Key Laboratory of CKD Prevention and Treatment

Beijing, China

Key Laboratory of CKD Prevention and Treatment

Beijing, China
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Zhang Y.-M.,Peking University | Zhang Y.-M.,Key Laboratory of Renal Disease | Zhang Y.-M.,Key Laboratory of CKD Prevention and Treatment | Gu Q.-H.,Peking University | And 27 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2016

Background and objectives Glomerular IgM deposition is commonly shown in primary FSGS and sometimes accompanied by C3 deposition. Clinical presentation and treatment outcomes of these patients are not investigated in detail. Design, setting, participants, & measurements: One hundred six consecutive patients with biopsy-proven primary FSGS from 2004 to 2014 were enrolled retrospectively. Clinical features and treatment outcomes were compared between patients with and without IgM/C3 deposition. Results: Fifty-eight (54.7%) patients presented with IgMglomerular deposition on sclerotic segments. C3 and C1q depositions were shown exclusively in patients with IgM deposition (34.5% versus 0.0%; P<0.001 and 8.6% versus 0.0%; P=0.04, respectively). Patients with IgM deposition were younger (median; range: 24.5; 18.8-39.0 versus 46.5; 26.0-64.0 years old; P=0.001), had higher level of serum IgM (142.5; 96.3-206.0 versus 107.0; 71.0- 140.0mg/dl; P=0.01), and had higher level of eGFR (median; range 97.7; 48.0-135.8 versus 62.1; 33.7-93.9 ml/min per 1.73 m2; P=0.01) at the time of kidney biopsy. The percentage of sclerosis lesions was significantly higher in patients with C3 deposition (median; range: 21.7%; 15.3%-31.1% versus 9.2%; 6.6%-20.0%; P=0.002). Although patients received comparable immunosuppressive treatments during 58.9 (29.5-81.1) months of follow-up, a significantly higher prevalence of refractory cases (no response or steroid dependent) occurred in patients with combined IgM and C3 deposition compared with patients with IgMdeposition alone or without IgM deposition (58.8%versus 22.2% versus 15.6%, respectively; P=0.004). Multivariate analysis identified combined IgM and C3 deposition (odds ratio, 11.32; 95% confidence interval, 2.26 to 56.65; P=0.003) as an independent risk factor for refractory patients; 19 of 98 patients developed renal dysfunction when their serum creatinine levels increased >30% from baseline and reached >1.5 mg/dl. Combined IgM and C3 deposition (hazard ratio, 5.67; 95% confidence interval, 1.34 to 23.84; P=0.02) was identified as an independent risk factor for renal dysfunction. Conclusions Patients with primary FSGS and IgM and C3 deposition showed unfavorable therapeutic responses and worse renal outcomes, which indicate that IgM and C3 deposition might involve disease progression via complement activation. © 2016 by the American Society of Nephrology.

Yang X.-W.,Peking University | Yang X.-W.,Key Laboratory of Renal Disease | Yang X.-W.,Key Laboratory of CKD Prevention and Treatment | Tan Y.,Peking University | And 8 more authors.
Human Immunology | Year: 2012

Autoantibodies against modified C-reactive protein (mCRP) are frequently found in patients with lupus nephritis and are associated with disease activity, suggesting their pathogenic role in lupus nephritis. The aim of this study was to investigate the influence of anti-mCRP autoantibodies from patients with lupus nephritis on the biofunctions of mCRP. mCRP plays important roles in the clearance of apoptotic cells and immune complex-mediated injuries via binding to C1q and factor H and acting as an opsonin. In this study, we confirmed that mCRP could bind to C1q and factor H, and the binding between mCRP and C1q was mainly via the collagen-like region of C1q by enzyme-linked immunosorbent assay and surface plasmon resonance. mCRP could significantly enhance the phagocytosis of late apoptotic cells in the presence of normal human serum. Autoantibodies against mCRP, purified from immunoglobulin G fractions of 3 patients with lupus nephritis by affinity chromatography, could significantly inhibit the binding between mCRP and C1q or factor H and reduce the clearance of late apoptotic cells enhanced by mCRP. Our observations suggest that anti-mCRP autoantibodies from patients with lupus nephritis might be pathogenic in systemic lupus erythematosus and lupus nephritis through interfering with the biofunctions of mCRP. © 2012 American Society for Histocompatibility and Immunogenetics.

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).

