Xuyang Cheng

Anti-glomerular basement membrane disease: outcomes of different therapeutic regimens in a large single-center Chinese cohort study.

Anti-glomerular basement membrane (GBM) disease usually presents with rapidly progressive glomerulonephritis accompanied by pulmonary hemorrhage. The low incidence and fulminant course of disease preclude a large randomized controlled study to define the benefits of any given therapy. We conducted a retrospective survey of 221 consecutive patients seen from 1998 to 2008 in our hospital, and report here the patient and renal survival and the risk factors affecting the outcomes. Considering the similar clinical features of the patients, we could compare the effects of 3 different treatment regimens: 1) combination therapy of plasmapheresis and immunosuppression, 2) steroids and cytotoxic agents, and 3) steroids alone.The patient and renal survival rates were 72.7% and 25.0%, respectively, at 1 year after disease presentation. The serum level of anti-GBM antibodies (increased by 20 U/mL; hazard ratio [HR], 1.16; p = 0.009) and the presentation of positive antineutrophil cytoplasmic antibodies (ANCA) (HR, 2.18; p = 0.028) were independent predictors for patient death. The serum creatinine at presentation (doubling from 1.5 mg/dL; HR, 2.07; p < 0.001) was an independent predictor for renal failure.The combination therapy of plasmapheresis plus corticosteroids and cyclophosphamide had an overall beneficial effect on both patient survival (HR for patient mortality, 0.31; p = 0.001) and renal survival (HR for renal failure, 0.60; p = 0.032), particularly patient survival for those with Goodpasture syndrome (HR for patient mortality, 0.29; p = 0.004) and renal survival for those with anti-GBM nephritis with initial serum creatinine over 6.8 mg/dL (HR for renal failure, 0.52; p = 0.014). The treatment with corticosteroids plus cyclophosphamide was found not to improve the renal outcome of disease (p = 0.73).In conclusion, the combination therapy was preferred for patients with anti-GBM disease, especially those with pulmonary hemorrhage or severe renal damage. Early diagnosis was crucial to improving outcomes.Abbreviations: ANCA = antineutrophil cytoplasmic antibodies, CI = confidence interval, ELISA = enzyme-linked immunosorbent assay, ESRD = end-stage renal disease, GBM = glomerular basement membrane, HR = hazard ratio.

Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein

BackgroundSubclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.MethodsIn this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height2), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis.Patients were classified into three subgroups by vitamin C level according to previous recommendation [1, 2] in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).ResultsPatients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups.Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log10hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects.ConclusionsThe investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.

Mortality rates among prevalent hemodialysis patients in Beijing: a comparison with USRDS data

BACKGROUND The raw annual mortality rate reported in Chinese patients on maintenance hemodialysis (MHD) was around 10% between 2005 to 2010, and it was around 20% in the US as reported by the United States Renal Data System (USRDS). Our hypothesis was that the large survival difference was caused by differences in race and practice pattern between nations in addition to differences in patient characteristics. METHODS Annual mortality in Beijing prevalent MHD patients per year in 2007, 2008, 2009 and 2010 was reported and relative risks of death were compared with the corresponding mortality of USRDS prevalent MHD patients (in whites, African-Americans and Asian-Americans) after age, gender and primary cause of end-stage renal disease (ESRD) were adjusted. A total of 11 675 MHD patients from 104 dialysis facilities under control of Beijing Blood Purification Quality Control and Improvement Center (BJBPQCIC) from 31 December 2006 to 31 December 2010 were included. A total of 1 937 819 MHD patients (only white, African-American and Asian-American were eligible for inclusion) were subtracted from the USRDS No-60-Day prevalent dataset from the year 2004 to 2009, using the RenDER system. Raw annual mortality for each race was reported as a number per 1000 MHD patients at risk for each year. Age, gender and primary cause of ESRD, adjusted annual mortality and relative risk race of death were reported comparing the Beijing patients and each race of the USRDS. RESULTS The raw annual mortality for the Beijing cohort increased gradually from 47.8 per 1000 patient-years in 2007 to 76.8 in 2010. The raw annual mortality for the white cohort in 2007 was 250.7 per 1000 patient-years, and gradually decreased to 236.3 in 2009. The raw annual mortality for African-Americans (167.8 and 156.7 per 1000 patient-years in 2007 and 2009, respectively) was much lower than that for whites. The annual mortality for Asian-Americans was slightly lower than that for African-Americans. After adjustment, Beijing MHD still had a survival benefit compared with each of the examined USRDS race. The annual mortality rates were 99.4, 80.6 and 94.3 per 1000 patient-years when adjusted to whites, African-Americans and Asian-Americans, respectively, in cohort 2009. CONCLUSIONS The annual mortality for the Beijing MHD patients was lower than that for their USRDS counterparts, and this difference existed after baseline demographics were adjusted. This survival difference between the Beijing and the USRDS MHD cohorts could be attributed to differences in race or practice pattern. More studies are needed to validate our hypothesis.

