咪唑立宾在肾脏疾病中的应用

咪唑立宾是一种免疫抑制剂,它作用于细胞合成过程中,选择性抑制淋巴细胞增殖,发挥免疫抑制作用.它在肾移植后的抗排斥反应,减缓狼疮性肾炎病理加重,减少IgA肾病的蛋白尿及肾小球硬化风险,减少激素依赖型肾病综合征蛋白尿及复发频次,降低过敏性紫癜性肾炎蛋白尿水平等方面均取得一定的疗效,且安全性较高,不良反应较少,但由于循证依据不多,仍需多中心大样本的观察.     

单中心341例紫癜性肾炎患儿不同病理分型一致性的病例系列报告

背景：临床常将国际儿童肾脏病研究协作组(ISKDC) 的分级标准用于紫癜性肾炎(HSPN),但其只能反映发病时肾脏活动性炎症情况,不能反映慢性病变的情况。 目的：探讨IgA肾病牛津分类（MEST-C）评分标准在儿童HSPN中的应用价值。 设计：病例系列报告。 方法：回顾性收集2015年1月至2017年12月于河南中医药大学第一附属医院住院、年龄≤14岁、符合HSPN诊断标准且行肾活检的患儿。采集患儿的一般情况、肾活检前尿和血标本实验室检查指标、临床表现、ISKDC分级、基于病理报告的免疫荧光分型。依据病理报告结果在病理科医生指导下参照MEST-C评分标准对肾脏病理重新评估,因本研究无管状萎缩/间质纤维化(T1/T2病变),故将肾小管间质病变分为急性（Ta）和慢性（Tc）评分,分为系膜细胞增生（M0/M1）、内皮细胞增生（E0/E1）、节段性硬化/粘连（S0/S1）、Ta0/Ta1、Tc0/Tc1、新月体形成（C0/C1/C2）组,对MEST-C与ISKDC病理分级和免疫荧光病理行kappa一致性检验。 主要结局指标：HSPN不同病理分型的一致性。 结果：①341例HSPN患儿进入本文分析,男191例,女150例,中位发病年龄9(8,11)岁,首发症状至出现尿检异常的间隔时间为10(3,21)d。②临床分型以血尿和蛋白尿型最常见,C1组血尿和蛋白尿型比例较高,M1、E1和Ta1组肾病综合征型比例较高,S1和Tc1组慢性肾炎型比例较高,P均<0.05;M1、Ta1、C2与较严重的镜下血尿有关,M1、E1、Ta1、C2与大量蛋白尿有关,P均<0.05;M1、Ta1、C1/C2与eGFR水平下降有关,P<0.05。③ISKDC分级中Ⅱ、Ⅲ级最常见,无Ⅰ、Ⅴ、Ⅵ级病例;MEST-C评分中以E1和C1病理改变较多见;MEST-C与ISKDC分级存在相关性,M1、E1、Ta1、C1/C2组ISKDC病理分级较重,S1、Tc1组ISKDC分级较轻。 结论：MEST-C评分与儿童HSPN临床表现、实验室指标的一致性符合临床预期;MEST-C病理指标均与ISKDC分级存在一致性,Ta和E指标分别与补体C3和Fib沉积严重程度存在一致性。     

上海单中心101例儿童狼疮性肾炎的长期随访分析

目的 分析儿童狼疮性肾炎(LN)的预后及其影响因素.方法 对101例LN的患儿进行回顾性分析.分为肾活检组与未肾活检组;病理分型包括A组(Ⅰ+Ⅱ型),B组(Ⅲ+Ⅳ型),C组(V型)3组;诱导期药物环磷酰胺(CTX)组与霉酚酸酯(MMF)组;临床结局缓解组(完全缓解和部分缓解)和无效组(治疗无效和死亡).用药不依从定义为诱导期CTX冲击间期大于45d或疗程不足,或MMF或其他免疫抑制剂自行停止服用1周以上.用SPSS 11.0软件中的Life-Tables分析累积生存率.结果 (1)LN患儿3年和5年的累积生存率为93.59％和87.80％;3年和5年的肾脏累积生存率为100％和91.12％.(2)单因素分析显示诱导期疾病缓解与是否肾活检、不同病理类型、不同药物诱导、治疗是否依从和发病时蛋白尿量5个因素有关;维持期疾病缓解与前4个因素有关.(3)多因素分析显示维持期与疾病缓解相关的主要因素为治疗是否依从(x2=9.818,P =0.002).用药依从性差主要发生在未行肾活检组(x2=9.569,P=0.002).(4)Ⅲ和Ⅳ型LN中,无用药不依从发生,MMF和CTX在此组中疗效无明显差异(P =0.405).结论 LN儿童疾病缓解的主要影响因素为免疫抑制剂的用药依从性.未行肾活检组患儿疾病缓解率低可能与病理类型不确定及用药依从性差有关.在Ⅲ和Ⅳ型LN中,MMF和CTX的诱导缓解疗效无差异.对尿液检查轻度异常的LN患儿应坚持行肾活检病理检查,可指导治疗、改善预后.     