Xu P.-C.,Peking University | Xu P.-C.,Key Laboratory of Renal Disease | Xu P.-C.,Key Laboratory of CKD Prevention and Treatment | Xu P.-C.,Tianjin Medical University | And 7 more authors.
Clinical and Experimental Nephrology | Year: 2013

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a common autoimmune disease in China. AAVs in the majority of Chinese patients are microscopic polyangiitis with antigenicity to myeloperoxidase. Propylthiouracil is the leading cause of drug-induced AAV. The genetic background and immunological characteristics of ANCA, such as the epitope, IgG subclass and avidity, might contribute to various clinical phenotypes of AAV. © 2012 Japanese Society of Nephrology.

Liu X.-J.,Peking University | Liu X.-J.,Key Laboratory of Renal Disease | Liu X.-J.,Key Laboratory of CKD Prevention and Treatment | Zhang Y.-M.,Peking University | And 6 more authors.
Nephrology | Year: 2014

Aim The current study was designed to observe the ultrastructural changes of podocyte foot processes during the remission phase and its relationship with the amount of the proteinuria in patients with minimal change disease (MCD). Methods Electron micrographs of glomerular capillaries were taken from 33 adult cases with MCD, including 12 cases with nephrotic syndrome, 15 cases in partial remission and six cases in complete remission. The foot processes were classified into three grades by the ratio of the height to basal width: 0.5-1, 1-2 and ≥2. The foot process width (FPW) and the number of foot processes in different grades per 10μm of glomerular basement membrane (GBM) were measured. Normal renal tissues from 12 nephrectomies for renal carcinoma were selected as controls. Results There were statistical differences (P=0.001) in the mean FPW among the nephrotic group (1566.4±429.4nm), partial remission group (1007.8±234.9nm), complete remission group (949.8±168.2nm) and normal controls (471.9±51.8nm). For the height-to-width ratio ≥2, the number of foot process per 10μm GBM was significantly greater in the normal group than that in the complete remission group (0.84±0.24 vs. 3.84±1.80, P=0.016). Taking all three groups of patients together, the mean FPW showed correlation with the level of proteinuria (r=0.506, P=0.003). Conclusion There may be no causal relationship between proteinuria and foot process effacement. In complete remission phase, both FPW and shape of foot process had not returned to normal while proteinuria disappeared. Summary at a Glance In the present paper, authors measured the morphometric parameters of podocyte foot processes and correlated them with the severity of proteinuria in patients with minimal change disease. The authors concluded that there might be no causal relationship between proteinuria and foot process effacement, since both foot process width and shape of foot process had not returned to normal in the complete remission phase. © 2014 Asian Pacific Society of Nephrology.

Wang Y.,Peking University | Wang Y.,Key Laboratory of Renal Disease | Wang Y.,Key Laboratory of CKD Prevention and Treatment | Yu F.,Peking University | And 12 more authors.
Rheumatology (United Kingdom) | Year: 2014

Objective. The podocyte lesion in LN is still an intriguing controversy. We assess the associations between podocyte lesions and clinico-pathological features in a large cohort of LN patients. Methods. The clinico-pathological data of 202 patients with renal biopsy-proven LN were retrospectively studied. The degree of podocyte lesions was assessed morphologically and its correlations with clinicopathological parameters were further analysed. Results. The podocyte foot processes of most LN patients significantly effaced, reflected by the median foot process width (FPW) of 1397.39 nm, and 13 patients met the histological criteria of lupus podocytopathy. The FPW was correlated with proteinuria (r = 0.509, P<0.001) and the cut-off value of FPW, >1240 nm, could differentiate nephrotic proteinuria from non-nephrotic proteinuria with sensitivity 81.5% and specificity 62.7%. The FPW varied significantly with different types of LN, and the patients with combined LN presented with the most severe lesions. The complete remission rate was significantly higher and the long-term renal outcome was better in the group with calcineurin inhibitors than that with other regimens in patients with FPW >1240 nm. Conclusion. Podocyte damage was common in LN. Pure lupus podocytopathy might act as an extreme form of lupus podocyte lesion, and more patients might present with severe podocyte effacement concealed in different types of LN, which needs further investigation. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Huang J.,Peking University | Huang J.,Key Laboratory of Renal Disease | Huang J.,Key Laboratory of CKD Prevention and Treatment | Liu G.,Peking University | And 21 more authors.
BMC Medicine | Year: 2014

