Donor Body Weight Research Articles

Kidney grafts from donors ≤5 yr of age: Single kidney transplantation for pediatric recipients or en bloc transplantation for adults?

Kidneys from donors ≤5 yr of age represent a controversial issue. The purpose of this study was to compare the transplant outcomes as single and single/en bloc grafts into pediatric and adult KT recipients, respectively. All recipients of kidneys from donors ≤5 yr old transplanted at our institution from 3/2003 to 12/2010 were evaluated, and corresponding data were analyzed. There were 11 pediatric and 14 adult recipients. Median donor age and body weight were 38 months and 14 kg, respectively. PNF, n = 2 and DGF, n = 1 were observed only among adult recipients. Five-yr graft survival was 100% for children and 86% for adults. There were no significant differences in graft and patient survival, PNF, DGF, acute rejection, or postoperative complications among children/single (n = 10), adults/en bloc (n = 10), and adults/single (n = 4) KT. Major complications were documented in six adult recipients and one pediatric recipient after en bloc KT. Pediatric recipients showed significantly higher GFR during the first post-transplant year. Kidneys from donors ≤5 yr of age have at least as good outcomes as when transplanted as single allografts into children. Although the study-volume is small, it seems that children benefit from a pediatric-oriented allocation policy.

Analysis of influence factors on G-CSF-mobilized hematopoietic stem cells of 191 healthy donors in a mono center

This study was aimed to investigate the factors influencing mobilization efficiency of peripheral hematopoietic stem cells with granulocyte colony stimulating factor (G-CSF) and their impact on healthy donors. 181 donors were mobilized subcutaneously with G-CSF at 5 - 10 µg/(kg·d), and 10 donors were mobilized with G-CSF at 3.3 - 4.9 µg/(kg·d), once 12 h, for 4 - 5 d. Peripheral blood mononuclear cell (MNC) and CD34(+) cell counts were analyzed by flow cytometry. Mobilization-related side effects were also monitored. The results showed that white blood cell counts increased by 6 times averaged after mobilization (P < 0.01). The platelet count obviously decreased (P < 0.01), while the hemoglobin level did not show significant difference. No significant differences were observed in MNC and CD34(+) cell counts between those subjects harvested on the 4th and 5th day after mobilization. Male donors were superior to female ones in cell harvest (P < 0.01). Donor body weight played positive role in cell yield, while impact of age on harvest was not remarkable. Neither MNC nor CD34(+) cell count showed a linear relationship with G-CSF dose. Only slight side effects were observed on the donors in this study. It is concluded that mobilization with G-CSF is sufficient in healthy donors without remarkable side effects.

Long-term outcome of en bloc pediatric kidney transplantation in adult recipients – up to 22 years of center experience

Renal transplantation has been shown to be the best therapeutic option in end-stage renal disease patients. En bloc transplantation of pediatric kidneys into adult recipients (EBKT) is one strategy to increase the donor pool. We here report on 10 to 22 years of follow-up (median of 12.8 years) of patients receiving EBKT in a single-center, retrospective cohort study. The mean donor age was 14 ± 12 months and mean donor body weight was 8 ± 3 kilograms. Thirteen recipients (6 females, 7 males) were followed for 10 to 22 years. The mean recipient age was 44 ± 13 years at the time of transplantation. Two of 13 patients lost their grafts in the first week because of hemorrhagic infarction of the kidney transplants or sepsis (septic shock). Only 1 patient had an acute cellular rejection, which was successfully treated with steroids and anti-CD3 antibody. Eleven out of 13 patients after EBKT survived and had a functioning graft 10 to 22 years after successful EBKT. The serum creatinine was 1.34 ± 0.6 mg/dl at 5 years (n=11), 1.37 ± 0.7 mg/dl at 10 years (n=11), 1.40 ± 0.6 mg/dl at 15 years (n=4), and 1.08 mg/dl at 20 years after EBKT (n=2). The eGFR, evaluated by using MDRD-2, was 66.5 ± 22 ml/min/m2 at 5 years (n=11), 62 ± 28 ml/min/m2 at 10 years (n=11), 56 ± 23 ml/min/m2 at 15 years (n=4), and 61 ml/min/m2 at 20 years after EBKT (n=2). Proteinuria did not increase significantly within the observation period. In our experience, if the acute post-operative phase is uncomplicated, EBKT has excellent long-term graft and patient survival.