miRNA表达在肾脏病中应用的研究进展

miRNAs是一组短小非编码RNA,在转录后调节基因表达水平从而影响机体重要的生理和病理生理过程。许多miRNA具有组织或器官特异性,可能成为潜在的生物标志物。同样,miRNAs在肾脏的生理功能和肾脏疾病方面发挥重要作用。文章综述miRNA对肾脏疾病影响的最新进展,为今后肾脏病的诊断和治疗提供参考。     

Invasive pneumococcal disease after implementation of a reduced three-dose pneumococcal conjugate vaccine program: a pediatric tertiary care center experience

Following the implementation of a government-sponsored reduced three-dose (2 + 1) heptavalent conjugate pneumococcal vaccine (PCV7) program, we report a 61.4% decrease in the number of cases of invasive pneumococcal diseases (IPD) treated at our institution. Four years after the implementation of the three-dose reduced vaccine program, only 7.4% of IPD were caused by PCV7 serotypes, and there was an increase in the proportion of IPD caused by nonPCV7 serotypes; serotype 19A represented 40.7% of the strains isolated during the last year of the study. These results, similar to those previously observed with a regular four-dose (3 + 1) PCV7 schedule, are reassuring as to the effectiveness of a reduced three-dose (2 + 1) PCV7 program. Increasing numbers of IPD caused by nonPCV7 serotypes warrant the use of a new conjugate pneumococcal vaccine that contains serotype 19A.     

Outcome of pediatric liver transplant recipients in Turkey: single center experience

To summarize the evolution of the pediatric liver transplant program in a developing country. Between April 1997, and September 2003, 32 cadaveric (CD) and 35 living donor (LD) liver transplantations were performed on 61 children (median age 3.8 yr, range 0.5-16) at Ege University Organ Transplantation and Research Center. The patient's charts were reviewed retrospectively. The outcome of patient and graft survival was analyzed and the incidence of graft loss, complications and rejections was calculated. Indications for liver transplantation were metabolic liver disease (n = 17), biliary atresia (n = 14), viral hepatitis (n = 4), autoimmune hepatitis (n = 6), cryptogenic cirrhosis (n = 11), fulminant liver failure (n = 5) and others (n = 5). Seven of 61 children with chronic liver disease had hepatocellular carcinoma concomitantly. Median pediatric end-stage liver disease score was 23 (range 1-54). Seven children (11.4%) were UNOS status I, 44 (72%) were UNOS status II and 10 (16.6%) were UNOS status III. The median follow-up of the study population was 3.6 yr (range 0.5-6). Actuarial patient survival rates at 1, 2, 3 and 4 yr were 86, 86, 71.3 and 65% in the CD group vs. 80, 76, 67 and 67% in the LR group, respectively (p = NS). Patients listed as UNOS status 1 had lower survival rates than patients listed as UNOS status 2 and 3 (p < 0.05). The mortality rate was 26.2%. Graft survival rates were 81, 81, 75 and 64% at 1, 2, 3 and 4-yr respectively. Six patients (9%) underwent retransplantation. The main complications were infections (64.7%) and surgical complications (43.2%) (including biliary complication, vascular problems, postoperative bleeding, small for size and large for size). The incidence of acute cellular rejection was 39.3%, whereas chronic rejection was 7.4%. The result of liver transplantation in Turkish children was slightly inferior to those reported for North American and European children. However, an important characteristic of these patients that distinguishes them from Europe and North America is that most were UNOS status IIa and UNOS status I (44%). Despite technical and medical progress, infectious and biliary problems have continued to be an important cause of mortality in these patients.     

Diagnosis and outcome of neutropenic enterocolitis: experience in a single tertiary pediatric surgical center in China

Background/purpose  

Neutropenic enterocolitis (NE) is clinically defined by the triad of neutropenia, abdominal pain and fever. This retrospective study is to review 24 cases of NE in a single Chinese tertiary center, to elucidate clinical feature, treatments and outcome for this dangerous gastrointestinal complication of neutropenia.     

