60例无症状性血尿和(或)蛋白尿患者的临床与病理分析研究

目的分析无症状性血尿和(或)蛋白尿的临床与病理资料,探讨二者之间的关系。方法回顾性分析福建医科大学附属龙岩市第一医院肾内科60例无症状性血尿和(或)蛋白尿患者的临床资料,根据24 h尿蛋白定量水平是否大于150 mg,分为单纯血尿组(14例,其中男6例,女8例)与蛋白尿组(单纯蛋白尿或蛋白尿合并血尿46例,男18例,女28例)。根据肾脏病理免疫荧光检查有无IgA在肾小球系膜区沉积,分为IgA组(36例,男11例,女25例)与非IgA组(24例,男13例,女11例),分别进行2组间统计分析。结果与单纯血尿组比较,蛋白尿组病理类型偏重。单纯血尿组血尿酸水平为(305.5±90.8)μmol/L,蛋白尿组血尿酸水平为(376.7±86.7)μmol/L,2组间差异具有统计学意义(P=0.03),但2组间血肌酐、血清胱抑素C(cystatin C,Cys C)、血清IgA、补体C3等无统计学差异(P0.05);非IgA组血肌酐水平为(59.2±14.8)μmol/L,IgA组血肌酐水平为(71.5±21.6)μmol/L,2组间差异具有统计学意义,但2组间Cys C、血尿酸、血清IgA、补体C3、24 h尿蛋白定量检查结果无统计学差异(P0.05),且除了24 h尿蛋白定量外,其他上述检验结果均在日常检测参考值范围内。结论无症状性血尿和(或)蛋白尿的临床表现及其血肌酐、Cys C、血尿酸、血清IgA、补体C3、24 h尿蛋白定量检查结果对肾脏病理损伤的指示不敏感,肾穿刺活检行病理检查是金标准,但目前缺乏统一的评分体系,建立一个量化的涵盖临床及病理资料的无症状性血尿和(或)蛋白尿肾脏疾病评分体系,对实验和临床有特殊意义。     

Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate previous treatment with lenvatinib, sorafenib was started. At 7 months of treatment with sorafenib, her lung metastases shrank and she could continue sorafenib without exacerbation of proteinuria or renal impairment. This case may suggest that sorafenib does not exacerbate the proteinuria or renal impairment induced by lenvatinib, and may be an effective treatment option for RAI-refractory DTC patients who are unable to tolerate lenvatinib.     

Predictive factors of response to steroids and cyclophosphamide therapy in idiopathic membranous nephropathy

Objectives To investigate demographic and clinical factors which could be predictive of clinical remission or relapse in patients with idiopathic membranous nephropathy treated with oral steroids and iv cyclophosphamide therapy. Methods This was a retrospective cohort study where a total of 83 patients with biopsy-proven IMN who had received oral prednisone and iv cyclophosphamide for at least 6 months were enrolled. Demographic and clinical factors of these patients were analyzed at baseline and three months after the initiation of therapy to evaluate their respective effects upon clinical remission and relapse. Results Median follow-up duration was 20 (12-30) months. At the end of follow-up, 80.7% (67/83) of the patients attained remission and 47.0% (39/83) attained complete remission (CR). The amount of proteinuria at baseline and the reduction rate of proteinuria three months after treatment predicted clinical remission and CR. 54 patients in the remission group were followed up to the endpoint and 14 of them relapsed with nephroticsyndrome. The presence of a PR versus CR significantly predicted relapse (HR: 40.198, 95%CI: 5.023-333.355, P=0.001). Infection was the most common adverse event. Two patients developed malignancies after onset of cyclophosphamide treatment. Conclusions A high rate of good response and a relatively low rate of adverse events were observed in this study. Baseline proteinuria and reduction rate of proteinuria 3 months after onset of cyclophosphamide regimen were independent predictive factors of response. Compared with CR, PR was predictive of a high probability of relapse.     

