Red Flags in the Living Kidney Donor Process.

BACKGROUND: Ideally, no live kidney donor should regret their decision or feel they were not fully prepared for the process. Unfortunately, this is not a reality for all donors. The aim of our study is to identify areas for improvement, focusing on factors (red flags) that predict less favorable outcomes from a donor perspective. MATERIALS AND METHODS: A total of 171 living kidney donors responded to a questionnaire with 24 multiple-choice questions and space for comments. Less favorable outcomes were defined as lower satisfaction, extended physical recovery period, long-term fatigue, and longer sick leave. RESULTS: Ten red flags were identified. Of these factors, more fatigue (range, P = .000-0.040) or pain (range, P = .005-0.008) than expected while still in hospital, the actual experience being harder or different than expected (range, P = .001-0.010), and the donor wishing to have had but not having been offered a previous donor as mentor (range, P = .008-.040) correlated significantly with at least 3 of the 4 less favorable outcomes. Another significant red flag was keeping existential issues to oneself (P = .006). CONCLUSION: We identified several factors indicating that a donor could be at an increased risk for a less favorable outcome after donation. Four of these factors have, to our knowledge, not been described earlier: more early fatigue than expected, more postoperative pain than anticipated, not having been offered a mentor at an early stage, and keeping existential issues to oneself. Attention to these red flags already during the donation process could help health care professionals to act early to avoid unfavorable outcomes.

Potential living kidney donors' positive experiences of an information letter from healthcare: a descriptive qualitative study.

BACKGROUND: Patients who need a live donor kidney transplant (LDKT) must often ask potential donors (PLDs) themselves. This is a difficult task and healthcare could unburden them by making this first contact, ensuring also that PLDs receive correct information. We investigated how PLDs experience receiving a letter from healthcare about LDKT, live kidney donation, and inviting them to meet with professionals to get more information. METHODS: The letter (LD-letter) was sent to a cohort of 46 individuals, from which a purposeful sample of 15 were interviewed using a semi-structured guide covering their experience of the letter, views on being approached by healthcare, and opinions on style and content. Interviews were analyzed using conventional inductive analysis. RESULTS: We identified three categories of experiences: Category (1) Reflections on receiving the letter, contains three subcategories relating to how the letter did not induce pressure to donate, did not affect the PLD's relationship with the patient with kidney disease, and made the letter-receiver feel important in the transplant process; Category (2) The letter creates clarification and trust, also contains three subcategories, relating to how it clarified the voluntariness of donation and neutrality of healthcare providers with respect to the PLD's decision, elucidated the patient with kidney disease's current stage of disease (where transplantation was approaching), and unburdened patients from the responsibility of contacting PLDs on their own; Category (3) Opinions and suggestions about the letter and further communication, with four subcategories, relating to preference of a letter as the first step for communication about LDKT, suggestions on style and content, views on following up the letter, and how open meetings about LDKT were an important information source. Furthermore, 80% of the interviewees found the letter's information comprehensive, 67% found it easy to read and respectful, and 86% rated it as good or very good. CONCLUSION: Potential donors prefer and recommend a letter as the first step for communication regarding LD. The LD-letter unburdens patients from the task of asking PLDs and stresses the voluntariness of donation, does not leave PLDs feeling coerced or lead to negative effects in their relationship with the patient.

Living Anonymous Renal Donors Do Not Regret: Intermediate and Long-Term Follow-Up with a Focus on Motives and Psychosocial Outcomes.

BACKGROUND Living anonymous donation (LAD) of kidneys was introduced in Sweden in 2004. This study reports on outcomes of Swedish LAD experiences from 2004 to 2016, focusing on donors' motives, the care they received, psychosocial aspects, and medical status at follow-up. MATERIAL AND METHODS Donor data were collected through a physician interview, medical check-up, review of medical charts, the Hospital Anxiety Depression Scale (HADS), and a routine national questionnaire. Of the 26 LADs during the study period, 1 donor died and 1 declined to participate, leaving a study population of 24. RESULTS Half of the donors were male, which is a higher proportion than for directed living donors. The major motive detected was altruism. Of the 24 LADs, 96% were very satisfied and would donate again if possible, 46% noted increased self-esteem, and a third were happier after the donation. Sixty-two percent received anonymous information about the recipient and 40% would have liked to meet the recipient. HADS scores were normal. Two donors had antidepressant treatment, 1 of whom had received treatment before donation. Half mentioned that the pre-donation assessment took too long. At follow-up, mean eGFR was 62±12 mL/min/1.73 m², of which 16 were in CKD II and 8 were in CKD III. Four donors had developed hypertension, 1 of whom also developed type 2 diabetes. CONCLUSIONS Swedish LADs are very satisfied and medical outcomes are acceptable. We propose that the transplant community and the National Board of Health and Welfare take a more active approach to informing the general public about LAD.

