The Minimisation of Cardiovascular Disease Screening for Kidney Transplant Candidates.

Background: There is increasing evidence that cardiac screening prior to kidney transplantation does not improve its outcomes. However, risk aversion to perioperative events means that, in practice, testing remains common, limiting the availability of 'real-world' data to support any change. Our objective was to assess perioperative and 1-year post-transplant cardiovascular events in a kidney transplant candidate cohort who received minimal cardiovascular screening. Methods: The retrospective cohort study included all adult kidney-only transplant recipients in a single UK region between January 2015 and December 2021. Kidney transplant recipients asymptomatic of cardiac disease, even those with established risk factors, did not receive cardiac stress testing. The perioperative and 1-year post-transplant cardiovascular event incidences were examined. Logistic regression was used to identify variables of statistical significance that predicted cardiovascular or cerebrovascular events. Results: A total of 895 recipients fulfilled the inclusion criteria. Prior to transplantation, 209 (23%) recipients had an established cardiac diagnosis, and 193 (22%) individuals had a diagnosis of diabetes. A total of 18 (2%) patients had a perioperative event, and there was a 5.7% incidence of cardiovascular events 1 year post-transplantation. The cardiovascular mortality rate was 0.0% perioperatively, 0.2% at 3 months post-transplant, and 0.2% at 1 year post-transplant. Conclusions: This study demonstrates comparable rates of cardiovascular events despite reduced screening in asymptomatic recipients. It included higher risk individuals who may, on the basis of screening results, have been excluded from transplantation in other programmes. It provides further evidence that extensive cardiac screening prior to kidney transplantation is unlikely to be offset by reduced rates of cardiovascular events.

When There is No Guidance From the Guidelines: Renal Transplantation in Recipients With Class III Obesity.

Whilst renal transplantation is the optimal treatment for many patients with end-stage kidney disease, the latest international guidelines are unable to make recommendations for the management of patients with end-stage kidney stage kidney disease and Class III Obesity (BMI ≥40 kg/m2). Data on all adult patients receiving a kidney-only-transplant in the UK between 2015-2021 were analysed from a prospectively collected database and interrogated across a range of parameters. We then analysed in detail the outcomes of patients transplanted at the highest-volume unit. There were 22,845 renal transplants in the study time-period; just 44 (0.2%) were performed in recipients with a BMI ≥40 kg/m2. Most transplant centres did not transplant any patients in this category. In the centre with the highest volume, there were 21 transplants (9 living donor) performed in 20 individuals (13 male, median age 46 years). One-year patient and death-censored graft survival was 95% and 85%. Successful transplantation is possible in patients with BMI ≥40 kg/m2 but carries additional risk. Obesity should not be the sole factor considered when deciding on transplant suitability. Restricting transplantation to a small number of high-volume centres in each country should be considered to optimize outcomes.

Patient education interventions for adolescent and young adult kidney transplant recipients- a scoping review.

BACKGROUND: Adolescence and young adulthood are high risk periods for kidney transplant recipients. The reasons for this are complex; but are predominantly thought to be due to poor adherence to immunosuppressive medications. Patient education can help support young recipients to reduce their risk of behaviour-related transplant loss. The aim of this review was to understand what is known about education interventions targeted at adolescent and young adult kidney transplant recipients. METHODS: Systematic scoping review methodology was utilised. Six online databases were searched for suitable articles. Articles were selected for full text review following title and abstract screening. Articles deemed eligible to be included in the review had data extracted, which were qualitatively analysed using thematic analysis. Findings were validated through a consultation exercise with both young recipients and healthcare professionals. RESULTS: 29 studies were eligible for inclusion in the review. There was a high level of heterogeneity in the content, mode, design, and measurement of efficacy of interventions in the selected studies. Traditional face-to-face education and transition clinics were the most common educational interventions. Using technology to enhance patient education was also a major theme identified. Few studies reported using educational theory or involving patients in intervention design. DISCUSSION: Four key research gaps were identified. 1.) Lack of educational theory in intervention design 2.) Lack of patient/ stakeholder involvement 3.) Identifying best way to measure efficacy 4.) identifying novel future research questions within already well established paediatric and educational frameworks. Addressing these gaps in future research will help inform best-practice in this vulnerable population.

Living Donor Kidney Transplantation in Older Individuals: An Ethical Legal and Psychological Aspects of Transplantation (ELPAT) View.