Outcomes of children receiving en bloc renal transplants from small pediatric donors

The utilization of en bloc renal allografts from small pediatric donors has been adopted as an effective strategy to expand the organ donor pool in adult recipients. Data in children are limited. The aim of our study is to describe the outcomes of en bloc renal transplants in children from our center. Medical records of children receiving pediatric en bloc renal transplants at our institution from January 2007 were abstracted. Data collected included recipient and donor demographics, operative technique and complications, and post-operative studies. Eight children received en bloc renal transplants at a median age of 17 yr; median follow-up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One kidney was lost to intra-operative thrombosis, while the other kidney from this en bloc graft remained viable. All grafts showed increased renal size at follow-up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At last follow-up, the median eGFR was 130 mL/min/1.73 m(2). The urinary protein to creatinine ratio was normal in four of seven patients. Our data suggest that in experienced centers, en bloc renal transplantation from young donors into pediatric recipients is effective. Long-term follow-up to monitor for complications, including hyperfiltration injury, is warranted.

Small-For-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811

Introduction: Pulmonary complications occurring after liver transplantation frequently lead to mortality. Transplantation of small-forsize liver grafts increases the risk of graft failure. Accordingly, the aim of this study was to investigate whether acute pulmonary injury occurs after small-for-size liver transplantation. Moreover, we reported that NIM811, an inhibitor of the mitochondrial permeability transition (MPT), prevents dysfunction of small-for-size liver grafts. Here, we investigated whether protection of liver grafts by NIM811 also attenuated acute pulmonary injury after small-for-size liver transplantation. Methods: Livers were reduced to 50% of original size, stored in cold UW solution for 6 h and then implanted into recipients of the same or about twice the donor body weight, resulting in half-size and quarter-size liver grafts, respectively. NIM811 (5 μM) was added to the storage solution. Lungs and livers were harvested at 5, 18 and 38 h after implantation. Results: Hepatic necrosis and alanine aminotransferase release were higher after transplantation of quarter-size than full-size and half-size grafts, indicating more severe liver injury. Liver regeneration increased in half-size grafts but was suppressed in quarter-size grafts. NIM811 blocked liver injury and promoted regeneration of quarter-size grafts, as observed previously. Pulmonary histological alterations were minimal at 5-18 h after liver transplantation. After 38 h, infiltration of neutrophils and monocytes/macrophages to pulmonary alveoli occurred with septal thickening and increased cellularity in quarter-size graft recipients. These changes were mild in lungs of full-size and half-size graft recipients. NIM811 decreased alveolar septal thickening, monocyte/macrophage infiltration and neutrophil infiltration by 52, 44 and 51%, respectively. Infiltrating leukocytes can produce reactive oxygen and nitrogen species, leading to cell death. 4-Hydroxynonenal and 3-nitrotyrosine adducts increased markedly in pulmonary leukocytes, vascular endothelial cells and alveolar epithelial cells in quarter-size graft recipients, indicating oxidative/nitrosative stresses. TUNEL-positive vascular endothelial/alveolar epithelial cells were 12- and 8- fold higher in lungs of quarter-size compared to full-size and half-size graft recipients, indicating apoptosis. NIM811 blunted 4-hydroxynonenal and 3-nitrotyrosine adduct formation and attenuated apoptosis by >80% after quarter-size liver transplantation. After transplantation, hepatic IL-1β and TNFα mRNA were 3.3 and 2.5-fold higher in quarter-size than full-size grafts. Pulmonary ICAM-1 expression was also markedly higher in quarter-size graft recipients. NIM811 decreased hepatic IL-1β and TNFα as well as pulmonary ICAM-1 expression. Conclusion: Together, failing small-for-size grafts produce toxic cytokines, leading to pulmonary inflammation and injury. NIM811 decreased hepatic injury and toxic cytokine formation, thus attenuating acute pulmonary injury after small-for-size liver transplantation (NIDDK).

Ratio of remnant to total liver volume or remnant to body weight: which one is more predictive on donor outcomes?