Clinical Significance of Alloantibodies in Hand Transplantation: A Multicenter Study.

BACKGROUND: Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. METHODS: We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. RESULTS: Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. CONCLUSIONS: While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.

Improved endothelialization of small-diameter ePTFE vascular grafts through growth factor therapy.

BACKGROUND: Prosthetic vascular grafts in humans characteristically lack confluent endothelialization regardless of the duration of implantation. Use of high-porosity grafts has been proposed as a way to induce endothelialization through transgraft capillarization, although early experiments failed to show increased healing in man. OBJECTIVES: We hypothesized that transduction of tissues around the prosthetic conduit with vectors encoding VEGF receptor-2 (VEGFR2) ligands would augment transinterstitial capillarization and induce luminal endothelialization of high-porosity ePTFE grafts. METHODS: Fifty-two NZW rabbits received 87 ePTFE uni- or bilateral end-to-end interposition grafts in carotid arteries. Rabbits were randomized to local therapy with adenoviruses encoding AdVEGF-A165, AdVEGF-A109 or control AdLacZ and analyzed at 6 and 28 days after surgery by contrast-enhanced ultrasound and histology. RESULTS: AdVEGF-A165 and AdVEGF-A109 dramatically increased perfusion in perigraft tissues at 6 days (14.2 ± 3.6 or 16.7 ± 2.6-fold increases, P < 0.05 and P < 0.01). At 28 days, the effect was no longer significantly higher than baseline. At 6 days, no luminal endothelialization was observed in any of the groups. At 28 days, AdVEGF-A109- and AdVEGF-A165-treated animals showed enhanced ingrowth of transinterstitial capillaries (66.0 ± 13.7% and 77.4 ± 15.7% of graft thickness vs 44.7 ± 24.4% in controls, P < 0.05) and improved luminal endothelialization (11.2 ± 26.3% and 11.4 ± 22.2%, AdVEGF-A109 and AdVEGF-A165 vs 0% in controls, P < 0.05). No increased stenosis was observed in the treatment groups as compared to LacZ controls. CONCLUSIONS: This study suggests that transient local overexpression of VEGFR2 ligands in the peri-implant tissues at the time of graft implantation is a novel strategy to increase endothelialization of high-porosity ePTFE vascular grafts and improve the patency of small-diameter vascular prostheses.

Healthcare Resource Use, Cost, and Sick Leave Following Kidney Transplantation in Sweden: A Population-Based, 5-Year, Retrospective Study of Outcomes: COIN.

BACKGROUND Improved understanding of the impact of kidney transplantation on healthcare resource use/costs and loss of productivity could aid decision making about funding allocation and resources needed for the treatment of chronic kidney disease in stage 5. MATERIAL AND METHODS This was a retrospective study utilizing data from Swedish national health registers of patients undergoing kidney transplantation. Primary outcomes were renal disease-related healthcare resource utilization and costs during the 5 years after transplantation. Secondary outcomes included total costs and loss of productivity. Regression analysis identified factors that influenced resource use, costs, and loss of productivity. RESULTS During the first year after transplantation, patients (N=3120) spent a mean of 25.7 days in hospital and made 21.6 outpatient visits; mean renal disease-related total cost was €66,014. During the next 4 years, resource use was approximately 70% (outpatient) to 80% (inpatient) lower, and costs were 75% lower. Before transplantation, 62.8% were on long-term sick leave, compared with 47.4% 2 years later. Higher resource use and costs were associated with age <10 years, female sex, graft from a deceased donor, prior hemodialysis, receipt of a previous transplant, and presence of comorbidities. Higher levels of sick leave were associated with female sex, history of hemodialysis, and type 1 diabetes. Overall 5-year graft survival was 86.7% (95% CI 85.3-88.2%). CONCLUSIONS After the first year following transplantation, resource use and related costs decreased, remaining stable for the next 4 years. Demographic and clinical factors, including age <10 years, female sex, and type 1 diabetes were associated with higher costs and resource use.

Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and Meta-analysis.

