The UK kidney donor risk index poorly predicts long-term transplant survival in paediatric kidney transplant recipients.

Background: The UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry. Methods: We performed Cox survival analysis on first kidney-only deceased brain-dead transplants in paediatric (<18 years) recipients from 2000-2014. The primary outcome was death-censored allograft survival >30 days post-transplant. The main study variable was UK-KDRI derived from seven donor risk-factors, categorised into four groups (D1-low risk, D2, D3 and D4-highest risk). Follow-up ended on 31-December-2021. Results: 319/908 patients experienced transplant loss with rejection as the main cause (55%). The majority of paediatric patients received donors from D1 donors (64%). There was an increase in D2-4 donors during the study period, whilst the level of HLA mismatching improved. The KDRI was not associated with allograft failure. In multi-variate analysis, increasing recipient age [adjusted HR and 95%CI: 1.05(1.03-1.08) per-year, p<0.001], recipient minority ethnic group [1.28(1.01-1.63), p<0.05), dialysis before transplant [1.38(1.04-1.81), p<0.005], donor height [0.99 (0.98-1.00) per centimetre, p<0.05] and level of HLA mismatch [Level 3: 1.92(1.19-3.11); Level 4: 2.40(1.26-4.58) versus Level 1, p<0.01] were associated with worse outcomes. Patients with Level 1 and 2 HLA mismatches (0 DR +0/1 B mismatch) had median graft survival >17 years regardless of UK-KDRI groups. Increasing donor age was marginally associated with worse allograft survival [1.01 (1.00-1.01) per year, p=0.05]. Summary: Adult donor risk scores were not associated with long-term allograft survival in paediatric patients. The level of HLA mismatch had the most profound effect on survival. Risk models based on adult data alone may not have the same validity for paediatric patients and therefore all age-groups should be included in future risk prediction models.

Kidney Donor Profile Index and allograft outcomes: interactive effects of estimated post-transplant survival score and ischaemic time.

Background: The Kidney Donor Profile Index (KDPI) is routinely reported by the donation agencies in Australia. We determined the association between KDPI and short-term allograft loss and assessed if this association was modified by the estimated post-transplant survival (EPTS) score and total ischaemic time. Methods: Using data from the Australia and New Zealand Dialysis and Transplant Registry, the association between KDPI (in quartiles) and 3-year overall allograft loss was examined using adjusted Cox regression analysis. The interactive effects between KDPI, EPTS score and total ischaemic time on allograft loss were assessed. Results: Of 4006 deceased donor kidney transplant recipients transplanted between 2010 and 2015, 451 (11%) recipients experienced allograft loss within 3 years post-transplant. Compared with recipients of kidneys with a KDPI of 0-25%, recipients who received donor kidneys with a KDPI >75% experienced a 2-fold increased risk of 3-year allograft loss {adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.53-2.71]}. The adjusted HRs for kidneys with a KDPI of 26-50% and 51-75% were 1.27 (95% CI 0.94-1.71) and 1.31 (95% CI 0.96-1.77), respectively. There were significant interactions between KDPI and EPTS scores (P-value for interaction <.01) and total ischaemic time (P-value for interaction <.01) such that the associations between higher KDPI quartiles and 3-year allograft loss were strongest in recipients with the lowest EPTS scores and longest total ischaemic time. Conclusion: Recipients with higher post-transplant expected survival and transplants with longer total ischaemia who received donor allografts with higher KDPI scores experienced a greater risk of short-term allograft loss compared with those recipients with reduced post-transplant expected survival and with shorter total ischemia.

A Long-Term Prospective Study of Quality of Life, Abdominal Symptoms, and Cosmesis of Donors After Hepatectomy for Live-Donor Liver Transplantation.

BACKGROUND: Comprehensive assessment of quality of life of live liver donors is required for adequate donor outcome reporting, but there is a lack of prospective data. Assessment of all aspects of liver donation over a long period is a necessity to have complete understanding of the donation process. METHODS: Prospectively collected data of liver donors operated between March 2012 to August 2013, examined donors (n = 52) from predonation to five years after the donation. Participants were administered 'World Health Organization quality of life Brief and questionnaires' regarding their attitude predonation, their overall well-being in terms of abdominal symptoms, cosmesis, and satisfaction with donation and consent process at predefined time points till five years after donation. The weight of the donors was recorded at predefined time points. RESULTS: The donors whose recipients died were less likely to continue with the study (8.9% vs. 71.4%; P < 0.001). After surgery, physical domain took 2 years to reach to predonation level while psychological and social relationship domains took 3 months and 1 month, respectively; environmental domain remained stable throughout. Even after recovery and discharge from hospital, donors experienced abdominal symptoms for a long period of time, but as the time increased from donation the reporting of symptoms decreased. Body image scores (12 ± 2.46 at 3 months vs. 14.9 ± 3.16 at five years, P < 0.001) and cosmesis scores (14.6 ± 3.67 at 3 months vs. 18.75 ± 3 at five years, P < 0.001) significantly improved over time. There was significant weight gain in donors (65.2 ± 6.1 kg predonation vs. 70.69 ± 2.4 kg at 2 years P < 0.001). Donors understood the consent process well, but did not use it for decision making. Overall, they showed a high level of satisfaction in the donation process. CONCLUSION: Donors have good quality of life and show steady recovery in all aspects. Recipient death affects attitude towards donation process.

