Syngeneic Living-Donor Liver Transplantation for Hemangioendothelioma: A Clinical Model for Studying Liver Regeneration

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.     

Early Calcification of Renal Allografts Detected by Protocol Biopsies: Causes and Clinical Implications

Interstitial calcification has been described in renal allografts, however, the etiology and significance of this finding for the graft are unclear. The aim of this study was to examine calcification in serial protocol biopsies, to test the hypothesis that calcification is related to parameters of calcium homeostasis in these patients and to analyze a possible relation between calcification and graft function at 1 year. We studied 213 patients with 586 protocol biopsies obtained 6 weeks, 3 and 6 months after transplantation. Calcifications increased over time, from 6.1% at 6 weeks to 17.8% at 6 months. Out of the 213 patients, 56 had calcification in one or more biopsies. Patients age and gender, underlying renal disease, dialysis mode and duration, previous transplantations, donor type, age and gender, HLA matches and ischemia time had no influence on calcification. Calcification was not related to rejection episodes, acute tubular lesions, calcineurin inhibitor toxicity or tubulointerstitial fibrosis and tubular atrophy. Patients with calcification had significantly higher serum parathormone and calcium levels. In patients with calcification, high PTH levels correlated with an inferior outcome of graft function at 1 year after transplantation (p < 0.05). Therefore, treatment of hyperparathyroidism should be considered earlier and more often in these patients.     

Sirolimus-Based Therapy Following Early Cyclosporine Withdrawal Provides Significantly Improved Renal Histology and Function at 3 Years

Graft function and histology are predictive of renal transplant survival. The Rapamune Maintenance Regimen study demonstrated that early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen improved renal function and blood pressure. We report the protocol-mandated biopsy findings from that study. Renal transplant patients (n = 430) receiving SRL-CsA-ST were randomized at 3 months after transplantation to remain on SRL-CsA-ST, or to have CsA withdrawn (SRL-ST group). Protocol-mandated biopsies were performed at engraftment and at 12 and 36 months. Two pathologists blindly evaluated 484 biopsies to obtain the Chronic Allograft Damage Index (CADI) scores. At 36 months among patients with serial biopsies (n = 63), the mean CADI score was significantly lower with SRL-ST(4.70 vs. 3.20, p = 0.003), as was the mean tubular atrophy score (0.77 vs. 0.32, p < 0.001). All six components of the CADI score were numerically lower in SRL-ST group; moreover, inflammation and the tubular atrophy scores decreased significantly in the SRL-ST group between 12 and 36 months. The calculated glomerular filtration rate at 36 months was significantly better in the CsA-withdrawal group (54.8 vs. 68.2 mL/min, p = 0.009). In conclusion, withdrawing CsA from the SRL-CsA-ST regimen resulted in improved renal histology and function.     

Liver Transplantation from an Identical Twin without Immunosuppression, with Early Recurrence of Hepatitis C

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon alpha and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.     

Donation After Cardiac Death: The University of Wisconsin Experience with Renal Transplantation

Owing to the shortage of organ donors, there is renewed interest in donation after cardiac death (DCD), formerly referred to as nonheart-beating donation. From January 1984 until August 2000, 382 renal transplants were performed from DCD donors. These were compared with 1089 renal transplants performed from donation after brain death (DBD) donors. The mean warm ischemic time in DCD donors was 16.5 min. There was no statistical difference in cold ischemic time, rate of primary nonfunction, or graft loss in the first 30 days after transplantation. The rate of delayed graft function (DGF) was higher for DCD donors (27.5% vs. 21.3%; p = 0.016) and discharge creatinine was higher in DCD donors (1.92 mg/dL vs. 1.71 mg/dL; p = 0.001). There was no statistical difference in the 5-, 10-, or 15-year allograft survival when DCD donors were compared with DBD donors (64.8%, 44.8%, 27.8% vs. 71.3%, 48.3%, 33.8%; p = 0.054). Likewise, no statistical difference in the rate of technical complications was seen. Our long-term data indicate that the results of renal transplantation from DCD donors are equivalent to long-term allograft survival from DBD donors despite an increase in the rate of DGF. Organ procurement organizations, transplant centers, and hospitals should work to expand the implementation of DCD policies.     

Pancreas Transplantation From Living Donors: A Single Center Experience of 20 Cases

Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage–related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK.     

