Protocol of a Randomized Controlled Trial of Culturally Sensitive Interventions to Improve African Americans' and Non-African Americans' Early, Shared, and Informed Consideration of Live Kidney Transplantation: The talking about Live Kidney Donation (TALK) study

<p>Abstract</p> <p>Background</p> <p>Live kidney transplantation (LKT) is underutilized, particularly among ethnic/racial minorities. The effectiveness of culturally sensitive educational and behavioral interventions to encourage patients' early, shared (with family and health care providers) and informed consideration of LKT and ameliorate disparities in consideration of LKT is unknown.</p> <p>Methods/Design</p> <p>We report the protocol of the Talking About Live Kidney Donation (TALK) Study, a two-phase study utilizing qualitative and quantitative research methods to design and test culturally sensitive interventions to improve patients' shared and informed consideration of LKT. Study Phase 1 involved the evidence-based development of culturally sensitive written and audiovisual educational materials as well as a social worker intervention to encourage patients' engagement in shared and informed consideration of LKT. In Study Phase 2, we are currently conducting a randomized controlled trial in which participants with progressing chronic kidney disease receive: 1) usual care by their nephrologists, 2) usual care plus the educational materials, or 3) usual care plus the educational materials and the social worker intervention. The primary outcome of the randomized controlled trial will include patients' self-reported rates of consideration of LKT (including family discussions of LKT, patient-physician discussions of LKT, and identification of an LKT donor). We will also assess differences in rates of consideration of LKT among African Americans and non-African Americans.</p> <p>Discussion</p> <p>The TALK Study rigorously developed and is currently testing the effectiveness of culturally sensitive interventions to improve patients' and families' consideration of LKT. Results from TALK will provide needed evidence on ways to enhance consideration of this optimal treatment for patients with end stage renal disease.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov number, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00932334">NCT00932334</a></p

Optimal integration of desensitization protocols into kidney paired donation (KPD) programs

© 2019 Blood type (ABO) incompatibility and antibody to donor human leukocyte antigen (HLA) remain the most significant barriers in transplantation. While pre-transplant desensitization can be administered to overcome such incompatibilities between living donors and their kidney recipients, desensitization alone is likely to fail for those pairs with significant incompatibilities. For these pairs, desensitization can be administered in combination with Kidney Paired Donor (KPD) exchange, the system that allows incompatible pairs to exchange donors with other incompatible pairs to improve donor–recipient compatibilities. Prior operations research literature on KPD investigates the optimal strategy to match donors to patients within a given set of incompatible pairs. However, models and algorithms in these studies exclusively look for the best possible match without considering the possibility of combining KPD and desensitization therapy. The current study adapted the existing models to incorporate desensitization as a way to increase KPD efficiency and embedded it into a simulation framework to evaluate the impact of optimally integrating a desensitization protocol in a KPD program. This is the first attempt to quantify the benefit of such an integration. Our results indicated that desensitization as part of a KPD exchange program is a promising approach to improve access to and to reduce wait time for a living donor renal transplant

Characterization of waiting times in a simulation of kidney paired donation

A national kidney paired donation (KPD) program will substantially increase transplant opportunities for recipients with blood type incompatible or cross-match positive donors. It seems likely that donor-recipient pairs with certain blood types, races or restrictions will wait longer than others for a match, although no data exist to confirm this assumption. We simulated patients and characterized the predicted waiting times for different blood type sub-groups, as well as the effects of patient-imposed restrictions on waiting time. We also compared waiting times of different racial sub-groups. Almost all patients with panel-reactive antibody (PRA) less than 80% match within a few months in a national KPD program, with the longest waiting time seen by O recipients with AB donors. Highly sensitized patients wait considerably longer, especially those unwilling to travel or accept older donors, and those with AB or B donors may not match in a timely manner. Although patients are better served by matching in a combined pool than within their own race, racial inequalities exist and bonus points can offset some of these differences. These data provide the first waiting time predictions that can aid patients with incompatible donors in choosing between KPD and desensitization, and can also facilitate planning for a national KPD program. Copyright © Blackwell Munksgaard 2005

Clinical relevance and igg subclass determination of Non-HLA antibodies identified using endothelial cell precursors isolated from donor blood