BackroundRight lobe donations are known to expose the donors to more surgical risks than left lobe donations. In the present study, the effects of remnant volume on donor outcomes after right lobe living donor hepatectomies were investigated. MethodsThe data on 262 consecutive living liver donors who had undergone a right hepatectomy from January 2004 to June 2011 were retrospectively analysed. The influence of the remnant on the outcomes was investigated according to the two different definitions. These were: (i) the ratio of the remnant liver volume to total liver volume (RLV/TLV) and (ii) the remnant liver volume to donor body weight ratio (RLV/BWR). For RLV/TLV, the effects of having a percentage of 30% or below and for RLV/BWR, the effects of values lower than 0.6 on the results were investigated. ResultsComplication and major complication rates were 44.7% and 13.2% for donors with RLV/TLV of ≤30%, and 35.9% and 9.4% for donors with RLV/BWR of < 0.6, respectively. In donors with RLV/TLV of ≤30%, RLV/BWR being below or above 0.6 did not influence the results in terms of liver function tests, complications and hospital stay. The main impact on the outcome was posed by RLV/TLV of ≤30%. ConclusionRemnant volume in a right lobe living donor hepatectomy has adverse effects on donor outcomes when RLV/TLV is ≤30% independent from the rate of RLV/BWR with a cut-off point of 0.6.

Development of an automated plasmapheresis procedure for the harvest of equine plasma in accordance with current good manufacturing practice

To develop a high-speed, continuous-flow, automated plasmapheresis procedure for the high-volume harvest of equine plasma in accordance with current good manufacturing practice. 143 horses (predominantly draft breeds) between 3 and 10 years of age at the time of purchase. Adaptations were made to automated plasmapheresis instruments and sterile disposable collection sets, which allowed for dual-instrument, continuous-flow operation. Donor horses were connected to the apparatus via 2 catheters (1 inserted in each jugular vein). The instruments removed whole blood from donors, fractionated the blood, diverted plasma to collection bags, and simultaneously returned concentrated cells to the donors. Plasmapheresis was performed on donor horses at 14-day intervals with a maximum of 22 mL of plasma/kg of donor body weight harvested during each plasmapheresis procedure. During a 5-year period, 3,240 plasmapheresis procedures were performed and > 50,000 L of sterile equine plasma was harvested in accordance with current good manufacturing practice. Donors typically remained calm during the plasmapheresis procedures and tolerated the procedures well. The high-volume and frequent plasma harvest did not result in sustained hypoproteinemia in donor horses. Adverse events associated with the automated plasmapheresis technique were infrequent, and the recurrence of adverse events was minimized by making minor adjustments to the procedure. The automated plasmapheresis procedure described in this report can be used to safely harvest equine plasma or to perform therapeutic plasmapheresis in horses.

Effects of serial harvest of plasma on total plasma protein and total immunoglobulin G concentrations in donor horses involved in a plasmapheresis program

To determine the effects of intensive serial plasmapheresis on total plasma protein and total IgG concentrations in donor horses involved in a plasmapheresis program. 18 horses (13 mares and 5 geldings; 13 Belgians, 3 Percherons, 1 Standardbred, and 1 warmblood) ranging from 7 to 14 years of age (mean ± SD, 10 ± 3 years) and weighing 822 ± 128 kg. Horses from which 22 mL of plasma/kg of donor body weight was harvested at 14-day intervals for a minimum of 8 consecutive plasmapheresis donations were retrospectively selected for use in the evaluation. Automated plasmapheresis procedures were performed by use of 2 modified plasmapheresis instruments/donor horse. Plasma samples were obtained at each donation and used for determination of total protein and total IgG concentrations. Total plasma protein concentrations were determined via refractometry. A commercially available ELISA was used to determine total equine IgG concentrations. The 18 donor horses were used in 8 to 19 serial donations (mean ± SD, 13 ± 3 donations) during the study. Donor horses had significant decreases in both plasma protein and IgG concentrations over the study period. Serial plasmapheresis procedures caused significant decreases in both plasma protein and IgG concentrations in donor horses; however, decreases were not physiologically relevant. Performing plasmapheresis in horses in accordance with the evaluated automated plasmapheresis procedures did not result in a critical decrease in total plasma protein or total IgG concentrations.

A Simplified Donor Risk Index for Predicting Outcome After Deceased Donor Kidney Transplantation

We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, P<0.001). A history of donor hypertension was also associated with increased risk (hazard ratio 1.30, P=0.001), and increased donor body weight, longer hospital stay before death, and use of adrenaline were also significantly associated with poorer outcomes up to 3 years posttransplant. Other donor factors including donation after circulatory death, history of cardiothoracic disease, diabetes history, and terminal creatinine were not significant. A donor risk index based on the five significant donor factors was derived and confirmed to be prognostic of outcome in a validation cohort (concordance statistic 0.62). An index developed in the United States by Rao et al., Transplantation 2009; 88: 231-236, included 15 factors and gave a concordance statistic of 0.63 in the UK context, suggesting that our much simpler model has equivalent predictive ability. A Kidney Donor Risk Index based on five donor variables provides a clinically useful tool that may help with organ allocation and informed consent.

