Key Laboratory of Renal Disease

Beijing, China

Key Laboratory of Renal Disease

Beijing, China
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Zhang Y.-M.,Peking University | Zhang Y.-M.,Key Laboratory of Renal Disease | Zhou X.-J.,Peking University | Zhou X.-J.,Key Laboratory of Renal Disease | And 2 more authors.
Kidney International Reports | Year: 2017

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, which is characterized by IgA1-containing immune-deposits in the glomerular mesangium. The epidemiologic observations of familial clustering as well as ethnic and regional discrepancies indicate a genetic component to IgAN. Large, international, genome-wide association studies have identified several susceptibility genes and loci for IgAN, many of which have been implicated in immune regulation and are shared with other autoimmune diseases. Notably, increasing numbers of genes involved in mucosal immunity have been detected; such genes may impact the susceptibility and progression of IgAN through interaction with environmental stimuli (especially infection). Here, we discuss the innate and adaptive immune mechanisms that drive protective immunity against pathogens. Our goal is to provide a representative overview of the synergistic roles between genetic predisposition and infection in IgAN pathogenesis. We anticipate that these results will provide potential therapeutic agents and advances in precision medicine. © 2017 International Society of Nephrology

Dong J.,Peking University | Dong J.,Key Laboratory of Renal Disease | Chen Y.,Peking University | Chen Y.,Key Laboratory of Renal Disease
Peritoneal Dialysis International | Year: 2010

Objective: We studied whether improper bag exchange predicts the first peritonitis episode in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients and Methods: Our single-center prospective observational study of 130 incident urban CAPD patients who started peritoneal dialysis (PD) between March 2005 and August 2008 aimed to determine the relationship between bag exchange procedures examined at the 6th month of PD and risk for a first peritonitis episode. All patients were followed until a first peritonitis episode, censoring, or the end of the study. Results: These 130 patients experienced 22 first peritonitis episodes during the 14-month follow-up. During bag exchange evaluation, 51.5% of patients washed their hands improperly, 46.2% failed to check expiration date or bag leakage, and 11.5% forgot to wear a face mask and cap. Patients experiencing peritonitis were more likely to forget to wear a face mask and cap. In multivariate Cox regression model, not wearing a face mask and cap [hazard ratio (HR): 7.26; 95% confidence interval (CI): 2.6 to 20.1; p < 0.001] and having anemia (HR: 0.96; 95% CI: 0.94 to 0.99; p = 0.005) were independent risk factors for a first episode of peritonitis. Conclusions: Not wearing a face mask and cap and having anemia were independent risk factors for peritonitis. A further randomized control study needs to verify the correlation between improper bag exchange technique and peritonitis in PD patients. © 2010 International Society for Peritoneal Dialysis.

Wang H.,Peking University | Wang H.,Key Laboratory of Renal Disease | Wang H.,Peking Tsinghua Center for Life science | Wang C.,Peking University | And 8 more authors.
Clinical and Experimental Immunology | Year: 2015

The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg-EGTA)-treated human serum. After incubation of serum with supernatants enriched in ANCA-induced NETs, levels of complement components in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b-9 on NETs incubated with heat-inactivated normal human serum (Hi-NHS) or EGTA-treated Hi-NHS (Mg-EGTA-Hi-NHS) were significantly less than that on NETs incubated with NHS or EGTA-treated NHS (Mg-EGTA-NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b-9 concentration decreased from 800·42±244·81 ng/ml, 7·68±1·50 ng/ml, 382·15±159·75 ng/ml in the supernatants enriched in ANCA induced NETs to 479·07±156·2 ng/ml, 4·86±1·26 ng/ml, 212·65±44·40 ng/ml in the supernatants of DNase I-degraded NETs (P<0·001, P = 0·008, P<0·001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV. © 2015 British Society for Immunology.

