The Discussion of Sexual Dysfunction Before and After Kidney Transplantation From the Perspective of the Renal Transplant Surgeon.

INTRODUCTION: Sexual dysfunction (SD) is a common problem in chronic kidney disease (CKD) and endures in 50% of patients after kidney transplantation (KTx), diminishing patients' expectations of life after KTx. Unfortunately, SD is often ignored by renal care providers. Research questions as part of a research project among all renal care providers, transplant surgeons' perspectives were obtained on sexual health care for KTx recipients, including their opinion on who should be accountable for this care. In addition, surgeons' practice and knowledge regarding SD were evaluated. DESIGN: A 39-item questionnaire was sent to all Dutch surgeons and residents specialized in KTx (n = 47). RESULTS: Response was 63.8%. None of the respondents discussed SD with their patients, before or after surgery. Most important barrier was that surgeons do not feel accountable for it (73.9%); 91.7% thought this accountability should lie with the nephrologist. Another barrier was insufficient knowledge (39.1%). In 75% of the respondents, (almost) no knowledge regarding SD was present and 87.5% noticed education on SD was insufficient during residence training. DISCUSSION: Dutch renal transplant surgeons rarely discuss SD with their patients with CKD, as they do not feel accountable for it; this accountability was appointed to the nephrologist. Knowledge and education regarding SD were found insufficient in enabling surgeons and for some it reflects in barriers toward discussing SD. Results emphasize that accountability for providing sexual health care to patients with CKD should lie elsewhere; however, surgeons could briefly provide information on sexual health after KTx, so unfulfilled expectations may be prevented.

Defective postreperfusion metabolic recovery directly associates with incident delayed graft function.

Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that included sequential establishment of postreperfusion arteriovenous concentration differences over the human graft, metabolomic and genomic analysis in tissue biopsies taken before and after reperfusion, we tested whether the preclinical observations translate to the context of clinical DGF. This report is based on sequential studies of 66 eligible patients of which 22 experienced DGF. Grafts with no DGF immediately recovered aerobic respiration as indicated by prompt cessation of lactate release following reperfusion. In contrast, grafts with DGF failed to recover aerobic respiration and showed persistent adenosine triphosphate catabolism indicated by a significant persistently low post reperfusion tissue glucose-lactate ratio and continued significant post-reperfusion lactate and hypoxanthine release (net arteriovenous difference for lactate and hypoxanthine at 30 minutes). The metabolic data for the group with DGF point to a persistent post reperfusion mitochondrial defect, confirmed by functional (respirometry) and morphological analyses. The archetypical mitochondrial stabilizing peptide SS-31 significantly preserved mitochondrial function in human kidney biopsies following simulated ischemia reperfusion. Thus, development of DGF is preceded by a profound post-reperfusion metabolic deficit resulting from severe mitochondrial damage. Strategies aimed at preventing DGF should be focused on safeguarding a minimally required post-reperfusion metabolic competence.

Longterm results of liver transplantation from donation after circulatory death.

Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic-type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET-DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107-1114 2016 AASLD.

Flushing the liver with urokinase before transplantation does not prevent nonanastomotic biliary strictures.

The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P < 0.001). This study has its limitations by its retrospective character. A multi-institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss.

Combined effect of donor and recipient risk on outcome after liver transplantation: Research of the Eurotransplant database.

Recently the Eurotransplant donor risk index (ET-DRI) was published, a model based on data from the Eurotransplant database that can be used for risk indication of liver donors within the Eurotransplant region. Because outcome after liver transplantation (LT) depends both on donor and recipient risk factors, a combined donor-recipient model (DRM) would give a more complete picture of the overall risk involved. All liver transplants in adult recipients from January 1, 2008 to December 31, 2010 in the Eurotransplant region were included. Risk factors in donors and recipients for failure-free (retransplant free) survival were analyzed in univariate and multivariate analyses. A simplified recipient risk index (sRRI) was constructed using all available recipient factors. A total of 4466 liver transplants were analyzed. Median donor risk index and ET-DRI were 1.78 and 1.91, respectively. The ET-DRI was validated in this new cohort (P < 0.001; concordance index [c-index], 0.59). After construction of a simplified recipient risk index of significant recipient factors, Cox regression analysis showed that the combination ET-DRI and sRRI into a new DRM gave the highest predictive value (P < 0.001; c-index, 0.62). The combined model of ET-DRI and sRRI gave a significant prediction of outcome after orthotopic LT in the Eurotransplant region, better than the ET-DRI alone. This DRM has potential in comparing data in the literature and correcting for sickness/physical condition of transplant recipients. It is a first step toward benchmarking of graft survival in the Eurotransplant region.