First Reported Use of a Biosimilar G-CSF in Allogeneic Stem Cell Mobilisation

Abstract 4571 OBJECTIVES:Biosimilar granulocyte colony-stimulating factor (G-CSF) has been approved on the basis of comparable quality, safety and efficacy as the originator product. Approval of biosimilar G-CSF is in the same indications as the originator, including autologous and allogeneic peripheral blood stem cell (PBSC) mobilisation, for which it is being used throughout our large hospital group in Paris, France. Concerns have been raised by professional bodies over use of biosimilar G-CSF in allogeneic transplants. To our knowledge, this is the first reported use of biosimilar G-CSF in healthy donors for allogeneic transplantation. METHODS:Healthy related donors received biosimilar G-CSF (EP-2006, Sandoz Biopharmaceuticals) 10 μg/kg/day for PBSC mobilisation. G-CSF was administered on days 1–4 with the first leukapheresis performed on day 5. If the required number of CD34+ cells per recipient body weight (4 × 106 CD34+ cells/kg) was not collected, G-CSF administration was continued and a second PBSC collection was performed on day 6. Further G-CSF administration and a third leukapheresis was done on day 7 if required. RESULTS:Twelve healthy donors (7 male, 5 female; mean ± SD age 61.0 ± 7.8 years, range 51–73) received biosimilar G-CSF for PBSC mobilisation. Median donor body weight was 82 kg (range 55–115 kg). Median CD34+ cell count on day 5 was 75/ml (range 23–140). A single leukapheresis after 4 injections of biosimilar G-CSF was sufficient to collect the CD34+ cell dose required in six donors with peripheral blood (PB) CD34+ counts ranging from 80–140 ml. Six donors underwent a second leukapheresis after 5 days of biosimilar G-CSF, one of whom (a 73-year old female) underwent a third leukaphereses on day 7 (PB CD34+ at first apheresis 23 ml). Median number of CD34+ cells per recipient bodyweight was 5.5 × 106 cells/kg (range 2.6–8.9). Five donors reported bone pain (4 mild, 1 moderate severity) which was effectively treated with paracetamol. No other adverse events were reported. Blood measurements were normal in all donors when assessed one week after the end of mobilisation. These findings are consistent with our previous use of originator G-CSF (Neupogen®) in allogeneic stem cell mobilisation. CONCLUSION:These preliminary findings suggest biosimilar G-CSF is effective and well-tolerated in allogeneic stem cell mobilisation. Further studies are required to assess longer-term safety outcomes. The use of biosimilar G-CSF may provide important cost-savings when compared with the originator product. Disclosures:No relevant conflicts of interest to declare.

Islet isolation from adult designated pathogen‐free pigs: use of the newer bovine nervous tissue–free enzymes and a revised donor selection strategy would improve the islet graft function

In clinical trials using adult porcine islet products, islets should be isolated from the designated pathogen-free (DPF) pigs under the current good manufacturing practice (GMP) regulations. Our previous studies suggested that male DPF pigs are better donors than retired breeder pigs and histomorphometrical parameters of donor pancreas predict the porcine islet quality. We aimed to investigate whether the use of the newer bovine nervous tissue-free enzymes and a revised donor selection strategy could improve the islet graft function in the context of islet isolation with DPF pigs. Using 30 DPF pigs within a closed herd, we compared the islet yield of porcine islets isolated with Liberase PI (n = 11, as a historical control group), Liberase MTF C/T, which is a GMP-grade enzyme (n = 12), and CIzyme collagenase MA/BP protease (n = 7). We analyzed the relationship between the diabetes reversal rate of recipient NOD/SCID mice (n = 75) and histomorphometric parameters of each donor pancreas as well as donor characteristics. Proportion of islets larger than 200 μm from the biopsied donor pancreas (P = 0.006) better predicted islet yield than age (P = 0.760) or body weight (P = 0.371) of donor. The proportion of islets larger than 200 μm from the biopsied donor pancreas was not related to the sex of the donor miniature pig (P = 0.358). The islet yield obtained with the three enzymes did not differ, even after stratification of the donor with the histomorphometric parameters of the biopsied donor pancreas and the sex of donor. The use of the newer bovine nervous tissue-free enzymes (P < 0.001), a higher proportion of large islets in donor pancreas (P = 0.006), and a male sex of the donor (P = 0.025) were independent predictors of earlier diabetes reversal. Use of the newer bovine nervous tissue-free enzymes including a GMP-grade enzyme resulted in better islet quality than that of islet isolated using Liberase PI. To obtain high-quality islet from DPF pigs, the donor should be male pig and histomorphometrical parameters from donor pancreas should be considered.