Venous thromboembolism in pediatric patients: epidemiologic data from a pediatric tertiary care center in Alabama

Venous thrombosis is an infrequent but serious cause of hospitalization in children. The epidemiology and natural history remains incompletely defined, especially in geographically distinct regions of the United States. We thus evaluated thrombosis in a single children's hospital over a 3-year period. Of 41,906 hospitalizations, 92 children were identified for review. The incidence of thrombosis was 21.9 per 10,000 admissions (0.22%). Venous thrombosis was of equal incidence in African-American and white patients. Locations of thrombosis included deep venous (51%), pulmonary (21%), renal vein (8%), intrahepatic (8%), and intracranial (12%). Risk factors for thrombosis included central catheter (32%), malignancy (18%), systemic infection (21%), neurologic disability (9%), cardiac (4%), nephrotic syndrome (3%), and autoimmune (6%). Six of 92 patients (7%) had thrombophilia. Positive family history of venous thromboembolism (VTE) or thrombophilic disorder predicted an abnormal test. Treatment included low-molecular-weight heparin (n=53), coumadin (n=12), heparin (n=10), tissue plasminogen activator (n=6), argatroban (n=1), thrombectomy (n=2), inferior vena cava filter (n=2), and no treatment (n=23). Seventy-seven percent demonstrated resolution of the VTE, 14% had persistent or recurrent VTE, and 9% died. Causes of death were malignancy, prematurity, septicemia, and congenital heart disease. Venous thrombosis is a serious comorbidity in hospitalized children. In our population, African-Americans had an equal incidence of VTE as whites. Positive family history predicted thrombophilia.     

Outcomes of single kidney transplantation from pediatric donors: A single‐center experience

Kidneys from pDDs are increasingly used to narrow the huge gap between incremental demand and static supply. However, there is still controversy on the clinical outcome of SKT from pDDs. We conducted a retrospective cohort study of 452 adult recipients in our center between March 2012 and February 2017. Outcomes of 3 groups, transplants with organs from pDDs (n=50), aDDs (n=207), and LDs (n=195), were compared. The mean age and weight of pDDs were 8.98 years (range 8 months‐17 years) and 30.05 kg (range 8.2‐55 kg), respectively. There was no difference in 1‐year (96.0%, 98.1%, and 99.0%, respectively, P=.277) and 3‐year patient survival (96.0%, 98.1%, and 99.0%, respectively, P=.277) or in 1‐year (96.0%, 96.6%, and 98.5%, P=.307) and 3‐year (96.0%, 96.6% and 97.9%, P=.437) graft survival. SCr, eGFR, and allograft size were similar among the 3 groups at 6th month post‐transplant and thereafter. Incidence of DGF was higher in patients of the aDD group than those in the pDD group (22.7% vs 10.0%, P<.001), but there was no difference in AR and infection. SKT from pDDs to adult recipients is effective and safe with acceptable outcomes, and it will be a promising expansion to the donor pool.     

Acute hemorrhagic edema of infancy: the experience of a large tertiary pediatric center in Israel

Background:Acute hemorrhagic edema of infancy (AHEI) is a rare leukocytoclastic vasculitis of the small vessels occurring at a young age and considered as a benign self-limited disease.Due to its low prevalence,there are limited data on the presentation and complications of this disease.Methods:All computerized files of children who were hospitalized at a tertiary pediatric center due to AHEI over a 10 year period were reviewed.Clinical,laboratory and histopathological data were collected.Results:Twenty-six patients were included in our study,accounting for 0.7 cases per 1000 admissions of children aged 2 years or less.Mean age was 12.9 months.More than two thirds of the children had preceding symptoms compatible with a viral infection.Upon admission,all patients presented with typical findings of a rash and edema.Edema was most profound over the lower extremities (73％).Concomitant viral or bacterial infections were found in six children.Skin biopsy was performed in six patients revealing leukocytoclastic vasculitis.Thirteen children (50％) had systemic involvement including joint involvement (n=9),gastrointestinal hemorrhage (n=4),microscopic hematuria (n=1) and compartment syndrome of the limb (n=1).The latter was diagnosed in a patient with familial Mediterranean fever.Conclusions:Our largest data series highlighted what is known regarding clinical and histological findings in children with AHEI.However,contrary to what was previously reported,we found a higher rate of systemic involvement.Although AHEI is a rare entity,pediatricians should be familiar with its presentation,management and our reported complications.     