Background: ABO and human leukocyte antigen (HLA) alloantibodies provide major immunologic barriers to successful transplantation; however, there is increasing recognition for the role of anti-endothelial cell antibodies (AECAs) in allograft rejection. We investigated the relationship between AECAs identified using donor-derived endothelial cell precursors (ECPs) and kidney allograft rejection and function. Methods: Sixty live donor kidney recipients were tested pretransplant for AECAs and HLA-antibodies using flow cytometric crossmatch tests and solid-phase bead immunoassays. Renal allograft function was assessed by serum creatinine (SCr) values collected at early (mean, 50 days) and late (mean, 815 days) time points posttransplant and by incidence and type of rejection. Immunoglobulin G (IgG) subtype determination of both AECAs and HLA antibodies bound to ECPs was performed using flow cytometry. Results: Fourteen patients (23%) tested positive for donor-reactive IgG AECAs and had statistically higher SCr values and incidences of cellular rejection early posttransplant compared with 46 patients who tested negative (P=0.014 and P\u3c0.05). SCr values were not statistically different late posttransplant. IgG subclass determination showed AECAs to be enriched for IgG2 and IgG4, subclasses that do not activate complement effectively. Detection of donor-reactive immunoglobulin M (IgM) AECAs did not correlate with increased SCr or incidence of rejection. CONCLUSION.: Crossmatch tests performed using donor-derived ECPs allow for the identification of alloantibodies that are associated with cellular rejection and are distinct from alloantibodies detected using lymphocytes. © 2011 by Lippincott Williams & Wilkins

Mild preischemia hypothermia adversely affects postischemic myocardial function in the neonatal piglet heart

Background: During cardiac surgery, operative hypothermia has been shown to be beneficial in certain situations, although in children perioperative hypothermia has been associated with several physiologic alterations that have proven detrimental to their postoperative function. Little attention has been given to the effects of mild (34.5°C) perioperative hypothermia on postischemic myocardial function in the pediatric population. It was hypothesized that mild hypothermia would be detrimental to postischemic ventricular function in the neonatal heart. Methods: Neonatal (0-2 days old) piglets were subjected to mild perioperative hypothermia without rewarming (HT-only, n = 6), hypothermia followed by rewarming (HT-RW, n = 6), or continuous normothermia (NT, n = 8). The hearts were rapidly excised, suspended on an isolated perfusion apparatus, and allowed to spontaneously beat while being perfused with an asanguinous solution. All hearts were subjected to 20 min global, normothermic, zero-flow ischemia followed by 45 min oxygenated crystallite buffer reperfusion (I-R). Results: Compared to that of NT piglets, there were significant (P \u3c 0.05) reductions in recovery of left ventricular (LV) diastolic and systolic function following ischemia and reperfusion in HT-RW animals. When the hearts were rendered ischemic without first rewarming, the degree of myocardial dysfunction was not as severe. In contrast to the NT piglets, HT-RW animals demonstrated significant (P \u3c 0.05) reductions in the final recovery of LV developed pressure (71 ± 6 vs 105 ± 6 in NT), LV rate pressure product (52 ± 4 vs 102 ± 9 NT), and LV end diastolic pressure (32 ± 7 vs 3 ± 1 in NT) following I-R. When compared to the HT-RW group, HT-only piglets did not exhibit significant differences in systolic function, although diastolic function was minimally altered initially as evidenced by the slight elevation of LV end diastolic pressure at 5 min, with reperfusion in the HT-only group (P \u3c 0.05). Conclusions: In this newborn piglet model, mild hypothermia significantly reduces recovery of systolic and diastolic left ventricular function when followed by an episode of global myocardial ischemia-reperfusion only when the animals are returned to normothermia prior to the ischemic insult. When hypothermia is immediately followed by the ischemic event, left ventricular function is unaffected

Liver allograft outcomes after laparoscopic-assisted and minimal access live donor hepatectomy for transplantation