“Consideration not Promotion”: In Selected Cases, We Can Try to Increase Donor Body Weight to Increase Graft Volume in Living Donor Liver Transplantation: Reply

“Consideration not Promotion”: In Selected Cases, We Can Try to Increase Donor Body Weight to Increase Graft Volume in Living Donor Liver Transplantation: Reply

Should We Promote “Increasing Donor Body Weight To Prevent Small‐for‐Size Syndrome in Living Donor Liver Transplantation”?

Should We Promote “Increasing Donor Body Weight To Prevent Small‐for‐Size Syndrome in Living Donor Liver Transplantation”?

Pediatric patients receiving ABO-incompatible living related liver transplantation exhibit higher serum transforming growth factor-β1, interferon-γ and interleukin-2 levels

ABO-incompatible liver transplantation (LTx) is becoming more common in response to the paucity of liver allografts. Several studies have expressed concern about the effect of ABO compatibility on graft survival. To evaluate the differences in serum cytokine levels between ABO-incompatible (ABO-i) and ABO-compatible (ABO-c; includes ABO-compatible and identical) pediatric LTx recipients during regular outpatient follow-up. Note that, in the field of organ transplantation, transplants are categorized as incompatible, compatible or identical; accordingly, these are the terms we use in the paper. A clinical outpatient study measuring serum transforming growth factor (TGF)-β1, interferon (IFN)-γ, interleukin (IL)-2 and IL-10 in 43 living related liver transplantation (LRLT) recipients, of whom 36 received ABO-c LRLT (34 were ABO-identical and 2 were non-identical) and 7 ABO-i LRLT. Serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase and bilirubin were measured as part of the patients' regular follow-up visits. There were no differences between the ABO-c and ABO-i groups in terms of recipient's age [mean 12.6 vs. 11.1years (y)], post-LTx duration (mean 7.3 vs. 7.3y), donor's age (mean 35.5 vs. 34.6y), body weight (28.9±2.9 vs. 27.9±6.9kg), or gender (19 female and 17 male vs. 4 female and 3 male). Serum TGF-β1, IFN-γ and IL-2 were significantly higher in the ABO-i group than in the ABO-c group. IL-10, however, did not differ between the two groups. There was a tendency toward higher γGTP levels in the ABO-i group, but this difference did not reach significance. ABO-incompatible LRLTx patients have higher serum TGF-β1, IFN-γ and IL-2 levels as measured at regular outpatient visits. As a result, they face a higher risk of T-helper 1 cell polarization, which could make graft rejection more likely.

Effects of a surface matching articular resurfacing device on tibiofemoral contact pressure: results from continuous dynamic flexion–extension cycles

The application of a defect-size metal implant for the treatment of focal articular cartilage lesions of the femoral condyle is of potential concern resulting in cartilage damage to opposing biological structures. This in vitro study aims to determine the tibiofemoral contact pressure with a contoured articular partial femoral resurfacing device under continuous dynamic pressure loads. Peak and area contact pressures were determined in eight fresh-frozen cadaveric specimens using a pressure-sensitive sensor placed in the medial compartment above the menisci. All knees were tested in the untreated condition and after implantation of the prosthetic device in the weight-bearing area of the medial femoral condyle. A robotic knee simulator was used to test each knee under continuous pressure load for 400s during 40 dynamic knee bending cycles (5°-45° flexion) with body weight ground reaction force (GRF). The GRF was adjusted to the living body weight of the cadaver donor and maintained throughout all cycles. Comparison of the untreated condition to focal inlay resurfacing showed no statistically significant differences (P≤0.05) between all testing conditions. The average maximum peak contact pressure across all 40 flexion cycles increased by 5.1% after resurfacing compared to the untreated knees. The average area contact pressure essentially stayed the same (+0.9%). The data suggest that resurfacing with the contoured articular prosthetic device does not pose any immediate deleterious effects to the opposing surfaces based on peak and area contact pressure in a continuous dynamic in vitro application. However, long-term in vivo effects remain to be evaluated.

