Tocilizumab en el tratamiento del rechazo humoral crónico activo resistente a terapia estándar

IntroductionThere is no consensus on the most appropriate treatment for chronic active antibody-mediated rejection (cAMR). Recent studies suggest that treatment with tocilizumab (TCZ) may stabilize graft function, decrease the intensity of donor-specific HLA antibodies (DSAs) and reduce inflammation of microcirculation.Patients and methodsObservational study with renal allograft recipients diagnosed with cAMR (n = 5) who had not submitted a response to traditional treatment based on the combination of plasma replacements, immunoglobulins, and rituximab. Patients were told to be treated with TCZ as compassionate use in six doses per month (8 mg/kg/month). Renal function, proteinuria, and the intensity of DSAs were monitored during follow-up.ResultsFive patients, average age 60 ± 13 years, three male and two retrasplants (cPRA average 55%) with preformed DSAs. Treatment with TCZ was initiated within 47 ± 52 days of biopsy. In two cases treatment was discontinued after the first dose, by severe bicitopenia with cytomegalovirus viremia and by graft failure, respectively. In the three patients who completed treatment, no stability of renal function (serum creatinine from 1.73 ± 0.70 to 2.04 ± 0.52 mg/dL, e-FGR 4 6 ± 15 to 36 ± 16 mL/min), showed increased proteinuria (3.2 ± 4.0 to 6.9 ± 11.0 g/g) and the intensity of DSAs maintain stable. No changes were observed in the degree of inflammation of microcirculation (g + pt 4.2 ± 0.8 vs. 4.3 ± 1.0) or in the degree of transplant glomerulopathy (cg 1.2 ± 0.4 vs. 1.8 ± 1.0).ConclusionsTCZ therapy does not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection, does not improve the degree of inflammation of microcirculation and does not reduces the intensity of DSAs.     

Clinical analysis of peritoneal dialysis in the treatment of rapidly progressive glomerulonephritis

Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time＞183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P＜0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P＜0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253，95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.     

Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

Background

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.

柴苓小方对大鼠肾小球系膜细胞异常增殖的影响

目的：探讨柴苓小方对大鼠肾小球系膜细胞（GMCs）异常增殖的影响及相关机制。方法：采用脂多糖刺激系膜细胞异常增殖。MTT法检测柴苓小方对㈣异常增殖的影响；免疫细胞化学方法检测药物作用后增殖细胞核抗原（PCNA）的表达；乳酸脱氢酶释放实验检测柴苓小方的细胞毒作用。采用RT—PCR检测药物作用不同时间点细胞周期蛋白依赖性激酶抑制剂p21的表达。结果：柴苓小方可以剂量依赖性的抑制系膜细胞异常增殖并显著减少PCNA阳性细胞数而没有明显的细胞毒作用。并且柴苓小方可以显著地上调p21基因的表达（P〈0．05）。结论：柴苓小方可剂量依赖性的抑制GMC8异常增殖．其机制可能与上调p21mRNA表达有关。     

拟诊高血压肾硬化患者的临床病理分析

目的 探讨拟诊高血压肾硬化(HN)患者的临床特征及影响预后的因素，以期提高临床对该病诊断及治疗的认识。方法 回顾性分析我科63例最初拟诊HN且有肾活检诊断的患者的临床资料。根据肾脏病理学结果分为原发性肾炎(PN)组、良性肾小动脉硬化症(BN)组及恶性肾小动脉硬化症(MN)组，比较各组间临床参数及组织学特征。对确诊HN的患者分析影响其预后的临床及病理因素。结果 63例临床拟诊为HN的患者经肾组织活检病理诊断，37例(58.7%)为BN；12例(19.0%)为MN；14例(22.2%)为PN，HN诊断符合率为77.7%。BN组患者男性较多，年龄较大，高血压家族史比例及高血压病程明显高于PN组，而PN组尿蛋白定量高于BN及MN组。MN组左心室心肌重量指数(LVMI)高于PN组。BN组视网膜病变主要为0~Ⅱ级，占78%，而MN组则主要为Ⅲ~Ⅳ级。PN组球性硬化肾小球比率及小管慢性化指数(CI)积分均高于MN及BN组。MN及BN组肌内膜细胞增殖、小动脉玻璃样变等血管病变均较PN组明显，其中BN组改变最为显著。多因素回归分析提示收缩压(SBP)、尿蛋白定量、尿酸(UA)、总胆固醇(TC)是影响肾脏病进展的危险因素，优势比分别为2.563、2.467、2.323、2.357。结论 临床拟诊HN的患者不能排除PN。部分HN与PN患者临床表现相似，单纯依据病史及实验室检查难以区分。肾组织病理检查是确诊的最佳手段。 SBP、尿蛋白、TC、UA等因素可加速HN的病变进展。     

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients

The influence of metabolic control (HbA_1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA_1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA_1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA_1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.     

