Development of an intervention to improve AccesS to living-donor Kidney transplantation (The ASK study)

A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK's LDKT activity falls behind that of many other countries, and there is evidence of socioeconomic inequity in access. We aimed to develop a UK-specific multicomponent intervention to support eligible individuals to access a LDKT. The intervention was designed to support those who are socioeconomically-deprived and currently disadvantaged, by targeting mediators of inequity identified in earlier work. We identified three existing interventions in the literature which target these mediators: a) the Norway model (healthcare practitioners contact patients' family with information about kidney donation), b) a home education model, and c) a Transplant candidate advocate model. We undertook intervention development using the Person-Based Approach (PBA). We performed in-depth qualitative interviews with people with advanced kidney disease (n = 13), their family members (n = 4), and renal and transplant healthcare practitioners (n = 15), analysed using thematic analysis. We investigated participant views on each proposed intervention component. We drafted intervention resources and revised these in light of comments from qualitative 'think-aloud' interviews. Four general themes were identified: i) Perceived cultural and societal norms; ii) Influence of family on decision-making; iii) Resource limitation, and iv) Evidence of effectiveness. For each intervention discussed, we identified three themes: for the Norway model: i) Overcoming communication barriers and assumptions; ii) Request from an official third party, and iii) Risk of coercion; for the home education model: i) Intragroup dynamics; ii) Avoidance of hospital, and iii) Burdens on participants; and for the transplant candidate advocates model: i) Vested interest of advocates; ii) Time commitment, and iii) Risk of misinformation. We used these results to develop a multicomponent intervention which comprises components from existing interventions that have been adapted to increase acceptability and engagement in a UK population. This will be evaluated in a future randomised controlled trial

Alemtuzumab preconditioning with tacrolimus monotherapy - The impact of serial monitoring for donor-specific antibody

BACKGROUND. Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning. METHODS. Of 279 renal allograft recipients transplanted between March 2003 and December 2004, 222 (80%) had spaced weaning (i.e., reduction of tacrolimus monotherapy dosing to every other day, three times a week, twice a week, or once a week) attempted. Routine monitoring for donor-specific antibody (DSA) was begun in September 2004. Mean follow-up is 34±6.5 months after transplantation and 26±8.1 months after the initiation of spaced weaning. RESULTS. One hundred and twenty-two (44%) patients remained on spaced weaning. One- and 2-year actual patient/graft survival was 99%/99%, and 97%/96%. Fifty-six (20%) patients experienced acute rejection after initiation of spaced weaning. One- and 2-year actual patient/graft survival was 100%/98%, and 94%/78%. Forty-two (15%) patients with stable renal function had spaced weaning stopped because of the development of DSA, which disappeared in 17 (40%). One- and 2-year actual patient and graft survival was 100% and 100%. CONCLUSION. Adult renal transplant recipients who are able to be maintained on spaced weaning have excellent outcomes. Patients with stable renal function who have reversal of weaning because of the development of DSA also have excellent outcomes. Routine monitoring for DSA may allow patients to avoid late rejection after spaced weaning. © 2008 Lippincott Williams & Wilkins, Inc

Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenance tacrolimus monotherapy

OBJECTIVE. Describe the safety and efficacy of antithymocyte globulin or alemtuzumab preconditioning, steroid avoidance and reduced calcineurin inhibitor (CNI) immunosuppression in 34 children undergoing renal transplantation. METHODS. ATG (n=8) or alemtuzumab (n=26) were infused at the time of transplantation. This was followed by low-dose twice a day tacrolimus monotherapy with consolidation to once daily dosing by 6 months and once every other day dosing by 12 months. Follow-up ranged from 0.5-2.9 years (mean 1.33 years), with a minimum of 6 months. RESULTS. Both ATG and alemtuzumab were well tolerated. Lymphopenia occurred routinely and resolved after 3-6 months. Acute cellular rejection occurred in 9%; it was related to medical nonadherence in two patients and resulted in one graft loss at 1.5 years. Important adverse events included transient neutropenia in 10 children (none with serious infection), and autoimmune hemolytic anemia in two (resolved with a steroid course in both and conversion to sirolimus in one). Estimated glomerular filtration rate (e-GFR) was stable and averaged 88 mL/min/1.73 m at latest follow-up. Fifteen preadolescents had a greater increase in height Z-score at 1 year (1.3 vs. 0.5, P=0.001), and a higher e-GFR (94.8±21 vs. 76.6±20 ml/min/1.73 m, P<0.05), when compared to case-matched historical controls who were weaned off steroids by 6 months after transplantation and received twice daily tacrolimus monotherapy. CONCLUSION. This simple regimen appears safe, has a low risk for acute cellular rejection or other adverse effects, and is associated with excellent growth and renal function. Such a regimen may also improve compliance and limit CNI nephrotoxicity. © 2007 Lippincott Williams & Wilkins, Inc