Single Kidney Transplantation from Young Pediatric Donors in the United States

To the Editor: In a recent issue of the American Journal of Transplantation, Kayler et al. reported on kidney transplantations from very young donors (1Kayler LK Magliocca J Kim RD et al.Single kidney transplantation from young pediatric donors in the United States.Am J Transplant. 2009; 9: 2745-2751Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar). In general, the elaborated analysis confirms the excellent results after pediatric en bloc kidney transplantation published by our group and others (2Thomusch O Tittelbach‐Helmrich D Meyer S et al.Twenty‐year graft survival and graft function analysis by a matched pair study between pediatric en bloc kidney and deceased adult donors grafts.Transplantation. 2009; 88: 920-925Crossref PubMed Scopus (39) Google Scholar, 3Sureshkumar KK Reddy CS Nghiem DD et al.Superiority of pediatric en bloc renal allografts over living donor kidneys: A long‐term functional study.Transplantation. 2006; 82: 348-353Crossref PubMed Scopus (68) Google Scholar, 4Dharnidharka VR Stevens G Howard RJ En‐bloc kidney transplantation in the United States: An analysis of United Network of Organ Sharing (UNOS) data from 1987–2003.Am J Transplant. 2005; 5: 1513-1517Crossref PubMed Scopus (65) Google Scholar). However, we disagree with the conclusion drawn from Kayler et al. (1Kayler LK Magliocca J Kim RD et al.Single kidney transplantation from young pediatric donors in the United States.Am J Transplant. 2009; 9: 2745-2751Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar) that the cut‐off for split versus en bloc kidney transplantation from very young donors ought to be set at a donor weight of 10 kg. Our first objection is that Kaylers’ analysis excludes the top and bottom percentiles. Especially the removal of very low‐weight donors may skew the results, because these very young donors (<12 months or <10 kg) present most complications and the highest risk for early graft loss. Furthermore, as shown by Kayler et al., early splitting in donors between 10 and 20 kg leads to results comparable with those from marginal adult donors. In contrast to Kaylers’ statement, we do not regard en bloc transplanted kidneys from young donors up to 20 kg as equal to organs from marginal donors, but as excellent organs (GFR approx. 100 mL/min 10 years after transplantation (2Thomusch O Tittelbach‐Helmrich D Meyer S et al.Twenty‐year graft survival and graft function analysis by a matched pair study between pediatric en bloc kidney and deceased adult donors grafts.Transplantation. 2009; 88: 920-925Crossref PubMed Scopus (39) Google Scholar)) with an increased risk of initial graft loss. In addition, Kayler et al. fail to consider the importance of adequate recipient selection criteria. In our experience, a recipient's BMI of less than 25 kg/m2, a recipient to donor body weight ratio between 0.2 and 0.25 as well as the absence of renal hypertension play a key role for transplantation outcome, especially following pediatric single and en bloc kidney transplantation. Moreover, en bloc kidney transplantation from pediatric donors is a surgical and technical challenge. This difficulty becomes even further pronounced after organ splitting. Thus, dividing en bloc kidneys does not always yield two transplantable organs due to an increased rate of discarded grafts. Finally, because of the high mortality rate of patients on the waiting list, the aim of transplantation should not be a high number of transplanted kidneys but primarily a good long‐term organ function, a low number of graft losses during follow‐up, and a good patient quality‐of‐life after kidney transplantation. For the above reasons, we advocate setting the cut‐off for organ splitting at a donor weight of 20 kg.

Increasing Donor Body Weight to Prevent Small‐for‐Size Syndrome in Living Donor Liver Transplantation

This study was designed to evaluate the possibility of avoiding small-for-size syndrome (SFSS) in living donor liver transplantation (LDLT) by increasing the donor's body weight (BW) before liver donation. Nineteen participants, including 15 volunteers and 4 liver donors, were enrolled in this study to increase their BW by 1.5-5 kg within 3 months by eating a high-protein and high-carbohydrate diet according to a flexible formula to increase calorie intake. Fifteen participants, including 12 volunteers and 3 live liver donors, successfully increased their BW by 1.5-5 kg within 3 months (failure rate, 21%). The actual liver weight (LW) gain was more than the expected LW gain using the formula for calculating standard liver volume (2.77- to 8.94-fold; median, 4.49-fold; mean, 4.45-fold, P < 0.005) and using the ratio of liver weight to body weight (1.36- to 4.49-fold; median, 2.01-fold; mean, 2.06-fold, P < 0.005). The enlargement of the livers was symmetrical without significant fatty change. The graft-versus-recipient weight ratio increased 0.17%, 0.07%, and 0.08%, respectively, for the three live liver donors and successful LDLTs were performed. By having liver donors eat a high-protein, high-carbohydrate diet to increase their BW in a short period of time, the actual LW may increase more than the expected LW gain without fatty change. This method of increasing LW may be used in selected cases of LDLT to avoid SFSS.

