多柔比星肾病肾损伤早期核因子-κB和血管紧张素ⅠⅡ的表达及关系探讨

目的　探讨在多柔比星 (阿霉素 )肾病综合征 (NS)幼年大鼠肾损伤过程中核因子 (NF) κB和血管紧张素ATⅠ、ATⅡ的表达及其相关性。方法　 4周龄雄性Wistar大鼠单侧肾切除加腹腔注射阿霉素造成NS模型 ,分别以免疫组织化学和原位杂交检测ATⅠ、ATⅡ和NF κB。结果　肾病组随着病变时间的延长 ,NF κB和ATⅠ、ATⅡ表达的强度和部位均呈增强趋势 ,治疗组在相同时间点则两者都有不同程度下调 (P <0 .0 5 )。结论　在阿霉素肾病损伤过程中NF κB和ATⅠ、ATⅡ起着介导作用。     

Effects of glycyrrhetinic acid on aminonucleoside nephrosis in rats

The effects of glycyrrhetinic acid (GA), an aglycon of glycyrrhizin extracted from the roots of Glycyrrhizae radix, on puromycin aminonucleoside (PA) nephrosis were studied in rats. Urine protein excretion in female rats (130g–150g) receiving PA (50 mg/kg) alone was significantly elevated on the 2nd day after injection of PA and reached a peak on the 14th day. Urinary protein on the 14th day was reduced to 74% in animals treated with GA (20 mg/kg) starting on the 2nd day after injection of PA. The increase in serum cholesterol and the decrease in serum protein were also suppressed by GA. Observation by electron microscopy revealed that the degree of abnormality in glomerular epithelial cells, i.e. loss or fusion of foot processes, was lower in the rats treated with GA after PA injection than in the rat treated with PA alone. Moreover, pretreatment with GA did not suppress urinary protein excretion but when it was given at the same time as PA and after PA a significant decrease in urinary protein excretion was observed. Correspondence to: H. Abe at the above address     

The mechanism of hyperlipidaemia in the nephrotic syndrome

The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase.     

温阳活血方对大鼠阿霉素肾病模型的影响

目的：探讨不同治法治疗原发性肾病综合征高脂血症的疗效差异。方法：用阿霉素（ADR）诱导一种类似人类微小病变肾病模型,然后用中药温阳方、活血方及温阳活血方对模型进行治疗,并设空白、病理及强的松组对照。结果：温阳活血方组尿蛋白、血脂、脂蛋白及肾脏病理损害明显改善;温阳方及活血方组血脂、脂蛋白部分指标及肾脏病理损害有所改善。结论：温阳活血方对ADR肾病的治疗作用较全面,其疗效优于温阳法和活血法。     

利妥昔单克隆抗体不宜作为继发性难治性肾病的挽救治疗措施

背景　利妥昔单克隆抗体（RTX）用于肾小球疾病的治疗已近20年,近年来其在治疗原发性和继发性肾病方面积累了一些循证医学证据,但对于较为明显的肾功能不全患者是否适合应用RTX进行挽救性治疗,目前尚无相关研究。目的　观察RTX挽救性治疗继发性难治性肾病患者的有效性和安全性。方法　回顾性选取2018-2019年北京大学国际医院收治的所有住院使用RTX治疗的成年难治性肾病患者48例。根据原发病诊断结果将患者分为原发性肾病（PN）组和继发性肾病（SN）组,再将SN组依据RTX治疗前血肌酐（Scr）分为SN-NST亚组（Scr<300 μmol/L）和SN-ST亚组（Scr≥300 μmol/L）。收集所有患者的一般资料（包括性别、年龄、体质量、身高、体表面积、原发病）,RTX治疗前、后实验室检查结果〔24 h尿蛋白（Upro）、白细胞计数（WBC）、红细胞计数（RBC）、血小板计数（PLT）、白蛋白（Alb）、Scr、CD4+细胞计数〕,计算CD4+细胞计数/WBC比例,记录RTX治疗期间严重不良事件〔包括严重感染全身（应用抗生素≥7 d或联合应用2种及以上抗感染药物）、肾脏替代治疗（RRT）、多脏器功能衰竭综合征（MODS）、死亡等〕,RTX末次治疗后3个月肾脏转归情况（即是否行维持性血液透析）。结果　48例使用RTX治疗的难治性肾病患者均进行肾穿刺活检;PN组19例（39.6%）,SN-NST亚组14例（29.2%）,SN-ST亚组15例（31.2%）。SN-ST亚组患者年龄小于PN组和SN-NST亚组（P<0.05）。PN组患者RTX治疗前24 hUpro、RBC、PLT高于SN-NST亚组、SN-ST亚组,Alb低于SN-NST亚组、SN-ST亚组（P<0.05）;SN-ST亚组患者RTX治疗前Scr高于PN组、SN-NST亚组,CD4+细胞计数低于PN组、SN-NST亚组（P<0.05）。SN-ST亚组患者RTX治疗后Scr高于PN组、SN-NST亚组（P<0.05）。PN组、SN-NST亚组患者RTX治疗后24 hUpro较同组治疗前降低（P<0.05）。SN-NST亚组、SN-ST亚组患者RTX治疗后WBC较同组治疗前降低（P<0.05）。SN-ST亚组患者RTX治疗后RBC较同组治疗前升高（P<0.05）。PN组患者RTX治疗后PLT较同组治疗前降低,SN-ST亚组患者RTX治疗后PLT较同组治疗前升高（P<0.05）。PN组、SN-NST亚组患者RTX治疗后Alb较同组治疗前升高（P<0.05）。三组患者RTX单位时间体表面积的累积剂量比较〔PN组、SN-NST亚组、SN-ST亚组依次为（437±322）、（503±344）、（331±312）mg?月-1?（m2）-1〕,差异无统计学意义（F=1.048,P=0.359）。SN-ST亚组患者RTX治疗期间严重感染发生率、行RRT者比例及RTX末次治疗后3个月行维持性血液透析者比例高于PN组（P<0.05）;SN-ST亚组患者RTX治疗期间行RRT者比例、RTX末次治疗后3个月行维持性血液透析者比例高于SN-NST亚组（P<0.05）。结论　Scr≥300 μmol/L的继发性难治性肾病患者应用RTX治疗对其肾病改善作用不明显,且会明显增加其严重感染和肾衰竭发生风险,故RTX不应作为这部分患者的挽救治疗措施。     