儿童原发性局灶节段性肾小球硬化的临床与病理特点

目的 探讨原发性局灶节段性肾小球硬化(FSGS)的病理诊断和病理特点,提高对本病的诊断水平.方法 对2005年6月至2013年6月病理确诊的72例原发性FSGS患儿的临床资料进行回顾性分析.依据2004年原发性FSGS组织病理学分型标准,分为非特异型、顶部型、细胞型、门部型、塌陷型5个亚型,比较不同病理分型的病理和临床特点.结果 72例原发性FSGS患儿中,非特殊型占56.9％,顶端型占22.2％,细胞型占16.7％,门部型占2.8％,塌陷型占1.4％.本病临床表现以肾病综合征为主,顶部型以单纯型肾病综合征为主(87.5％),非特殊型以肾炎型肾病综合征为主(78.0％).结论 FSGS临床及病理表现不均一,不同病理类型之间存在差异.顶部型FSGS诊断的确立依赖标本中肾小球的数目,细胞型FSGS诊断不依赖标本中肾小球的数目.电镜下足细胞空泡变性易见于非特殊型局灶节段性肾小球硬化患儿.全面评价各型FSGS临床病理特征,有助于提高诊断的准确性.     

贝伐珠单抗对小鼠肾脏损害作用及机制研究

目的了解贝伐珠单抗及不同剂量鼠源贝伐珠单抗对小鼠肾脏的损害作用并探讨其机制。方法将42只C57BL/6小鼠随机分为对照组（12只）及贝伐珠单抗组、低剂量鼠源贝伐珠单抗组、高剂量鼠源贝伐珠单抗组（各10只）。4周后处死小鼠,收集尿液、血清,检测尿微量白蛋白（MA）、血清半胱氨酸蛋白酶抑制剂C（Cys-C）、血尿素氮（BUN）及血肌酐（Cr）;取肾脏组织,HE染色后光镜观察肾脏组织结构,免疫荧光染色观察免疫复合物IgM、IgG、IgA沉积,免疫组化染色观察IgM、IgG、IgA、血管内皮生长因子（VEGF）及Nephrin表达,电镜观察肾脏组织超微结构。结果贝伐珠单抗组、低剂量鼠源贝伐珠单抗组及高剂量鼠源贝伐珠单抗组尿MA、血清Cys-c水平均明显高于对照组,差异均有统计学意义（均P＜0.05）。贝伐珠单抗组和高剂量鼠源贝伐珠单抗组血清BUN、Cr水平均高于对照组,差异均有统计学意义（均P＜0.05）。高剂量鼠源贝伐珠单抗组血清BUN及Cr水平与贝伐珠单抗组、低剂量鼠源贝伐珠单抗组比较,差异均有统计学意义（均P＜0.05）。贝伐珠单抗组免疫荧光IgG+~++;高剂量鼠源贝伐珠单抗组免疫荧光IgM++,免疫组化VEGF表达下调,电镜见肾小球足细胞足突融合。结论贝伐珠单抗引起肾脏损害的机制可能是下调VEGF的表达,引起免疫复合物沉积,导致肾小球内皮细胞足突融合,损害肾小球滤过膜,最终导致蛋白尿的形成及肾功能的损害。     

白塞病合并肾脏损害三例分析并文献复习

目的 分析白塞病合并肾脏病变的临床和肾脏活组织检查（简称：肾活检）组织学特点。方法 分析3例白塞病患者肾脏表现的临床、实验室检查及肾脏活检表现，对相关文献进行复习并与本研究结果对比。结果 3例患者出现肾脏病变时均伴有全身病变活动。2例表现为无症状蛋白尿，肾活检为肾小球病变；另1例表现为肾小管酸中毒和蛋白尿，肾脏活检为肾小管间质病变，3例均有不同程度的肾间质病变。所有3例的肾脏病变均较轻，经糖皮质激素和免疫抑制剂联合治疗后临床表现减轻。结论 白塞病肾脏受累在临床上不多见，肾脏损害以蛋白尿多见。病理上肾小球、肾小管及肾间质均可以受累，而肾血管则均未累及。本研究报道的3例患者均有肾间质病变，肾脏组织学损害较轻微。     

The treatment of tacrolimus in primary IgA nephropathy with mild or moderate renal injury: a randomized controlled study

