补体旁路途径过度活化在恶性高血压肾硬化中的作用

目的研究补体旁路途径(alternative complement pathway)过度活化在恶性高血压肾硬化中的作用。方法(1)选取本院经肾穿刺活检证实为恶性高血压肾硬化患者50例为病例组,零点行肾穿刺活检的供肾者25例为正常对照组,采用酶联免疫吸附法(ELISA)检测血浆及尿液中的补体旁路途径活化起始B因子、正向调节P因子、负向调节H因子及补体活化终末产物C3a、C5a水平。(2)免疫组化法检测补体活化终末产物C5b-9、C4d及凝集素途径活化产物甘露糖结合凝集素(MBL)在肾活检组织的沉积;免疫荧光双染检测C5b-9与CD34(内皮细胞标志物)在小动脉内皮及肾小球毛细血管内皮的沉积。结果(1)恶性高血压肾硬化患者血浆及尿液中补体B因子、P因子、C3a及C5a均高于正常对照组(均P<0.05),而H因子则低于正常对照组(P<0.05)。(2)恶性高血压肾硬化患者血浆中补体P因子与24 h尿蛋白量呈正相关(rs=0.465,P=0.001),而补体B因子、H因子、C3a、C5a与血肌酐及24 h尿蛋白量无明显相关性。恶性高血压肾硬化患者尿B因子/尿肌酐、尿P因子/尿肌酐、尿C3a/尿肌酐与血肌酐均呈正相关(rs=0.483,P<0.001;rs=0.352,P=0.012;rs=0.319,P=0.024),尿H因子/尿肌酐与血肌酐及24 h尿蛋白量均呈负相关(rs=-0.299,P=0.035;rs=-0.342,P=0.015),尿C5a/尿肌酐与血肌酐及24 h尿蛋白量均呈正相关(rs=0.525,P<0.001;rs=0.496,P<0.001)。(3)免疫组化显示,恶性高血压肾硬化患者C5b-9沉积于小动脉壁及肾小球毛细血管壁,而正常对照组肾组织中未见沉积。恶性高血压肾硬化患者肾脏C5b-9沉积强度评分与血肌酐及24 h尿蛋白量呈正相关(rs=0.791,P<0.001;rs=0.345,P=0.014)。双重免疫荧光标记法可见C5b-9、CD34沉积于小动脉内皮及肾小球毛细血管内皮。(4)恶性高血压肾硬化患者血浆中B因子与C3a(r=0.331,P=0.022)、P因子与C5b-9评分(rs=0.300,P=0.034)均呈正相关;尿液中补体旁路途径活化B因子与C3a、C5a及C5b-9均呈正相关(rs=0.311,P=0.028;rs=0.465,P=0.001;rs=0.428,P=0.002),P因子与C3a、C5a也均呈正相关(rs=0.307,P=0.030;rs=0.442,P=0.001)。恶性高血压肾硬化患者免疫组化可见C4d沉积于小动脉及肾小球,而未见凝集素途径活化产物MBL沉积。结论补体旁路途径过度活化可能参与恶性高血压肾硬化的发生。恶性高血压肾硬化严重程度与补体旁路途径的活化水平相关。     

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension

Objective To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN). Methods Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients. Results The total number of enrolled patients was 275 cases, 170 (61.82%) of which had normal pressure and 105 individuals (38.18%) resulted in hypertension. The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P＜0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P＜0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN-NTN group (all P＜0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test: χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension. Conclusions The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.     

Clinico-pathological features and renal outcomes of primary IgA nephropathy with IgM deposition