Discussing Sexual Dysfunction with Chronic Kidney Disease Patients: Practice Patterns in the Office of the Nephrologist.

INTRODUCTION: Sexual dysfunction (SD) is a common problem in patients suffering from chronic kidney disease (CKD). Sexual health remains a difficult subject to detect and discuss. Although many studies have been performed on the incidence of SD, little is known about practice patterns when it concerns quality of life (QoL)-related questions such as SD in the nephrologists' practice. AIM: The aim of this study was to determine to which extent nephrologists, important renal care providers, discuss SD with their patients and their possible barriers toward discussing this subject. METHODS: A 50-item questionnaire was sent to all Dutch nephrologists (n = 312). MAIN OUTCOME MEASURES: The survey results. RESULTS: The response rate of the survey was 34.5%. Almost all responders (96.4%) stated to address SD in less than half of their new patients. The most important barrier not to discuss SD was patients not expressing their concern regarding SD spontaneously (70.8%). Other important barriers were: "the lack of a suitable moment to discuss" (61.9%) and "insufficient time" (46.9%). Eighty-five percent of the nephrologists stated that insufficient attention was paid to SD and treatment options during their training. Sixty-five percent of the respondents stated to be in need of extending their knowledge on the discussing of SD. CONCLUSIONS: Dutch nephrologists do not discuss problems with sexual function routinely. The lack of knowledge, suitable education, and insufficient time are factors causing undervaluation of SD in CKD patients. Implementation of competent sexual education and raising awareness among nephrologists on the importance of paying attention to SD could improve care and QoL for patients with CKD. More research should be performed among patients and other renal care providers to develop an adequate method to enhance our current system.

Elderly donor liver grafts are not associated with a higher incidence of biliary complications after liver transplantation: results of a national multicenter study.

BACKGROUND: Liver transplantation with livers grafts from elderly donors has been associated with a higher risk of biliary complications. The aim of this study was to examine whether our national protocol could contribute to a lower incidence of biliary complications. METHODS: All adult recipients in the Netherlands transplanted with a liver from an elderly donor (≥ 65 yrs; n = 68) in the period January 2000-July 2011 were matched with recipients of a liver from a donor <65 yr (n = 136). Outcome parameters were 90-d, one-yr, and three-yr patient/graft survival rates, biliary complications (non-anastomotic stricture, anastomotic stricture, biliary leakage, and post-transplant cholangitis), and postoperative hepatic ischemic injury serum markers (AST/ALT). RESULTS: The median cold ischemia time (CIT) was 7:25 (h:min) in the group recipients of an elderly donor liver graft. Ninety-day, one-yr, and three-yr patient/graft survival rates were similar between the group with an elderly donor liver and their younger controls. Moreover, no differences were found in the incidence of biliary complications and postoperative levels of AST/ALT between the two groups. CONCLUSION: Transplantation of livers from elderly donors (≥ 65 yr) is not associated with a higher incidence of biliary complications, in a national policy wherein the CIT is kept short.

Interleukin-9 release from human kidney grafts and its potential protective role in renal ischemia/reperfusion injury.

OBJECTIVE AND DESIGN: The pathophysiology of ischemia/reperfusion (I/R) injury is dominated by an inflammatory response. In the identification of new therapeutic agents, the role of individual cytokines may be essential. Interleukin (IL)-9 is a pleiotropic cytokine recently identified to be involved in various immune responses. In this study, the role of IL-9 in renal I/R injury was assessed. METHODS: We performed repeated direct measurements of arteriovenous IL-9 concentration differences over the reperfused graft in human kidney transplantation. RESULTS: Substantial renal IL-9 release was observed from deceased donor kidneys (P = 0.006). In contrast, living donor kidneys, which have a more favourable clinical outcome, did not release IL-9 during early reperfusion (P = 0.78). Tissue expression of IL-9 did not change upon reperfusion in both living and deceased human donor kidneys. To assess the role of IL-9 in I/R injury, an experimental study comprising IL-9 inhibition in mice undergoing renal I/R was performed. Although there was no difference in kidney function, structural damage was significantly aggravated in anti-IL-9 treated mice. CONCLUSIONS: Deceased donor grafts show a substantial IL-9 release upon reperfusion in clinical kidney transplantation. However, inhibition of IL-9 aggravated kidney damage, suggesting a regulating or minor role of IL-9 in clinical I/R injury.

Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature.

It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.

Validation of the donor risk index in orthotopic liver transplantation within the Eurotransplant region.