Yu F.,Peking University | Yu F.,Key Laboratory of Renal Disease | Yu F.,Key Laboratory of CKD Prevention and Treatment
Lupus | Year: 2012

Objective: The objective of this article is to assess clinicopathological characteristics and outcomes of patients with male lupus nephritis in a cohort of Chinese patients. Methods: Clinical, pathological and outcome data of lupus nephritis patients with different gender were retrospectively analyzed and compared. Results: Among 315 patients with renal biopsy-proven lupus nephritis, 45 were male and 270 were female. The average ages of disease onset of the male and female patients were comparable. The interval between presentation of lupus nephritis and diagnosis was significantly longer in the male group than in female group (p=0.003). Clinical presentation was similar except that males had a significantly lower proportion of alopecia (p=0.005). In laboratory data, male lupus nephritis patients had higher hemoglobin (p=0.023) and higher serum creatinine (p<0.001) than female patients. As for pathological classification and index, no significant difference was found between the two groups. The male patients presented with significantly lower ratios of complete remission and partial remission, and higher ratios of treatment failure and relapse than the female group. Regarding long-term survival and renal outcome, male patients had significantly worse prognosis than females (p=0.005). Conclusions: The male lupus nephritis presented with later diagnosis, worse renal function, lower remission rate and higher relapse rate compared with female patients. The male patients had significantly higher mortality and poorer renal outcome. © 2012 The Author(s).

Shi S.-F.,Peking University | Wang S.-X.,Peking University | Jiang L.,Peking University | Ji-Cheng L.,Peking University | And 7 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011

Background and objectives: The Oxford classification of IgA nephropathy (IgAN) may aid in predicting prognosis and providing therapeutic strategy but must be validated in different ancestry. Design, setting, participants, & measurements: A total of 410 patients with IgAN, enrolled from one of the largest renal centers in China, were evaluated for the predictive value of the Oxford classification to prognosis defined as end stage renal disease. A total of 294 of these patients were prospectively treated with renin-angiotensin system blockade and immunosuppressants sequentially and were evaluated separately to assess the predictive value to therapeutic efficacy (defined as time-averaged proteinuria <1 g/d). Three pathologists reviewed specimens independently according to the Oxford classification and were blinded to clinical data. Results: Segmental glomerulosclerosis and tubular atrophy and interstitial fibrosis were independent predictive factors of end stage renal disease. Patients who had >25% of glomeruli with endocapillary hypercellularity showed higher proteinuria, lower estimated GFR, and higher mean BP than patients with less endocapillary hypercellularity. Immunosuppressive therapy showed a protective effect to prognosis of endocapillary hypercellularity in patients with endoncapillary hypercellularity could benefit from immunosuppressive therapy. Mesangial hypercellularity and tubular atrophy and interstitial fibrosis were independent factors of inefficiency of renin-angiotensin system blockade alone. Crescents were not significant in predicting prognosis or in therapeutic efficacy. Conclusions: The Oxford classification may aid in predicting prognosis and providing a therapeutic strategy in Chinese patients with IgAN. © 2011 by the American Society of Nephrology.

Wang H.,Peking University | Wang H.,Key Laboratory of Renal Disease | Gou S.-J.,Peking University | Gou S.-J.,University of Sichuan | And 2 more authors.
Clinical and Experimental Immunology | Year: 2014

Increasing evidence suggested that Toll-like receptors (TLRs) were critically involved in immune responses of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to investigate the expression of TLR-2, TLR-4 and TLR-9 in kidneys of patients with ANCA-associated vasculitis. Renal biopsy specimens were collected from 24 patients with AAV. The expression of TLR-2, TLR-4 and TLR-9 in kidneys was detected by immunohistochemistry. Double immunofluorescence staining was performed to detect the expression of TLRs on various kinds of cells. In renal specimens, immunohistochemical examination revealed that expression of TLR-2 and TLR-4 could be detected in the glomeruli of AAV patients, while TLR-2 and TLR-4 were scarcely detected in the glomeruli of normal controls. Double immunofluorescence staining of TLR-2, TLR-4 and CD31 indicated that TLR-4 and TLR-2 were expressed on endothelial cells in the glomeruli. In the tubulointerstitial compartment, expression of TLR-2, TLR-4 and TLR-9 could be detected in both AAV patients and normal controls. The mean optical density of TLR-2 and TLR-4 in the tubulointerstitial compartment in AAV patients were significantly higher than that in normal controls. Among AAV patients, correlation analysis showed that the mean optical density of TLR-4 in the glomeruli correlated inversely with the initial serum creatinine, the proportion of total crescents and the proportion of cellular crescents in renal specimens (r=-0·419, P=0·041; r=-0·506, P=0·012; r=-0·505, P=0·012, respectively). The expression of TLR-2 and TLR-4 was dysregulated in kidneys of AAV patients. The expression of TLR-4 in glomeruli was associated with the severity of renal injury. © 2014 British Society for Immunology.

