Emphysematous pyelonephritis in renal allograft related to antibody‐mediated rejection: A case report and literature review

Emphysematous pyelonephritis (EPN) is a rare condition which can rapidly progress to sepsis and multiple organ failure with high mortality. We experienced a rare case of EPN in a renal allograft related to antibody‐mediated rejection (AMR). The patient received a deceased donor kidney transplant due to end‐stage renal disease secondary to diabetes mellitus. Cross‐match test was negative but she had remote history of anti‐HLA‐A2 antibody corresponding with the donor HLA. Surgery concluded without any major events. Anti‐thymoglobulin was given perioperatively for induction. She was compliant with her immunosuppressive medications making urine of 2 L/d with serum creatinine of 1.9 mg/dL at discharge on post‐operative day (POD) 6. She did well until POD 14 when she presented to the clinic with features of sepsis, pain over the transplanted kidney area and decline in urine volume with elevated serum creatinine. CT revealed extensive gas throughout the transplanted kidney. Renal scan revealed non‐functional transplant kidney with no arterial flow. Based on these findings, a decision to perform transplant nephrectomy was made. At laparotomy, the kidney was completely necrotic. Pathology showed non‐viable kidney parenchyma with the tubules lacking neutrophilic casts suggestive of ischemic necrosis. Donor‐specific antibody (DSA) returned positive with high intensity anti‐HLA‐A2 antibody. This is the first case of early EPN in allograft considered to have occurred as a result of thrombotic ischemia secondary to AMR. This case suggests consideration of perioperative anti‐B‐cell and/or anti‐plasma cell therapies for historical DSA and strict post‐operative follow‐up in immunologically high‐risk recipients to detect early signs of rejection and avoid deleterious outcomes.     

Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report

BACKGROUNDThe liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARYA 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor. The recipient MELD at the time of transplant was 28. The flow cytometric crossmatches were noted to be positive for T and B lymphocytes. The patient had an uneventful recovery postoperatively. Starting on postoperative day 5 the patient developed fevers, elevated liver function tests, distributive shock, renal failure, and hepatic encephalopathy. She went into ALF with evidence of antibody mediated rejection with portal inflammation, bile duct injury, endothelitis, and extensive centrizonal necrosis, and C4d staining on allograft biopsy and elevated DSA. Despite various interventions including plasmapheresis and immunomodulating therapy, she continued to deteriorate. She was relisted and successfully underwent liver retransplantation.CONCLUSIONThis very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.     

大剂量IVIG、PP联合小剂量IVIG对高致敏肾移植受者脱敏效果比较

目的观察并比较大剂量静注免疫球蛋白（IVIG）和血浆置换（PP）联合小剂量IVIG对高致敏肾移植受者脱敏的效果。方法高致敏肾移植受者28例,随机分为观察组15例和对照组13例。观察组采用PP联合小剂量IVIG静注,对照组采用大剂量IVIG静注脱敏。结果脱敏后对照组4例、观察组9例群体反应性抗体（PRA）下降,肾移植术l a后11、6例PRA反弹。两组PRA下降率和反弹率相比P均〈0.05。对照组敏感者中4例、观察组6例发生急性排斥反应,两组急性排斥反应发生率相比P〈0.05。结论与单用大剂量IVIG静注相比,PP联合小剂量IVIG静注能更有效降低高致敏肾移植受者PRA水平,降低术后急性排斥反应发生率。     