Objective To investigate the clinico-pathological features and renal outcomes of primary IgA nephropathy (IgAN) with glomerular IgM deposition. Methods Primary IgAN diagnosed with biopsy from January 2006 to December 2011 were recruited. Patients were divided into groups according to IgM deposition (Group A) and without IgM deposition (Group B). In addition, Group A was subdivided into two groups based on the position of IgM deposits as the mesangium (Group A1) and both mesangium and capillary wall (Group A2). Renal outcomes were defined as end stage renal disease (ESRD) and/or the doubling of baseline serum creatinine. Clinico-pathological features were retrospectively compared. Kaplan-Meier was conducted for renal outcomes, and Cox regression model was used to analyze the prognostic value of IgM deposition and the position of IgM deposition in the progression of nephropathy in IgAN patients. Results 939 patients were enrolled with 422 (44.9%) having IgM deposition (Group A). Of the 422 patients, 382 patients were divided as Group A1, whereas 40 patients were noted as Group A2. Compared to Group B, hemoglobin, serum protein, albumin and serum IgG levels in group A were significantly lower, and the cholesterol and serum IgM levels were significantly higher (all P＜0.05). There was no significant difference in serum creatinine, estimated glomerular filtration rate (eGFR), urinary protein, blood pressure and uric acid between group A and B. In terms of pathological manifestations, patients in Group A exhibited more severe histological lesions including glomerular sclerosis, S1, M1 and interstitial inflammatory cell infiltration (all P＜0.05). Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A was significantly higher than that in group B (all P＜0.05). By Kaplan-Meier, cumulative renal survival rate has no significant difference between Group A and B (Log-rank test χ2=0.019, P=0.891). Univariate and multivariable Cox regression analysis showed that IgM deposition had no significant effect on the renal progression in IgAN patients. Subgroup analysis showed that patients in Group A2 exhibited higher urine protein, creatinine and blood pressure, and lower eGFR and serum albumin, also had worse histological lesions including M1, E1 and T1-2 of Oxford classification (all P＜0.05), Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A2 was significantly higher than that in group A1 (all P＜0.05). By Kaplan-Meier, renal survival rates calculated from outcomes were lower in Group A2 (Log-rank test χ2=18.207, P＜0.001). In addition, IgM deposited both in the mesangium and capillary wall was a risk factor for renal progression of IgAN patients with IgM deposition by a univariate Cox hazards regression mode and multivariable-adjusted Cox models (HR=3.621, 95%CI 1.924-6.814, P＜0.001; HR=2.309, 95%CI 1.176-4.533, P=0.015 respectively). Conclusions The IgAN patients with IgM deposition relatively had more severe clinico-pathological changes, especially those with IgM deposited both in the mesangium and capillary wall. In this study, IgM deposition was not found to be an independent risk factor for the prognosis of kidney in IgAN patients. However, IgM deposited both in the mesangium and capillary wall was an independent risk factor for renal prognosis in IgAN patients with IgM deposition.     

Postoperative hypoalbuminemia is an independent risk factor for acute kidney injury after cardiac surgery under cardiopulmonary bypass

Objective To investigate the effect of postoperative hypoalbuminemia on acute kidney injury (AKI) after cardiac surgery under cardiopulmonary bypass (CPB). Methods The clinical data of adult patients undergoing cardiac surgery under CPB were retrospectively analyzed. The difference between preoperative and postoperative serum albumin level was compared. The patients were divided into hypoalbuminemia group (≤35 g/L) and non-hypoalbuminemia group (＞35 g/L) according to the lowest serum albumin concentration within 48 hours after surgery. The incidence and severity of postoperative AKI were compared between the two groups. Univariate analysis and binary logistic regression analysis were used to evaluate the effect of postoperative hypoalbuminemia on the incidence of postoperative AKI. Results Among the 749 patients, the serum albumin level after cardiac surgery was significantly lower than that before surgery (Z=-15.739, P＜0.001), and the proportion of patients with hypoalbuminemia increased from 9.6% to 27.6%( χ2=83.516, P＜0.001). Postoperative AKI occurred in 273 patients, including 109 cases (52.7%) in hypoalbuminemia group and 164 cases (30.3%) in non-hypoalbuminemia group. The incidence of AKI in hypoalbuminemia group was significantly higher than that in non-hypoalbuminemia group ( χ2=32.443, P＜0.001), and the severity of AKI in hypoalbuminemia group increased than that in non-hypoalbuminemia group (Z=-2.098, P=0.036), and the time of hospital stay extended (Z=-2.442, P=0.015). After adjusted by gender, age, preoperative hypoalbuminemia, comorbidities (hypertension, hyperuricemia, diabetes mellitus, cerebrovascular disease), renal insufficiency, preoperative heart function, coronary angiography, CPB time, aorta blocking time, type of heart surgery and postoperative hypotension, binary logistic regression analysis revealed that postoperative hypoalbuminemia was an independent risk factor for CPB-associated AKI (OR=2.319, 95%CI 1.586-3.392, P＜0.001). Conclusions AKI is a common complication following cardiac surgery under CPB. Serum albumin after CBP is significantly lower than that before CBP, and postoperative hypoalbuminemia within 48 hours after surgery is an independent risk factor for AKI.     

The predictive value of crescents in adult Henoch-Sch?lein purpura nephritis

Objective To study the renal prognosis with the type and proportion of crescentic in adult Henoch Schonlein purpura nephritis (HSPN). Methods A total of 275 HSPN cases diagnosed in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. According to the pathological results, they were divided into four groups: 99 patients in none crescent group (NC), 35 patients in segmental crescents group (SC), 122 patients with circumferential crescent ＜25% (C1), and 19 patients with circumferential crescent≥25% (C2). Renal prognostic events were defined as estimated glomerular filtration rate (eGFR) decreased by 30% over baseline within 2 years, doubling of serum creatinine or end-stage renal disease during follow-up. Kaplan-Meier survival analysis was used to compare the renal survival rate of each group. Univariate and multivariate Cox regression model was used to recognize the risk factor of poor renal outcome. Results There was no significant difference in age, extra renal organ performance and mean arterial pressure among groups. Among NC group, SC group, C1 group and C2 group, difference in serum creatinine (P=0.001), eGFR (P=0.003) and proteinuria levels (P＜0.001) were statistically significant. There was no significant difference in the ratio of global sclerosis, mesangial hypercellularity and interstitial inflammation/fibrosis among the groups. The patients were followed up for 86(58, 116) months. The renal survival rates of NC group, SC group, C1 group and C2 group were 96%, 100%, 83.6% and 68.4% respectively. Kaplan-meier survival analysis showed significant differences (Log Rank=23.24, P＜0.001). Cox multivariate regression analysis indicated that presence of circumferential crescent (HR=3.59, 95%CI 1.34-9.62, P=0.008) and low eGFR (HR=0.979, 95%CI 0.968-0.989, P＜0.001) were independent prognostic factors. Conclusion The presence of circumferential crescent and low eGFR level are independent risk factors for poor renal prognosis in HSPN patients.     