Background: Long-term health risks for adults who donate kidneys are unclear. Purpose: To summarize evidence about mid- and long-term health risks associated with living kidney donation in adults. Data Sources: PubMed, Embase, Scopus, and PsycINFO without language restriction from April 1964 to July 2017. Study Selection: Observational studies with at least 1 year of follow-up that compared health outcomes in adult living kidney donors versus nondonor populations. Data Extraction: Two investigators independently extracted study data and assessed study quality. Data Synthesis: 52 studies, comprising 118 426 living kidney donors and 117 656 nondonors, were included. Average follow-up was 1 to 24 years. No evidence suggested higher risk for all-cause mortality, cardiovascular disease, hypertension, type 2 diabetes, or adverse psychosocial health outcomes in living kidney donors than in nondonor populations. Donors had higher diastolic blood pressure, lower estimated glomerular filtration rates, and higher risk for end-stage renal disease (ESRD) (relative risk [RR], 8.83 [95% CI, 1.02 to 20.93]) and preeclampsia in female donors (RR, 2.12 [CI, 1.06 to 4.27]). Despite the increased RR, donors had low absolute risk for ESRD (incidence rate, 0.5 event [CI, 0.1 to 4.9 events] per 1000 person-years) and preeclampsia (incidence rate, 5.9 events [CI, 2.9 to 8.9 events] per 100 pregnancies). Limitation: Generalizability was limited by selected control populations, few studies reported pregnancy-related outcomes, and few studies were from low- and middle-income countries. Conclusion: Although living kidney donation is associated with higher RRs for ESRD and preeclampsia, the absolute risk for these outcomes remains low. Compared with nondonor populations, living kidney donors have no increased risk for other major chronic diseases, such as type 2 diabetes, or for adverse psychosocial outcomes. Primary Funding Source: National Health Service Blood and Transplant and National Institute for Health Research. (PROSPERO: CRD42017072284).

Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time.

BACKGROUND We sought to study gender differences and differences over time with respect to demographics, relation to recipient, donor motives, and experiences of live kidney donation. MATERIAL AND METHODS In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008 were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving 413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers was analyzed for gender differences and, where relevant, for changes over time. RESULTS In all sub-periods, female donors made up the majority (55-62%), except for sibling donors (45%) and child-to-parent donors (40%). No significant gender differences were seen in perceived information given before donation. For males, it was more common that the recipient took the initiative to donate. For females, the motivation for donating was more frequently to help the recipient and because others wanted them to donate. For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference. CONCLUSIONS Females donate more frequently than males, a difference that did not change over time. Only a few gender differences were seen in donor motives and the donation experience; however, these differences may be relevant to address the gender imbalance in kidney donations.

[Hand transplantation in Sweden ­ preparations under way]. / Handtransplantation snart verklighet i Sverige.

English summary: Hand transplantation in Sweden - preparations under way Some patients with a uni- or bilateral hand- or forearm amputation cannot use a hand prosthesis, although high-tech prostheses have been developed. A hand transplantation, particularly for those with bilateral amputations, may be an alternative solution. In a hand-transplanted patient, grip function, strength, sensibility and subsequent improved quality of life can be restored. Risks related to immunosuppression must be balanced by expected benefits, and thorough selection of patients has to be performed from both medical and psychological point of view. Therefore, a national network has been established in Sweden to achieve coordination with the needed competence.

A Prospective Randomized Trial on the Effect of Using an Electronic Monitoring Drug Dispensing Device to Improve Adherence and Compliance.

BACKGROUND: Outcome after renal transplantation depends on patient compliance and adherence for early detection of complications and identification of intervention opportunities. Compliance describes the degree to which patients follow medical advice and take their medications. Adherence has been defined as the extent to which a patients' behavior coincides with clinical prescriptions. MATERIALS AND METHODS: Patients were randomized 7 to 14 days after transplantation into groups with (n = 40) and without (n = 40) an electronic medication dispenser (EMD). The EMD, which was used for the 1-year study period, recorded the date and time the patient took their medications and was monitored via a web-based application. Patients were monitored for 1 year regarding outpatient follow-up visits, emergency hospitalizations, renal biopsies, rejection episodes, renal function, and blood concentration of medications. RESULTS: Compliance in the intervention group was 97.8% (the control group was not assessed). Number of missed doses varied significantly by weekday (P = 0.033); patients were most likely to miss doses on Saturdays and Thursdays. Patients missed a total of 11 follow-up visits. During the study, 92 biopsies were performed on 55 patients (intervention group: 32 [17]; control group, 60 [38]). Biopsy-verified rejection was three times more common among controls (13 patients vs. 4; P = 0.054, not significant). Average P-creatinine level was slightly lower in the intervention group than the control group (131 vs. 150 µmol/L, not significant), whereas mean tacrolimus was similar (7.32 vs. 7.22 ng/mL, n.s.). CONCLUSIONS: The EMD is associated with high compliance, and there are also indications of a lower rejection rate.

