The Value Of Noninvasive Urinary Biomarkers And Serum Cystatin C In The Progression Of IgA Nephropathy

Objective:The aim of this study was to demonstrate the correlation between noninvasive urinary biomarkers IL-6,IL-18,TGF-β1 and KIM-1 with clinical and histological damages in IgA nephropathy.And provide an effectively noninvasive examination method for clinical to predict the progression in IgAN patients.Methods:115 patients with IgA nephropathy were classified separately according to Lee's histological classification.among which pathological grading (Ⅰ-Ⅱ),patients 15 cases,male 7 cases,female 8 cases;(Ⅲ):patients 63 cases,male 38 cases,female 25 cases;The lesions with grade(Ⅳ-Ⅴ):patients 37 cases,male 20 cases,female 17 cases.and to establish a control group of non-IgAN nephropathy 30 cases(minor glomerular abnormalities 8 cases;minimal change disease 11 cases,membranous nephropathy 11 cases),male 15 cases,female 15 cases; Control group for healthy adults with 30 cases,male 15 cases,female 15 cases. urinary IL-6,IL-18,TGF-β1 and KIM-1 level were detected with ELiSA.Results:(1).There was no statistical difference among each group of patients' age and body mass index,P＞0.05;(2).Noninvasive marker were examined in the urine of each group(P＜0.05);The levels of urinary IL-6,IL-18, TGF-β1,KIM-1,in IgAN group were higher than that of healthy adults, Distinguishable difference existed between the two above-mentioned groups. (P＜0.05);(3).The urinary level of IL-6,IL-18,TGF-β1,KIM-1 increased in the patients with IgAN with the pathological grade increased.(4).There were no apparent differences between the levels of urinary IL-6,IL-18,TGF-β1,KIM-1 of patients with IgAN classified pathological grading(Ⅰ-Ⅱ)and non-IgAN's;but there were distinguishable differences between the levels of urinary IL-6,IL-18, TGF-β1,KIM-1 of patients with IgAN classified pathological grading(Ⅳ-Ⅴ)and non-IgAN's.(5).The four biomarkers were correlated with some clinical indices such as glomerular filtration rate and some pathological indices such as pathological grade,fibrosis degree,among which correlated with pathological grade biomarkers:urine IL-6,urine IL-18,urine TGF-β1 and urine KIM-1; correlated with proliferation of mesangial cells:urine IL-6,urine KIM-1; correlated with the degree of glomerulosclerosiss such as urine IL-6,urine TGF-β1,urine KIM-1;correlated with the degree of renal interstitial fibrosis such as urine IL-6,urine IL-18,urine TGF-β1 and urine KIM-1;correlated with the infiltration of inflammatory cell in renal interstitium such as urine IL-6,urine IL-18,urine TGF-β1 and urine KIM-1;correlated with the degree of renal tubular atrophy such as urine IL-6,urine IL-18,urine TGF-β1,urine KIM-1; correlated with general standards of renal fibrosis(combination of glomerulosclerosiss and renal tubular atrophy and renal tubulointerstitial fibrosis): urine IL-6,urine IL-18,urine TGF-β1,urine KIM-1;(6).We took advantages of urine IL-6 and urine KIM-1,(combined diagnosis)to diagnose general standards of renal fibrosis,pathological grade,found that the method(combined diagnosis)should be more valuable than singular marker.conclusion:noninvasive biomarkers such as urine Il-6,urine IL-18,urine urine TGF-β1,urine KIM-1,can reflect clinical and pathological lesion of IgA nephropathy patients,combined diagnosis should have clinical values. Objective:To investigate serum Cystatin C's practical values in IgA nephropathy and the correlation with clinical lesions,pathological lesions as well as noninvasive biomarkers of urine.Methods:96 cases of IgA nephropathy patients were classified separately according to Lee's histological classification and Glomerular filtration rate; According to Lee's histological classification,among which pathological grading (Ⅰ-Ⅱ),patients 10 cases,male 6 cases,female 4 cases;(Ⅲ):patients56 cases,male 35 cases,female 21 cases;The lesions with gradeⅣ-Ⅴ:patients30 cases,male16 cases,female14 cases;GFR with grade as follows:GFR≥90 groups with 46 cases,male 30 cases,female 16 cases;60≤GFR≤89 groups with 26 cases,male 16 cases,female 10 cases;30≤GFR≤59 groups with18 cases,male 8 cases, female 10 cases;GFR＜30 groups with 6 cases,male 3 cases,female 3 cases.and to establish a control group of non-IgAN nephropathy 25 cases(minor glomerular abnormalities 8 cases;minimal change disease7 cases,membranous nephropathy 10 cases),male 10 cases,female 15 cases;Control group for healthy adults with 30 cases,male 15 cases,female 15 cases.Discovering concentration of serum Cystatin C's standards in different groups,and comparing with blood creatinine and glomerular filtration rate,meanwhile,discovering the correlation of serum Cystatin C with clinical indices,pathological indices,and noninvasive biomarker of urine,By Automatic protein analyzer,serum Cystatin C should be detected. Various pathological parameters such as glomerular sclerosis,renal tubulointerstitial lesion should be marked by Katafuchi's semi-quantitative test.Results:(1).Concentration of serum Cystatin C increased with decreasing of GFR in IgAN patients.3 GFR-abnormal groups of IgAN patients in accordance with renal function,their concentration of serum Cystatin C had apparent difference in comparison with each other,there was distinguishable difference between GFR-normal group and healthy adults,but there was nothing valuable by comparing with non-IgAN nephropathy group.(2).With increase of severity of pathological lesion in IgAN patients,concentration of serum Cystatin C increased rapidly.There existed statistical difference between pathological groupⅣ-ⅤandⅠ-Ⅱas well asⅢ,by comparison.P＜0.05.(3).serum Cystatin C was correlated with some clinical indices such as Urinary protein in 24hours(R=0.539 P＜0.01),glomerular filtration rate(R=-0.776 P＜0.01),serum albumin level (R=-0.412 P＜0.01),and some pathological indices such as pathological grade(R=0.647 P＜0.01),glomerular sclerosis(R=0.494 P＜0.01),renal interstitial fibrosis(R=0.674 P＜0.01),infiltration of inflammatory cell in renal interstitium(R=0.602 P＜0.01),Renal Tubular Atrophy(R=0.651 P＜0.01) (4).all Noninvasive biomarkers correlated with serum Cystain C,the correlation was IL-6(R=0.481 P＜0.01),IL-18(R=0.579 P＜0.01),TGF-β1(R=0.258 P＜0.05),KIM-1(R=0.474 P＜0.01)respectively.(5).By means of a receiver operating characteristic curve(ROC)analysis,We found that the ability of serum Cystatin C to estimate renal sclerosis and interstitial fibrosis was superior to serum creatinine.Conclusion:serum Cystatin C reflected early stage of renal function,and serum Cystatin C correlated with many indices of clinical and pathological standards,which can reflect kidney's clinical and pathological injury.serum Cystatin C superior to serum creatinine should have clinical values in IgAN patients.