Increasing Donor Body Weight to Prevent Small‐for‐Size Syndrome in Living Donor Liver Transplantation

The Hollywood actress Renee Zellweger famously put on 20 lb in weight to make her appearance more suitable for the title role in the successful film Bridget Jones’s Diary [1]. In this issue of the World Journal of Surgery, Liu and colleagues from Taipei have advocated that in certain cases, potential living liver donors could be asked to gain weight, to increase the size of the future donor liver [2]. There is a clear association between graft recipient weight ratio and risk of development of small-for-size syndrome in living donor liver transplantation. Thus increasing the future liver may be a mechanism of reducing risk to the recipient. Normally, weight gain is seen in the context of potential health disadvantage, and so this article represents a somewhat controversial but very novel approach to the problem of a potentially small liver for donation. One of the fundamental questions in this approach is whether the whole body weight gain is detrimental not only to the health of the donor but also to the quality of the liver. Current evidence seems to suggest that an excessive and long-term increase in body weight is associated with an increase in the fat content of the liver and a higher risk of developing metabolic syndrome [3]. This may lead to fatty liver diseases (NAFLD or NASH) that are a fast rising indication for transplantation. Liu and colleagues challenge this concept and demonstrate that a short and well-controlled period of body weight gain does not translate into a deterioration of the liver quality. Instead, it leads to an increase in the overall liver volume that allows for a safe donation and transplantation. It is conceivable that the changes seen by Liu et al. are partially due to the high protein and carbohydrate diet, a strict control of weight gain, and the lack of pre-existent fatty changes in the liver. This short-lived weight gain seems to be rapidly reversible. Following cessation of the weight gain in the volunteers or completion of the donation process, a return to the initial body weight parameters appears to have taken place in all patients, without any immediate ill effects. Although this answers the question of immediate risks, it remains to be seen whether this rapid fluctuation in weight has any longterm impact on the donor’s health, increasing the risk of cardiovascular disease or the susceptibility to develop a metabolic syndrome later in life. This controversial approach has paid off and recipients received an appropriately sized graft that prevented the development of small for size syndrome. Our understanding of the pathophysiology of small-for-size syndrome and its clinical implications has made tremendous progress in recent years [4]. Several strategies for improving the outcome are now well established. One could argue that a less controversial approach, concentrating on recipient measures with inflow modulation, rather than donor weight modulation, is likely to be more successful and would be ethically more acceptable. Nevertheless, in a system where living liver donation is the only realistic option, and when there are no other potential donors for a given recipient, such an approach will save the life of patients who would otherwise have no alternative. Clearly, this is not a ‘‘one for all’’ measure, and the authors point out that only a few selected (and determined, G. C. Oniscu Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK

Pediatric Sibling Donor Complications of Hematopoietic Stem Cell Collection: EBMT Pediatric Diseases Working Party Study.