Retroperitoneoscopic Live Donor Nephrectomy (RPLDN): Establishment and Initial Experience of RPLDN at a Single Center

Objective: We tried to establish the technique of retroperitoneoscopic live donor nephrectomy (RPLDN).
Patients and method: Between July 2001 and March 2004, 135 renal transplant donors underwent RPLDN. Low (average: 7 mmHg) CO₂ gas pressure was employed during the procedure. All procedures were performed through a three-port retroperitoneal approach without opening the peritoneal cavity. The hand-assisted technique was not used. One hundred and twenty-seven cases were of left and eight cases were of right nephrectomy.
Results: Donor nephrectomy was carried out successfully in all patients. In one donor, the procedure was changed to open donor nephrectomy because of severe adhesion around the renal vein due to previous surgery. No serious complications, such as massive bleeding or bowel injury were encountered. Return of bowel function took 0.7 days on average. Post-operative hospital stay was 4.9 days on average, and return to work was 12 days on average. Ureteral complications occurred in 2 patients and were treated with temporally retrograde ureteral stenting. Average serum creatinine levels were 1.5 mg/dL, 1.3 mg/dL and 1.3 mg/dL at 3, 7 and 14 days after transplantation, respectively. No patients required hemodialysis after transplantation due to acute tubular necrosis.
Conclusion: RPLDN could be an option for laparoscopic live donor nephrectomy.     

Simultaneous Pancreas-Kidney Transplantation Utilizing a Common Arterial Conduit: Early Experience and Potential Applications

Simultaneous pancreas-kidney transplantation has gained acceptance as a therapeutic modality for patients with end-stage renal disease secondary to diabetes mellitus. In some instances, performing the procedure as conventionally described with renal revascularization from the left iliac vessels and pancreatic arterial inflow from the right iliac vessels may be difficult or undesirable. We describe our experience with an alternate operative technique utilizing a single arterial conduit to vascularize both organs. We believe that this technique may be of use in certain patients undergoing simultaneous pancreas-kidney transplantation.     

Renal Cell Carcinoma in Kidney Allografts: A Case Series from a Single Center

In kidney transplant recipients, renal cell carcinoma (RCC) occurs either in the native kidney or, less frequently, in the grafted kidney. Here, we report a series of rare cases involving 5 patients from a single center who developed RCC in their grafts. The diagnosis was made serendipitously by ultrasound. The time lapse post-transplant varied from 4 to 17 years. Surgical treatment consisted of nephron-sparing surgery (NSS) in four cases and a secondary radical nephrectomy in one case. All tumors were less than 4 cm in diameter. The histopathology was clear cell type in four cases and papillary RCC in one case. Patients treated by NSS retained kidney function for 2 years or more, and none of them presented early neoplasia recurrence. In conclusion, NSS can be performed safely in grafted kidneys to treat incidental RCC. It prevents an immediate return to dialysis for patients.     

Improved Outcomes of Renal Transplantation from Cardiac Death Donors: A 30-Year Single Center Experience

Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989 (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long-term outcomes.     

Renal Transplantation After Ex Vivo Normothermic Perfusion: The First Clinical Study

Ex vivo normothermic perfusion (EVNP) is a novel method of preservation that restores circulation and allows an organ to regain function prior to transplantation. The aim of this study was to assess the effects of EVNP in kidneys from marginal donors. Eighteen kidneys from extended criteria donors (ECD) underwent a period of EVNP immediately before transplantation. Kidneys were perfused with a plasma free red‐cell based solution at a mean temperature of 34.6°C. The outcome of these kidneys was compared to a control group of 47 ECD kidneys that underwent static cold storage (CS). The mean donor age was 61 ± 1 years in the EVNP and 62 ± 6 years in the CS group (p = 0.520). EVNP kidneys were perfused for an average of 63 ± 16 min and all were transplanted successfully. The delayed graft function rate (DGF), defined as the requirement for dialysis within the first 7 days was 1/18 patients (5.6%) in the EVNP group versus 17/47 (36.2%) in the CS group (p = 0.014). There was no difference in graft or patient survival at 12 months (p = 0.510, 1.000). This first series of EVNP in renal transplantation demonstrates that this technique is both feasible and safe. Our preliminary data suggests that EVNP offers promise as a new technique of kidney preservation.     

移植肾输尿管梗阻的原因与处理方法

目的:探讨移植肾输尿管梗阻的发病原因及其处理方法。方法:报告行肾移植后发生移植肾输尿管梗阻29例的临床资料。全部经手术探查证实,包括输尿管膀胱吻合口狭窄9例,输尿管下段狭窄5例,输尿管全段闭锁2例,膀胱肌层包埋过紧1例,输尿管下段穿孔4例,输尿管全段坏死2例,输尿管下段血块堵塞1例,输尿管外周血肿压迫2例,脓肿压迫1例,移植肾输尿管结石2例。14例移植输尿管坏死患者中有10例梗阻前发生急性排斥反应。结果:患者尿路重建后移植肾功能均恢复良好,随访1年均无再次梗阻发生。结论:移植肾输尿管梗阻以输尿管狭窄和坏死最为多见,排斥反应是发生输尿管梗阻的重要病因之一。对于影像学提示梗阻而移植肾功能无明显受损的病例,应积极行移植肾活检。手术是解决移植肾输尿管梗阻最有效的方法。     

