慢性髓性白血病骨髓移植后的细胞遗传学改变及移植物抗白血病作用

对４４例由同胞供髓行骨髓移植的Ｐｈ染色体阳性慢性髓性白血病（ＣＭＬ）患者进行了系列的染色体研究。１２例移植后短期内，有２～９次检出３％～６８％的Ｐｈ阳性受者核型，但是并不伴有临床和血液学复发的迹象，患者在＋６月～＋１年后逐步由供者细胞完全代替造血，作者观察到其中７例的Ｐｈ阳性／Ｐｈ阴性的动态变化与临床发生的轻度移植物抗宿主病（ＧＶＨＤ）密切相关，患者的Ｐｈ染色体往往随着ＧＶＨＤ的发生而减少或消失，研究表明单纯放、化疗几乎不能完全清除白血病克隆，而且移植后短期内细胞遗传学的复发不一定说明血液学复发，持久植活病例的恶性细胞的消失过程提示，异基因骨髓移植物不仅具有代替受者造血的作用，而且其免疫活性细胞通过ＧＶＨＤ发挥着重要的抗白血病作用（ＧＶＬ）。     

儿童肾移植术后激素减撤对生长和预后影响的随机对照试验Meta分析

目的对比激素减撤/避免与基于类固醇的免疫抑制方案在儿童肾移植受者中的安全性和有效性。方法全面检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据、维普等数据库,纳入研究儿童肾移植受者行激素减撤/避免与使用激素方案对比的文献,并用RevMan 5.4进行分析。结果最终纳入6项随机对照实验,共634例患者,其中激素减撤组320例,激素使用组314例。结果显示,激素的减撤/避免与身高的改善有关〔MD=0.39,95%CI(0.14,0.65),P<0.01〕,青春期前的患者获益更大。身高的增长在短期内并未伴随排斥反应的增加或人肾存活率的降低,长期预后同样乐观。结论在儿童肾移植受者中施行激素减撤/避免方案,对儿童的身高增长有显著改善,其中青春期前的患者受益更大。最为重要的是,从短期来看,生长发育的获益并非以急性排斥反应的增加为代价,从长期随访来看,人/肾存活率与使用激素的受者相当。     

Advantages of cyclosporin A using 2-h levels in pediatric kidney transplantation

Clinical trials in adult liver and heart recipients have shown that management of cyclosporine (CsA) dose with 2-h levels (C2) leads to lower rejection rates and serum creatinine levels compared with C0 monitoring. Therefore, we investigated whether C2 monitoring might also improve late graft survival after kidney transplantation in children. To date, no results in adult renal transplantation and in pediatric transplantation have been published. Forty-nine stable pediatric kidney recipients with a minimum time of 1 year after transplantation (mean=7±5 years) entered the study. None of the patients had experienced an acute rejection up to 6 months before entering the study. CsA dosing was based on C0 monitoring for the first 6 months and then based on C2 monitoring for the following 6 months. C0 and C2 levels were measured at 4-weekly intervals. Percentage decline in glomerular filtration rate (GFR) and mean coefficients of variation of CsA levels (C_var) were calculated and compared during the 6-months periods. At the beginning of the study, the mean calculated GFR was 53±15 ml/min per 1.73 m². During the 6 months of C0 monitoring, the mean GFR decreased to 49±12 m/min per 1.73 m² (P=0.001, paired t-test). Six months after switching to C2 monitoring, the mean GFR remained stable, at 49±15 ml/min per 1.73 m² (P=0.3 paired t-test). The largest increase in GFR (3.9±7.9%) was found in patients with a decrease of their CsA dose of more than 5% under C2 monitoring. C_var was significantly lower under C2 than under C0 monitoring (0.24±0.10 vs. 0.30±0.15, P=0.02, unpaired t-test). We conclude that the switch to C2 monitoring helped to identify patients with CsA overdosing as well as to reduce variation in CsA level, which resulted in a halt in GFR decline.     