Clinicopathological and prognostic analysis of IgA nephropathy patients with anemia

Objective To analyze the clinicopathological features of IgA nephropathy (IgAN) patients with anemia and the influencing factors of prognosis. Methods The clinical and pathological data of patients diagnosed with primary IgAN at the First Affiliated Hospital of Fujian Medical University from January 1, 2006 to December 31, 2016 were retrospectively analyzed. The patients were divided into anemia group and non-anemia group according to whether the patient was anemia or not. The clinical and pathological data of the two groups were collected. All of them were followed up from the date of renal biopsy to January 1, 2018. Survival curves of the two groups were drawn by Kaplan-Meier method, and compared by Log-rank test. Multivariate Cox proportional hazards regression model was adopted to explore the influencing factors of prognosis in IgAN patients. Results A total of 231 subjects were enrolled, including 122 males (52.8%), and the male-female ratio was 1.12∶1. Their age was (34.8±10.1) years (15-68 years). There were 70 patients (30.3%) in anemia group, 161 cases (69.7%) in non-anemic group. Compared with non-anemia group, anemia group had higher proportion of females, lower serum albumin, higher proportion of tubular atrophy/interstitial fibrosis (T1/2), endothelial cell proliferation (E1) and crescent formation (C1/2), which were statistically significant (all P＜0.05). The patients had a median follow-up time as 6.3 years (0.3-12.9 years). Survival analysis showed that patients in anemia group had lower cumulative renal survival rate than that in non-anemia group ( χ2=15.234, P＜0.001). Multivariate Cox hazards regression analysis revealed that anemia (HR=3.820, 95%CI 1.674-8.719, P=0.001), tubular atrophy/interstitial fibrosis (T1/2) (HR=3.770, 95%CI 1.026-13.852, P=0.046), glomerular segmental sclerosis/adhesion (S1) (HR=4.211, 95%CI 1.139-15.576, P=0.031), hypertension (HR=2.988, 95%CI 1.276-6.999, P=0.012), increased 24 h urinary protein (HR=1.103, 95%CI 1.046-1.163, P＜0.001) and estimated glomerular filtration (eGFR)＜60 ml?min-1?(1.73 m2)-1 (HR=3.725, 95%CI 1.639-8.462, P=0.002) were the independent risk factors for poor renal prognosis in patients with IgAN. Conclusions The clinicopathological features of IgAN patients with anemia are relatively serious, and the renal cumulative survival rate is lower. Anemia, tubular atrophy/interstitial fibrosis (T1/2), glomerular segmental sclerosis/adhesion (S1), hypertension, increased urinary protein and eGFR＜60 ml?min-1?(1.73 m2)-1 are the independent risk factors for poor renal prognosis in patients with IgAN.     

血清透明质酸和层黏蛋白等对肾脏纤维化早期诊断的研究

目的 探讨慢性肾脏病不同分期时血清透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1的变化,初步评价其对肾脏纤维化的早期诊断意义.方法 收集健康对照组以及慢性肾脏病不同分期患者的血清标本,采用放射免疫及酶联免疫吸附法测定各组患者的血清肌酐、尿素氮、肌酐清除率、血清胱抑素C、β2微球蛋白指标水平,同时测定血清透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1指标的变化,分析各组患者血清中透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1与血清肌酐、尿素氮、肌酐清除率、血清胱抑索C、β2微球蛋白血生化等指标的相关性,比较各组患者血清中透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1指标在慢性肾脏病Ⅰ、Ⅱ期中的变化.结果 慢性肾脏病Ⅰ期患者透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1与健康对照组比较差异有统计学意义(P＜0.05).多元相关分析表明,透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1与β2微球蛋白和血清胱抑素C相关(r分别=0.664、0.458、0.566、0.369、0.408,P均＜0.05).结论 随着慢性肾脏病的发展,血清透明质酸、层黏蛋白、Ⅲ型前胶原、Ⅳ型胶原、组织基质金属蛋白酶抑制剂1水平逐渐升高,特别是在慢性肾脏病早期(Ⅰ、Ⅱ期)其水平已经升高,可以作为评价慢性肾脏病早期纤维化的标志物.     