雷帕霉素联合环孢素A预防肾移植急性排斥反应

目的 :研究雷帕霉素 (rapamycin ,RPM)预防移植肾早期急性排斥反应 (AR)的临床疗效及其安全性。　 方法 :采用RPM、环孢素A(CsA)和强的松“三联”免疫抑制方案。RPM首次负荷剂量 6mg/d口服 ,第 2天开始改为维持剂量 2mg/d。肾移植术后 4 8h内给予首次剂量 ,在给予CsA后约 4h服用RPM ,并持续使用至 12个月。根据患者的临床情况和血药谷值浓度 (Co) ,调整RPM和CsA剂量。　 结果 :术后 1、3、6个月 ,全血RPMCo分别为 (5 12± 0 2 1) μg/L、(6 39± 0 73) μg/L、(5 18± 0 12 ) μg/L ;CsACo分别为 (2 5 1 6 8± 98 3) μg/L、(2 2 4 92± 88 9) μg/L、(10 1 91± 5 9 31) μg/L 16例患者完成 6～ 12个月的随访 ,提前中止治疗 9例 (中止原因包括 2例进食困难和腹泻 ,1例体重明显减轻 ,3例肝毒性反应 ,1例移植肾功能延迟恢复和 2例并发肺部感染 )。随访期间无一例死亡和移植肾丧失 ,AR 2例 (占 12 5 % ) ,分别发生于术后第 12天和 2 6天 ,经肾活检病理证实均为急性细胞性排斥反应 ,经甲基强的松龙冲击治疗后逆转 ,仍维持RPM 2mg/d治疗。并发症包括消化道症状 (恶心 2 4 % ,呕吐 2 4 % ,胸骨后烧灼样疼痛 12 % ,进食困难 8% ,腹泻 12 % )和高脂血症 (高胆固醇血症 37 5 % ,高甘油三酯血症 31 5 % )     

Polyomavirus in kidney and kidney--pancreas transplant recipients

Abstract: Purpose. To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney–pancreas transplant (KPTX) recipients. Methods. Single center retrospective analysis of all cases of PV nephritis in KTX and KPTX patients transplanted between 1994 and 1999. Results. Thirteen (5 KTX and 8 KPTX) patients (2.1%) had PV nephritis diagnosed on multiple biopsies (n = 22) among 504 KTX and 106 KPTX recipients. The incidence of PV nephritis was higher in cadaver donor transplants (2.6% cadaver vs. 0.7% living donors), after KPTX (1% KTX vs. 7.5% KPTX), in males (3.3% male vs. 0.7% female), and in diabetic patients (4.4% diabetic vs. 0.8% nondiabetic). The mean time to diagnosis of PV nephritis was 18 (range 6–48) months after KTX and 17 (range 9–31) months after KPTX. Three KTX patients and 5 KPTX patients had calcineurin inhibitor toxicity on biopsy prior to developing PV nephritis. Reduction in immunosuppression occurred in 100% of KTX and 63% of KPTX patients. Three patients (23%) developed rejection within 3 months of diagnosis of PV, 1 after a reduction in immunosuppression. Despite multiple antiviral treatment regimens, renal allograft failure requiring dialysis occurred in 60% of KTX and 50% of KPTX patients. All KPTX patients remain insulin independent and 2 were successfully retransplanted with living donor kidneys. 2 patients (15%) died but there was no mortality directly related to the virus. Conclusions. Polyomavirus nephritis may be increasing in incidence and appears to be unresponsive to either conventional antiviral agents or a reduction in immunosuppression. Most of our cases occurred in male diabetic patients undergoing cadaveric donor transplantation and were preceded by biopsy‐proven nephrotoxicity. Further studies are needed to better define the pathogenesis of PV and effective antiviral treatment.     

Long-term liver allograft fibrosis: A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

Liver transplantation (LT) is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease. With improvements in organ preservation techniques, perioperative care, and immunosuppression, there is better patient and graft survival following LT, and assessment of the liver allograft in long-term survivors is becoming increasingly important. Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults. However, no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients, as they have been transplanted for non-recurrent liver diseases. Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes. Pathological findings are frequently present in liver biopsies obtained after a year post LT. The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters. This narrative review summaries the factors predisposing to long-term liver allograft fibrosis, highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.     