Comparison of bioimpedance methods for estimating total body water and intracellular water changes during hemodialysis

BACKGROUND The accurate assessment of body fluid volume is important in many clinical situations. Hannan et al. proposed a single-frequency bioimpedance equation (HE) to calculate extracellular water (ECW) and total body water (TBW). There are two equations based on the bioimpedance spectroscopy (BIS) method for the evaluation of body fluid volume: Xitron equations (XE) and body composition spectroscopy equations (BCSE). The aim of the study was to compare the accuracy of these three equations in body fluid volume point estimation in maintenance hemodialysis (MHD) patients. METHODS The BIS method was performed in MHD patients before and after a hemodialysis (HD) session. TBW, ECW and intracellular water (ICW) were calculated by XE, BCSE and HE, respectively. Hydration status (HS) was calculated using inputs of XE, BCSE and HE. ICW before dialysis was compared to ICW after dialysis. The change of TBW and HS using different equations was compared to actual ultrafiltration volume (AUV) that was calculated as weight difference of pre- to postdialysis. RESULTS Fifty MHD patients (27 females) were included in the study. Significant changes in ICW were observed using the XE and HE method with ultrafiltration (XE: 15.51 ± 5.07 versus 16.17 ± 5.34 L, P < 0.01; HE: 17.40 ± 5.13 versus 16.55 ± 4.71 L, P < 0.01). However, no significant ICW change was observed using BCSE (17.47 ± 4.35 versus 17.54 ± 4.36 L, P > 0.05). ΔTBW_XE and ΔTBW_HE were significantly different from AUV (XE 1.76 ± 0.89 versus 2.46 ± 0.89 L, P < 0.01; HE 4.16 ± 1.36 versus 2.46 ± 0.89 L, P < 0.01); however, ΔTBW_BCSE was much closer to AUV (2.27 ± 0.90 versus 2.46 ± 0.89 L, P = 0.129). The change of HS using inputs of BCSE was also closer to AUV (2.41 ± 0.86 versus 2.46 ± 0.89 L, P = 1.0). CONCLUSION Our study indicated that BCSE provided a better point estimation of ICW and TBW.

Association between vitamin C deficiency and dialysis modalities.

Aim:  We designed a cross‐sectional study to investigate plasma vitamin C level in patients who underwent maintenance haemodialysis (MHD) and continuous ambulatory peritoneal dialysis (CAPD) to explore whether there is a difference in vitamin C deficiency between MHD patients and CAPD patients.

Development and validation of a new dry weight estimation method using single frequency bioimpedance in hemodialysis patients.

Background: We proposed a new method to estimate dry weight (DW) using single frequency bioimpedance. Methods: We hypothesized that the change in whole body resistance at 50 kHz (R50) was proportional to the ultrafiltration volume (UFV) during a hemodialysis (HD) session. When the targeted resistance estimated in healthy subjects was reached, the patient achieved his/her DW. UFV and R50 were monitored in 40 HD patients. Another 43 HD patients were stratified into 2 groups to validate this method. Results: The change in whole body resistance was proportional to UFV in each of the 40 HD patients. In the DWdecrease group, pre-dialysis systolic blood pressure (n = 29, 154.5 ± 22.8 vs. 146.9 ± 22.3, p < 0.05) and antihypertensive medicine (4.7 ± 3.6 vs. 3.3 ± 2.2, p < 0.05) decreased without adverse symptoms change. In the DWincrease group, the number of adverse symptoms in 1 week (n = 14, 26 vs. 6, p < 0.05) decreased without a change in systolic blood pressure. Conclusion: This method may become a convenient and cheaper way to estimate DW in HD patients.

T cell responses to peptides of Goodpasture autoantigen in patients with anti‐glomerular basement membrane disease

Cell‐mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti‐glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti‐GBM patients, aiming to identify the epitopes and their clinical significance.

HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy

Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy. Here, we investigated HLA associations with demographic characteristics, anti-phospholipase A2 receptor (PLA2R) antibody, treatment response and kidney outcome after a median follow-up of 52 months in 258 patients. DRB1*0301, but not DRB1*1501, was associated with a significantly higher level of PLA2R antibody (odds ratio 1.58, 95% confidence interval 1.13-2.22). Although DRB1*1502, which differs from DRB1*1501 by a single amino acid, was not a risk allele for primary membranous nephropathy (odds ratio 1.01), it was associated with significantly lower estimated glomerular filtration rates both at baseline (1.79, 1.18-2.72) and at last follow-up (1.72, 1.17-2.53), a significantly worse renal outcome by Kaplan-Meier analysis and a significantly higher risk of end-stage renal disease by Cox regression analysis (hazard ratio 4.52, 1.22-16.74). Nevertheless, the absence of remission remained the only independent risk factor for end-stage renal disease by multivariate analysis. DRB1*1502 was also associated with a significantly higher median PLA2R antibody level [161.4 vs. 36.3 U/mL] and showed interaction with DRB1*0301 for this variable. Thus, HLA genes control PLA2R antibody production and primary membranous nephropathy severity and outcome. Additionally, DRB1*1502 behaves like a modifier gene with a strong predictor value when associated with HLA risk alleles. Other modifier genes need further investigations in larger cohorts.

Comparison of Bioimpedance and Clinical Methods for Dry Weight Prediction in Maintenance Hemodialysis Patients

Background: Bioelectrical impedance analysis (BIA) is a promising technique to evaluate dry weight. We compared the dry weight calculated by the three BIA equations Carlo Basile (CB) , Yanna Dou (YD) and the body composition spectroscopy (BCS) with clinical evaluation in maintenance hemodialysis (MHD) patients. Methods: The dry weight of enrolled MHD patients (DW_Clin) was evaluated under strict clinical surveillance. The whole-body resistances at 50 kHz, intra- and extracellular resistances were measured to calculate the dry weight (DW_CB, DW_YD and DW_BCS) using each of the three equations. Results: Neither DW_CB nor DW_BCS were statistically different compared to DW_Clin (DW_CB 63.2 ± 17.2 vs. 63.1 ± 16.1 kg; DW_BCS 62.8 ± 16.8 vs. 63.1 ± 16.1 kg, p > 0.05). DW_YD was significantly lower than DW_Clin (DW_YD 62.0 ± 16.1 vs. 63.1 ± 16.1 kg, p < 0.05). The bias between DW_CB and DW_Clin was the smallest among these three methods (ΔDW_CB -0.1 ± 1.4 kg; ΔDW_YD 1.1 ± 2.9 kg; ΔDW_BCS 0.3 ± 1.8 kg). Conclusion: The CB equations have better consistency with clinical dry weight in MHD patients.

Prevalence and risk factors for vascular calcification in Chinese patients receiving dialysis: baseline results from a prospective cohort study.

Abstract Objective: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD). Methods: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline. Coronary artery calcification (CAC) was assessed by electron beam or multi-slice computed tomography (EBCT/MSCT), abdominal aortic calcification (AAC) by lateral lumbar radiography, and cardiac valvular calcification (ValvC) by echocardiography. Serum phosphorus, calcium, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D and FGF-23 were evaluated. A logistic regression model was used to evaluate the association between risk factors and VC. Results: Of 1,497 patients, 1,493 (78.3% HD, 21.7% PD) had ≥1 baseline calcification image (final analysis cohort, FAC) and 1,423 (78.8% HD, 21.2% PD) had baseline calcification data complete (BCDC). Prevalence of VC was 77.4% in FAC (80.8% HD, 65.1% PD, p < .001) and 77.5% in BCDC (80.7% HD, 65.8% PD). The proportion of BCDC patients with single-site calcification were 20% for CAC, 4.3% for AAC, and 4.3% for cardiac valvular calcification (ValvC), respectively. Double site calcifications were 23.4% for CAC and AAC, 6.5% for CAC and ValvC, and 1.1% for AAC and ValvC, respectively. In total, 17.9% patients had calcification at all three sites. Conclusions: High prevalence of total VC in Chinese CKD patients will supplement current knowledge, which is mostly limited, contributing in creating awareness and optimizing VC management.