Clinicopathological and prognostic analysis of children with primary IgA nephropathy with C1q deposition

Objective To investigate the clinical and pathological features and prognosis of children with IgA nephropathy with C1q deposition. Methods The children with IgA nephropathy diagnosed by renal biopsy from January 1, 2000 to December 30, 2017 were retrospectively analyzed and divided into C1q deposit group and C1q negative group according to glomerular immunofluorescence examination. Follow-up until the patient's serum creatinine doubled, glomerular filtration rate decreased by more than 50%, entering end-stage kidney disease, renal replacement therapy or death. Kaplan-Meier survival analysis was used to evaluate the renal survival rate in two groups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of C1q deposition on the prognosis of patients with IgA nephropathy. Results There were 60 cases in C1q deposition group and 60 cases in C1q negative group. (1) the initial eGFR and plasma albumin in C1q deposition group were lower than those in C1q negative group, while the levels of serum creatinine, serum cholesterol and 24 hour urinary protein in C1q group were higher than those in C1q negative group (all P＜0.05). (2) pathological indexes: Mesangial cell proliferation, tubular atrophy/interstitial fibrosis, and cell/fibrocytic crescein score in C1q negative group were significantly higher than those in C1q negative group (all P＜0.0.5). (3) Kaplan-Meier analysis showed that there was significant difference in renal cumulative survival rate between the two groups (Log-rank test: χ2=6.801, P=0.009). Cox proportional hazard regression model showed that the risk of renal end-point events in IgAN children with C1q deposition group was 5.772 times higher than that in C1q negative group (HR=5.772, 95%CI: 1.353-24.6211, P=0.018). Conclusion C1q deposition is an independent risk factor for the progress of renal function in IgA nephropathy children.     

Study of 25-OH vitamin D3 in patients with lupus nephritis and its association with disease activity

Objective To explore the level of 25-OH vitamin D3 in patients with lupus nephritis (LN) and its association with the activity of disease. Method Clinical data of 154 patients with lupus nephritis in our hospital from January 2008 to May 2015 were collected. Another 63 healthy adults were recruited as normal controls. Results The level of 25-OH vitamin D3 in patients with LN was significantly lower than that in normal controls (P﹤0.01). The concentration of serum 25-OH vitamin D3 was negatively correlated with 24 h urinary protein (r=-0.18, P=0.02), antinuclear antibody (r=-0.20, P=0.01), SLEDAI scores (r=-0.20, P﹤0.01), while positively correlated with serum complement C3 (r=0.32, P﹤0.01). The'full-housed' patients with all 5 antibodies positive in renal biopsy had lower level of 25-OH vitamin D (P＜0.05). Conclusion The level of 25-OH vitamin D3 in patients with LN is inversely correlated with the disease activity.     

Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

直接抗病毒药物抗丙型肝炎病毒治疗改善肝纤维化程度的疗效

目的探讨应用直接抗病毒药物（DAAs）成功清除丙型肝炎病毒（HCV）后慢性丙型肝炎（CHC）患者肝纤维化程度的改善。 方法共纳入111例经DAAs治疗后获得持续病毒学应答（SVR）的CHC患者,比较患者治疗前后白细胞（WBC）、红细胞（RBC）、血小板（PLT）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBil）、血尿素氮（BUN）、血肌酐（Cr）、肝硬度（LSM）、AST和血小板比率指数（APRI）和Fib-4评分（Fib-4 score）的变化;将患者按应用DAAs治疗前的诊断进行分组,其中慢性肝炎组77例,代偿期肝硬化组13例,失代偿期肝硬化组21例,比较各组患者DAAs治疗前后LSM、APRI和Fib-4评分的变化;采用Logistic二元回归分析性别、基因型、体重指数（BMI）、WBC、PLT、ALT、AST、TBil、APRI和Fib-4评分的基线值对LSM变化值的影响。 结果入组111例患者,WBC、PLT升高,ALT、AST和TBil降低,与治疗前差异均有统计学意义（Z =－3.842、P < 0.001,Z =－3.854、P < 0.001,Z =－8.919、P < 0.001,Z =－8.882、P < 0.001,Z =－4.487、P < 0.001）,而入组111例患者血肌酐（Cr）和血尿素氮（BUN）与治疗前差异均无统计学意义（Z =－0.287、P = 0.774,Z =－0.424、P = 0.671）。111例患者的3种无创肝纤维化指标,即LSM、APRI和Fib-4下降,与治疗前差异均有统计学意义（Z =－6.955、P < 0.001;Z =－8.836、P < 0.001;Z =－6.838、P < 0.001）,其中代偿期肝硬化组、失代偿期肝硬化组患者LSM、APRI和Fib-4下降幅度均较慢性肝炎组显著（LSM：χ² = 13.52、P < 0.001,χ² = 34.00、P < 0.001;APRI：χ² = 10.84、P < 0.001,χ² = 28.38、P < 0.001;Fib-4：χ² = 16.83、P < 0.001,χ² = 29.36、P < 0.001）。代偿期肝硬化组与失代偿期肝硬化组患者LSM、APRI和Fib-4下降幅度差异均无统计学意义（LSM：χ² = 1.08、P = 0.58,Fib-4：χ² = 0.84、P = 0.66,APRI：χ² = 0.09、P = 0.96）。较高ALT基线值[P = 0.045,OR（95%CI）= 0.918（0.844～0.998）]、AST [P = 0.013,OR（95%CI）= 0.862（0.767～0.969）]和APRI基线值[P = 0.032,OR（95%CI）= 0.001（0.000～0.555）]或较低WBC基线值[P = 0.019,OR（95%CI）= 2.508（1.161～5.421）]患者获得SVR后LSM得到显著改善。 结论成功清除CHC患者的HCV可使其肝纤维化显著改善,且肝硬化患者肝纤维化程度改善更为显著。对CHC患者应尽早启动抗病毒治疗,尽早实现SVR可阻滞CHC患者肝脏炎症及肝纤维化进展,从而减少肝硬化失代偿并发症的发生。     