The Significance of Subclinical Rejection and the Value of Protocol Biopsies

Subclinical rejection (SCR) is diagnosed by protocol histology with a maximal prevalence occurring early after transplantation, falling to low levels by 1 year. Needle-core biopsy is safe, and the histology obtained fairly reflects subclinical immune activity. Several studies have consistently shown that SCR is associated with chronic tubulointerstitial damage, subsequent renal dysfunction and reduced graft survival. SCR is effectively treated by pulse corticosteroid therapy, although increased baseline immunosuppression may be necessary. A single randomized clinical trial of biopsy and corticosteroid therapy demonstrated significantly improved early structural and functional outcomes, and a (nonsignificant) 17% risk reduction in 4-year graft survival. Three possible approaches include: no protocol biopsies (usually accompanied by powerful immunosuppression); biopsies only in high-risk recipients (who may be difficult to reliably predict) or universal screening protocol biopsy (comprehensive but limited by cost and resource utilization). The appropriate screening methodology for a transplant unit is both a clinical and an economic decision; influenced by the SCR prevalence and potential gains of treatment, against costs and resource utilization. Further trials to quantify the cost-benefit balance in a typical, heterogeneous recipient population using modern immunosuppression are required.     

10例心脏死亡器官捐献移植总结

目的通过分析我院实施的心脏死亡器官捐献(DCD)移植病例,探讨国内DCD器官和移植方面的问题。方法对我院2010～2011年期间参与实施的DCD器官移植的临床资料进行回顾性总结。结果本组有4例DCD者共实施了7例肾移植和3例肝移植。捐献者1属于中国DCD器官分类标准(中国标准)二类(MaastrichtⅣ类),热缺血时间40 min,经快速病理检查后放弃了肝脏和左侧肾脏,右侧肾脏进行了移植后患者出现移植肾功能延迟恢复,最终移植肾因破裂出血而被切除。捐献者2～4属于中国标准三类(MaastrichtⅢ类),热缺血时间分别为15、15、10 min,其中捐献者4在器官捐献前已经出现血压下降,需要大剂量多巴胺维持血压,供肝进行了快速病理检查,确认可以使用;捐献者2和3由于是在手术室进行可控性心跳及呼吸终止,热缺血时间均为15 min,未进行病理学检查;共实施了3例肝移植和6例肾移植,手术顺利,移植物功能恢复良好,无并发症发生,无移植患者死亡。结论通过选择符合中国标准三类的捐献者,实施可控的DCD程序,DCD器官移植可以获得满意的效果。供体器官的快速病理检查有利于器官质量的判断,减少移植手术后并发症的发生。     

Renal Transplantation in Obese Patients: Experience in an Argentine Center

Possible complications of renal transplants in obese patients have raised concerns among nephrologists. We describe the outcomes of 110 renal transplant patients according to body mass index (BMI). Recipient BMI was calculated by using height and weight at time of transplantation and categorized according to World Health Organization guidelines. The patients' BMI values were as follows: underweight, n = 8 (7.27%); normal weight, n = 55 (50%); overweight, n = 30 (27.27%); and obese, n = 17 (15.45%). Mean age was significantly different among groups: underweight, 27.62 ± 7.57 years; normal weight, 44.98 ± 15.55 years; overweight, 50.53 ± 13.90 years; and obese, 52.11 ± 10.41 years (P < .05). Donor age and mean time of dialysis treatment were comparable in all groups. Underweight patients had a significantly larger proportion of living donors than those with higher BMIs. Calculated glomerular filtration rate (using the Modification of Diet in Renal Disease equation) were significantly different among the groups at 30, 60, and 90 days' posttransplantation. At 180 days, however, it was comparable: underweight, 62.96 ± 40.77 mL/min/1.73 m²; normal weight, 53.55 ± 26.23 mL/min/1.73 m²; overweight, 47.52 ± 16.37 mL/min/1.73 m²; and obese, 46.19 ± 17.56 mL/min/1.73 m² (P = .34). Incidence of delayed graft function was as follows: underweight, 0%; normal weight, 30.4%; overweight, 53.3%; and obese, 64.1% (P < .05). The incidence of surgical complications, incidence of rejection within the first 6 months' posttransplantation, and graft and patient survival rates over 6 months did not differ among the groups. Because transplantation in obese patients may be associated with higher risks and costs, the evaluation of each center experience is imperative. Longer term assessments are warranted, but our short-term results show that outcomes in overweight or obese renal transplant patients are comparable to those in patients with lower BMI.     

