| ObjectiveIt is well known that renal biopsy plays a fundamental role not only to establish an accurate diagnosis but also to help deciding on appropriate treatment and assess the prognosis. Quite a number of cases were diagnosed only clinically at basic-level hospitals in China, where some renal doctors couldn’t operate renal biopsy or some patients wouldn’t like accepting the operation. Among the 5 PGN, nephrotic syndrome is the first indication for renal biopsy as the most common glomerular disease in kidney department. In that regard, we choose nephrotic syndrome as the research object to analyze its related factors of prognosis and its mechanism. Membranous nephropathy is a major cause of adults nephrotic syndrome, most of whose patients are not sensitive to hormone. The treatment experience from superior hospital is not suitable for doctors from the basic-level hospitals because of the difference in the face of areas and spectrum of disease. In order to early predict the prognosis and guide the timing of the immune inhibitor application, the clinical characteristics of refractory membranous nephropathy were analyzed. To look for the markers of hormone resistance, we selected IgG4 and P glycoprotein as research target from many biological indicators to analyse the relevance to early membranous nephropathy patients with hormone sensitivity.MethodsPart 1:This is a retrospective analysis of PNS patients of early-stage-IMN, from Tai’an central hospital during the period between July 2011 and June 2014. All samples were obtained by percutaneous method using a trucut needle under ultrasound guidance. Three renal biopsy samples were taken from each patient, evaluated by the same pathologist. Sections were made from formalin fixed paraffin embedded tissue and stained by hematoxylin-eosin(HE), periodic-acid schiff (PAS), Periodic Acid-silver Methe-namine (PASM)and Masson. All biopsies were conventionally processed for light microscopy, electron microscopy (EM)and immunofluorescence. Immunofluorescence microscopy panel included staining for IgA, IgM, IgG, C3, C1q and fibrinogen. All biopsy specimens were evaluated according to clinical data with standard histological methods and the results were analyzed for sex, age, onset season and inpatient days. All patients, given regular treatment of hormone and cyclophosphamide, were divided into 3 groups according to the hormone work time, which are sensitive group (less than 4 weeks), non- sensitive group(4-12weeks) and resistant group (more than 12 weeks), compared the difference of their sex, age, onset season, length of stays. Data were stored in a database file (Excel 2003).All statistical calculations were carried out with the statistical package SPSS for Windows 17.0. Age are represented as mean±SE, Analysis of variance was used to test the significance of differences; Frequency counts were compared by the chi square test. Risk factors for hormone drug resistance were analyzed by logistic multi-factor regression analysis. p -values< 0.05 were considered significant.Part 2:The serum of patents before the treatment of hormone was collected, who were line with inclusion criteria during from July 2013 to June 2014. The concentration of serum IgG4 and IgG were tested by ELISA method, the ratio of them was the final result. Analysis of variance was used to test the significance of differences; IgG4/IgG and serum albumin of the same patient were analyzed by spearman correlation analysis. p -values< 0.05 were considered significant.Part 3:Renal tissue of 30 patents, divided into 2 groups according to the hormone work time, effective egroup (less than 12 weeks) and resistant group (more than 12 weeks), was collected, who were line with inclusion criteria, P-gp of them were tested by SP-2-steps immuno- histochemical staining. The expression of p-GP were meaned by IOD values. T tset was used to test the significance of differences between 2 groups; IgG4/IgG and P-gp of the same patient were analyzed by spearman correlation analysis. p -values< 0.05 were considered significant.ResultsPart 1:A total of 84 patients were analyzed, who were 19 cases of sensitive group,28 cases were of non-sensitive group,37 cases of resistant group. There was no significant difference in 3 groups of patients with urinary protein, serum albumin quantitative and serum creatinine level (P> 0.05). The sex ratio was 1.71:1 and the difference of sex comparison were significant between 3 groups(x2-test, p<0.01), of which the male and female ratio of hormone resistant group as high as 2.36.Their average age was 43.66 years, the average age of the 3 groups respectively were 31.55,42.00 and 57.77 years. The difference of 3 groups on average age were significant (analysis of variance, p=0.001).There respectively were 29,19, 15 and 21 in Spring, summer, autumn and winter seasons. The number of winter and spring obviously more than in summer and fall season. The number of steroid sensitive group and steroid insensitive group in spring and summer were much more than in autumn and winter, and the number of steroid resistan group in winter and spring than in summer and fall. The difference of 3 groups were significant (x2-test, p=0.005).The average length of stay of 84 patients was 22.13 days. The average length of stay steroid sensitive group (15.05 days) was shortest in 3 groups, followed by steroid resistan group (22.51 days) and steroid insensitive group (26.44 days). The difference of 3 groups on average length of stay were significant (analysis of variance, p=0.001). There were significant difference by logistic multi-factor regression analysis (p< 0.05). The OR value of the gender was 0.532, age was 3.048, onset seasons was 0.703.Part 2:A total of 39 patients were analyzed, who were 9 cases of sensitive group,12 cases were of insensitive group,18 cases of resistant group. The correlation coefficient of IgG4/IgG and serum albumin was 0.331 (p< 0.01), low degree of correlation, by spearman correlation analysis. The difference of IgG4/IgG in 3 groups was statistically significant by analysis of variance (p< 0.05). The increased number of resistant group was more obviously than sensitive group in the comparison of each two groups.Part 3:A total of 30 patients were analyzed, who were 17 cases of effective group and cases 13 cases of resistant group. The results of immunohistochemical staining meaned that P-gp170 expressed chocolate particles mainly in the renal tubular and interstitial. The average IOD of 2groups were 185.4±34.5 and 215.2±36.9. There was significant difference by t-test (p< 0.05). The correlation coefficient of IgG4/IgG and P-gp was 0.758 (p< 0.01), high degree of correlation, by spearman correlation analysis.ConclusionsThere were significant difference among 3 different steroid sensitive groups of early IMN in gender, age, onset seasons and average length of stays. Man, old age and the onset of spring and summer were risk factors of steroid resistance. The correlation of IgG4/IgG and serum albumin was low. The increased number of resistant group was more obviously than sensitive group. P-gp170 expressed chocolate particles mainly in the renal tubular and interstitial. The average IOD of resistant group was significantly increased than effective group. The correlation of IgG4/IgG and P-gp was high. |
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