Complications of chronic kidney disease in children post-renal transplantation – A single center experience

Abstract:  Similar to adults, CKD may persist after pediatric RTx. Clinical and laboratory parameters were analyzed retrospectively in 23 RTx recipients (13 males, age 11.9 ± 5.2 yr), initially treated with prednisone, calcineurin inhibitor (TAC = 18, cyclosporine neoral = 5), and MMF at four months post-RTx (T1) and at 3.4 ± 2.8 yr post-RTx (T2). Mean (±s.d.) cystatin C GFR (mL/min/1.73 m²) was 72 ± 19 at T1 and 70 ± 22 at T2 (NS). At T2, CKD stage I was present in five patients (22%), stage II in eight patients (35%), and stage III in 10 patients (43%). At T2, calcineurin inhibitors were utilized in 19, MMF in 13, and SIR in 13 patients. The prevalence of hypertension was 69% at T1 and 87% at T2 (p = NS). Anemia was diagnosed in 61% at T1 and 69% at T2 with average therapeutic MMF (2.78 ± 1.3 mg/mL) and SIR (7.62 ± 2.3 mg/mL) trough levels. Hypercholesterolemia was detected in 44.0% at T1 and 47% at T2. Bone disease was diagnosed in 26.0% at T1 and 21.7% at T2. Mean height Z-scores were −1.0 ± 1.2 (T1) and −1.0 ± 1.59 (T2, NS), with 21% at T1 and 30% at T2 below two SDS. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease, and anemia in a significant proportion of transplanted children.     

Donor-specific antibodies by flow single antigen beads in pediatric living donor kidney transplants: single center experience

Flow PRA and SAB are now routinely performed to identify HLA antibodies in the recipient sera. The presence of DSA is considered a risk factor for graft failure. However, this risk is not clearly defined. We reviewed all the pediatric recipients of living donor kidney transplants since Flow PRA and Flow SAB became routinely done at our institution. All children had negative CDC and Flow XMs. Comparison of clinical outcome was done between those with and without pretransplant DSA. Six children had positive DSA by Flow SAB. They received thymoglobulin, steroids, tacrolimus, and MMF. Five had anti-HLA class I antibodies and one anti-HLA class II. Only one child had an AR. Graft survival: 100% at last visit with GFR >70 mL/min/1.73 m(2). A control group without DSA was used for comparison (n = 44). They received our standard protocol: basiliximab, tacrolimus, MMF, and steroids. AR rate was 9%. Both groups had similar follow-up time, and patient and graft survival rates. In our small series, we saw excellent outcome despite the presence of DSA pretransplant. No unequivocal ideal to establish the ideal immunosuppressive regimen for this cohort of patients has been established and the long-term outcome of these recipients has not been delineated.     

Mycophenolate mofetil in pediatric renal transplantation: a single center experience

We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p < 0.0001). In conclusion, the use of MMF in pediatric renal transplantation was not associated with a lower rejection rate or immunological graft loss. It did, however, result in a significantly higher rate of viral infections.     

小儿先天性心脏病术后体外膜肺氧合治疗:单中心经验

目的回顾总结先天性心脏病(congenital heart disease,CHD)术后体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)辅助患儿的临床预后及死亡原因,拟进一步提高ECMO治疗存活率。方法回顾性分析上海儿童医学中心心胸外科2017年1月至2019年12月收治的CHD术后进行VA-ECMO辅助的105例患儿的临床资料,对死亡原因进行分析。结果105例ECMO患儿,平均年龄110(38,341)d,体重5.30(3.75,8.45)kg,先天性心脏病手术风险调整评分3(2~3)分。存活组(n=51)与死亡组(n=54)患儿的性别、年龄、体重、身长、先天性心脏病手术风险调整评分、手术室安装ECMO例数、经心肺复苏后安装ECMO例数及ECMO持续时间比较差异均无统计学意义(P均>0.05);连续性肾脏替代治疗使用率差异有统计学意义[7.8%(4/51)比38.9%(21/54),P<0.001]。ECMO撤离后死亡主要发生在撤离后1周(83.3%,45/54)。ECMO安置以1月龄~1岁患儿最多(52.4%,55/105),2017至2019年存活率从31.6%(6/19)上升至65.0%(13/20)。ECMO安置时3~5 kg患儿最多(39.0%,41/105),2017至2019年存活率从28.6%(4/14)上升至75.0%(9/12)。死亡原因以心力衰竭为主(48.1%,26/54),其次为出血(18.5%,10/54)和肺动脉高压(13.0%,7/54)。结论随着外科手术、体外循环技术的进步以及术后监护能力的提高,近3年我院CHD患儿ECMO后病死率逐年下降,但ECMO期间需要连续性肾脏替代治疗辅助的患儿病死率较高。因此,临床工作中仍需加强ECMO期间各脏器功能的维护。