Living donor transplantation is the optimal treatment for suitable patients with end-stage kidney disease. There are particular advantages for older individuals in terms of elective surgery, timely transplantation, and early graft function. Yet, despite the superiority of living donor transplantation especially for this cohort, older patients are significantly less likely to access this treatment modality than younger age groups. However, given the changing population demographic in recent decades, there are increasing numbers of older but otherwise healthy individuals with kidney disease who could benefit from living donor transplantation. The complex reasons for this inequity of access are explored, including conscious and unconscious age-related bias by healthcare professionals, concerns relating to older living donors, ethical anxieties related to younger adults donating to aging patients, unwillingness of potential older recipients to consider living donation, and the relevant legislation. There is a legal and moral duty to consider the inequity of access to living donor transplantation, recognising both the potential disparity between chronological and physiological age in older patients, and benefits of this treatment for individuals as well as society.

Seven leadership and followership lessons from kidney transplantation during lockdown.

BACKGROUND: The renal transplant team in Northern Ireland performed 70 transplants in 61 days during the first wave of COVID-19, an 8-fold increase in their typical activity. Mobilising diverse professional skills to achieve this number, especially under COVID-19 conditions, required extraordinary effort on the part of everyone involved along the transplant patient pathway, management and staff from other patient groups. METHODS: Fifteen transplant team members were interviewed to explore their experiences during this time. RESULTS: Seven key leadership and followership lessons, contextualised within The Healthcare Leadership model, were learnt from these experiences. CONCLUSIONS: While circumstances were untypical, the achievement and motivation of staff were no less commendable. We contend that this was not only because of the unusual circumstances but as a result of extraordinary leadership and followership, teamworking and individual agility.Recommendations for those leading services which require a quick response and collaborative effort are made.

The Educational Needs of Adolescent and Young Adult Renal Transplant Recipients-A Scoping Review.

Renal transplantation is the gold-standard treatment for adolescents and young adults with end-stage renal disease. Despite enjoying excellent short-term outcomes, they suffer the worst rates of premature transplant function loss. Health behaviors: such as lack of adherence to immunosuppressive medications, are felt to be the major contributory factor. Understanding the educational needs of young renal transplant recipients allows healthcare practitioners to better support patients in managing their chronic disease. The aim of this scoping review was to understand what is known about their educational needs. A scoping review methodology was followed. Following an online search, study titles, and abstracts were screened for eligibility, followed by full-text assessment and data extraction. Data were qualitatively analyzed using thematic analysis. A total of 29 studies were included in the scoping review. In young people who struggled with self-management, three themes were identified (1) the Needs of the disrupted youth, (2) the Needs of the disorganized youth (3) the Needs of the distressed youth. There was a paucity of research to identify the protective factors that enable young recipients to successfully manage their health. This review outlines current knowledge of the patient education needs of young transplant recipients. It also highlights remaining research gaps that will need to be addressed with future research.

Early clinical and economic outcomes of expanded criteria living kidney donors in the United States.

BACKGROUND: The donation of what might be termed expanded criteria kidneys has become an increasingly common practice. This study aimed to assign expanded criteria and non-expanded criteria donation status and examine early clinical and economic outcomes among expanded criteria and non-expanded criteria living kidney donor (LKD) hospitalizations in the US. METHODS: Healthcare cost and Utilization Project-National (Nationwide) Inpatient Sample (HCUP-NIS) data (Jan 2008-Dec 2019, N = 12,020) were used. Expanded criteria LKDs were identified as admitted patients aged ≥ 60 years, or 50-59 years with any comorbidity that historically precluded donation. The Clavien-Dindo system was applied to classify surgical complications as grade I-IV/V. RESULTS: The number of LKD admissions decreased by 31% over the study period, although this trend fluctuated over time. Compared to non-expanded criteria LKD admissions, expanded criteria LKD admissions had comparable surgical complication rates in Grade I (aOR 1.0, 0.8-1.3), but significantly higher surgical complication rates in Grade II (aOR 1.5, 1.1-2.2) and Grade III (aOR 1.4, 1.0-2.0). The two groups had comparable hospital length of stay and cost in the adjusted models. Notably, Grade II complications were significantly higher in private, for-profit hospitals (15%) compared to government hospitals (2.9%). CONCLUSIONS: Expanded criteria LKDs had comparable early outcomes compared to non-expanded criteria LKDs, but the trends evident in LKDs over time and the variation in complication records warrant further research.

Dialysis, Distress, and Difficult Conversations: Living with a Kidney Transplant.