脂蛋白（a）对肾小球系膜细胞的作用

目的探讨脂蛋白（ａ）［Ｌｐ（ａ）］对肾小球系膜细胞（ＧＭＣ）的作用。方法将体外培养的系膜细胞，加脂蛋白（ａ）刺激后，测定细胞生长率和细胞上清中血小板活化因子（ＰＡＦ）、肿瘤坏死因子（ＴＮＦ）、乳酸脱氢酶（ＬＤＨ）及纤维连结蛋白（ＦＮ）水平，并以未经刺激者作对照。结果经脂蛋白（ａ）刺激４８小时，在终浓度５～２０ｍｇ／Ｌ时细胞生长率轻度增加，而在５０～４００ｍｇ／Ｌ时细胞生长率明显下降。刺激１８小时，细胞上清中ＰＡＦ的水平明显高于对照，且与脂蛋白（ａ）浓度呈明显正相关（ｒ＝０．９３７，Ｐ＜０．０１）；Ｌ９２９细胞的杀伤率有所增加，但未达５０％；ＬＤＨ的水平在脂蛋白（ａ）１００ｍｇ／Ｌ以下时有所增加；刺激１８、４８、７２小时后的细胞上清纤维连结蛋白均为阴性。结论脂蛋白（ａ）对系膜细胞体外增殖有低浓度轻度促进、高浓度抑制的双向作用，对细胞ＰＡＦ的产生具有浓度依赖的促进作用，并能增加细胞上清中ＬＤＨ及ＴＮＦ水平，因而可通过多种途径介导肾小球损伤。     

雷帕霉素对炎性反应状态下肾小球系膜细胞内脂质稳态的影响

Objective To investigate the effect of rapamycin on cholesterol homeostasis of glomerular mesangial cells and the underlying mechanism. Methods Glomerular mesangial cell line (HMCL) cells were cultured and divided into control group, IL-1β group and different concentration rapamycin groups. Intracellular cholesterol accumulation was observed and measured by oil O staining and HPLC. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression of LDLR, PPARγ, LXRα, ABCA1 in HMCL after the treatment with IL-1β and rapamycin. Results Rapamycin had no significant influence on intracellular cholesterol concentration under normal condition. IL-1β significantly increased the intracellular cholesterol concentration by 143％ of control (P<0.05), and 10, 50, 100 ?滋g/L rapamycin could significantly inhibit the effect of IL-1β (87％, 116％, 96％ of control respectively, all P<0.05). Rapamycin could suppress the increased expression of LDLR caused by IL-1β on both mRNA and protein level in a dose-dependent manner（P<0.01）. Rapamycin dose-dependently up-regulated the reduced mRNA and protein expression of ABCA1, the decreased mRNA expression of PPARγ and LXRα induced by IL-1β as well (P<0.01）. Conclusion Rapamycin may contribute to the maintenance of intracellular cholesterol homeostasis in glomerular mesangial cells under inflammatory state by both reducing cholesterol uptake and promoting cholesterol efflux.     

血清胱抑素C对高血压和糖尿病早期肾功能损伤的诊断价值

目的探讨血清胱抑素C(Cys-C)水平对高血压、糖尿病早期肾功能损害的临床价值。方法收集22例高血压患者、28例糖尿病患者及44例肾病患者的血清标本,用酶法测定血清肌酐、尿素氮,用颗粒增强免疫比浊法测定血清Cys-C,放射免疫法测定β2-微球蛋白。结果血清Cys-C和β2-微球蛋白的异常检出率显著高于血清肌酐、尿素氮;高血压及糖尿病两组患者血清Cys-C水平均较正常对照组明显升高(P<0.01);肾病组各项检测指标均显著高于高血压组、糖尿病组和正常对照组。结论对早期肾功能损害的诊断价值,血清Cys-C测定敏感性稍次于β2-微球蛋白,但其特异性优于血清β2-微球蛋白,综合比较,血清Cys-C可作为高血压及糖尿病早期肾功能损害的辅助诊断指标之一。