Implantation of Autologous Selected Renal Cells in Diabetic Chronic Kidney Disease Stages 3 and 4-Clinical Experience of a "First in Human" Study.

INTRODUCTION: Animal models of chronic kidney disease demonstrate that a redundant population of therapeutically bioactive selected renal cells (SRCs) can be delivered to the kidney through intraparenchymal injection and arrest disease progression. Direct injection of SRCs has been shown to attenuate nuclear factor-κB, which is known to drive tissue inflammation, as well as the transforming growth factor-ß-mediated plasminogen activator inhibitor-1 response that drives tissue fibrosis. METHODS: We present experience from the first-in-human clinical study with SRCs. Seven male type 2 diabetic patients (63 ± 2 years of age) with chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate 25 ± 2 ml/min) were recruited. After blood and urine sampling, iohexol clearance, magnetic resonance imaging, and renal scintigraphy, patients underwent ultrasound-guided renal biopsy. Two cores of renal tissue were shipped to the manufacturing plant for cell isolation, culture, and product preparation. Formulated SRCs were transported back to study sites (range 59-87 days after biopsy) for intracortical injection using a retroperitoneoscopic technique. RESULTS: Laparoscopically assisted implantation of SRCs was uneventful in all patients. However, postoperative complications were common and suggest that other techniques of SRC delivery should be used. Kidney volume, split function, and glomerular filtration rate did not change during 12 months of follow-up. An extended 24-month follow-up in 5 of the patients showed a decline in estimated glomerular filtration rate (cystatin C). DISCUSSION: Postoperative complications following retroperitoneoscopic implantation of SRC in the kidney cortex seem to be related to the surgical procedure rather than to injection of the cell product. No changes in renal function were observed during the original 12-month protocol. Beyond the first 12 months after cell implantation, individual renal function began to deteriorate during further follow-up.

Single-centre long-term follow-up of live kidney donors demonstrates preserved kidney function but the necessity of a structured lifelong follow-up.

BACKGROUND: The increase of live kidney donation (LKD) demands that we scrutinize its long-term consequences. Socialized medicine in Sweden has allowed us to survey long-term consequences of LKD with a high response rate. METHODS: Between 1974 and 2008, 455 LKDs were performed; 28 donors were deceased and 14 had moved abroad at the time of the survey. Of the remaining 413, 96% agreed to participate in a retrospective study with laboratory testing and answering a questionnaire. RESULTS: Mean age at donation was 49 ± 10 years, and the mean time since nephrectomy was 11 ± 7 years (range 1-33). No death was of renal cause. S-creatinine at follow-up was 93 ± 18 µmol/L, 28% had treated hypertension, of whom only 52% had BP <140/90. Eleven per cent had spot microalbuminuria, and 1% were diagnosed with diabetes mellitus. Seventy-one per cent had check-ups at least every second year, but 14% had no check-ups. Eighty per cent would be willing to donate again if it were possible, and only 3% regretted the donation. CONCLUSION: Renal function is well preserved in the long term after donation, no case of end-stage renal disease was identified, and a large majority of our donors would donate again if it were possible. Although rates of microalbuminuria and hypertension were at expected levels, a significant number of donors demonstrated elevated blood pressure levels and inadequate antihypertensive treatment. A relatively large number of donors did not receive regular check-ups. Both of these issues demonstrate the need for a better-structured lifelong follow-up.