Background: Providing holistic care to kidney patients is important; however, without full consideration of the perspectives of people living with a kidney transplant, the provision of truly 'holistic healthcare' cannot be possible. It is imperative to understand patient experiences by including kidney patients in key strategies and future renal service planning. Ignoring these important patient views means that there is a significant risk of inappropriate renal service provision and lack of adequate support, impacting overall health. The aim of this study was to develop an in-depth understanding of the lived experiences of kidney transplant recipients. Methods: A total of 23 participants were recruited between two regional nephrology units within the United Kingdom via clinical gatekeepers. In-depth interviews were undertaken. Interviews were digitally recorded, transcribed verbatim, and subjected to interpretative phenomenological analysis. Results: Two themes emerged: "managing ongoing fears of dialysis, distress, and COVID-19" and "dealing with difficult conversations". Conclusions: Renal healthcare professionals need to understand more than the biological impact of receiving a kidney transplant. Understanding the holistic and multidomain experiences that these participants experience will help healthcare professionals to recognize the needs of this group and ensure more responsive psychosocial care.

Donor Autonomy and Self-Sacrifice in Living Organ Donation: An Ethical Legal and Psychological Aspects of Transplantation (ELPAT) View.

Clinical teams understandably wish to minimise risks to living kidney donors undergoing surgery, but are often faced with uncertainty about the extent of risk, or donors who wish to proceed despite those risks. Here we explore how these difficult decisions may be approached and consider the conflicts between autonomy and paternalism, the place of self-sacrifice and consideration of risks and benefits. Donor autonomy should be considered as in the context of the depth and strength of feeling, understanding risk and competing influences. Discussion of risks could be improved by using absolute risk, supra-regional MDMs and including the risks to the clinical team as well as the donor. The psychological effects on the donor of poor outcomes for the untransplanted recipient should also be taken into account. There is a lack of detailed data on the risks to the donor who has significant co-morbidities.

Successful living kidney donation from a patient with a Gitelman's syndrome.

Living kidney donation from Gitelman's syndrome (GS) patients remains very rare. Long-term renal prognosis of donor and recipient patients remains unknown. We report a 67-year-old man with GS, harbouring a mutation of the SLC12A3 gene, who donated his kidney for transplant. Five years post-transplantation, his clinical condition and biochemical parameters remained stable with close monitoring and follow-up. Patients with non-complicated GS can be considered eligible to donate their kidney for transplant.

Application of Enhanced Recovery After Surgery in Patients Undergoing Kidney Transplant: the Belfast Protocol.

BACKGROUND: The aim of this study was to assess the impact of the Belfast Protocol for enhanced recovery after surgery on hospital length of stay (LOS) after kidney transplant. METHODS: A prospectively collected database was analyzed for all consecutive renal transplant recipients in 2010 and compared with consecutive renal transplant recipients in 2018 before and immediately after the full implementation of the Belfast Protocol. RESULTS: There were 73 renal transplants in 2010 and 115 in 2018. Between 2010 and 2018 there was a significant decrease in LOS from 12 to 7 days (P < .0001). Compared with 2010, in 2018 there was a significant increase in donor age (47 vs 54 years, P < .0001) and kidney transplant from donation after circulatory death donors (0% vs 9%, P < .0001). Although there was no change in the proportion of living donors (59% vs 50%, P = .32), in 2018 there were more blood group incompatible living donors (0% vs 7%, P = .21). Compared with 2010, in 2018 there was a significant increase in recipient age (43 vs 54 years, P = .0002), diabetic nephropathy (5% vs 16%, P = .03), and recipient body mass index >35 kg/m2 (0% vs 9%, P = .02). CONCLUSIONS: Implementation of the Belfast Protocol has decreased LOS in renal transplant recipients despite increasingly complex donor and recipient profiles.

Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

Living Donor Kidney Transplantation Improves Graft and Recipient Survival in Patients with Multiple Kidney Transplants.