In Eurotransplant, more than 50% of liver allografts come from extended criteria donors (ECDs). However, not every ECD is the same. The limits of their use are being explored. A continuous scoring system for analyzing donor risk has been developed within the Organ Procurement and Transplantation Network (OPTN), the Donor Risk Index (DRI). The objective of this study was the validation of this donor risk index (DRI) in Eurotransplant. The study was a database analysis of all 5939 liver transplants involving deceased donors and adult recipients from January 1, 2003 to December 31, 2007 in Eurotransplant. Data were analyzed with Kaplan-Meier and Cox regression models. Follow-up data were available for 5723 patients with a median follow up of 2.5 years. The mean DRI was remarkably higher in the Eurotransplant region versus OPTN (1.71 versus 1.45), and this indicated different donor populations. Nevertheless, we were able to validate the DRI for the Eurotransplant region. Kaplan-Meier curves per DRI category showed a significant correlation between the DRI and outcomes (P < 0.001). A multivariate analysis demonstrated that the DRI was the most significant factor influencing outcomes (P < 0.001). Among all donor, transplant, and recipient variables, the DRI was the strongest predictor of outcomes.

Prospective comparison of single encounter versus distributed laparoscopic training in novice learners: A controlled trial.

BACKGROUND: The traditional model of teaching surgical skills on "real" patients using graded responsibility is being seriously questioned, and there is a paradigm shift toward exploiting simulators. There is a lack of clarity on the impact of using simulation as a teaching strategy in novice learners. The purpose of our study was to determine if the number and duration of training sessions influence the acquisition and retention of laparoscopic skills in naïve learners. There are some data to suggest that distributed training programs might have better outcomes, but the results are inconclusive. We designed a controlled trial at Aga Khan University, Karachi, with the hypothesis that students trained using the distributed method may have enhanced learning outcomes. MATERIALS AND METHODS: 100 medical students were assigned in a 1:1 ratio to one of two groups. Group A underwent a single orientation and supervised practice session of 3 h duration. Group B underwent distributed teaching with three learning sessions of 1 h each spread over 3 consecutive weeks. Participant scores were analyzed before and after the intervention and at 3- and 6-month intervals using repeat measures of ANOVA. RESULTS: Pretest and immediate posttest scores were comparable between the two groups. The 3-month interval test showed significantly higher scores in Group B (difference = -2.90, P < 0.001). The 6-month interval test showed no differences in scores between the two groups (P = 0.178). CONCLUSIONS: Distributed teaching resulted in significantly enhanced scores at 3-month assessment. However, similar scores at 6 months suggest the need for repeated intervention.

Clinical value of myocardial perfusion scintigraphy as a screening tool in liver transplant candidates.

A cardiac evaluation before orthotopic liver transplantation (OLT) is imperative. Previous investigations have demonstrated that mild to moderate reversible perfusion defects on myocardial perfusion scintigraphy (MPS) in general are associated with a low risk for perioperative cardiac events. The objective of this study was to assess any perfusion defects in consecutive patients with chronic liver disease who were undergoing OLT. OLT candidates underwent extensive cardiovascular screening that included, among other methods, MPS. Patients who had no contraindications for surgery and underwent OLT were followed up. The occurrence and risk of complications and mortality were compared in 3 groups of patients: patients with normal MPS results, patients with any reversible defect, and patients with a fixed perfusion defect on MPS. In all, 156 subsequent patients underwent OLT. One or more reversible segmental perfusion defects on MPS were present in 14 patients (<3 segments, n = 12; 3 segments without obstructive coronary artery disease, n = 2). The risk of complications did not differ significantly between patients with normal MPS findings and patients with a reversible perfusion defect (odds ratio = 3.04, 95% confidence interval = 0.65-14.26, P = 0.16), although the study was not sufficiently powered to show a difference. The presence of 1 or more reversible defects on MPS was significantly associated with an increased incidence of all-cause 1-year mortality (hazard ratio = 3.17, 95% confidence interval = 1.02-9.83, P = 0.046). No significant difference in the outcomes of patients with normal MPS findings and patients with a fixed defect on MPS was found; the study was, however, not adequately powered to do so. In conclusion, the results of this small cohort study indicate that patients with mild to moderate reversible perfusion defects on MPS may have inferior survival characteristics in comparison with patients with normal MPS results. A prospective, adequately powered study is required to confirm the results of this study.

Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation.