Relationship between serum B-cell activating factor levels and clinicopathology in children with lupus nephritis

Objective To analyze the relationship between the serum B-cell activating factor (BAFF) levels and clinical characters and pathological features in children with lupus nephritis (LN). Methods ELISA was used to detect the serum BAFF (sBAFF) levels of the 54 LN children diagnosed in the First Affiliated Hospital, Sun Yat-sen University during October 1, 2014 to December 31, 2016 and with complete clinical data. According to whether glucocorticoid or immunosuppressive agents has been used at their first admission, patients were divided into treated group (n=44) and non-therapy group (n=10). According to the renal response after induction treatment for 6 months, patients were divided into remission group (n=20) and non-response group (n=34). According to whether there was renal recurrence, they were divided into recurrence group (6 cases) and non-recurrence group (48 cases). According to renal biopsy, patients were divided into class-Ⅲ, class-Ⅳ and class-Ⅴ group. Another 15 healthy children were taken as a control group. The correlations between sBAFF and clinical manifestation, laboratory examination, renal biopsy and clinical outcome were analyzed. Results (1) Compared with the control group, the sBAFF was significantly increased in LN group (t=3.821, P＜0.001). Compared with the non- neuropsychiatric systemic lupus erythematosus (NPSLE) group, sBAFF was significantly increased in NPSLE group (t=2.202, P=0.032). (2) Compared with that in treated group, sBAFF was significantly higher in untreated group (LSD-t=2.309, P=0.025). Compared with non-response group, sBAFF was significantly decreased in response group (LSD-t=2.035, P=0.046). (3) No significant difference was observed between class-Ⅲ, class-Ⅳ and class-Ⅴ pathological classification group (F=1.080, P=0.459). sBAFF in LN children was not significantly correlated with the active index (AI) or chronic index (CI) of Austin index (r=-0.273, P=0.063; r=0.150, P=0.314). (4) In LN children, sBAFF has positive correlation with ESR and IgG level (r=0.289, P=0.036; r=0.340, P=0.017) and negative correlation with WBC (r=-0.337, P=0.013). Multiple linear regression model showed that serum IgG level (β'=0.517, P=0.001) and renal response (β'=-0.271, P=0.037) were independent influencing factors of sBAFF level. Conclusions Renal remission and serum IgG levels in LN children are influencing factors of sBAFF levels. sBAFF is helpful to clinical assessment on renal response of LN children.     

血红蛋白与IgA肾病患者肾小管萎缩/间质纤维化的关系

目的探讨IgA肾病(IgA nephropathy,IgAN)患者血红蛋白(Hb)水平与肾脏病理牛津分级中肾小管萎缩/间质纤维化(T)的关系。方法回顾性分析2010年1月1日至2015年12月31日在深圳市第二人民医院肾活检确诊为IgAN、同时有完整实验室及影像学资料的患者。将所有患者分为贫血组与非贫血组。采用Logistic回归分析确定Hb与肾小管萎缩/间质纤维化的关系;采用平滑曲线拟合分析Hb与肾小管萎缩/间质纤维化可能的曲线关系;采用受试者工作特征曲线(ROC)分析Hb对肾小管萎缩/间质纤维化的诊断价值。结果本研究共纳入IgAN患者630例,贫血组130例(20.63%),非贫血组500例(79.37%);两组间年龄差异无统计学意义,而性别差异有统计学意义(男性35.38%比53.80%,χ2=10.740,P<0.001)。与非贫血组相比,贫血组的患者肾小管萎缩/间质纤维化的比例和24 h尿蛋白量较高(χ2=62.586,P<0.001;Z=-6.082,P<0.001),估算的肾小球滤过率(eGFR)较低(t=7.126,P<0.001)。Logistic回归分析显示,高Hb水平为肾小管萎缩/间质纤维化发生风险减少的独立保护因素(OR=0.973,95%CI 0.958~0.987,P<0.001)。平滑曲线拟合分析显示Hb与肾小管萎缩/间质纤维化呈线性负相关。ROC曲线提示Hb诊断肾小管萎缩/间质纤维化的最佳临界值为120.5 g/L,即提示Hb>120.5 g/L时,肾小管萎缩/间质纤维化的程度可能降低。结论IgAN合并贫血的患者其肾小管萎缩/间质纤维化发生率较高。Hb>120.5 g/L可能减少肾小管萎缩/间质纤维化发生的风险。     