氨基酸残基配型在致敏受者肾移植中的应用

目的:探讨人类白细胞抗原(HLA)-氨基酸残基配型(Res M)标准在致敏患者中的应用。 方法:根据HLA分子结构的氨基酸残基不同,将HLAⅠ类抗原分成10个组, Ⅱ类抗原分成7个组,确定Res M 配型标准;并与标准HLA抗原配型(Ag M)进行比较。回顾性分析Res M对102例致敏患者早期肾功能、急性排斥、术后抗HLA-IgG抗体水平及人/肾存活率的影响。 结果:应用Res M 标准,可明显提高供受者相配概率,0 MM受者由Ag M组1.89%提高到Res M组18.87% (P<0.001) ,0~1MM组受者由9.43%提高到60.37%(P<0.001) ;临床研究结果显示:残基相配的移植肾短期存活率和1、3年长期存活率接近HLA抗原相配水平;与错配组相比,早期移植肾功能延迟恢复发生率、急性排斥反应发生率显著减少,术后抗HLA-IgG抗体水平升高或出现抗供者特异性抗体发生率明显降低,1、3年移植肾存活率明显提高。 结论:HLA-Res M,可大幅度增加供受者的相配概率, 显著降低术后的致敏性,适合在致敏患者肾移植中应用。     

他克莫司在移植肾功能延迟恢复患者中的临床应用

目的:探讨他克莫司(FK506)在移植肾功能延迟恢复(DGF)患者中的临床应用价值与合理用药方案.方法:17例DGF患者临床结合移植肾病理确立诊断.肾移植术后早期均接受三联(FK506 MMF Pred)免疫抑制药物治疗至少3个月.不用任何生物制剂诱导治疗,观察临床疗效及副作用.结果:17例患者无一例死亡或摘除移植肾.15例在术后第2～3天开始血液透析(HD)/连续性血液净化(CBP)治疗,2例在术后第5天开始HD/CBP.HD/CBP治疗2～15次后,10例在术后7天内停止,7例在术后7天后仍需CBP治疗,最长1例在术后第18天停止透析.FK506治疗后8～17天患者尿量开始明显增多,SCr开始明显下降.17例患者诊断DGF时SCr水平在489～1028μmol/L,14例在治疗后8～17天降至＜200μmol/L,另3例中2例SCr分别在术后第24天,28天降至＜200μmol/L.副作用主要是腹泻(3例),血糖升高(1例)及手颤,肢体麻木(4例),但未出现CMV等严重感染病例.结论:FK506 MMF Pred三联免疫抑制治疗方案治疗肾移植DGF安全有效,可作为肾移植术后DGF患者的过渡治疗方法之一.     

Rhabdomyolysis associated with cytomegalovirus infection in kidney transplant recipients

Rhabdomyolysis is a pathological syndrome caused by skeletal muscle cell damage that affects the integrity of the cellular membrane and leads to the release of toxic intracellular constituents into the bloodstream. Although cytomegalovirus (CMV) has rarely been reported as a cause of rhabdomyolysis, CMV infection could be considered as a possible cause because of its clinical significance in kidney transplant recipients (KTRs). We report 2 cases of rhabdomyolysis associated with CMV infection in KTRs. A 64‐year‐old woman (Case 1) and a 65‐year‐old man (Case 2), who had each received a kidney from a living unrelated donor, were admitted with complaints of weakness in both legs and myalgia. Laboratory findings revealed highly increased creatine phosphokinase and myoglobinuria. In both cases, no recent alterations of medications had occurred, and other causes of rhabdomyolysis—such as trauma, alcohol, drugs, and electrolyte abnormalities – were excluded. CMV pp65 antigen was positive, and patients were diagnosed with rhabdomyolysis associated with CMV infection. Both patients recovered without complications after ganciclovir treatment. In conclusion, CMV infection should be considered as a possible cause of rhabdomyolysis in KTRs.     

Effect of post-transplant double filtration plasmapheresis on recurrent focal and segmental glomerulosclerosis in renal transplant recipients

In the present study, we reviewed the effect of post-transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post-transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 +/- 40.7 months (range 7-125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 +/- 23.05 g/day (range 3.34-62.6 g/day) to 2.95 +/- 3.42 g/day (range 0.02-8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post-transplant DFPP appears to be effective for reducing urinary protein levels and improving long-term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post-transplant DFPP to prevent the progression of recurrent FSGS.     

Double filtration plasmapheresis combined with rituximab for donor-specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case–control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10–21) and 13 (10–29) days respectively. Although the cumulative incidence of II–IV aGVHD (41.4% vs. 28.1%) and 3-year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3-year non-relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo-HSCT.