Analysis of Renal Transplant Protocol Biopsies in ABO-Incompatible Kidney Transplantation

Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6–12 months, respectively. At 6–12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.     

Sparing Native Upper Lobes in Living‐Donor Lobar Lung Transplantation: Five Cases From a Single Center

Living‐donor lobar lung transplantation (LDLLT) is indicated for rapidly deteriorating patients, and the total volume of two lower lobe grafts must be sufficient for the recipient. To rescue patients with small lobar grafts, we performed five LDLLTs sparing native upper lobes. This strategy was used when upper lobes or segments were preoperatively less impaired. There were no hospital deaths. Extracorporeal circulation time and operative time were similar to those of conventional LDLLTs. The length of intensive care unit stay was also similar. Late complications attributed to the spared lungs were airway infection in one recipient and pneumothorax in two but they were successfully managed. All recipients were discharged without supplemental oxygen. The spared lung volumes measured by volumetry did not change after LDLLT. Lung perfusion scintigraphy performed at 1 year showed remaining perfusion in the spared lungs, although much less than in the grafts. These results suggested that the spared lobes kept adequate space in the thoracic cavity and kept functioning to a limited extent. The new lobar‐sparing strategy appears feasible and effective in LDLLT using small grafts for selected patients when the upper lobes or segments are less impaired.     

Analysis of Histologic Changes During Early Rejection After Renal Transplantation by Performing Protocol Biopsy at 1 Year After Kidney Transplantation

Background

In this retrospective study, we analyzed histologic changes identified through protocol biopsy (PB) at 1 year after kidney transplantation (KT). We focused on the pathologic changes observed in patients with a history of treatment for graft rejection within 1 year of transplantation.

Methods

Between January 2008 and December 2011, 56 patients underwent KT at our center. We assessed the histologic findings observed at 1 year after renal transplantation using the Banff 2007 classification. At our center, PBs are performed immediately after or at 1 hour after transplantation, and at 1 year after KT. PBs were performed in 39 patients; PBs could not be performed in 17 patients because of various causes. Of the 39 patients, 29 stabilized without clinical rejection and without treatment (the NTx group); 10 patients showed pathologic changes or clinical rejection after steroid pulse therapy within 1 year (the Tx group). We compared these 2 groups with respect to baseline data, renal function, and pathologic scores.

Results

The interstitial fibrosis (“ci”) score, according to the Banff classification, was significantly greater in the NTx group (0.89) than in the Tx group (0.50) at 1 year after transplantation.

Conclusions

The currently applied early steroid withdrawal regimen may be not be ideal for preventing pathologic changes occurring after KT. In addition to the PB performed 1 year after KT, PB should be performed within 1 year of renal transplantation to identify early signs of rejection and to provide access to appropriate treatment regimes.     

Renal Transplantation in Patients With Atypical Hemolytic Uremic Syndrome: A Single Center Experience

PurposeHemolytic uremic syndrome (HUS) is characterized by microangiopathic anemia, thrombocytopenia, and acute kidney injury. HUS is mostly associated with diarrhea (90%). However, 10% of cases are not associated with diarrhea and are thus called as atypical HUS (aHUS); these cases are usually caused by dysregulation of the complement system. Eculizumab, a monoclonal antibody against C5, is the drug of choice for treating aHUS. Herein we aimed to present 8 cases of renal transplantation performed on patients with aHUS.Materials and MethodsA total of 8 patients who had been diagnosed with aHUS between the years 2012 to 2018 were enrolled and underwent transplantations. All patients received induction treatment, standard immunosuppresive treatment (tacrolimus, mycophenolic acid, prednisolone), and eculizumab. Eculizumab was administered at a dosage of 900 mg/wk for the first month and 1200 mg every 2 weeks thereafter. Patients were followed up and recorded in terms of demographic features, serum creatinine, lactate dehydrogenase, acute rejection episodes, and allograft outcomes.ResultsMean age was 34 ± 8 years (Male/Female: 6/2). One of the patients had a second transplantation. Median hemodialysis vintage (25%–75% interquartile range) was 37 (9–63) months. Four patients had pretransplant plasmapheresis and 2 patients had posttransplant plasmapheresis. Induction treatment was ATG in 7 patients, and basiliximab was used only in 1 patient. The median follow-up period was 25 (13–59) months. Mean serum creatinine levels were 1.9 ± .6, 1.2 ± .7, and 1 ± .1 mg/dL for the first day, first month, and last values, respectively. Mean lactate dehydrogenase levels were 286 ± 203, 239 ± 27, and 218 ± 86 U/L for first day, first month, and last values, respectively. None of the patients had an acute rejection episode. Currently, all patients have functioning allografts.ConclusionPatients with aHUS may be transplanted successfully with eculizumab with good allograft outcomes.