Key Laboratory of Chronic Kidney Disease Prevention and Treatment

Beijing, China

Key Laboratory of Chronic Kidney Disease Prevention and Treatment

Beijing, China
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Yu J.-T.,Peking University | Yu J.-T.,Key Laboratory of Renal Disease | Yu J.-T.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Yu J.-T.,Peking Tsinghua Center for Life science | And 16 more authors.
Kidney International | Year: 2016

Myeloperoxidase (MPO) is a common target antigen of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and is recognized in one-third of patients with anti-glomerular basement membrane (GBM) disease. Our previous study identified over 60% of patients with anti-GBM disease recognizing linear peptides of MPO heavy chain. Here we tested whether aberrant glycosylation alters MPO antigenicity through exposure of neo-epitopes on MPO molecules. Atypical glycosylated MPO molecules, including all possible glycosylation types, were prepared by exoglycosidase and endoglycosidase treatments. Antibodies were detected from the sera of 40 patients with anti-GBM disease without the coexistence of MPO-ANCA. Circulating antibodies against aberrant glycosylated MPO existed in 21 of these patients. Non-glycan MPO and MPO with only N-acetylglucosamine had high frequencies of recognition (16 and 15 patients, respectively). Antibodies binding to aberrant glycosylated MPO could not be inhibited by intact MPO or GBM antigen. When applied to ethanol-fixed neutrophils from normal individuals, these antibodies yielded a typical cytoplasmic staining pattern (c-ANCA). Antigen specificity was detected in 90% of the antibodies using five peptides containing one of the five N-glycosylation sites each, mostly on N323, N355, and N391. The antibodies were restricted to IgG1 subclass, could activate complement, and induce neutrophil degranulation in vitro. Thus, aberrant glycosylated MPO exposed neo-epitopes and was recognized by half of the patients with anti-GBM disease. Their antibodies possessed pathogenic characteristics and may be associated with kidney injury. © 2016 International Society of Nephrology.

Wang J.,Peking University | Wang J.,National Health and Family Planning Commission | Wang J.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Wang F.,Peking University | And 16 more authors.
BMC Nephrology | Year: 2017

Background: Previous studies have indicated that reduced kidney function and albuminuria are associated with increased risk of mortality and adverse cardiovascular outcomes, however, the evidence from the Asian population is limited. We investigated the association between the indicators of chronic kidney disease (CKD) and all-cause mortality, as well as cardiovascular mortality among a general population in China. Methods: We conducted an observational study among 47,204 Chinese adults, from a cross-sectional survey, whose survival status is identified through December 31, 2013. Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) were used as indicators of CKD. We determined the rates of all-cause and cardiovascular mortality. Results: The incidence rates for both all-cause and cardiovascular mortality increased with the advanced stages of reduced eGFR or elevated ACR. Elevated ACR levels were found to be significantly associated with increased risk of both all-cause and cardiovascular mortality, as shown in the Cox proportional hazards regression model. The multivariable adjusted hazard ratios (HR) associated with all-cause mortality were 1.26 (95% confidence interval [CI]: 1.04-1.53) for those with ACR 30-299 mg/g and 2.07 (95% CI: 1.40-3.04) with ACR ≥ 300 mg/g, compared to those with ACR <30 mg/g. The corresponding HRs for the above ACR levels associated with cardiovascular mortality were 1.08 (95% CI: 0.77-1.50) and 2.32 (95% CI: 1.31-4.12), respectively. We did not identify reduced eGFR as a risk predictor in the multivariable adjusted model for the adverse outcomes in the population, however, an interaction between eGFR and age were detected. Stratified analyses revealed that the associations of reduced eGFR (<60 mL/min/1.73 m2) with all-cause mortality were prominent among participants aged less than 65 years. Conclusions: Albuminuria was associated with an elevated risk of all-cause and cardiovascular mortality among the Chinese population, however, the association of reduced kidney function with all-cause mortality was not clear. © 2017 The Author(s).

Song D.,Peking University | Song D.,Key Laboratory of Renal Disease | Song D.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Guo W.-Y.,Peking University | And 15 more authors.
American Journal of the Medical Sciences | Year: 2017

Objective The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. Materials and Methods Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed. Results Plasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = −0.412, P < 0.001 and r = −0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P < 0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group. Conclusions Our findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes. © 2017 Southern Society for Clinical Investigation

He Y.,Peking University | Xu B.,Peking University | Song D.,Peking University | Song D.,Key laboratory of Renal Disease | And 9 more authors.
American Journal of Reproductive Immunology | Year: 2016