The novel bone alkaline phosphatase B1x isoform in children with kidney disease

The bone alkaline phosphatase (BALP) B1x isoform has previously only been identified in some adults with chronic kidney disease on dialysis and in human bone tissue. Twenty-nine patients, 3–20 years of age, with reduced renal function due to a variety of kidney diseases were examined. We measured parathyroid hormone (PTH), biointact (whole 1-84) PTH, osteoprotegerin (OPG), CrossLaps (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) type I procollagen intact amino-terminal propeptide (PINP), osteocalcin, total alkaline phosphatase (ALP), and BALP isoforms B/I, B1x, B1, and B2. Fifty percent higher levels were detected of PTH vs. biointact PTH, demonstrating non-(1-84) PTH fragments detected by the PTH assay. Increased activities were found in five, four, and three patients for total ALP, B1, and B2, respectively. Sixteen (55%) patients had increased B/I levels. B1x was identified in two (7%) patients, who had OPG levels in the higher range independently of age, glomerular filtration rate (GFR), and biointact PTH. B1x was identified prior to and after 9 days of growth hormone (GH) therapy in one patient but not after 1, 3, 6, and 12 months, however. In conclusion, our study demonstrates that the novel BALP B1x isoform is occasionally found to be present in children with kidney disease but to a lesser degree in comparison with adults with chronic kidney disease on dialysis. It is essential to perform bone histomorphometry for future investigations in order to elucidate the exact nature of circulating B1x in patients with kidney disease for accurate classification of type of renal bone disease.     

Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement

Growth failure is a clinically important issue in children with chronic kidney disease (CKD) and is associated with significant morbidity and mortality. Many factors contribute to impaired growth in these children, including abnormalities in the growth hormone (GH)–insulin-like growth factor-I (IGF-I) axis, malnutrition, acidosis, and renal bone disease. The management of growth failure in children with CKD is complicated by the presence of other disease-related complications requiring medical intervention. Despite evidence of GH efficacy and safety in this population, some practitioners and families have been reluctant to institute GH therapy, citing an unwillingness to comply with daily injections, reimbursement difficulties, or impending renal transplantation. Suboptimal attention to growth failure management may be further compounded by a lack of clinical guidelines for the appropriate assessment and treatment of growth failure in these children. This review of growth failure in children with CKD concludes with an algorithm developed by members of the consensus committee, outlining their recommendations for appropriate steps to improve growth and overall health outcomes in children with CKD.Members of the Consensus Committee that participated in this survey: Paul Fielder, PhD; Debbie S. Gipson, MD; Larry Greenbaum, MD, PhD; Marisa D. Juarez-Congelosi, BS, RD, LD; Frederick J. Kaskel, MD, PhD; Craig B. Langman, MD; Lynn D. Long, RN, MS; Dina Macdonald, RN, BSN, CNN; Deborah H. Miller, RN, MSN, CNN; Mark M. Mitsnefes, MD, MS; Valerie M. Panzarino, MD; Ron G. Rosenfeld, MD; Mouin G. Seikaly, MD; Brian Stabler, PhD; Sandra L. Watkins, MD.     

Effects of growth hormone administration in pediatric renal allograft recipients

The efficacy of recombinant human growth hormone (rGH) was assessed in five pediatric allograft recipients with severe growth retardation despite successful renal transplants. rGH 0.05 mg/kg per dose was given six times weekly by subcutaneous injection to five prepubertal children (mean age 15.2±2.0 years) all of whom had bone ages less than or equal to 12 years (10.0±1.4 years), a height standard deviation score of less than –2.5 (–4.9±1.5), no evidence of catch-up growth, a calculated glomerular filtration rate (GFR) of more than 40ml/min per 1.73 m² (51±6.8 ml/min per 1.73 m²), and stable renal function on alternate-day prednisone (16.7±2.6 mg/m² per dose). Growth hormone profiles were abnormal in all children before treatment. rGH administration led to a significant increase in both growth rate (3.5±1.6 cm/year pre therapy, 8.5±1.4 cm/year post therapy,P<0.001) and percentage of expected growth velocity for bone age (67±31% pre therapy, 163±27% post therapy,P<0.001) with evidence of true catch-up growth. During the study period, three children had the appearance of secondary sexual characteristics, and one had premature advancement of his bone age. GFR decreased in three children, and in one rGH was discontinued due to a steady rise in serum creatinine. No significant changes were seen in serum calcium, phosphorus, cholesterol, triglycerides, glucose, or thyroid function, although a significant increase in alkaline phosphatase was found. In summary, growth-retarded pediatric renal allograft recipients may have abnormal endogenous GH production and respond favorably to rGH. The potential risk of deterioration in renal function due to rGH-induced hyperfiltration must be investigated.     