Objective To investigate the efficacy and safety of immunosuppressive therapy (Tacrolimus or CTX) in primary IgA nephropathy (IgAN) with mild or moderate renal dysfunction. Methods Thirty-six primary IgAN patients diagnosed by renal biopsy, with mild or moderate renal dysfunction[30 ml•min-1•(1.73m2)-1≤eGFR＜90 ml•min-1•(1.73m2)-1, proteinuria＞1.0 g/24 h] were recruited in this randomized controlled trial. All the patients were assigned into steroid therapy alone, steroid combined with CTX (CTX group) and steroid combined with tacrolimus (tacrolimus group). Results The 24-hour proteinuria at baseline were (1.91±0.81) g/24 h, (2.42±1.46) g/24 h, (2.57±1.87) g/24 h in steroid group, CTX group and tacrolimus group respectively. Compared with baseline, it was significantly decreased in steroid group at 3 months [(0.90±0.75) g/24 h, P＜0.05], 6 months [(0.76±0.73) g/24 h, P＜0.05] and 12 months [(0.35±0.35) g/24 h, P＜0.05], in CTX group at 3 months [(1.40±1.24) g/24 h, P＜0.05], 6 months [(0.87±0.83) g/24 h, P＜0.05] and 12 months [(0.68±0.70) g/24 h, P＜0.05], and in FK506 group at 3 months [(1.10±1.33) g/24 h, P＜0.05], 6 months [(0.78±0.69) g/24 h, P＜0.05] and 12 months [(0.69±0.82) g/24 h, P＜0.05]. At 6 months, serum creatinine were decreased in steroid alone [(111.72±31.23) μmol/L vs (121.17±36.51) μmol/L, P＜0.05] and in CTX group [(111.33±22.76) μmol/L vs (124.33±35.51) μmol/L, P＜0.05], while no significant difference was detected in tacrolimus group. At 12 months, there was no significant difference in terms of serum creatinine in all three groups. Besides, there was no significant difference in terms of eGFR (CKD-EPI) in all three groups. One case presented hyperglycemia and one case had liver dysfunction during the treatment in steroid group. Two cases had hyperglycemia, one case had impaired glucose tolerance and one case had liver dysfunction in the tacrolimus group. Conclusions Steroid along, steroid combined with tacrolimus or combined with CTX are efficient in reducing urine protein in the treatment of primary IgAN with mild or moderate renal dysfunction without inducing increased serum creatinine. Given the occurrence of hyperglycemia during the treatment with steroid combined with tacrolimus, it is important to monitor tacrolimus concentration during the treatment.     

第474例——贫血,骨痛,蛋白尿

患者女,49岁,临床主要表现为骨痛和蛋白尿。因间歇性头晕、疲倦7年,症状加重并伴骨痛4个月余入院。患者在当地医院被诊断为贫血,并疑诊多发性骨髓瘤(MM)。实验室和影像学检查结果提示为获得性范科尼综合征(FS)伴有冒烟型多发性骨髓瘤(SMM),经肾活检、电子显微镜检查和反复入院检查证实为轻型近端肾小管病(LCPT)。LCPT常引起近端肾小管功能障碍,其特征是近端小管中结晶,多为kappa单克隆轻链的胞质内结晶状沉积。具有FS和LCPT特征的MM患者在临床上较少见,且难以准确诊断。希望通过此病例的分析,使临床医生关注LCPT等类型的有肾脏意义的单克隆球蛋白病(MGRS),以及与浆细胞病(如MM)的鉴别诊断。     

整合素连接激酶在大鼠阿霉素肾病模型中的表达

目的动态观察大鼠阿霉素肾病模型中整合素连接激酶(ILK)的表达变化,探讨其与肾小球疾病的关系。方法用尾静脉注射阿霉素建模,用光镜、电镜观察肾脏病理改变,免疫荧光观察ILK在不同时间点模型组肾组织的表达改变。结果 1与对照组比,前4周,模型组24 h尿蛋白量7 d增加,21 d达高峰(P<0.01);后8周,模型组24 h尿蛋白量逐渐减少,84 d降到最低值(P<0.01);2与对照组比,前4周,模型组肾小球ILK的表达7 d减少,14 d明显增加(P<0.05);后8周,模型组ILK表达逐渐减少(P<0.05);3电镜显示:前4周模型组大鼠足细胞足突广泛融合;后8周,模型组足细胞病变进一步加重,出现了其与基底膜的分离、脱落;4足细胞ILK表达的变化与模型组24 h尿蛋白定量的变化呈正相关(r=0.897,P<0.01)。结论 1 ILK早期出现表达增加及分布异常,可能是导致蛋白尿的原因及判断肾小球足细胞损伤的一个早期重要指标。2 ILK与蛋白尿呈正相关,其在肾组织中表达的高低对肾脏疾预后的判断具有一定意义。