Problem: To investigate the expression of complement activation factors in plasma of patients with early/late-onset severe pre-eclampsia. Methods: A case–control study was performed. The study group consisted of 30 cases of early-onset severe pre-eclampsia (EOSPE) and 30 cases of late-onset severe pre-eclampsia (LOSPE). Thirty cases were selected as the early-onset control group (E-control) and 30 as the late-onset control group (L-control). ELISA was used to test C1q, C4d, MBL, Bb, C3a, C5a, and MAC in the maternal peripheral circulation. Results: The complement activation factors Bb, C3a, C5a, and MAC were increased significantly in EOSPE (all P<.01) and LOSPE (P value:.027, <.001,.001, and <.001, respectively) compared with E/L-control. C1q and C4d were increased significantly in LOSPE (P value:.003 and.014, respectively) compared with L-control. Conclusion: Abnormal activation of the complement system exists in the maternal circulation of patients with early- and late-onset severe pre-eclampsia. In patients complicated with LOSPE, the complement system was activated through both the classical and alternative pathways, while in EOSPE, the complement system was activated mainly through the alternative pathway. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Li Q.,Peking University | Li Q.,Key Laboratory of Renal Disease | Li Q.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Song D.,Peking University | And 14 more authors.
The Scientific World Journal | Year: 2014

Objective. To assess clinicopathological characteristics of lupus nephritis patients with scanty immune deposits. Methods. The data of patients with scanty immune deposits lupus nephritis were retrospectively analyzed. Plasma ANCA and complement components were detected. Results. Among 316 cases with renal biopsy-proven lupus nephritis, 40 cases were diagnosed as scanty immune deposits. There were significantly higher value of serum creatinine (P=0.002) and lower hemoglobin level (P=0.009) and higher score of cellular crescents (P=0.015) in scanty immune deposits group compared with immune complex deposits group. The frequency of positive plasma ANCA was significantly higher in scanty immune deposits group than that in immune complex deposits group (52.5% versus 10.1%, P<0.001). As for comparisons of plasma complement components, there were significantly higher levels of C1q (P=0.005) and Bb (P=0.02) and lower level of factor H (P=0.003) in scanty immune deposits group. The ratio of treatment failure was significantly higher in scanty immune deposits group than that in immune deposits group (42.5% versus 19.20%, P=0.001). The renal outcomes were similar between the two groups. Conclusions. Patients with scanty immune deposits lupus nephritis had more severe kidney damage. ANCA and activation of complement alternative pathway might be involved in the pathogenesis of the disease. © 2014 Qiuyu Li et al.

Yang X.-W.,Peking University | Yang X.-W.,Key Laboratory of Renal Disease | Yang X.-W.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Tan Y.,Peking University | And 8 more authors.
Nephrology Dialysis Transplantation | Year: 2012

Background. Although nephritogenic autoantibodies are considered to play a central role in the initiation of lupus nephritis, whether these autoantibodies are associated with renal clinical and pathological activity or renal outcome is still controversial. Here, we investigated the associations of certain serum autoantibodies with renal disease activity and renal outcome in a large cohort of Chinese patients with lupus nephritis. Methods. One hundred and thirty-six Chinese patients with biopsy-proven lupus nephritis and with long-term follow up data were studied. Sera at renal biopsy were tested for a panel of autoantibodies, including anti-nuclear antibodies, anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen antibodies, anti-C-reactive protein antibodies, anti-C1q antibodies, anti-cardiolipin antibodies and anti-β2-glycoprotein I antibodies. Associations of these autoantibodies with clinical features, laboratory findings, histopathological data and renal outcomes were further investigated. Results. Among the various autoantibodies, anti-dsDNA and anti-C1q antibodies were better than other antibodies to evaluate the renal disease activity. Anti-dsDNA antibodies were correlated with higher incidence of leukocyturia (P< 0.05), total pathological activity index (AI) score (P< 0.05), endocapillary hypercellularity (P< 0.05), subendothelial hyaline deposits (P< 0.05) and leukocyte infiltration (P< 0.05). Anti-C1q antibodies were correlated with leukocyturia (P< 0.01), hematuria (P< 0.003) and the majority of the histopathological AIs including total AI score (P< 0.003), endocapillary hypercellularity (P< 0.003), cellular crescents (P< 0.05), karyorrhexis/fibrinoid necrosis (P< 0.003), subendothelial hyaline deposits (P< 0.003) and leukocyte infiltration (P< 0.01). Patients with both anti-dsDNA and anti-C1q antibodies had higher renal disease activity and poorer renal outcome (log-rank test: P = 0.048) compared with those without the two antibodies. In univariate survival analysis of renal prognosis, neither the presence of anti-C1q nor the presence of anti-dsDNA antibodies was a risk factor of renal survival. However, the combination of the two antibodies predicted renal prognosis (hazard ratio 4.40, 95 confidence interval: 1.26815.269, P = 0.02). Conclusions. Anti-C1q antibodies are more closely correlated with renal disease activity than the other autoantibodies. The combination of anti-C1q and anti-dsDNA autoantibodies indicates higher renal disease activity and predicts poor renal outcome. © 2012 The Author.

