Expression And Significance Of OPN And NF-κb In Serum Of Patients With IgA Nephropathy

Objective: Primary Ig AN(Immunoglobulin A nephropathy, Ig AN) i s the most common primary glomerulonephritis in the world, and it is a lso the most common cause of end-stage renal disease(End stage renal disease, ESRD). At present, the mainly risk factors of Ig AN include age,sex, a lot of proteinuria, hypertension,renal insufficiency, glomerular scle rosis, renal interstitial fibrosis, crescent and loop necrosis,in which renali nterstitial fibrosis is the main factor for progress. Recent studies have fo und that osteopontin(OPN) is a Th1 type cytokine.There are a number of studies have demonstrated that OPN plays an important role ina vari ety of inflammatory and immune-mediated diseases.That is possiblebecau se OPN can enhance the auxiliary Th1 mediated immune responseby im mune cell interactions.OPN is involved in the development of various re nal diseases, and many reports indicate that increased OPN expression is closely related to renal tubular interstitial inflammation and fibrosis.How ever, the mechanism by which OPN causes renal injury remainsunclear. Nuclear factor kappa B(NF-κB) belongs to the Rel family. Many studie s showed that NF-κB plays a crucial role in regulating immuneresponse by chemokines factor, cytokine, adhesion molecule gene proteinexpressio n. NF-κB caused interstitial inflammation in renal interstitial fibrosis thr ough the glomerular mesangial cells, renal tubular epithelial cells. The s tudy aims to investigate the possible role and relevance of OPNand NF-κB in the pathogenesis of Ig AN by detecting serum levels of OPN and NF-κB in Ig A nephropathy patients with different clinical and pathologic al levels.Methods: The 60 patients(41 males,19 females,the age of 32.6±6.4years old) selected from department of Nephrology, the second hospita l of Hebei Medical University, from October 2014 to October 2015;and diagnosed by renal biopsy,excepting clinical secondary renal disease in p atients with diabetic nephropathy,lupus nephritis, high blood pressure and kidney damage,purpura nephritis,hepatitis B virus associatednephritis, tum or associated nephropathy, renal damage in patients with rheumatoid arth ritis, thyroid disease associated renal damage,inflammatory bowel disease,and with the exception of the interstitial nephritispatients caused by dru g,contrast agent and rhabdomyolysis acute renal injury.Glucocorticoids an d immunosuppressive agents were not used before biopsy.10 cases(male6, female 4,average 30.90+9.36 years old)were taken as the normal cont rol group.Selected healthy subjects were excluded from the central nervo us system disease, cardiovascular disease,and liver and kidney disease,dia betes and other systemic diseases;in nearly three months without history of infection and vaccination history,no immunizationhistory.Grouping:Ig A nephropathy were devided into three pathological groups by Oxford clas sification of Ig A nephropathy in 2009(mild pathological change group T0 0%~25%;moderate pathological change group T1 26%~50%;severe pat hological change group T2>50%).Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of OPN and NF-κB in serum of patients with Ig A nephropathy. Collection of clinical data:age,sex,blood p ressure,serum albumin,serum creatinine,CKD-EPI assessment of glomerula r filtration rate(glomerular filtration rate estimate,e GFR),serum uric acid,24 hours urinary protein quantitation.Correlation was analysised among O PN,NF-κB and their clinical data.Results: 1 The clinical data: according to interstitial fibrosis group, each group sex, age, serum albumin, serum uric acid had no significan t difference(P>0.05); T2 group systolic pressure was higher than that i n group T1, T1 group systolic blood pressure higher than T0 group(P<0.05);T2 group diastolic blood pressure was higher than that in group T1 and T0 group(P<0.05),T0 and T1 group had no statistical significanc e; 24 hours urine protein increased with the degree of interstitial fibrosi s and increased(P<0.05); glomerular filtration rate increased with the degree of interstitial fibrosis and reduced(P<0.05);2 The level of Serum OPN: T2 group is higher than T1 group, T1 group was higher than T0 group,T0 group is higher than normal control group,the difference was s tatistically significant(P<0.05);the serum level of OPN with renal interst itial fibrosis aggravated gradually increased, the difference is statistically significant(P<0.05);3 The level of serum NF-κB:T2 group is higherthan T1 group, T1 group was higher than T0 group, T0 group is higherthan normal control group, the difference was statistically significant(P<0.05);t he serum level of NF-κB with renal interstitial fibrosis aggravated gradu ally increased, the difference is statistically significant(P<0.05);4 Correl ation analysis between serum OPN and clinical indexes: serum OPNleve l was positively correlated with systolic blood pressure, diastolic blood pressure and 24 hours urinary protein(correlation coefficient was r=0.798, r=0.513, r=826, P<0.05).Serum OPN was negatively correlated with g lomerular filtration rate(r=-0.592, P<0.05);5 Correlation analysis betwee n serum of NF-κB and clinical indexes: serum level of NF-κB was posi tively correlated with systolic blood pressure, diastolic blood pressure, 24 hour urinary protein(correlation coefficient was r=0.799,r=0.567,r=0.837,P<0.05);serum NF-κB and glomerular filtration rate showeda negative co rrelation(r=-0.648, P<0.05);6 Correlation analysis between serum OPN a nd NF-κB:the positive correlation between the serum OPN and NF-κB(r=0.968, P<0.05).Conclusions:1 In Ig A nephropathy, with the increase of interstitial fibrosis, serum OPN level gradually increased, urinary protein excretion increased gradually, glomerular filtration rate decreased.The positive correlation between serum levels of OPN and 24 h urinary protein quantitative suggests that OPN is involved in the progression of Ig A nephropathy and its serum level can response to the disease severity.2 The study showed that serum levels of NF-κB expression level increased with the increase of the degree of renal interstitial lesions. It suggests that NF-κB is also involved in the mechanism of renal interstitial lesions.