Association of secretory IgA with clinical pathological characteristics and complement activation in IgA nephropathy / 中华肾脏病杂志

Objective To further investigate the association among clinical pathology,complement activation and renal secretory IgA (SIgA) deposition in patients with IgA nephropathy (IgAN).Methods The activation of serum complements were detected by immunoturbidimetry and ELISA.Renal deposition of SIgA and activation of complements were detected by immunofluorescence.Then the association among clinical pathology,complement activation and renal SIgA deposition were analyzed in IgAN patients.Results In all 201 patients with IgAN,59 patients had SIgA deposition with higher incidences of mucosal infection history and hematuria (P ＜ 0.05),lower levels of serum cystatin C,β2 microglobulin and lower tubulointerstitial lesion grades and T-grade in the Oxford classification (P ＜ 0.05),when compared with patients without SIgA deposition.Both alternative and mannose binding lectin (MBL) pathways were activated in patients with or without SIgA deposition.Patients with MBL pathway activation had lower estimate glomerular filtration rate (P ＜ 0.01),higher serum creatinine,higher proportion of glomerulosclerosis and S-grade in the Oxford classification,more severe tubulointerstitial lesion (P ＜ 0.05).Conclusions Compared with patients without SIgA deposition,patients with SIgA deposition have a stronger link to mucosal immune.The deposition of SIgA is associated with different clinical and pathological manifestations;however,the complement activation is similar in both groups of patients.Patients with MBL pathway activation show more severe kidney injury.

Deficiency of C3a/C5a receptors protect kidney from injury in IgA nephropathy / 中国免疫学杂志

Objective:To investigate the role of C3a,C5a and their receptors in the pathogenesis of IgA nephropathy (IgAN). Methods:A total of twenty-eight 6-8 weeks old female BALB/c mice were investigated.And they were negative control group , WT group,C3aR-/-group,C5aR-/-group(the latter three groups were named as experimental groups ),seven mice in each group.All the mice were infected through respiratory tract with infectious SV (experimental groups) or PBS(negative control group),combined with tail vein challenge to make IgAN animal model.Testing 24 h total urinary protein , serum urea nitrogen ( BUN ) and creatinine ( Cr ) , using direct immunofluorescence to test the renal deposition of IgA and C 3,observing renal pathologic lesion under PAS staining with light microscopy.RT-qPCR was used to test the relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1.Results: After 15 weeks,the level of UTP in experimental group was significantly higher than negative control group ,and the same results as WT group than C3aR-/-group and C5aR-/-group.There was no significant difference among groups for BUN and Cr.Combined with negative control group , experimental groups had significant renal pathological lesions , and the changes of WT group was more severe than C3aR-/-group and C5aR-/-group.The results of relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1 was the same as the level of 24 h UTP,at the same time,the relative mRNA expression of IL-1β,IL-6,MCP-1 in C3aR-/-group was significantly less than C5aR-/-group.Conclusion:The deficiency of C3a/C5a receptors can protect kidney from injury in IgAN ,and C3a receptor has more significant role in protect kidney from injury in IgAN.

Retrospective study of mycophenolate mofetil treatment in IgA nephropathy with proliferative pathological phenotype / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases. However, whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases, such as endocapillary proliferation, cellular crescents, and/or capillary loops fibrinoid necrosis is still unknown. We, therefore, initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.</p><p><b>METHODS</b>One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled. All patients were treated with prednisone; 48 patients received prednisone only (Pred group), 40 received MMF and prednisone (MMF + Pred group), and 31 were treated with CTX and prednisone (CTX + Pred group). The median time of follow-up was 30 months (maximum: 96 months). The primary endpoint was defined as renal survival. The incidence of remission of proteinuria was the secondary endpoint.</p><p><b>RESULTS</b>Serum creatinine in all groups declined significantly at different follow-up times (P = 0.002), and the differences among the three groups were significant (P < 0.001). At 24 months of follow-up, the decline rates were 12.35%, 32.95%, and 24.14% in the Pred, MMF + Pred, and CTX + Pred groups respectively. For urine protein excretion, the decline rates were 49.12% (Pred), 73.67% (MMF + Pred), and 63.53% (CTX + Pred) respectively at 24 months of follow-up. The differences among the three groups were not significant (P = 0.714). Renal survival (the primary endpoint) was significantly different (P = 0.027); however, the sencondary endpoint was similar for all the three groups (P = 0.100).</p><p><b>CONCLUSIONS</b>For IgA nephropathy patients with endocapillary proliferation, cellular crescents, and/or fibrinoid necrosis of capillary loops, prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX. Combined MMF and prednisone treatment led to a better renal survival compared to that of prednisone with CTX.</p>

Rosiglitazone reduces renal interstitial fibrosis in chronic cyclosporine nephropathy rats / 中华肾脏病杂志

Objective To investigate the effect of rosiglitazone on renal interstitial fibrosis in chronic cyclosporine nephropathy (CCN) rats.Methods Twenty-eight rats were randomly assigned to control group,rosiglitazone (RGZ,5 mg·kg-1·d-1) group,cyclosporine A(CsA,15 mg·kg-1·d-1) group,rosiglitazone (5 mg·kg-1·d-1) +CsA group.Real-time PCR and RT-PCR methods were used to investigate the expressions of OPN,RANTES on the 14th day and MMP-9,TIMP-1 on the 35th day in kidney of CCN respectively.Results In comparison with control group,the expressions of OPN,RANTES,MMP-9,TIMP-1 in CsA and RGZ+CsA groups were increased (P＜0.05).In comparison with the CsA group,the expressions of OPN,RANTES,MMP-9,TIMP-1 in CsA+RGZ group significantly decreased (P＜0.05).Conclusion Rosiglitazone may protect renal tissue after CCN by decreasing expressions of OPN,RANTES,MMP-9,TIPM-1.

Clinicopathological analysis of lupus nephritis with antinucleosome antibody / 中华肾脏病杂志

Objective To explore the clinicopathological characteristics of lupus nephritis (LN) with antinucleosome antibody (AnuA).Methods Data of 481 patients with biopsy-proven LN in the First Affiliated Hospital of Zhengzhou University from 2004 to 2011 were analyzed retrospectively.The patients were divided into two groups:AnuA-positive group (76 patients) and AnuA-negative group (405 patients).The clinical manifestations,laboratory examinations,histopathologic classes of LN,disease activity measured by SLE disease activity index (SLEDAI) of two groups were investigated and compared.Results There were 15 male patients in positive group (15/76,19.74％) with mean age of (27.99±10.88) years and 45 patients in negative group (45/405,11.11％) with mean age of (31.15±12.15) years respectively,which showed that male patients were more common in positive group (P＜0.05).Incidences of oral ulcer,fever,anemia,low complement and positive anti-dsDNA antibody were higher in positive group (P＜0.05).Percentage of diffuse proliferative lupus nephritis (class Ⅳ ) and pathological activity index (AI) in positive group were higher compared to negative group (all P＜0.05),while no significant differences of other pathological types,chronic index (CI) and SLEDAI were found between two groups.Conclusion LN patients with positive AnuA have special clinicopathological characteristics and AnuA may be used as a promising biomarker for the proliferative LN.