Clinicopathological Features Of Anti-glomerular Basement Membrane Nephritis

Anti-glomerular basement membrane(GBM)disease is an anti-GBM antibody-mediated autoimmune disorder usually presenting as rapidly progressive glomerulonephritis with linear deposition of IgG along the GBM.The outcome is poor with mortality of 75%?90%without treatment.Pathologic parameters shows outstanding performance for a large crescent formation and Bauman wall rupture.Severity of interstitial inflammation and fibrosis are paralleled with glomerular lesions and directly affect the prognosis.In recent years,with diagnosis improving,the number of cases of anti-GBM nephritis have increased.Since the anti-GBM antibodies play an important role in anti-GBM disease,treatments focus on decreasing the inflammation caused by the circulating antibodies and the removal of it.In recent years,doe to the use and improvement of various immunosuppressants and blood purification technology clearing the antibody,patients with anti-GBM nephritis appear significantly improved kidney and patient survival rates.This study analyzed the epidemiology,clinical and pathologic parameters,treatment,and outcomes of anti-GBM nephritis.The efficacy and safety of DFPP(Double filtration plasmapheresis)in the treatment of anti-GBM nephritis and the impact of anti-GBM nephritis prognostic factors.In addition,previous studies have found that mast cells(MCs)promotes tubulointerstitial damage and cause chronic renal progress.In animal models of anti-GBM,the role of MC has come to different conclusions.evidence of the involvement of mast cells in human anti-GBM nephritis is still scarce.In this study,the immuno-histochemical localization of MCs in the kidney was examined in patients with anti-GBM nephritis,and its correlation with clinical and histopathological parameters was investigated.Part 1.Clinical and pathological features of anti-glomerular basement membrane nephritisObjective:To investigate the clinical and pathological features of patients with anti-glomerular basement membrane nephritis.Method:sixty-six patients diagnosed as anti-GBM nephritis by renal biopsy were collected from 2003 to 2013 hospitalized in Institute of Nephrology,Jinling Hospital and divided into two groups according to levels of serum creatinine(Scr):Scr<530?mol/L(6.0 mg/dl)as group A(n=34),Scr? 530 ?mol/L(6.0 mg/dl)as group B(n=32),.Clinical,laboratory tests and renal biopsy and pathological features were compared between the two groups of patients.Result:36 males,30 females with average age of 41.0±17.1 years,the average time from onset to diagnosis was 13.3 weeks.About half(48.5%)of the patients had level of Scr>530?mol/L when diagnosed.37(56.0%)of the patients had manifestation of rapidly progressive glomerulonephritis syndrome.22(33.3%)of the patients had manifestations of rapidly progressive glomerulonephritis accompanied with massive proteinuria and hypoproteinemia.60.6%of the patients had gross hematuria.Compared with the groupA,the group B was older in age and had significantly longer course and higher Scr.Clinical manifestations of oliguria anuria was more common in group A;laboratory indicators of renal interstitial injury also had statistically significant differences between the two groups.The patients in group A had more severe urinary protein excretion and hematuria,but without statistically significance.The group A crescent formation,package wall fracture,tube inflammation,inflammatory cell infiltration were significantly lighter than the group B with significant differences.Patient survival and renal survival in group A was better.The patients with crescentic class of pathology had a better renal survival compared with the other classes.And PE treatment would improve the prognosis of these patients.Conclusion High incidence of gross hematuria were observed in this group of patients.The majority had the performance of uremia when diagnosis.Creatinine levels,oligurla or anuria occured in the course of disease and the laboratory indicators of renal interstitial injury,the crecentic formation and the proportion of cellular crecent formation could predict the degree of kidney damage and the prognosis.The patient with less crescent formation and the cellular accounted for more of the composition could be given plasma treatnent to improve the prognosis.Part 2.Comparison of double filtration plasmapheresis with immunoadsorption therapy in patients with anti-glomerular basement membrane nephritisBackground:Double filtration plasmapheresis(DFPP)and immunoadsorption(IA)are both used to clear antibody.However,the clinical efficacy and safety of DFPP in patients with anti-glomerular basement membrane(anti-GBM)disease are unclear.Methods:Twenty-eight