BACKGROUND: Failed kidney transplant recipients benefit from a new graft as the general incident dialysis population, although additional challenges in the management of these patients are often limiting the long-term outcomes. Previously failed grafts, a long history of comorbidities, side effects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplantation population, leading to significant complex immunological and technical aspects and often compromising the short- and long-term results. Although recipients' factors are acknowledged to represent one of the main determinants for graft and patient survival, there is increasing interest in expanding the donor's pool safely, particularly for high-risk candidates. The role of living kidney donation in this peculiar context of repeated kidney transplantation has not been assessed thoroughly. The aim of the present study is to analyse the effects of a high-quality graft, such as the one retrieved from living kidney donors, in the repeated kidney transplant population context. METHODS: Retrospective analysis of the outcomes of the repeated kidney transplant population at our institution from 1968 to 2019. Data were extracted from a prospectively maintained database and stratified according to the number of transplants: 1st, 2nd or 3rd+. The main outcomes were graft and patient survivals, recorded from time of transplant to graft failure (return to dialysis) and censored at patient death with a functioning graft. Duration of renal replacement therapy was expressed as cumulative time per month. A multivariate analysis considering death-censored graft survival, decade of transplantation, recipient age, donor age, living donor, transplant number, ischaemic time, time on renal replacement therapy prior to transplant and HLA mismatch at HLA-A, -B and -DR was conducted. In the multivariate analysis of recipient survival, diabetic nephropathy as primary renal disease was also included. RESULTS: A total of 2395 kidney transplant recipients were analysed: 2062 (83.8%) with the 1st kidney transplant, 279 (11.3%) with the 2nd graft, 46 (2.2%) with the 3rd+. Mean age of 1st kidney transplant recipients was 43.6 ± 16.3 years, versus 39.9 ± 14.4 for 2nd and 41.4 ± 11.5 for 3rd+ (p < 0.001). Aside from being younger, repeated kidney transplant patients were also more often males (p = 0.006), with a longer time spent on renal replacement therapy (p < 0.0001) and a higher degree of sensitisation, expressed as calculated reaction frequency (p < 0.001). There was also an association between multiple kidney transplants and better HLA match at transplantation (p < 0.0001). A difference in death-censored graft survival by number of transplants was seen, with a median graft survival of 328 months for recipients of the 1st transplant, 209 months for the 2nd and 150 months for the 3rd+ (p = 0.038). The same difference was seen in deceased donor kidneys (p = 0.048), but not in grafts from living donors (p = 0.2). Patient survival was comparable between the three groups (p = 0.59). CONCLUSIONS: In the attempt to expand the organ donor pool, particular attention should be reserved to high complex recipients, such as the repeated kidney transplant population. In this peculiar context, the quality of the donor has been shown to represent a main determinant for graft survival-in fact, kidney retrieved from living donors provide comparable outcomes to those from single-graft recipients.

Has the UK living kidney donor population changed over time? A cross-sectional descriptive analysis of the UK living donor registry between 2006 and 2017.

BACKGROUND: A living-donor kidney transplant is the best treatment for most people with kidney failure. Population cohort studies have shown that lifetime living kidney donor risk is modified by sex, age, ethnicity, body mass index (BMI), comorbidity and relationship to the recipient. OBJECTIVES: We investigated whether the UK population of living kidney donors has changed over time, investigating changes in donor demographics. DESIGN: We undertook a cross-sectional analysis of the UK living kidney donor registry between January 2006 to December 2017. Data were available on living donor sex, age, ethnicity, BMI, hypertension and relationship to recipient. SETTING: UK living donor registry. PARTICIPANTS: 11 651 consecutive living kidney donors from January 2006 to December 2017. OUTCOME MEASURES: Living kidney donor demographic characteristics (sex, age, ethnicity, BMI and relationship to the transplant recipient) were compared across years of donation activity. Donor characteristics were also compared across different ethnic groups. RESULTS: Over the study period, the mean age of donors increased (from 45.8 to 48.7 years, p<0.001), but this change appears to have been limited to the White population of donors. Black donors were younger than White donors, and a greater proportion were siblings of their intended recipient and male. The proportion of non-genetically related non-partner donations increased over the 12-year period of analysis (p value for linear trend=0.002). CONCLUSIONS: The increasing age of white living kidney donors in the UK has implications for recipient and donor outcomes. Despite an increase in the number of black, Asian and minority ethnic individuals waitlisted for a kidney transplant, there has been no increase in the ethnic diversity of UK living kidney donors. Black donors in the UK may be at a much greater risk of developing kidney failure due to accumulated risks: whether these risks are being communicated needs to be investigated.

Hyperamylasemia Post Living Donor Nephrectomy Does Not Relate to Pain.