Kidney transplantation with and without simultaneous bilateral native nephrectomy in patients with polycystic kidney disease: a comparative retrospective study.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) often need to undergo native nephrectomy and are candidates for kidney transplantation. The necessity and timing of nephrectomy are controversial. Some authors recommend simultaneous bilateral native nephrectomy (SBN) as the preferred option in living-donor kidney transplantation (LDKT). These recommendations are based on small study populations. We therefore set out to study outcomes of LDKT with SBN, compared with LDKT alone in a larger single-center cohort. METHODS: A consecutive series of 159 patients with ADPKD undergoing LDKT were included in the study. Of the 159 patients, 2 were excluded because of missing data, 79 underwent LDKT alone (group A), and 78 underwent LDKT with SBN (group B). Demographic data and intraoperative and postoperative data were collected from patient charts and the national kidney registry. RESULTS: There were no differences regarding background data. Group B experienced significantly longer operating times (183.7 vs. 319.3 min, P<0.001), a greater need for blood transfusions (0.1 vs. 1.6 units, P<0.001) and plasma products (35.1 vs. 438.3 mL, P<0.001), and longer hospital stays (11.8 vs. 15.4 days, P<0.001). It also experienced more intraoperative events and postoperative complications but fewer reoperations/reinterventions. There were no differences in patient and graft survival rates. CONCLUSIONS: SBN in patients undergoing LDKT for ADPKD does not have a significant negative impact on patient and graft survival rates. It obviates a separate surgical procedure but requires longer hospital stay. It may be associated with more postoperative complications and risk of graft loss. These considerations should be communicated to the recipient and the donor.

Desensitization with antigen-specific immunoadsorption interferes with complement in ABO-incompatible kidney transplantation.

BACKGROUND: Complement activation was characterized during and after desensitization treatment in 19 consecutive patients receiving ABO-incompatible (ABOi) living donor kidney transplants to assess the effect of desensitization protocol including antigen-specific immunoadsorption (IA) on complement activation. METHODS: All patients received rituximab- and tacrolimus-based triple treatment. Anti-A/B antibodies were removed by IA. Serial determinations of C3, C3a, the C3a/C3 ratio, and sC5b-9 were carried out between day -30 and postoperative day 30. C1q was measured on day -30 and the day before the transplantation. In two recipients, eluates from immunoadsorbent columns were analyzed for C3a, C1q, and immunoglobulins by western blotting. Same complement analysis was performed in eluate from a control column after in vitro perfusion of AB-plasma. RESULTS: Patient and graft survival were 100% for a median follow-up of 40 months (range, 12-60 months). There were no humoral rejections based on ABO-antigen-antibody interactions. C3a and the C3a/C3 ratio declined with the start of IA treatment, and this decline was maintained postoperatively. C1q declined from day -30 to a lower value on the day before transplantation (P<0.05). In eluates from both patient and control, immunoadsorbent column immunoglobulins together with C3a and C1q were detected. CONCLUSIONS: The current protocol including antigen-specific IA interferes with the complement system; this effect may be partially responsible for the absence of humoral rejection resulting from ABO-antigen-antibody interactions and the excellent outcomes obtained after ABO-incompatible kidney transplantation.

Comparison of hand-assisted laparoscopy versus open and laparoscopic techniques in urology procedures: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Hand-assisted laparoscopic surgery (HALS) is an integral part of the urologist's armamentarium. We aimed to perform a comprehensive meta-analysis comparing HALS renal surgery with open and laparoscopic techniques. METHODS: A systematic review and meta-analysis of HALS renal procedures (donor nephrectomy, nephrectomy, or nephroureterectomy) from 1996 to 2007 was performed. RESULTS: Sixty-two studies of 30 donor nephrectomy, 21 radical nephrectomy, and 14 nephroureterectomy procedures in 5446 patients were included in the analysis. In donor nephrectomy, estimated blood loss (EBL) was statistically significant for HALS vs the open and laparoscopic cohorts, -69.0 mL (95% confidence interval [CI], -129.7, -8.2) and -40.1 mL (95% CI, -68.2, -12.0), respectively. Length of stay (LOS) was shorter compared with the open group, -1.7 days (95% CI, -2.3, -1.1). For nephroureterectomy, EBL (-29.9 mL (95% CI, -242.3, 182.5)), and LOS (-1.5 d [95% CI, -2.8, -0.3]) again favored HALS vs open procedures. Operating room (OR) time and warm ischemia time (WIT) were statistically significant in favor of HALS donor nephrectomy vs the laparoscopic cohort; -36.8 minutes (95% CI, -61.3, -12.3) and -1.3 minutes (95% CI, -1.8, -0.7), respectively. For radical nephrectomy, both EBL -232.9 mL (95% CI, -383.6, -82.2) and LOS -2.4 days (95% CI, -3.5, -1.3) were statistically significant, favoring HALS vs the open group. CONCLUSION: We report the largest meta-analysis of HALS renal surgery to date. When compared with open surgery, HALS allows for a significant decrease in EBL and LOS. Compared with laparoscopic donor nephrectomy, HALS resulted in a significant decrease in blood loss, OR time, and WIT.