Wang F.-M.,Peking University | Wang F.-M.,Key Laboratory of Renal Disease | Wang F.-M.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Yu F.,Peking University | And 11 more authors.
Rheumatology (United Kingdom) | Year: 2012

Objective: The aim of this study was to investigate serum complement factor H (CFH) and its associations with clinical and pathological features in patients with LN. Methods: Serum CFH was detected in 241 LN patients, 38 active and 11 inactive patients with SLE without clinical evidence of renal involvement and 51 normal controls. Serum CFH autoantibodies and CFH Tyr402His were screened in the 241 LN patients. CFH deposition in kidneys was detected in some patients. Results: Serum CFH levels in patients with LN at active phase were significantly lower than in 38 SLE patients or in normal controls. No serum anti-CFH autoantibodies were detected in patients with LN, and there was no significant difference in CFH Tyr402His distribution between patients with LN and normal controls. Glomerular expression of CFH was stronger than in normal controls. Serum CFH levels were mildly negatively associated with SLEDAI scores (r = -0.204, P = 0.001) and positively associated with serum C3 (r = 0.367, P < 0.001) and haemoglobulin levels (r = 0.193, P = 0.003). Patients with LN class III, subclass IV-S and those with thrombotic microangiopathy had the lowest serum CFH. Conclusion: Serum CFH levels were associated with disease activity of LN. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Zhou J.,Peking University | Zhou J.,Key Laboratory of Renal Disease | Zhou J.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Chen Y.,Peking University | And 13 more authors.
BMC Nephrology | Year: 2014

Background: Hyperuricemia appeared to be a common symptom in IgA nephropathy (IgAN), even in those with normal eGFR. IgAN was characterized by variation of pathological features, especially variable tubulointerstitial lesions. Since tubular reabsorption and excretion appeared to be more important in determination of plasma uric acid levels in persons without obvious decrease of glomerular filtration rate, we took advantage of our IgAN cohort to investigate whether plasma uric acid level associated with tubular interstitial lesions, and could be considered as a maker for tubular interstitial lesions, especially at early stage with normal eGFR. Methods. 623 IgAN patients were involved in the present study. Morphological changes were evaluated with Oxford classification scoring system as well as Beijing classification system of IgAN. Statistical analysis was done with SPSS 13.0. Results: We found that plasma uric acid level associated with percentage of interstitial fibrosis/tubular atrophy. Higher plasma uric acid levels indicated higher tubulointerstitial scores, either with Oxford system (P = 0.012) or with Beijing classification system (P = 4.8*10-4) in the whole cohort. We also found that in the subgroup of 258 IgAN cases with normal baseline eGFR (eGFR > =90 ml/min/1.73 M2), higher plasma uric acid associated with more severe tubulointerstitial lesions with Beijing scoring system (P = 3.4*10 -5). The risk of having more than 10% tubulointerstitial lesions in patients with hyperuricemia increased 58% compared with normal uric acid level. In subgroup with normal eGFR, only hyperuricemia predicted tubulointerstitial leisions, and the risk of having more tubulointerstitial changes increased 100%. Among these patients, hyperuricemia was associated with more tubulointerstitial lesions with a specificity of 60.3%. Specificity increased to 65% among those patients with eGFR > =90 ml/min/1.73 m2. Conclusions: Plasma uric acid levels indicate tubular interstitial lesions in IgAN and hyperuricemia may be considered as a marker for tubulointerstitial lesions. © 2014 Zhou et al.; licensee BioMed Central Ltd.

Tan Y.,Peking University | Tan Y.,Key Laboratory of Renal Disease | Tan Y.,Key Laboratory of Chronic Kidney Disease Prevention and Treatment | Yu F.,Peking University | And 5 more authors.
Current Opinion in Nephrology and Hypertension | Year: 2014

PURPOSE OF REVIEW: Vascular injury is one of the typical symptoms of systemic lupus erythematosus (SLE), and may play a key role in the choice of treatment strategy and prediction of prognosis. In this review, diverse vascular lesions in SLE and their clinical significance are discussed. RECENT FINDINGS: The clinical features of vascular disease in SLE differ from organ to organ, and may be extreme with regard to renal vascular lesions. Vascular lesions in SLE may be of inflammatory or thrombotic origin, and immune system dysfunction is considered to be a predominant feature. Numerous lines of evidence suggest that the activation and injury of endothelial cells might play a key role in the pathogenesis. SUMMARY: Vascular lesions in SLE are mediated by a complex interaction between the immune system and other contributing factors. Different therapies developed for vascular lesions, both immunosuppressive and nonimmunosuppressive, should be selected based on the different clinical and pathological characteristics, and our future understanding of the different mechanisms involved. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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