Background: Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. Recent studies have proposed that plasma soluble urokinase receptor (suPAR) might be a causative circulating factor but this proposal has caused controversy. This study aimed to measure urinary suPAR levels in patients with primary FSGS and its significance in the pathogenesis of FSGS.Methods: Sixty-two patients with primary FSGS, diagnosed between January 2006 and January 2012, with complete clinical and pathologic data were enrolled, together with disease and normal controls. Urinary suPAR levels were measured using commercial ELISA kits and were corrected by urinary creatinine (Cr). The associations between urinary suPAR levels and clinical data at presentation and during follow up were analyzed. Conditionally immortalized human podocytes were used to study the effect of urinary suPAR on activating β3 integrin detected by AP5 staining.Results: The urinary suPAR level of patients with primary FSGS (500.56, IQR 262.78 to 1,059.44 pg/μmol Cr) was significantly higher than that of patients with minimal change disease (307.86, IQR 216.54 to 480.18 pg/μmol Cr, P = 0.033), membranous nephropathy (250.23, IQR 170.37 to 357.59 pg/μmol Cr, P <0.001), secondary FSGS (220.45, IQR 149.38 to 335.54 pg/μmol Cr, P <0.001) and normal subjects (183.59, IQR 103.92 to 228.78 pg/μmol Cr, P <0.001). The urinary suPAR level of patients with cellular variant was significantly higher than that of patients with tip variant. The urinary suPAR level in the patients with primary FSGS was positively correlated with 24-hour urine protein (r = 0.287, P = 0.024). During follow up, the urinary suPAR level of patients with complete remission decreased significantly (661.19, IQR 224.32 to 1,115.29 pg/μmol Cr versus 217.68, IQR 121.77 to 415.55 pg/μmol Cr, P = 0.017). The AP5 signal was strongly induced along the cell membrane when human differentiated podocytes were incubated with the urine of patients with FSGS at presentation, and the signal could be reduced by a blocking antibody specific to uPAR.Conclusions: Urinary suPAR was specifically elevated in patients with primary FSGS and was associated with disease severity. The elevated urinary suPAR could activate β3 integrin on human podocytes.Please see related article © 2014 Huang et al.; licensee BioMed Central Ltd.

Chu H.,Peking University | Chu H.,Key Laboratory of Renal Disease | Chu H.,Key Laboratory of CKD Prevention and Treatment | Wu L.H.,Ningxia Medical University | And 9 more authors.
Lupus | Year: 2014

In this study, we assessed the clinicopathological features of lupus nephritis patients with renal noninflammatory necrotizing vasculopathy (NNV). A total of 142 renal biopsies with lupus nephritis were reviewed, including nine cases presented with NNV and 36 without renal vascular lesions. The comparisons of clinical, laboratory and pathological features, treatments, as well as renal outcome between the two groups were further performed. In comparison with the no renal vascular lesions group, patients with NNV changes had significantly higher proportions of noninfection leukocyturia (p = 0.013) and leukocytopenia (p = 0.042), significantly higher serum creatinine (p = 0.012), lower hemoglobin (p = 0.002) and serum C3 (p < 0.001) levels. Renal pathological activity indices and chronicity indices were significantly higher in the NNV group (p = 0.002 and p = 0.006, respectively) than those in the no vascular lesions group. Regarding renal prognosis, the presence of NNV was not a risk factor for renal outcome (p = 0.327). In conclusion, NNV was not infrequent in renal biopsies of lupus nephritis. It was commonly associated with active clinical status and proliferative glomerular lesions of lupus. © The Author(s) 2013.

Jia X.-Y.,Peking University | Jia X.-Y.,Key Laboratory of Renal Disease | Jia X.-Y.,Key Laboratory of CKD Prevention and Treatment | Hu S.-Y.,Peking University | And 18 more authors.
Kidney International | Year: 2014

The association of anti-glomerular basement membrane (GBM) disease, also known as Goodpasture's disease, with membranous nephropathy (MN) has been well documented. However, little is known about the clinical and immunological features of patients with such a combination. This study was designed to investigate the clinical and immunological features of anti-GBM patients with MN and to provide insight into the pathogenesis of this rare entity. Eight patients with combined anti-GBM disease and MN were found to have significantly lower levels of serum creatinine, a significantly lower proportion of oliguria/anuria, and significantly better renal outcomes compared with 30 patients with classical anti-GBM disease. Antibody levels against the E B conformational epitope of anti-α3(IV)NC1 were significantly lower in these patients, as was their levels of anti-α3(IV)NC1 immunoglobulin G1 (IgG1) and IgG3. Serum antibodies against the M-type phospholipase A 2 receptor were undetectable in anti-GBM patients with MN but presented in 13 of the 20 patients with primary MN. Thus, patients with combined anti-GBM disease and MN have distinct clinical features and a different immunological profile of MN. © 2013 International Society of Nephrology.

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