Abstract 806 Objective:The analysis of donor safety and early side effects related to hematopoietic stem cells (HSC) collection from bone marrow (BM) or peripheral blood (PB) in pediatric HLA-identical sibling donors. Methods:From 2005 to 2009, data regarding pediatric (<18 years) sibling donors undergoing HSC collection from 38 participating EBMT Centers were registered on specific forms sent to the PDWP Office. Data were centrally analyzed as of July 2009. A multiple logistic regression was performed to express an estimate of the relative risk of BM versus PB donation for the following variables: pain, blood transfusion, prolonged hospital stay, and need for iron supplementation. Results:A total number of 410 pediatric sibling donors with median age of 9 (range; 0.3-18) years were enrolled into the study; including 12% aged <4 yrs and 64% with body weight <40 kg. Children donated BM in 272 (66%), and PB in 138 (34%) cases. The criteria used by transplant centers for PB-HSC collection in children were: discrepancy between donor and recipient body weight, parents decision, undergoing clinical trial (pediatric centers), or transplant protocol (adult centers). Consents for donation were given by parents (49%), court (23%), ethical committee (28%) or social board (0.4%). All BM and 56% of PB donors had general anesthesia (PB donors for central catheter placement), for a median 90 (range; 30-300) and 30 (range 8-285) minutes, respectively. One (0.2%) serious adverse event (SAE) was reported (pneumothorax+hydrothorax) after catheter placement for PB collection. Tachycardia, decrease of blood pressure, sore throat or vomiting after anesthesia occurred in 5-11% cases. Autologous blood transfusion was done in 26% of BM and 7% of PB donors, at median age of 12 years (range 2.8-18). Erythropoietin was administered in 23 BM donors. BM was collected in median volume 18.8 (range; 2-49) ml/kg of donor weight and no severe complications of BM collection were observed. G-CSF priming was performed in all PB donors with median G-CSF dose of 10 (range; 5-20) mcg/kg/day. Median WBC count before collection was 46 (range; 24-101) G/L. Muscle/bone pain, fever, headache, abdominal or back pain, nausea or vomiting related to G-SCF were reported only in 6% of PB donors. Median number of apheresis was 1 (range; 1-3), which lasted for a median of 4 (range; 2-8) hrs. 21% donors experienced hypocalcemia. Thrombocytopenia <70G/L occurred in 3% of PB donors, however platelet transfusion was not required in any case. Blood allotransfusion was done in 23% of BM and 2.6% of PB donors. Iron was supplemented in 73% of BM and 31% of PB donors (p<0.001). Pain after collection occurred in 64% of BM and 15% of PB donors (p<0.001) and persisted for median of 1 day (range; 1-21 for BM and 1-3 for PB donors, respectively). No infections or thrombotic events were reported. Median number of nights spent in hospital before collection was 1 (range; 0-14) for BM and 3 (range; 0-7) for PB donors; while after collection 1 (range; 0-7) for BM and 0 (range; 0-6) for PB donors (p<0.001). Donors felt helpful, happy and proud in most cases, irrespectively of stem cell source. They felt responsible for recipient in 58% of BM and 53% of PB of donors (ns). Willingness to donate again was expressed by 86% and 71% of the BM and PB of donors, respectively (p=0.007). In multiple logistic regression analysis following complications and risk factors were determined: pain (BM collection, OR=12.3, p<0.001; age >4 yrs, OR=9.9, p<0.001), blood allotransfusion (BM collection, OR=22.7, p<0.001; body weight <40 kg, OR=4, p=0.004), prolonged hospital stay (BM collection, OR=3.5, p<0.001), and need for iron supplementation (BM collection, OR=6.9, p<0.001). Conclusions:BM or PB HSC collection in pediatric sibling donors is safe, however there is a risk of mild, short-term and easy to prevent or control early side effects. The risk of SAE in healthy pediatric donors exists, although it is small. Donors and parents must be informed about the risk of possible complication. There is a need of donor outcome and follow-up registry. Disclosures:No relevant conflicts of interest to declare.

Interactions among donor characteristics influence post-transplant survival: A multi-institutional analysis

Quantification of donor-associated risk in a specific heart transplant recipient is often difficult. Our aim was to identify donor characteristics that affect survival in the contemporary era. Between 1990 and 2006, 7,322 patients from 32 centers in the Cardiac Transplant Research Database underwent heart transplantation. Multivariable logistic regression analysis was used to identify donor-associated risk predictors and important interactions between these donor characteristics. Recipient survival was examined using parametric regression analysis in the hazard function domain. Donor characteristics associated with post-transplant death included donor age, donor requirement for vasoactive therapy, positive donor cytomegalovirus serology, longer graft ischemic time, and lower donor body weight. Several interactions between individual donor characteristics affected survival. In male donors, history of hypertension and diabetes mellitus were risk factors for death (p = 0.006, p = 0.04, respectively), but not in female donors (p = 0.5, p = 0.8, respectively). There was a significant interaction between donor age and recipient-donor weight difference. If the donor was of younger age, increasing recipient-donor weight difference did not result in increased death. With increasing donor age, weight difference did result in compromised survival (p < 0.0003). Donor and recipient gender further modified the degree of risk: risk was higher in female donors and when recipients were male (p < 0.0003). This multi-institutional analysis identified important interactions between donor characteristics that affect post-transplant survival that explain some of the discrepancies in the results of previous studies. The results are likely to aid in efficient organ allocation.