Donor ventilation parameters as predictors for length of mechanical ventilation after lung transplantation: Results of a prospective multicenter study.

BACKGROUND: The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval. METHODS: A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV. RESULTS: In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20-63 hours). Peak inspiratory pressure and dynamic compliance (Cdyn) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = -0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and Cdyn was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293). CONCLUSION: In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that Cdyn is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.

Donor wound satisfaction after living-donor liver transplantation in the era of pure laparoscopic donor hepatectomy.

BACKGROUND: Donor safety and cosmetic outcome are the main concerns raised by most living-donors. Pure laparoscopic living-donor hepatectomy (PLLDH) can provide the balance between those concerns. No studies evaluated the donors' satisfaction after PLLDH. The aim of this study is to evaluate the donors' satisfaction after PLLDH compared with donors who underwent open approach. METHODS: We randomly assigned a questionnaire (Donor satisfaction questionnaire) to the donors, operated between 2011 and 2017, during their follow-up visits in the outpatient clinic. Donors who responded to the questionnaire were included in our study. Donors were divided into 3 groups: L group (conventional inverted L incision), M group (midline incision), and PL group (laparoscopic approach). RESULTS: 149 donors were included in our study. L group included 60 donors (40.3%), M group included 39 patients (26.2%), and PL group included 50 patients (33.5%). There were no significant differences between the groups regarding preoperative and perioperative outcomes apart from shorter operation time in PL group and higher wound infection in M group. Body image scale was significantly better in PL group (p = 0.001). Cosmetic scale was significantly higher in PL group (p = 0.001). Regarding self-confidence scale, it was significantly higher in PL group (p = 0.001). There was no significant difference between the groups regarding the sense of dullness or numbness on the scar (p = 0.113). CONCLUSION: PLLDH is safe and feasible for living-donor hepatectomy. Donors operated by pure laparoscopic approach have better satisfaction scores compared to conventional open approach.

Donor Kidney Quality and Transplant Outcome: An Economic Evaluation of Contemporary Practice.

OBJECTIVES: The study had two main aims. First, we assessed the cost-effectiveness of transplanting deceased donor kidneys of differing quality levels based on the Kidney Donor Profile Index (KDPI). Second, we assessed the cost-effectiveness of remaining on the waiting list until a high-quality kidney becomes available compared to transplanting a lower-quality kidney. METHODS: A decision analytic model to estimate cost-effectiveness was developed using a Markov process. Separate models were developed for 4 separate KDPI bands, with higher values indicating lower quality. Models were simulated in 1-year cycles for a 20-year time horizon, with transitions through distinct health states relevant to the kidney recipient from the healthcare payer's perspective. Weibull regression was used to calculate the time-dependent transition probabilities in the base analysis. The impact uncertainty arising in model parameters was included by probabilistic sensitivity analysis using the Monte Carlo simulation method. Willingness to pay was considered as Australian $28 000. RESULTS: Transplanting a kidney of any quality is cost-effective compared to remaining on a waitlist. Transplanting a lower KDPI kidney is cost-effective compared to a higher KDPI kidney. Transplanting lower KDPI kidneys to younger patients and higher KDPI kidneys to older patients is also cost-effective. Depending on dialysis in hopes of receiving a lower KDPI kidney is not a cost-effective strategy for any age group. CONCLUSION: Efforts should be made by the health systems to reduce the discard rates of low-quality kidneys with the view of increasing the transplant rates.

Should we use liver grafts repeatedly refused by other transplant teams?