UNLABELLED: Infectious complications after orthotopic liver transplantation (OLT) are a major clinical problem. The lectin pathway of complement activation is liver-derived and a crucial effector of the innate immune defense against pathogens. Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (MBL2), the ficolin-2 gene (FCN2), and the MBL-associated serine protease gene (MASP2) of recipients and donors were determined. Recipients receiving a donor liver in the principal cohort with polymorphisms in all three components i.e., MBL2 (XA/O; O/O), FCN2+6359T, and MASP2+371A, had a cumulative risk of an infection of 75% as compared to 18% with wild-type donor livers (P = 0.002), an observation confirmed in the second cohort (P = 0.04). In addition, a genetic (mis)match between donor and recipient conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52; P = 8.1 x 10(-6)) and the donor-recipient (mis)match genotype (hazard ratio = 6.41; P = 1.9 x 10(-7)), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and P < 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality (P = 0.9 x 10(-8)), of which 80% was infection-related. CONCLUSION: Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT.

Kidneys from donors after cardiac death provide survival benefit.

The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait for a conventional kidney from a brain-dead donor (DBD). This observational cohort study included all 2575 patients who were registered on the Dutch waiting list for a first kidney transplant between January 1, 1999, and December 31, 2004. From listing until the earliest of death, living-donor kidney transplantation, or December 31, 2005, 459 patients received a DCD transplant and 680 patients received a DBD transplant. Graft failure during the first 3 months after transplantation was twice as likely for DCD kidneys than DBD kidneys (12 versus 6.3%; P=0.001). Standard-criteria DCD transplantation associated with a 56% reduced risk for mortality (hazard ratio 0.44; 95% confidence interval 0.24 to 0.80) compared with continuing on dialysis and awaiting a standard-criteria DBD kidney. This reduction in mortality translates into 2.4-month additional expected lifetime during the first 4 years after transplantation for recipients of DCD kidneys compared with patients who await a DBD kidney. In summary, standard-criteria DCD kidney transplantation associates with increased survival of patients who have ESRD and are on the transplant waiting list.

Use of a liver from donor after cardiac death: is it appropriate for the sick or the stable?

PURPOSE OF REVIEW: Liver transplantation following donation after cardiac death (DCD) continues to be a subject for heated debate. Opinion is divided in the literature as to who benefits the most from receiving a liver from a DCD donor. This review will focus on some important questions regarding the outcome of transplantation and the selection and matching of donor and recipient. RECENT FINDINGS: Liver transplantation with an organ from a donor after cardiac death is becoming an accepted way to treat patients on the waiting list with end-stage liver disease. However, there are still some major issues to address such as ischemic-type biliary lesions, retransplantation rates, criteria for donor and patient selection and whether conversion of donation after brain death to DCD exists. Accepting a DCD liver has the potential for reduced recipient quality of life after transplant. Death on the waiting list must be balanced against the inherent risks of a DCD liver. SUMMARY: Success of liver transplantation is mostly measured as graft and patient survival. DCD liver transplantation is a potential tool to decrease mortality on the waiting list. Careful selection and matching of donor organ and recipient can lead to good outcomes. However, ischemic-type biliary lesions after DCD liver transplantation remain an important obstacle to overcome and have a serious impact on quality of life after transplantation.

Psychological Symptoms and Quality of Life After Simultaneous Kidney and Pancreas Transplantation.

Patients that have undergone successful simultaneous pancreas/kidney (SPK) transplantation attain normoglycemia and are free from dialysis. However, only a minor improvement in quality of life (QOL) has been demonstrated. Here, we evaluated the role of psychological symptoms in QOL after SPK transplantation. METHODS: We assessed patients with type 1 diabetes and end-stage renal disease waitlisted for SPK transplantation (pre-SPK, n = 47), and recipients of an SPK transplant (post-SPK, n = 72). Matched patients with type 1 diabetes without end-stage renal disease were included as reference group (type 1 diabetes [T1D] reference group, n = 42). The brief symptom inventory (BSI) was used to measure psychological symptoms. The Short Form-36 (SF-36) was used to determine QOL. RESULTS: Post-SPK patients scored slightly better on the SF-36 than pre-SPK patients ("General health" 47.2 ± 23.1 versus 37.5 ± 18.1 [P = 0.017]). In the T1D reference group, this score was 60.6 ± 22.3. Post- and pre-SPK patients had similar BSI scores (0.54 ± 0.55 and 0.45 ± 0.42, respectively [P = 0.34]). This score was better in the T1D reference group (BSI score 0.32 ± 0.33). The BSI score inversely correlated with the SF-36 (r = -0.61, P < 0.001). CONCLUSIONS: Psychological symptoms are prevalent in both pre-SPK and post-SPK patients and could play an important role in the reduced QOL observed in these groups.