Kidney Transplant Outcomes after Prolonged Delayed Graft Function

Background: The protracted recovery of renal function may be an actionable marker of post-transplant adverse events, but a paucity of data are available to determine if the duration of graft recovery serves to stratify risk. Materials and Methods: Single-center data of adult-isolated deceased-donor kidney transplant (KTX) recipients between 1 July 2015 and 31 December 2018 were stratified by delayed graft function (DGF) duration, defined as time to serum creatinine < 3.0 mg/dL. Results: Of 355 kidney transplants, the time to creatinine < 3.0 mg/dL was 0–3 days among 96 cases (DGF ≤ 3), 4–10 days among 85 cases (DGF4-10), 11–20 days among 93 cases (DGF11-20), and ≥21 days for 81 cases (DGF ≥ 21). DGF ≥ 21 recipients were significantly more likely to be male, non-sensitized, and receive kidneys from donors that were older, with donation after circulatory death, non-mandatory share, hypertensive, higher KDPI, higher terminal creatinine, and longer cold and warm ischemia time. On multivariate analysis, DGF ≥ 21 was associated with a 5.73-fold increased odds of 12-month eGFR < 40 mL/min compared to DGF ≤ 3. Lesser degrees of DGF had similar outcomes. Conclusions: Prolonged DGF lasting over 20 days signifies a substantially higher risk for reduced eGFR at 1 year compared to lesser degrees of DGF, thus serving as a threshold indicator of increased risk

Association of Dialysis Duration With Outcomes After Kidney Transplantation in the Setting of Long Cold Ischemia Time

Background. There is no mechanism that matches hard-to-place kidneys with the most appropriate candidate. Thus, unwanted kidney offers are typically to recipients with long renal replacement time (vintage) which is a strong risk factor for mortality and graft failure, and in combination with prolonged cold ischemia time (CIT), may promote interactive effects on outcomes. Methods. Consecutive adult isolated kidney transplants between October 2015 and December 2017 were stratified by vintage younger than 1 year and CIT longer than 30 hours. Results. Long (n = 169) relative to short (n = 93) vintage recipients were significantly more likely to be younger (32.2 years vs 56.9 years, P = 0.02), black race (40.8% vs 18.3%, P = 0.02), have higher estimated posttransplant survival (52.6 vs 42.0, P = 0.04), and have a comorbid condition (45.6% vs 30.1%, P = 0.02); they were less likely to receive a donation after circulatory death kidney (27.8% vs 39.8%, P = 0.05). Long vintage was significantly associated with length of stay longer than 4 days (45.5% vs 30.1%, P = 0.02), and 30-day readmission (37.3% vs 22.6%, P = 0.02) but not additional operations (17.8% vs 15.1%, P = 0.58), short-term patient mortality (3.0% vs 2.2%, P = 0.70), or overall graft survival (P = 0.23). On multivariate logistic regression, long vintage remained an independent risk factor for 30-day readmission (adjusted odds ratio, 1.92; 95% confidence interval, 1.06-3.47); however, there was no interaction of vintage and CIT for this outcome (P = 0.84). Conclusions. Readmission is significantly associated with pretransplant dialysis duration; however, CIT is not a modifying factor for this outcome

