The Correlation Analysis Of Tubulointerstitial Lesions In Lupus Nephritis

OBJECTIVE:Systemic lupus erythematosus(SLE)is a prototypic autoimmune disease,which comprises a range of multisystem disorders,nearly 50% patients of SLE has renal damages.Lupus nephritis(LN)affects all compartments of the kidney,including glomerulus,tubulointerstitium and blood vessels.Tubulointerstitial(TIN)abnormalities were present in 38%~71% of the patients with lupus nephritis.The prognostic value of tubulointerstitial abnormalities were increasingly recognized.Investigating a large cohort of 205 SLE-glomerulonephritis(GN)patients who underwent kidney biopsy,this paper focuses on the feature of TIN lesions and its relationship with pathological and clinical feature in LN.METHODS:This retrospective study included the complete pathological data and partial clinical information on 205 patients with a histological diagnosis of SLE nephritis over a 11 year time span(from 2007 to 2017),who underwent kidney biopsy in Tianjin Medical University General Hospital.Clinical information was available in particular blood pressure levels,hemoglobin level,albumin level,platelet level,Uric acid level,serum creatinine,complement c3 and c4 levels and proteinuria(24h collection).Estimated glomerular filtration rate(eGFR)is calculated by EPI formula.Pathological files were included the activity and chronic indexes of lupus nephritis,the glomerular activity index,indices of glomerular sclerosis,grades of interstitial infiltration,tubular atrophy,and interstitial fibrosis.Patients with different classes of International Society of Nephrology/Renal Pathology Society(INR/RPS)were divided into groups to analysis the characteristic of interstitial lesions in LN.Then analysis the association of tubulointerstitial lesions and glomerulopathy and the patient's clinical renal performance.RESULTS:1.The baseline clinical characteristics of the patients and the occurring rate of tubulointerstitial lesions: Patients were more commonly female(84.4%),with a mean age of 34.4 years(standard deviation[SD]=12.4).The ratio of male to female was 1:5.4.Most cases were young and middle-aged(96.6%).The systemic lupuserythematosus nephritis tubulointerstitial(SLE-TIN)features as assessed by four-tiered classes: grade 0,I,II and III.The ratios of four-tiered classes in interstitial infiltration were 33.3%,22.4%,26.9%,17.4%.The ratios of four-tiered classes in interstitial fibrosis/tubular atrophy were respectively 26.4%,23.9%,30.8%,18.9%.For the study,156(77.6%)of patients with tubulointerstitial lesions,108(69.2%)of them with moderate-severe tubulointerstitial lesions.There was a strongly positive correlation between the degrees of interstitial inflammatory cell infiltration and interstitial fibrosis/tubular atrophy(r=0.803,P<0.05).2.The link between systemic lupus erythematosus nephritis tubulointerstitial(SLE-TIN)features and ISN/RPS classification.The scores of interstitial inflammatory cell infiltration and interstitial fibrosis/tubular atrophy among the four classes were significantly different(P<0.05,P<0.05,respectively).They were found to be the most severe in class IV,moderate in class III,and mild in classes II and V.The severity of interstitial inflammatory cell infiltration and interstitial fibrosis/tubular atrophy were significantly higher in the class IV-G group than in the class III group(P<0.05,P<0.05,respectively).The score of interstitial inflammatory cell infiltration and interstitial fibrosis/tubular atrophy in patients with subclass IV-G was significantly higher than that in those with class IV-S(P<0.05,P<0.05,respectively).There was no significant difference of interstitial inflammatory cell infiltration and nterstitial fibrosis/tubular atrophy between III and IV-S.3.The association of tubulointerstitial lesions and glomerular lesions:The score of glomerular lesions was positively correlated with the score of tubulointerstitial lesions(r=0.173,P<0.05),the glomerular activity index was positively correlated with the score of glomerular sclerosis(r=0.215,P<0.05),the glomerular activity index was not correlated with the degree of interstitial inflammatory cell infiltration(r=0.145,P> 0.05)and the score of glomerular sclerosis was not correlated with the level of interstitial fibrosis/tubular atrophy(r=0.145,P>0.05).4.The relationship between patient's clinical feature and tubulointerstitial lesions: The degree of interstitial inflammatory cell infiltration in lupus nephritis was positively correlated with the age of onset and blood pressure level(r=0.158,0.272,all P<0.05),negatively correlated with the levels of hemoglobin,blood platelet,albumin,eGFR(r=-0.234,-0.114,-0.132,-0.445,all P<0.05).There was no correlation with complement C3 and C4 levels(r=0.056,0.064,all P>0.05).The degree of interstitial fibrosis/tubular atrophy was positively correlated with the age of onset and blood pressure level(r=0.157,0.306,all P<0.05),negatively correlated with the levels of hemoglobin,blood platelet,albumin and eGFR(r=-0.232,-0.127,-0.162,-0.439,all P<0.05).There was no correlation with complement C3 and C4 levels(r=0.065,0.077,all P>0.05).5.The risking factors of eGFR: The level of eGFR was positively correlated with the levels of hemoglobin,albumin,platelet,complemen C3(r=0.535,0.357,0.324,0.279,all P<0.05),and negatively correlated with the age of onset,blood pressure level,the scores of AI and CI,the glomerular activity index,indices of glomerular sclerosis,the degree of interstitial inflammatory cell infiltration and interstitial fibrosis/tubular atrophy(r=-0.298,-0.448,-0.500,-0.457,-0.378,-0.164,-0.571,-0.549,all P<0.05).The age of onset,the levels of hemoglobin and platelet,the grade of interstitial inflammatory cell infiltration were independent risk factors of eGFR(B=-0.685,0.361,0.109,-1.447,-7.496,all P<0.05).CONCLUSION:1.Among the 205 patients of LN,77.6% of patients with tubulointerstitial lesions,approximately two thirds of them with moderate-severe tubulointerstitial lesions.2.Tubulointerstitial lesions in lupus nephritis are connected with ISN/RPS classification.But in human lupus nephritis,the severity of interstitial nephritis does not necessarily correlate with glomerular activity.3.For lupus nephritis,interstitial inflammatory cell infiltration is an independent risking factor of renal function at the time of biopsy.