patients diagnosed serologically and pathologically with anti-GBM disease from 2003 to 2013 were enrolled into this retrospective study.According to the ways of plasma therapy they were divided into two groups,treated with DFPP(n=16)and with IA(n=12).All patients were administered immunosuppressive agents.DFPP consisted of an EC50W filter for plasma separation and an EC20W filter for plasma fractionation.A double volume of plasma was processed,and each patient received a 30?40 g human albumin supplement during each session.IA consisted of 10 cycles per session,with 8-10 sessions performed daily or every other day and each session regenerating 30-60 L of plasma.Serum anti-GBM antibodies and IgG were measured,and urinary and blood tests were performed,before and after each procedure.Renal function and outcome were determined.Results:28 patients consisted of 13 males and 15 females,of median age 44.5 years(range,22.5-57 years).Six patients had pulmonary hemorrhage and 18 had serum creatinine concentrations>500 umol/L.The average serum creatinine concentration at early onset of disease was 525 ?mol/L while the peak concentration was 813?mol/L.All patients showed progressive increases in serum creatinine and required CRRT during the course of disease.Pathological examination showed an average 73.9%of crescents(range,54.6-95.4%).The clinical and pathological features of the DPPP and IA groups were similar.Efficacy of clearing anti-GBM antibody was similar in the two groups(61.9 vs.70.8%,P=0.261),although fewer patients in the DFPP group experienced reduced IgG(62.7 vs.83.5%,p=0.022).One patient each had a pulmonary hemorrhage and a subcutaneous hemorrhage during treatment,but there were no other serious complications.At the end of follow-up,patient survival and renal survival were similar in the DFPP and IA groups.Conclusion:DPPP plus immunosuppressive therapy efficiently and safely removed anti-GBM antibodies.The fewer plasma-associated side effects and reduced loss of IgG suggest that DFPP may be a better treatment choice for anti-GBM disease.Part 3.Roles of renal mast cells in patients with Anti-GBM nephritisObjective:Increased mast cells have been detected in various glomerular diseases,mostly in experimental animal models.However,evidence of the involvement of mast cells in human anti-GBM nephritis is still scarce.For the first time,this study investigated whether mast cell renal infiltration is involved in progression of human anti-GBM nephritis.Methodology:Thirty eight patients diagnosed as anti-GBM nephritis in our institute from 2001 to 2010 were enrolled in this study.Renal biopsies were performed in all patients.The clinical and pathological data were collected.The tryptase was stained by immunohistochemistry for detecting mast cells in renal tissue.According to the infiltrating renal mast cell count,the patients were dividedinto group 1(mast cell<50/mm2,n=18)and group 2(mast cell? 50/mm2,n=20,).The clinical,laboratory and pathological indices were compared between the two groups.Correlation between mast cells and patients' clinical and pathological indices was investigated.Results:In patients of group 2,they had longer disease course,older in age,higher percents of gross hematuria,oliguria/anuria,a more serious degree of anemia and less urine protein and microscope hematuria,as well as a higher level of anti-GBM antibodies.Moreover,the patients in group 2 were more serious in renal dysfunctions,which expressed as higher levels of serum creatinine(Scr,791 ± 324 versus 412±241 ?mol/L,P<0.001)and urine retinol-binding protein(RBP,29.8±13.9 versus 15.7±11.5mg/dl,P=0.005),but lower urinary osmotic pressure.In pathology,the patients in group2 were observed to have a higher percentage of glomerular sclerosis and Bowman's wall fracture and more serious degree of fibrosis although no significant differences were observed.They also had a higher percentage of fibrous/fibrocellular crescents(66.7±21.9 versus 47.0±33.6%,P=0.037)while a lower cellular crescents in group2.There were more inflammatory cells including CD4,CD8 and CD68 positive cells infiltrated in the interstitium of group2.Among these inflammatory cells,the infiltration of CD8 positive T cell(268/mm2 versus 180/mm2,p=0.045)and CD68 positive T cell(792 versus 534/mm2,P=0.017)had a significant difference between the two groups.Furthermore,renal MCs correlated significantly with the total number of crescents and the tubular interstitial inflammatory cells,including macrophages and T lymphocytes.Conclusion:Mast cell infiltrations were associated with chronic lesion in anti-GBM nephritis and contributed to loss of renal function with pathological changes of both glomerular and tubular-interstitial damage and inflammatory.