Neoral induction in pediatric renal transplantation

Neoral was instituted in pediatric renal transplant patients with the hypothesis it would have more predictable kinetics than Sandimmun. However, significant questions have arisen concerning potential toxicity and dosing interval related to its rapid absorption with subsequent high initial peak. This is compounded by the fact that children appear to metabolize cyclosporine at a greater rate than adults. This combination of a rapid peak and rapid absorption may then result in lower trough levels at 12 h. We compared the trough cyclosporine levels of nine children who received Neoral with nine who received Sandimmun at the time of initial transplantation. More frequent dosing (every 8 h) was required in the Neoral population compared with the Sandimmun population for the 1st month in order to obtain comparable trough levels. Beyond the initial 4–6 weeks, trough levels were similar for Neoral and Sandimmun. Whereas 1-month creatinine levels and blood pressures were similar, the number of blood pressure medications was significantly higher in the Neoral group. At 5.5 ± 1.1 months’ followup, a single patient in the current Neoral group and in the retrospective Sandimmun group each experienced a single OKT3 allograft-treated rejection. We suggest that the area under the curve is different in Neoral than Sandimmun, and the initial dosing frequency may need to be adjusted accordingly. Received August 21, 1996; received in revised form June 27, 1997; accepted June 30, 1997     

Successful kidney transplantation in a patient with pre-existing chronic myeloid leukemia treated with imatinib

Active malignancy is an absolute contraindication to kidney transplantation. As for chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal into a manageable chronic disease with a close-to-normal life expectancy. To date it is unknown whether kidney transplantation can be safely performed in patients with pre-existing CML. We describe the clinical course of a 57-year-old male patient with chronic kidney disease caused by reflux nephropathy. This patient had undergone first kidney transplantation 20 years earlier and had again been on chronic hemodialysis for 6 years when CML was diagnosed. First-line therapy with 400 mg imatinib daily was well tolerated and induced an optimal cytogenetic and molecular response 3 months after initiation. One and a half years after CML diagnosis, a second kidney transplantation from a deceased donor was performed. Immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids. Currently, 2 years posttransplant, renal allograft function is stable (serum creatinine 1.09 mg/dL, estimated glomerular filtration rate 75 mL/min per 1.73 m²), and CML remains in deep molecular remission with imatinib. Imatinib-treated CML in deep molecular remission could be regarded as inactive malignancy and may therefore not be viewed as an absolute contraindication to kidney transplantation.     

儿童心脏死亡器官捐献供者双肾整块移植早期临床疗效观察

目的：观察儿童心脏死亡器官捐献（ DCD ）供者双肾整块移植的早期临床疗效。方法回顾性分析中山大学附属第一医院器官移植中心2010年2月至2013年9月儿童DCD供者双肾整块移植供、受者临床资料。6例儿童DCD供者中位年龄3岁（10个月～6岁）,均捐献给相同血型受者。6例受者中位年龄39．5岁（17～48岁）,成年人5例,17岁男性1例,原发病均为慢性肾小球肾炎;均为首次肾移植,群体反应性抗体均阴性, HLA错配数1～4个。均采用右侧髂窝整块移植法。结果6例受者手术均获成功。移植肾热缺血时间中位数为17．5 min （0～23 min）,冷缺血时间中位数为6．6 h （4．8～7．4 h）。术后肾功能恢复均较顺利,未发生急性排斥反应、移植肾原发性无功能和移植肾功能延迟。其中4例为移植肾功能立即恢复（即术后第5天血清肌酐≤265μmol/L ）,2例为移植肾功能缓慢恢复（即术后第5天血清肌酐＞265μmol/L）。1例受者术后7 d右侧移植肾动脉血栓形成;1例受者术后15 d诊断为肺结核行正规抗结核治疗;1例受者术后1年出现移植肾动脉吻合口狭窄,介入治疗后恢复。术后随访1～36个月,受者和移植肾全部存活,所有受者肾功能均正常。结论儿童DCD供者双肾整块移植早期临床疗效良好,是一种扩大供者来源的良好途径。     

婴儿双供肾成人肾移植的改良简化术式四例

目的总结婴儿双供肾成人肾移植的改良简化术式的手术方式及临床效果。方法总结山西省第二人民医院肾移植透析中心2017年1月至2019年9月采用改良简化术式进行的4例婴儿双供肾成人肾移植资料。4例均为心死亡供者,男性3例,女性1例,年龄(54±22.69)d,体重为(5.6±0.79)kg。受者中男性1例,女性3例,年龄(41.5±5.97)岁,体重(45±3.56)kg。俢肾过程中将双侧供肾缝合固定,使双肾位置相对固定,行供肾腹主动脉瓣-受者髂外动脉、供肾下腔静脉瓣-受者髂外静脉端侧吻合,以降低手术难度、避免血流动力学紊乱。结果4例手术过程均顺利,供肾修整平均历时20 min,移植手术平均历时68.75 min。未出现血管及泌尿系统并发症,随访12个月移植肾功能恢复良好,受者及移植肾远期存活满意。结论改良简化婴儿双供肾成人整块肾移植优化了手术方式,操作简便且降低血管并发症,提高手术成功率,值得在临床实践中推广应用。     