BACKGROUND & AIMS: In France, liver grafts that have been refused at least 5 times can be "rescued" and allocated to a centre which chooses a recipient from its own waiting list, outside the patient-based allocation framework. We explored whether these "rescued" grafts were associated with worse graft/patient survival, as well as assessing their effect on survival benefit. METHODS: Among 7,895 candidates, 5,218 were transplanted between 2009 and 2014 (336 centre-allocated). We compared recipient/graft survival between patient allocation and centre allocation, considering a selection bias and the distribution of centre-allocation recipients among the transplant teams. We used a propensity score approach and a weighted Cox model using the inverse probability of treatment weighting method. We also explored the survival benefit associated with centre-allocation grafts. RESULTS: There was a significantly higher risk of graft loss/death in the centre allocation group compared to the patient allocation group (hazard ratio 1.13; 95% CI 1.05-1.22). However, this difference was no longer significant for teams that performed more than 7% of the centre-allocation transplantations. Moreover, receiving a centre-allocation graft, compared to remaining on the waiting list and possibly later receiving a patient-allocation graft, did not convey a poorer survival benefit (hazard ratio 0.80; 95% CI 0.60-1.08). CONCLUSIONS: In centres which transplanted most of the centre-allocation grafts, using grafts repeatedly refused for top-listed candidates was not detrimental. Given the organ shortage, our findings should encourage policy makers to restrict centre-allocation grafts to targeted centres. LAY SUMMARY: "Centre allocation" (CA) made it possible to save 6 out of 100 available liver grafts that had been refused at least 5 times for use in the top-listed candidates on the national waiting list. In this series, the largest on this topic, we showed that, in centres which transplanted most of the CA grafts, using grafts repeatedly refused for top-listed candidates did not appear to be detrimental. In the context of organ shortage, our results, which could be of interest for any country using this CA strategy, should encourage policy makers to reassess some aspects of graft allocation by restricting CA grafts to targeted centres, fostering the "best" matching between grafts and candidates on the waiting list.

Sequence of refusals for donor quality, organ utilization, and survival after lung transplantation.

BACKGROUND: Lung donor utilization rates remain low, with many organs refused for donor quality. However, some centers have successfully transplanted these organs despite multiple refusals for donor quality (RDQs) by other centers. We hypothesized that the number of refusals due to donor quality does not impact post-transplant outcomes. METHODS: Lung transplants (LTxs) from 2006 to 2015, identified using the United Network for Organ Sharing (UNOS) database, were matched against the potential transplant recipient (PTR) data set by donor identification. Transplants were categorized into 2 groups: low RDQ (0 to 3 RDQs) and high RDQ (>3 RDQs). Post-transplant survival and predictors for high RDQ were observed using Kaplan‒Meier and logistic regression analyses, respectively. RESULTS: Of 10,126 adult (>18 years) LTxs, 77% had at least 1 RDQ, with a median of 4 RDQs. Post-transplant 1-year survival was similar for both the low and high RDQ groups (p = 0.49). Furthermore, groups of recipients who received donors with an increasing number of RDQs (>3, >6, or >10) also had similar post-transplant 1-year survival (p = 0.77). Treatment for rejection within 1 year and intubation at 72 hours post-transplant were higher in the high RDQ group (p < 0.01). An inverse relationship was identified between the number of RDQs and likelihood of utilization. After 10 RDQs, the likelihood of utilization varied significantly by donor characteristics. CONCLUSIONS: Lung transplant survival is not associated with number of refusals due to donor quality. When determining whether an organ is suitable for transplant, the number of refusals due to donor quality should not influence one's decision, especially in this era of limited donor supply.

Quantification of hepatic functional capacity: a call for standardization.

Reliable assessments of liver function are becoming increasingly important as more patients with surgically amenable liver disease are considered for treatment. Static markers of liver function are not sufficient to provide accurate assessments of hepatic function in order to risk stratify patients undergoing hepatic resection. Metabolic tests are dynamic indicators of liver function, but can be unreliable under certain conditions and thus difficult to make comparisons. Clearance tests avoid some of the pitfalls encountered during metabolic testing, but depend on hepatic blood flow and say little about hepatocyte function. Testing that combines imaging with measures of hepatocyte uptake may offer the most utility when planning surgical resections.

Effect of Donor Graft Quality on Clinical Outcomes After Penetrating Keratoplasty for Keratoconus.