Investigating strategies to improve AccesS to Kidney transplantation (the ASK trial): a protocol for a feasibility randomised controlled trial with parallel process evaluation

Abstract Background The UK’s living-donor kidney transplant (LDKT) activity falls behind that of many other countries internationally, with less than 20% of those eligible receiving a LDKT each year. Certain individuals with kidney disease in the UK appear to be particularly disadvantaged in accessing a LDKT; the most socioeconomically deprived people with kidney disease are 60% less likely to receive a LDKT than the least deprived. Improving equity in living-donor kidney transplantation has been highlighted as an international research priority. Methods This feasibility trial was designed to determine the feasibility of delivery and acceptability of a multicomponent intervention designed to improve access to living-donor kidney transplantation. The intervention comprises three main components: (i) a meeting between a home educator and the transplant candidate for a dedicated discussion about living-donor kidney transplantation, living kidney donation and potential donors; (ii) a standardized letter from a healthcare professional to a candidate’s potential donors and (iii) a home-based education and family engagement session including two home educators, the transplant candidate and their family. The primary objectives are to establish the feasibility (i) of delivering the developed intervention in existing care pathways and (ii) of undertaking a randomised controlled trial of the intervention. A mixed-methods parallel process evaluation will investigate the acceptability, implementation and mechanisms of impact of the intervention. The trial is based at two UK hospitals: a transplanting hospital and a non-transplanting referral hospital. Individuals are eligible if they are ≥ 18 years old, are active on the kidney transplant waiting list or have been referred for transplant listing and do not have a potential living-donor undergoing surgical assessment. Randomisation will be undertaken with concealed allocation. Participants will be randomly allocated 1:1 to (i) the intervention or (ii) usual care, stratified by site to ensure a balance in terms of local differences. Minimisation will be used to ensure balance in sex, age group and socioeconomic strata, with probability weighting of 0.8 in order to reduce predictability. The primary outcomes are recruitment (% of those eligible and invited who consent to randomisation) and retention (% of participants completing follow-up). Discussion Findings will inform the design of a future fully powered, randomised controlled trial to formally evaluate the effectiveness of the intervention at improving equitable access to living-donor kidney transplantation. Trial registration ISRCTN Registry ISRCTN10989132 Applied 30/10/20

Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenance tacrolimus monotherapy

Objective. Describe the safety and efficacy of antithymocyte globulin or alemtuzumab preconditioning, steroid avoidance and reduced calcineurin inhibitor (CN!) immunosuppression in 34 children undergoing renal transplantation. Methods. ATG (n=8) or alemtuzumab (n=26) were infused at the time of transplantation. This was followed by low-dose twice a day tacrolimus monotherapy with consolidation to once daily dosing by 6 months and once every other day dosing by 12 months. Follow-up ranged from 0.5-2.9 years (mean 1.33 years), with a minimum of6 months. Results. Both ATG and alemtuzumab were well tolerated. Lymphopenia occurred routinely and resolved after 3-6 months. Acute cellular rejection occurred in 9%; it was related to medical nonadherence in two patients and resulted in one graft loss at 1.5 years. Important adverse events included transient neutropenia in 10 children (none with serious infection), and autoimmune hemolytic anemia in two (resolved with a steroid course in both and conversion to sirolimus in one). Estimated glomerular filtration rate (e-GFR) was stable and averaged 88 mLimin/I.73 m 2 at latest follow-up. Fifteen preadolescents had a greater increase in height Z-score at 1 year (1.3 vs. 0.5, P=O.OOI), and a higher e-GFR (94.8:!:21 vs. 76.6:!:20 mllmin/1.73 m 2 , P&lt;0.05), when compared to case-matched historical controls who were weaned off steroids by 6 months after transplantation and received twice daily tacrolimus mono therapy. Conclusion. This simple regimen appears safe, has a low risk for acute cellular rejection or other adverse effects, and is associated with excellent growth and renal function. Such a regimen may also improve compliance and limit CNI nephrotoxicity