Gastrointestinal surgical emergencies following kidney transplantation

This study reports major gastrointestinal complications in a group of 416 patients following kidney transplantation. Three hundred and ninety-nine patients received a cadaveric kidney while the other 17 received a living related organ. The immunosuppressive regimen changed somewhat during the course of the study but included azathioprine, prednisolone, antilymphocyte globulin, and cyclosporin. Perforations occurred in the colon (n=6), small bowel (n=4), duodenum (n=2), stomach (n=1), and esophagus (n=1). There were five cases of acute pancreatitis, four of upper gastrointestinal and two of lower intestinal hemorrhage, two of acute appendicitis, one of acute cholecystitis, one postoperative mesenteric infarction, and two small bowel obstructions. Fifty percent of the complications occurred while patients were being given high-dose immunosuppression to manage either the early postoperative period or episodes of acute rejection. Ten percent of the complications had an iatrogenic cause. Of the 31 patients affected, 10 (30%) died as a direct result of their gastrointestinal complication. This high mortality appears to be related to the effects of the immunosuppression and the associated response to sepsis. Reduction of these complications can be achieved by improved surgical management, preventive measures, prompt diagnosis, and a reduced immunosuppressive protocol.     

Results of kidney transplantation in 25 pediatric patients

Outcome, long-term prognosis, growth activity and rehabilitation after kidney transplantation were studied in 25 pediatric patients transplanted with a kidney graft from one-haplotype identical parent. Excellent patient and graft survival with low incidences of acute rejection or serious complications could be achieved in this population, as compared with the results of adult recipients. Growth retardations in height and weight were observed in these patients before transplantation, and were significantly correlated with the duration of low or no kidney function. In 12 recipients who were transplanted at ages of younger than 15 years and followed up over two years, a dramatic increase in weight appeared within one year after transplantation and a greater increase in height was exhibited in the second and third year than in the first. Increase in height was significantly greater in those children transplanted at ages of younger than 10 years than in those transplanted at ages of older than 11 years. Catch-up growth was observed in one-third of these children. Retrospectively, there was no difference in the doses of prednisolone given between the two groups of patients with, and without catch-up growth, but the incidence of acute rejection was higher in the group without catch-up growth. Currently, 18 recipients have functioning grafts and 16 (88.9 per cent) of them are in full-time school or working. From these results it is concluded that kidney transplantation is the first feasible manoeuvre for those children with chronic renal failure and it should be performed as soon an possible in order to preserve their growth activity. This paper was presented at the 86th Annual Meeting of Japan Surgical Society.     

肾移植术后巨细胞病毒感染的诊治体会

目的探讨肾移植术后巨细胞病毒(CMV)感染的诊疗策略。方法对2000年1月至2004年3月我院218例肾移植术后患者资料进行回顾性分析,根据实验室检查结果以及临床症状,共有57例(26%)诊断为CMV感染,24例(11%)进展为CMV肺炎,给予调整免疫抑制剂、抗感染、支持、对症处理。结果17例治愈,死亡7例。结论CMV感染应积极预防,并坚持早发现、早治疗。     

婴幼儿供肾成人双肾移植42例

目的回顾性分析单中心婴幼儿供肾成人双肾移植临床疗效,探讨供、受者选择及不同手术方式的效果差异。方法回顾性总结2012年12月至2019年5月中南大学湘雅二医院实施的婴幼儿供肾成人双肾移植42例,根据供肾是否满足三5标准(供者年龄>5个月、供者体重>5 kg、供肾长径>5 cm)分为两组,两组受者再根据采用不同的手术方式分为术式A亚组(经典En-bloc术式)、术式B亚组(分离式双肾移植)、术式C亚组(改良术式)。分析其临床资料及预后。结果经中位随访时间56个月(11~92个月)。供肾满足三5标准组受者均未发生栓塞事件;末次随访估算肾小球滤过率:术式A为123.4 ml/min(92.2~156.6 ml/min)、术式B为97.2 ml/min(81.3~116.6 ml/min)、术式C为133.9 ml/min(133.9~133.9 ml/min);供肾不满足三5标准的受者中,术式A和术式C受者均未发生栓塞事件(0%),术式B中3例受者发生移植物栓塞(2例单肾栓塞、1例双肾栓塞)(3/5,60%),显著高于术式A、C组(P<0.05);末次随访尿蛋白(+):术式A 1例(1/2,50%)、术式B 3例(3/5,60%),术式C 0例,术式C受者尿蛋白阳性率显著低于术式A、B(P<0.05);末次随访估算肾小球滤过率:术式A为82.4 ml/min(80.9~83.9 ml/min)、术式B为71.8 ml/min(46.1~114.2 ml/min)、术式C为122 ml/min(83.3~142.4 ml/min)。满足三5标准供者组和不满足三5标准供者组的受者1年移植肾存活率分别为100%和89.5%;3年移植肾存活率分别为100%和84.2%。结论婴幼儿供肾可以加以利用,满足三5标准的供肾对术式的要求不高,预后较好;不满足三5标准的极低龄、极低体重供者的供肾,采用利用主动脉远端建立流出道的改良术式似可降低栓塞的发生率、改善近期预后,并减轻移植物高灌注损伤、改善远期预后。     