移植肾IgA肾病临床病理及预后分析

目的探讨移植肾IgA肾病(IgAN)复发或新发的诱因及移植肾生存的危险因素。方法选取2012年11月至2018年12月浙江大学医学院附属第一医院经肾活检确诊为移植肾IgAN的患者,按照血肌酐(Scr)增高水平、估算肾小球滤过率(eGFR)下降率分为稳定组(Scr升高值<20μmol/L,eGFR下降率<10%)和进展组(Scr增高但未达翻倍值,30%相似文献   

连续性肾脏替代疗法治疗难治性急性左心衰竭患者的预后危险因素分析

目的通过分析因难治性急性左心衰竭而行连续性肾脏替代疗法(continuous replacement therapy,CRRT)患者的资料,寻找患者预后的影响因素。方法通过佛山市第一人民医院的病历系统及血液透析系统,筛选2012年1月1日至2019年1月1日因难治性急性左心衰竭而行CRRT治疗的所有患者,将所有的患者按照最终治疗结果分为生存组及死亡组。通过分析患者的年龄、性别、心脏原发病、使用血管活性药情况、治疗起始平均动脉压、治疗前尿量、血红蛋白、血清肌酐、血白蛋白、C反应蛋白、脑钠肽、左心室射血分数及CRRT治疗时长等资料,寻找患者预后的影响因素。结果共130例患者被纳入本研究,其中生存组96例,死亡组34例,病死率为26.15%。生存组男性所占比例高于死亡组(71.88%比50.00%,χ2=5.366,P=0.021),起始平均动脉压、治疗前尿量、血清肌酐显著高于死亡组(t=4.677,P<0.001;Z=3.904,P<0.001;Z=2.866,P=0.004),血红蛋白低于死亡组(Z=-2.587,P=0.011),治疗时长短于死亡组(Z=-3.447,P=0.001)。多因素Logistic回归分析结果显示,女性(OR=2.950,95%CI 1.102~7.898,P=0.031)及较高水平血红蛋白(OR=1.024,95%CI 1.004~1.045,P=0.019)是CRRT治疗难治性急性左心衰竭患者死亡的危险因素,而较高水平治疗前平均动脉压(OR=0.959,95%CI 0.930~0.989,P=0.008)和治疗前尿量(OR=0.998,95%CI 0.997~0.999,P=0.004)是患者预后的保护因素。结论即使采用CRRT治疗难治性急性左心衰竭,其病死率仍较高,女性及血红蛋白水平升高是患者预后的危险因素,而治疗前较高水平尿量和治疗前平均动脉压是患者预后的保护因素。     

Comparative analysis of clinico-pathological characteristics and outcomes in malignant hypertension patients with and without primary glomerular diseases