Introduction The aetiology of pain after laparoscopic donor nephrectomy remains unclear. Given the proximity of the left kidney to the tail of the pancreas, we aimed to assess whether mobilisation and retrieval of the left kidney might inflame the pancreas, leading to pain and hyperamylasaemia in the post-operative period. Patient and methods In the present study, 16 consecutive live kidney donors were analysed in the same three months period. Amylase levels were measured on days 1 and 2. For each 24-hour period post-operatively analgesia consumption was recorded, as well as pain scores at rest on a visual analogue scale (VAS). Results Three out of 16 donors presented hyperamylasemia. A multiple regression analysis found levobupivacaine dose, propofol dose, transversus abdominis plane block and day 1 amylase did not significantly predict pain scores. Interestingly, body mass index significantly correlated with increased pain scores (p = 0.041). Also, increasing CO2 insufflation pressure and use of local anaesthetic infusion catheters predicted a decreased deep pain score (p = 0.036 and p = 0.037). Conclusion There was no correlation of amylase levels and pain scores. Pancreatitis is a rare complication of nephrectomy and no overt cases were seen in the case of donor nephrectomy.

Genomic Mismatch at LIMS1 Locus and Kidney Allograft Rejection.

BACKGROUND: In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection. METHODS: We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses. RESULTS: In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype vs. nonrisk genotypes, 1.84; 95% confidence interval [CI], 1.35 to 2.50; P = 9.8×10-5). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2004 donor-recipient pairs (hazard ratio, 1.55; 95% CI, 1.25 to 1.93; P = 6.5×10-5). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10-8). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses. CONCLUSIONS: We found that the LIMS1 locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (Funded by the Columbia University Transplant Center and others.).

Long-Term Outcomes of Renal Transplant in Recipients With Lower Urinary Tract Dysfunction.

OBJECTIVES: Lower urinary tract dysfunction can lead to chronic kidney disease, which, despite surgical intervention, will progress to end-stage renal disease, requiring dialysis. Urologic pathology may damage a transplanted kidney, limiting patient and graft survival. Although smaller studies have suggested that urinary tract dysfunction does not affect graft or patient survival, this is not universally accepted. Northern Ireland has historically had the highest incidence of neural tube defects in Europe, giving rich local experience in caring for patients with lower urinary tract dysfunction. Here, we analyzed outcomes of renal transplant recipients with lower urinary tract dysfunction versus control recipients. MATERIALS AND METHODS: We identified 3 groups of kidney transplant recipients treated between 2001 and 2010; those in group 1 had end-stage renal disease due to lower urinary tract dysfunction with prior intervention (urologic surgery, long-term catheter, or intermittent self-catheterization), group 2 had end-stage renal disease secondary to lower urinary tract dysfunction without intervention, and group 3 had end-stage renal disease due to polycystic kidney disease (chosen as a relatively healthy control cohort without comorbid burden of other causes of end-stage renal disease such as diabetes). The primary outcome measured, graft survival, was death censored, with graft loss defined as requirement for renal replacement therapy or retransplant. Secondary outcomes included patient survival and graft function. RESULTS: In 150 study patients (16 patients in group 1, 64 in group 2, and 70 in group 3), 5-year death-censored graft survival was 93.75%, 90.6%, and 92.9%, respectively, with no significant differences in graft failure among groups (Cox proportional hazards model). Five-year patient survival was 100%, 100%, and 94.3%, respectively. CONCLUSIONS: Individuals with a history of lower urinary tract dysfunction had graft and patient survival rates similar to the control group. When appropriately treated, lower urinary tract dysfunction is not a barrier to successful renal transplant.

Transplantation of a Gitelman Syndrome Kidney Ameliorates Hypertension: A Case Report.

Gitelman syndrome is caused by inactivating mutations of the gene that encodes the renal sodium/chloride cotransporter (NCC; encoded by SLC12A3), resulting in hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Renal salt wasting commonly provokes mild hypotension. The paucity of previous kidney transplants from donors with known tubulopathies suggests that such conditions may be considered contraindications to donation. A 76-year-old man received a live unrelated kidney transplant from a donor with known Gitelman syndrome secondary to a pathogenic mutation of SLC12A3. Immediate graft function preceded the emergence of the Gitelman syndrome biochemical phenotype and blood pressure subsequently improved. The recipient developed unexpected hyponatremia. Potential causes are discussed, including the possibility that it paralleled the physiologic changes seen in the high-volume state of thiazide-induced hyponatremia. Transplanted kidneys are subject to nephrotoxicity from the use of calcineurin inhibitors. Acquired Gitelman syndrome may confer a potential long-term advantage to the recipient through both improved blood pressure control and protection against the calcineurin inhibitor-induced side-effect profile caused by NCC overactivation. Both the donor and recipient remain well. In conclusion, Gitelman syndrome need not preclude kidney donation and transference of the phenotype may have benefits for the recipient.