Zhao N.,Peking University | Zhao N.,Key Laboratory of Renal Disease | Hou P.,Peking University | Hou P.,Key Laboratory of Renal Disease | And 9 more authors.
Kidney International | Year: 2012

Although high serum levels of galactose-deficient IgA1 (an important biomarker of IgA nephropathy (IgAN)) are found in most patients with IgAN, their relationship to disease severity and progression remains unclear. To help clarify this we prospectively enrolled 275 patients with IgAN and followed them for a median of 47 months (range 12-96 months). Serum galactose-deficient IgA1 was measured at the time of diagnosis using a lectin-based ELISA, and renal survival was modeled using the Cox proportional hazards method. The serum levels of galactose-deficient IgA1 were higher in patients with IgAN compared to those in healthy controls. Importantly, in adjusted analysis, higher levels of galactose-deficient IgA1 were independently associated with a greater risk of deterioration in renal function with a hazard ratio of 1.44 per standard deviation of the natural log-transformed galactose-deficient IgA1 concentration. In reference to the first quartile, the risk of kidney failure increased such that the hazard ratio for the second quartile was 2.47, 3.86 for the third, and 4.76 for the fourth quartile of the galactose-deficient IgA1 concentration. Hence, elevated serum levels of galactose-deficient IgA1 are associated with a poor prognosis in IgAN. © 2012 International Society of Nephrology.

Zhou X.-J.,Peking University | Zhou X.-J.,Key Laboratory of Renal Disease | Lu X.-L.,Peking University | Lv J.-C.,Peking University | And 10 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective: Recent genome-wide association studies suggested the PRDM1-ATG5 gene region as a systemic lupus erythematosus (SLE)-associated locus both in Caucasian and Chinese populations; however, the candidate gene was still obscure and the possible functional significance needed to be determined. Methods: In this study, by a multistage integrative strategy, the authors first performed a case - control association study involving 1745 individuals in the Chinese population by genotyping nine single nucleotide polymorphisms within this region, and a meta-analysis was conducted. Correlation between associated genotypes and expression levels of messenger RNA in B-cell lines from 210 unrelated HapMap data was examined, and was validated in vitro. To determine the biological significance, a genetic association study was also checked in a pathway-based manner and the significant associations were validated in a second 844 Chinese cohort. Results: A peak of association was found in the intergenic region (p=0.036-3.26×10-4). Meta-analysis consolidated the association between rs548234 and SLE (OR 1.254, p=1.28×10-16). Significant positive correlations with ATG5 expression were identified, suggesting ATG5 as a candidate gene in the region. Epstein - Barr virus B-cell-based downstream gene expression analysis supported a functional effect of rs548234 and rs6937876, and in-vitro experiments confirmed the regulatory effect of rs6937876 in B-cell populations. Finally, an autophagy pathway-based genetic association study identified ATG7 (p=1.12×10-4) and IRGM (p=0.015) as novel candidate genes, and gene - gene interactions were observed between ATG5 , ATG7 and IRGM. Conclusion: These data may demonstrate that autophagy is involved in the pathogenesis of SLE and imply a common biological pathway in autoimmunity.