Objective To investigate the clinico-pathological characteristics, outcomes and their predictors in malignant hypertension related kidney injury with and without primary glomerular diseases. Methods Patients with clinical diagnosis of malignant hypertension, biopsy-proven kidney injury caused by malignant hypertension and complete clinical data from January 2010 to December 2018 were retrospectively analyzed. According to clinical and renal pathology, patients were divided into malignant hypertension related kidney injury without primary nephropathy group and with primary nephropathy group. Clinico-pathological characteristics and outcomes were evaluated and compared between malignant hypertension related kidney injury with and without primary glomerular diseases. Results Totally 31 biopsy-proven kidney injury patients were analyzed. Among them, there were 18 cases with primary glomerular diseases and 13 cases without primary glomerular diseases, with age of (32.5±6.5) years old and (34.7±8.1) years old, respectively. There were 12 males in both group. The proportion of primary IgA nephropathy was higher (16/18) in the group of malignant hypertension related kidney injury with primary glomerular diseases. Malignant hypertension with primary glomerular diseases patients had lower plasma albunin level [(32.7±6.4) g/L vs (38.5±7.3) g/L, P=0.027], higher 24-hour proteinuria level [(4.03±2.71) g vs (1.45±0.98) g, P=0.002] and higher incidence rates of dysmorphic hematuria (14/18 vs 0, P=0.001) than those without primary glomerular diseases patients. Glomerular sclerosis, mesangial proliferation, tubular atrophy and interstitial fibrosis were more severe in malignant hypertension with primary glomerular diseases patients (all P＜0.05), but the ischemic wrinkling of glomerular capillary was more severe in malignant hypertension without primary glomerular diseases (P＜0.01). There were no differences of acute or chronic malignant hypertensive injury in small artery and in afferent arterioles between the two groups. Cox regression analysis showed that loss of brush-border with flattening of tubular epithelium was the predictor for renal partial recovery (HR=5.956, 95%CI 1.198-29.614, P=0.029). Kaplan-Meier analysis showed that malignant hypertension patients with primary glomerular diseases had shorter renal survival time than those without primary glomerular diseases [(24.1±9.3) months vs (56.6±12.4) months], and accumulative renal survival rate of malignant hypertension patients with primary glomerular diseases was lower than that without primary glomerular diseases (11.6% vs 53.3%, Log-rank χ2=5.022, P=0.025). Multivariate Cox regression analysis showed that severe tubular atrophy and interstitial fibrosis were independent risk factors for end-stage renal disease in malignant hypertension patients (HR=5.870, 95%CI 1.372-25.112, P=0.017). Conclusions Malignant hypertension with primary glomerular diseases patients have more severe clinico-pathological renal impairment and poorer prognosis of long-term renal survival than those without primary glomerular diseases. Acute renal tubular injury (loss of brush-border with flattening of tubular epithelium) is the only predictor of renal function improvement in patients with malignant hypertension and renal impairment within one year. Tubular atrophy/interstitial fibrosis is a risk factor for end-stage renal disease in patients with malignant hypertension. Renal biopsy is an indispensable tool for predicting short-term and long-term renal outcomes.     

狼疮肾炎患者循环miRNA表达谱研究及循环miR-130b-3p的临床意义

目的分析处于不同进展阶段的狼疮肾炎(LN)患者循环miRNA的表达变化并探讨其可能存在的临床意义。 方法本研究共94份血清标本,包括58例LN患者和36名健康体检者(作为对照组)。挑选出其中性别、年龄匹配的12份血清标本用于循环miRNA表达谱筛选,包括早期LN组4份(CKD 1～3期),晚期LN组4份(CKD分期4～5期)及对照组4份作为芯片组,使用miRNA PCR芯片检测血清miRNA变化;剩余50例LN患者(40例早期LN患者、10例晚期LN患者)及32名对照者血清样本作为验证组,用于验证miRNA表达谱筛选结果;以Nanodrop 2000检测血清总RNA抽提浓度;选择miR-130b-3p和miR-1233-3p作为验证对象;进行Spearman相关性分析。 结果芯片组结果显示,与对照组相比,早期LN组中7个表达上升的miRNA差异具有统计学意义,分别是：miR-1233-3p (P＝0.019)、miR-130b-3p (P＝0.021)、miR-18a-3p (P＝0.021)、miR-628-3p (P＝0.023)、miR-1260b (P＝0.030)、miR-1539 (P＝0.041)和miR-378e (P＝0.047);晚期LN组分别与对照组及早期LN组比较,未发现表达上调大于2倍或者上调差异具有统计学意义的miRNA。验证组结果显示：晚期LN组患者分别与对照组、早期LN组比较,血清总RNA浓度下降(U＝4.5,P<0.001;U＝18.0,P<0.001);早期LN组与对照组比较,血清中miR-130b-3p表达升高[IQR 16.2(8.7,42.7)与9.6(4.8,17.4), U＝405.5,P＝0.008];晚期LN组分别与对照组及早期LN组比较,MiR-130b-3p和miR-1233-3p表达均下降(U＝69.0、P＝0.008,U＝46.0、P<0.001;U＝80.0、P＝0.019,U＝70.0、P＝0.002);相关性分析显示循环miR-130b-3p的相对表达量与24 h尿蛋白(r＝0.404,P＝0.010)、肾脏慢性活动指数(r＝0.389,P＝0.013)、甘油三酯(r＝0.376,P＝0.017)呈正相关。 结论严重肾功能衰竭患者可能存在循环miRNA广泛表达下调,循环miRNA-130b-3p在早期LN患者中表达升高并与肾脏损伤和血脂调节异常相关,在LN发生发展中可能起作用。     