Reduced Endothelial Factor VIII Staining in Renal Microcirculation Correlates with Hemodynamic Alteration in Nephrosis

Endothelial factor VIII staining in renal microcirculation was performed in eight nephrotic patients associated with mesangial proliferation (MesP) and six nephrotic patients associated with focal segmental glomerulosclerosis (FSGS). The result in MesP revealed a greater staining for glomerular endothelial factor VIII (35 ± 15%) and for postglomerular capillary endothelial factor VIII (65 ± 21%) than that observed in FSGS, which revealed a 11 ± 8% staining for glomerular endothelial factor VIII and 19 ± 15% staining for postglomerular capillary endothelial factor VIII. This finding implies that there is a greater loss of endothelial cell in renal microcirculation in FSGS. Such a finding correlates with the intrarenal hemodynamics which illustrated (Futrakul, P.; Sitprija, V.; Yenrusi, S. Glomerular endothelial dysfunction determines disease progression: a hypothesis. Am. J. Nephrol. 1997, 17, 533–540.) a mild reduction in renal plasma flow (535 ± 106 mL/min/1.73 m², normal 600 mL/min/1.73 m²) and in peritubular capillary flow (422 ± 80 mL/min/1.73 m², normal 480 mL/min/1.73 m²) in MesP and (Futrakul, P. Coagulation in glomerulonephritis and nephrotic symdrome: Its therapeutic intervention. In Asian Manual of Nephrology, Takeuchi, T.; Sugino, N.; Ota, K., Eds.; SEAMIC Publication, Tokyo, 1981; pp. 89–95.) a greater reduction in renal plasma flow (108 ± 50 mL/min/1.73 m²) and in peritubular capillary flow (87 ± 42 mL/min/1.78 m²) in FSGS. Therefore the study has emphasized both the structural and functional defects of endothelium in renal microcirculation in particular in FSGS.     

最新KDIGO急性肾损伤指南在新月体肾炎中的应用

目的 分析2012年国际改善全球肾脏病预后组织（KDIGO）发表的急性肾损伤（AKI）和急性肾脏病（AKD）定义在不同类型的新月体肾炎中的应用.方法 2009年1月至2012年12月在北京大学第一医院肾内科住院接受肾活检其光镜病理检查超过50％肾小球内有新月体形成的患者.根据2012年KDIGO指南AKI/AKD的定义,以血肌酐（Scr）和24h尿量为指标将入选的患者分为AKI组,非AKI的AKD组,非AKD组和无法分类组.结果 AKD能够识别84.2％的新月体肾炎患者,而AKI仅能识别61.4％的患者.对于不同类型的新月体肾炎,AKI识别抗GBM抗体型最高,达91％.新月体性肾小球肾炎较肾小球肾炎伴多数新月体形成更易被AKI识别（P =0.002）.不同成分为主的新月体肾炎,AKI/AKD的识别无统计学差异.结论 2012年KDIGO AKD的定义比AKI更能够早期识别急性肾功能不全的患者.     

PERITUBULAR CAPILLARY FLOW DETERMINES TUBULOINTERSTITIAL DISEASE IN IDIOPATHIC NEPHROTIC SYNDROME

The spatial relationship between renal perfusion and nephronal structure was determined in 51 nephrotic patients consisting of 11 patients with steroid sensitive, minimal change (MC) nephrosis, 12 patients with steroid resistant, mesangial proliferative (MesP) nephrosis and without tubulointerstitial fibrosis (TIF), 11 patients with steroid resistant, MesP nephrosis and with low grade TIF and 17 patients with focal segmental glomerulosclerosis (FSGS). The intrarenal hemodynamic study revealed a unique correlation between renal perfusion and nephronal structure. A normal or slight reduction in peritubular capillary flow observed in MC or mild MesP nephrosis correlates with an intact tubulointerstitial structure. A moderate reduction in peritubular capillary flow observed in steroid resistant, MesP nephrosis induces a low incidence of TIF. A severe reduction in peritubular capillary flow denotes a higher incidence of TIF as that observed in nephrosis with FSGS. Thus, it is of notion that the reduction in renal perfusion precedes the development of tubulointerstitial fibrosis and thereby supports the concept of renal perfusion as a crucial determinant of nephronal structure.     

高脂血症肾损害35例综合治疗分析

目的探讨高脂血症肾损害的综合治疗效果。方法非药物治疗组：给予非药物干预，包括高脂血症相关的健康知识宣教、调整饮食及不良生活方式等；药物治疗组：辛伐他汀10mg，1次／d；综合治疗组：辛伐他汀10mg，1次／d，联合非药物干预。三组观察期均为24周。结果三组均可不同程度的改善血脂，总有效率分别为81％、100％、100％；综合组治疗24周后24h尿白蛋白、血清cystatin C均明显下降，疗效明显优于非药物治疗组和药物治疗组，组间比较差异有统计学意义（P〈0．05）。结论三种方法均可不同程度的降低血脂水平，延缓高脂血症肾损害的进展，综合治疗在改善肾功能方面优于单纯非药物治疗或药物治疗。