Cui Z.,Peking University | Cui Z.,Key Laboratory of Renal Disease | Cui Z.,First Hospital | Zhao J.,Peking University | And 6 more authors.
American Journal of Kidney Diseases | Year: 2011

Background Anti-glomerular basement membrane (GBM) disease is being recognized increasingly in older patients. Disease presentation and outcomes of these patients are unclear. Study Design Case series. Setting & Participants 221 consecutive Chinese patients with anti-GBM disease diagnosed in 1998-2008 in our tertiary referral center. Anti-GBM disease was defined as positive anti-GBM antibodies in circulation and/or linear immunoglobulin G deposition along the GBM on kidney biopsy. Predictor Older age, defined as 65 years or older, and antineutrophil cytoplasmic antibody, detected using immunofluorescence and enzyme-linked immunosorbent assay, at presentation. Outcomes Clinical features, kidney pathologic characteristics, end-stage renal disease (ESRD), and mortality. Multivariate Cox proportional hazard models were used to assess the contribution of age, sex, clinical measures, and treatments to ESRD and mortality. Results 50 of 221 (22.6%) patients were 65 years or older. Older patients had a male predominance (male/female ratio, 1.9:1). They had a higher proportion of positive antineutrophil cytoplasmic antibody results (46.0% vs 14.6%; P < 0.001), lower prevalence of hemoptysis (26.0% vs 46.2%; P = 0.01), lower urine protein excretion (1.4 ± 1.0 vs 3.9 ± 3.3 g/d; P = 0.001), and higher estimated glomerular filtration rate (eGFR) at presentation (8.4 vs 5.1 mL/min/1.73 m2; P = 0.007) compared with younger patients. During follow-up, 30 of 37 (81.1%) and 21 of 37 (56.8%) patients developed ESRD and died in the older group compared with 115 of 139 (82.7%) and 35 of 139 (25.2%) in the younger group (P = 0.1 and P = 0.001, respectively). For older patients, multivariate Cox regression analysis showed that higher initial eGFR was an independent predictor for both ESRD (HR, 0.86; 95% CI, 0.78-0.96; P = 0.005) and death (HR, 0.79; 95% CI, 0.66-0.94; P = 0.008). Limitations Not all patients underwent kidney biopsy, especially those with very old age or ESRD at presentation. Conclusions Older patients with anti-GBM disease had milder kidney damage and less pulmonary involvement. Outcomes were predicted by initial eGFR. Thus, early diagnosis was crucial to improve outcomes. © 2011 National Kidney Foundation, Inc.

Li C.,Peking University | Li C.,Key Laboratory of Renal Disease | Su T.,Peking University | Su T.,Key Laboratory of Renal Disease | And 6 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2014

Background and objectives Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered a rare cause of acute tubulointerstitial nephritis (ATIN) that is usually associated with renal recovery. This study sought to investigate the diagnosis, prognosis, and contributing factors of TINU syndrome using a large cohort of patients with prospective follow-up. Design, setting, participants, & measurements This study included patients with TINU syndrome from a prospective cohort of patients with ATIN from 2007 to 2012. Clinical-pathologic datawere collected at biopsy and autoantibodies against modified C-reactive protein (mCRP-Ab) were measured. Serum levels and renal tissue expression of Kreb von den Lunge-6 were also detected. Independent risk factors for poor renal outcome at 12 months and late-onset uveitis were analyzed. Results Thirty-one patients (28%) with biopsy-proven ATIN were classified as having TINU syndrome. Of these patients, 18 (58%) developed late-onset uveitis and were misdiagnosed as having drug-induced ATIN at the time of biopsy. An abnormal level ofmCRP-Ab was an independent risk factor for late-onset uveitis (odds ratio, 14.7; 95% confidence interval, 3.4 to 64.0). Patients with TINU syndrome and drug-induced ATIN had comparable levels of Kreb von den Lunge-6 in both serum and renal tissues. Ninety-two percent of patients developed stage 3-4 CKD and/or tubular dysfunction by 12 months postbiopsy. Age, serum creatine level, erythrocyte sedimentation rate, and the presence of concomitant thyroid disease or leukocyturia were related to poor renal outcome. Relapse was seen in 36% (11 of 31) of patients and potentiated poor renal outcome. Conclusions The diagnosis of TINU syndrome can be missed in a large fraction of patients with ATIN because uveitis can present well after the onset of tubulointerstitial nephritis. Elevated mCRP-Ab levels may be useful in predicting late-onset uveitis TINU syndrome. Unfortunately, patients with TINU tended to have frequent relapses and most patients had incomplete renal recovery. Long-term follow-up is needed to prevent misdiagnosis and properly manage TINU syndrome. © 2014 by the American Society of Nephrology.

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