. The EI of KIM-1in MCD with ATN and MPGN with ATN were significantly higher comparedwith other two non ATN groups （P <0.05）. The EI of KIM-1in MCD withnon ATN group, MCD with ATN group, MPGN with non ATN group,MPGN with ATN group respectively were（5.52±0.72、8.40±2.21、6.39±0.76、8.05±1.29）.3. Both the urinary level of KIM-1and the expression of KIM-1inkidney were positively correlated with serum creatinine, serum blood ureanitrogen, serum β₂MG and24h urine protein quantitation. No correlation wasfound between the two indexes and plasma albumin,.Moreover expression ofKIM-1in kidney was positively correlated the urinary level of KIM-1.Conclusion:1. The urinary level of KIM-1was significantly increased in patients ofPNS, and more significantly in patients of PNS complicated with ATN. Therewere no difference among different pathological types.2. The expression of KIM-1in kidney tissue is increased in PNS patients,and more significantly in patients of PNS complicated with ATN. There wereno difference among different pathological types.KIM-1in kidney tissue alsoreflect the acute tubular necrosis.3. Urinary KIM-1may be a sensitive biomarker that reflects the acute tubular necrosis. KIM-1was specific and sensitive biologic factors in thediagnosis of AKI.4. The expression of KIM-1in kidney tissue was highly correlated withthe urinary level of KIM-1. Renal tissue KIM-1could reflect the PNScomplicated with acute kidney injury lesions occurring in site and degree.