乙型肝炎病毒相关膜性肾病患者抗血清磷脂酶A2受体-IgG特点及其相关因素的临床研究

目的研究乙型肝炎病毒相关膜性肾病(HBV-MN)患者血清抗磷脂酶A2受体(PLA2R)-IgG阳性率,分析与PLA2R-IgG滴度相关的因素。 方法本研究纳入经肾穿刺活检确诊的HBV-MN患者108例,检测血清PLA2R－IgG滴度、肌酐、白蛋白和24 h尿蛋白定量等,计算肾小球滤过率,分别统计患者肾活检组织中PLA2R及免疫荧光IgG、C3、C1q及IgG亚型阳性率,分析年龄、性别、蛋白尿与血清中和肾活检组织中PLA2R-IgG检测结果的关系。 结果108例HBV-MN患者中,血清PLA2R-IgG阳性率为37%,肾组织PLA2R阳性率54.6%,血清PLA2R-IgG的阳性率和滴度与年龄、性别无统计学相关性(P>0.05),与尿蛋白水平相关(χ²＝9.159,P＝0.010;χ²＝11.327,P＝0.004);尿蛋白>3.5 g/d组患者PLA2R－IgG阳性率显著高于尿蛋白<1g/d及1～3.5 g/d组(Z＝2.863,P＝0.012和Z＝2.356,P＝0.049)。 结论HBV-MN患者中PLA2R-IgG阳性率较高,阳性率及滴度均与蛋白尿水平相关,尿蛋白越多,阳性率和滴度也随之升高。     

Relationship between islet α - cell function and glomerular filtration rate in type 2 diabetic patients

Objective To analyze the islet α-cell function in type 2 diabetic patients with different levels of glomerular filtration rate(eGFR). Methods Three hundred and eighty-eight cases of type 2 diabetic patients were classified into four groups according to eGFR: glomerular hyperfiltration group, normal renal function group, mild renal dysfunction group and moderate-severe renal dysfunction group. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were conducted to compare the changes of glucagon(GLA), insulin/glucagon ratio（INS/GLA）, glucose/glucagon ratio（GLU/GLA）, the area under the curve of glucagon(AUCGLA) among the groups and correlation analysis were performed among glucagon and glomerular filtration rate and other indicators. Results With the decline of eGFR, the change curve of glucagon level was“J”shaped; the level of fasting glucagon in each group were（82.21±15.06）ng/L,（74.25±15.34）ng/L,（81.16±20.18）ng/L, （100.21 ± 24.73）ng/L, respectively. Compared with normal renal function group, GLA, AUCGLA in glomerular hyperfiltration group and renal dysfunction group increased significantly(P＜0.05), GLU/GLA, INS/GLA decreased significantly. Pearson correlation coefficient analysis showed that fasting glucagon had a negative correlation with eGFR（r＝-0.360,P＜0.01）, plasma albumin (ALB)（r＝ -0.170,P＜0.01）and high - density lipoprotein cholesterol (HDL - C)（r＝-0.128,P＜0.05）, had a positive correlation with fasting venous blood glucose (FPG)（r＝0.339,P＜0.01）, postprandial 2 hours venous blood glucose(2hPG)（r＝0.443,P＜0.01）, the area under the curve of blood glucose (AUCG)（r＝0.475,P＜0.01）, duration（r＝0.257,P＜0.01）and glycosylated hemoglobin(HbA1c) （r＝0.202,P＜0.01）. Multiple stepwise regression analysis showed that fasting glucagon was negatively correlated with eGFR（β ＝-0.290,t＝-5.393,P＜0.01） and HDL - C（β ＝-0.157,t＝ -3.026,P＜0.01）. Conclusions Glucagon level is influenced by eGFR in type 2 diabetic patients. Glucagon in patients with glomerular hyperfiltration or renal dysfunction is significantly higher than those with normal renal function. The inhibition effect of blood glucose and insulin to glucagon are both weakened.     

Correlation between levels of serum immunoglobulin、complement and immunopathology in glomerular disease

目的 探讨肾小球疾病免疫球蛋白、补体水平与免疫病理的相关性.方法 112 例肾小球疾病患者,14 例健康人测定血清免疫球蛋白及补体,112 例肾小球疾病患者,112 例患者行肾活组织病理检查.结果 112 例肾小球疾病患者 IgG 升高 11 例(9.82%),降低 29 例(25.89%),IgA 升高 33 例(29.46%),降低 2 例(1.79%).IgM 升高 7 例(6.25%),降低 3 例(2.68%),三种免疫球蛋白的变化有显著差异(x2=70.587,P=O.000);C3 减低 29 例(25.89%),C4减低 32 例(28.57%),两者比较无显著差异(X2=0.203,P=0.653).免疫荧光阳性率依次为C3(50%)>lgA(49.11%)>IgG(40.18%)>lgM(21.43%)>C4(14.29%)(x2=49.303,P=0.000);免疫荧光 IgA 阳性者血清 lgA 水平较阴性者高(P=0.042),C3、CA阳性者血清 C3、c4 水平较阴性者低(P=0,P=0.007),IgG、IgM 阳性者血清 IgG、lgM 水平与阴性者比较无差异(P=0.136,P=0.383).结论 肾小球疾病存在体液免疫紊乱,测定血清免疫球蛋白、补体及行肾组织免疫病检有助于了解体液免疫状况,估计疾病活动度,判断疗效,但两种检查之间无明显的相关性,可相互补充,不能相互替代.