Case report of rare chronic myelogenous leukemia related multibacterial splenic abscess presenting with scrotal swelling

INTRODUCTION

Splenic abscesses associated with leukemia are rare. Most reported cases of splenic abscesses occur after chemotherapy and are related to the immunosuppressive effects of the chemotherapy. Their etiology is most frequently fungal.

PRESENTATION OF CASE

A 58-year-old male presented with splenomegaly and scrotal swelling secondary to a multibacterial splenic abscess which required a splenectomy. Upon investigation he was found to suffer from chronic myeloid leukemia (CML) and epididymitis.

DISCUSSION

Splenic abscesses are rarely found in leukemic patients. Reported cases are fungal and commonly occur after chemotherapy due to immunosuppression. Scrotal swelling with concurrent splenomegaly can be found in other pathologies including brucellosis, Lyme disease and even non-Hodgkin primary testicular lymphoma. Scrotal swelling in our case was likely secondary to epididymitis and exacerbated by the effects of splenomegaly upon the systemic circulation promoting venous congestion.

CONCLUSION

This case illustrated an unusual presentation of CML because the patient presented with splenomegaly, a multibacterial splenic abscess, and scrotal swelling.     

Reversal of pancytopenia following kidney transplantation in a patient of primary hyperoxaluria with bone marrow involvement

Combined liver and kidney transplantation is the ideal treatment for patients with end-stage renal failure secondary to primary hyperoxaluria and systemic oxalosis, with a functioning liver providing replacement of the deficient enzyme and a functioning kidney providing the route of excretion for the oxalate crystals. Pancytopenia from bone marrow infiltration of oxalate crystals is a rare complication of primary hyperoxaluria, and its reversal following transplant has not been described. We report the first case of pancytopenia from marrow infiltration by oxalate crystals reversing following a successful kidney transplant alone. Although kidney alone transplants do not provide the best chance of survival or quality of life as compared to a combined kidney and liver transplant, a well functioning kidney transplant is able to take care of the systemic oxalate load and ameliorate, at least for a period of time, the systemic complications of oxalosis.     

低龄婴儿双供肾移植给成人22例报道

目的总结单中心低龄婴儿双供肾移植给成人的临床效果。方法回顾性纳入2013年7月至2017年10月华中科技大学同济医学院附属同济医院实施的所有儿童双供肾移植给成人受者共22例临床资料和随访数据。22例供者年龄(2.9±1.7)个月,体重(4.9±1.4)kg,其中15例小于3月龄。受者多为低体重女性成人,体重(46.3±5.6)kg。总结早期移植失败及随访期间移植肾失功或受者死亡原因。根据是否发生单侧移植肾血栓,移植肾功能恢复者又进一步分为双肾存活组和单肾存活组,比较移植肾中-长期功能。结果4例受者在术后早期出现移植失败,包括双肾血栓2例、移植肾破裂切除1例和受者多器官功能衰竭死亡1例。18例受者移植肾功能恢复出院,随访期间因移植肾新生肿瘤切除双肾1例、因复杂全身原因死亡1例、因间质性肺炎死亡1例,余15例受者双肾均存活者10例(中位随访59个月),单肾存活者5例(中位随访48个月)。移植1年时双肾存活组估算肾小球滤过率为(95±27)ml/(min·1.73 m2),显著高于单肾存活组(61±24)ml/(min·1.73 m2)(P<0.05),但3年时分别为(95±21)ml/(min·1.73 m2)和(69±31)ml/(min·1.73 m2),差异缩小,差异无显著统计学意义(P=0.12)。结论低龄婴儿双供肾移植虽然可以扩大供肾来源,但发生早期移植失败和单肾栓塞的风险较高。在单肾存活的情况下,受者仍具有相对满意的中-长期移植效果。