PURPOSE: To evaluate the effect of donor and eye bank characteristics on graft rating and clinical outcomes after penetrating keratoplasty (PK) for keratoconus. METHODS: This retrospective interventional case series included 252 keratoconic eyes which underwent PK. Donor data included age and sex, cause of death, death-to-preservation time, preservation-to-surgery time, epithelial and stromal status, endothelial cell density (ECD) and morphology, and graft rating. Postoperative outcomes included visual acuity, refractive error, epithelial problems, suture-related complications, graft rejection, and graft transparency. Multivariate regression analysis assessed correlations between donor and eye bank characteristics and graft quality, and postoperative outcomes. RESULTS: Mean recipient and donor age was 29.7 ± 10.0 and 26.2 ± 8.8 years, respectively and mean follow-up period was 66.7 ± 38.5 months. Death-to-preservation time was significantly associated with the presence of graft epithelial sloughing (P = 0.005) and stromal cloudiness (P < 0.001). Donor age significantly influenced ECD (P = 0.02), mean cell area (P = 0.04), and hexagonality (P = 0.01). The presence of epithelial defects on postoperative day 1 correlated significantly with death-to-preservation time (P = 0.004). Graft stromal edema on postoperative day 1 was significantly associated with graft epithelial sloughing (P < 0.001). Postoperative visual and refractive outcomes, complications, and graft survival were not correlated with any donor or eye bank factors. CONCLUSION: Donor and eye bank variables affected the quality of donor corneas and early postoperative course. However, their long term effect on clinical outcomes, complications, and graft survival were insignificant.

Histopathologic and molecular evaluation of the Organ Procurement and Transplantation Network selection criteria for intestinal graft donation.

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) has formulated criteria for the selection of donors for intestinal transplantation. To date, however, no study has correlated histologic findings of intestinal injury with the OPTN criteria. We aimed to describe histopathologic and molecular features of allograft injury in relation to donor conditions defined by the OPTN criteria. MATERIALS AND METHODS: Graft histology (Park Score), Claudin-3 staining, systemic inflammatory markers (C-reactive protein/lipopolysaccharide-binding protein) and expression of heat shock protein 70, heme oxygenase 1, and interleukin 6 were evaluated in multiorgan deceased donors (donation after brain death [DBD] and donation after cardiac death [DCD]). RESULTS: Ninety-seven samples (52 jejunum/45 ileum) were recovered from 59 donors (46 DBD/13 DCD). The OPTN criterion cold ischemia time correlated with histologic injury (Park score) to which the jejunum appeared more susceptible than the ileum. Claudin-3 staining was higher, and heat shock protein 70 expression lower in donors meeting the OPTN criteria compared with donors not meeting the criteria and in DBD versus DCD. In DBD donors, interleukin 6 expression was higher compared with DCD donors and inversely related to C-reactive protein. CONCLUSIONS: Our multiparameter analysis suggests that the OPTN criteria can be discriminative concerning intestinal graft quality. Our data suggest that DCD intestinal allografts are qualitatively inferior and that the jejunum is more sensitive to ischemia than the ileum.

Non-standard kidneys for transplants: clinical margins, medical morality, and the law.

Advances in kidney transplantation over the past six decades have been impressive, but have not eliminated the significant variability in outcome related to donor organ quality. Organ shortage means that, in addition to 'standard' deceased donor kidneys (SD), 'non-standard donor' (NSD), 'expanded criteria donor', or 'marginal' kidneys, which fail to meet standard criteria and are often associated with less good outcomes, are now being transplanted into selected recipients as a means of increasing the donor pool. A similar, but less-documented, practice has developed in living donation. This article outlines the clinical rationale and ethical argument underpinning the use of such donor kidneys and examines their legal status in the UK, which we claim remains largely undefined and untested. While it is probable that the general principles governing medico-legal consent and liability also apply to organ donation, the special circumstances of donation, notably the inadequate supply of donors and the emphasis on a 'gift relationship', make it difficult to know how far existing medico-legal precedents can or should apply. The non-standard status of deceased donor organs creates potential problems for the validity of 'appropriate consent' to donation required by statute. It may also be relevant to the use of interventions intended to optimise deceased donor organ quality. Furthermore, the SD/NSD distinction in clinical practice may produce unexpected legal effects. For example, the recent UK Regulations 2012, which bring into force the EU Directive on standards of quality and safety of human organs intended for transplantation, could produce a negative legal restraint on the use of NSD kidneys. There is an urgent need for clarification of the effect of using NSDs in areas such as recipient and donor consent, liability for negligence, and the law of product liability.  Some argue that the need for non-standard organs results from society's failure to compel the retrieval of all suitable standard organs from the deceased as a community resource. However, the Human Tissue Acts of 2004 and 2006 (Scotland), which govern organ donation and transplantation in the UK, expressly require individual consent or authorisation in the decision to donate. This emphasis on individual autonomy appears to chime with prevailing public opinion. However, the sense of medico-legal security gained by uncritical observance of the existing law and of directives published under its authority may be an obstacle to the development of a system which adequately meets the needs of recipients while safeguarding donor autonomy.