Background: The critical shortage of deceased organ donors has led to live-donor hepatectomy as an alternative donor option for transplantation. Although laparoscopic hepatectomy has been well described for management of liver tumors and can be performed safely, few studies have examined early recipient allograft outcomes after laparoscopic live-donor hepatectomy. We describe our initial experience with laparoscopic-assisted and minimal-access donor hepatectomy and its potential as a safe alternative with graft function comparable with open resection in live-donor liver transplantation. Methods: We performed a retrospective analysis of our past 30 successive live-donor transplants between 2005 and 2009. Fifteen allografts were procured by standard open live-donor (OLD) hepatectomy, and 15 by laparoscopic-assisted (LALD) or minimal-access (MA) live-donor hepatectomy. Left lateral segment grafts were subcategorized and analyzed further. Results: Mean donor age, sex, and liver anatomy were comparable between donor groups. Early graft function as measured by peak total bilirubin level, aspartate aminotransferase level, alanine aminotransferase level, and international normalized ratio on postoperative days 2, 7, 30, and 90 were similar between groups, although the international normalized ratio was slightly more increased on postoperative day 7 in LALD grafts (1.75 ± .45 vs 1.28 ± .16; P = .02). Perioperative allograft biliary (2 of 15 vs 0 of 15; P = .48) and vascular (3 of 15 vs 1 of 15; P = .6) complication rates also were comparable between OLD and LALD/MA grafts. One-year graft and patient survival for LALD/MA was 100% compared with 93% for OLD. Conclusions: Our experience shows that LALD or MA live-donor hepatectomy is a safe procedure and produces early graft function comparable with standard OLD hepatectomy. Multicenter, larger-volume experience will determine the widespread application of this technique. © 2011 Elsevier Inc

Liver allograft outcomes after laparoscopic-assisted and minimal access live donor hepatectomy for transplantation

Background: The critical shortage of deceased organ donors has led to live-donor hepatectomy as an alternative donor option for transplantation. Although laparoscopic hepatectomy has been well described for management of liver tumors and can be performed safely, few studies have examined early recipient allograft outcomes after laparoscopic live-donor hepatectomy. We describe our initial experience with laparoscopic-assisted and minimal-access donor hepatectomy and its potential as a safe alternative with graft function comparable with open resection in live-donor liver transplantation. Methods: We performed a retrospective analysis of our past 30 successive live-donor transplants between 2005 and 2009. Fifteen allografts were procured by standard open live-donor (OLD) hepatectomy, and 15 by laparoscopic-assisted (LALD) or minimal-access (MA) live-donor hepatectomy. Left lateral segment grafts were subcategorized and analyzed further. Results: Mean donor age, sex, and liver anatomy were comparable between donor groups. Early graft function as measured by peak total bilirubin level, aspartate aminotransferase level, alanine aminotransferase level, and international normalized ratio on postoperative days 2, 7, 30, and 90 were similar between groups, although the international normalized ratio was slightly more increased on postoperative day 7 in LALD grafts (1.75 ± .45 vs 1.28 ± .16; P = .02). Perioperative allograft biliary (2 of 15 vs 0 of 15; P = .48) and vascular (3 of 15 vs 1 of 15; P = .6) complication rates also were comparable between OLD and LALD/MA grafts. One-year graft and patient survival for LALD/MA was 100% compared with 93% for OLD. Conclusions: Our experience shows that LALD or MA live-donor hepatectomy is a safe procedure and produces early graft function comparable with standard OLD hepatectomy. Multicenter, larger-volume experience will determine the widespread application of this technique. © 2011 Elsevier Inc

Outcome at 3 years with a prednisone-free maintenance regimen: A single-center experience with 349 kidney transplant recipients

Historically, late steroid withdrawal after kidney transplants has been associated with an increased rejection rate. Recently, low rejection rates have been reported for recipients treated with complete avoidance or rapid elimination of steroids. However, follow-up has been short. We herein report on 3-year outcome in recipients whose prednisone was rapidly eliminated and who were maintained on a steroid-free regimen. From 10/1/1999 through 5/1/2003, 349 recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone. Actuarial 3-year patient survival was 95%; graft survival, 93%. Acute rejection-free graft survival at 1 year was 94%; at 3 years, 92%. There was no difference between LD and CAD. At 2 years, the mean (± SE) serum creatinine level for LDs was 1.6 ± 0.5 mg/dL; for CAD, 1.6 ± 0.4 mg/dL. We have no new cases of PTLD or avascular necrosis; 22 recipients (6%) developed CMV. Currently, 84% of recipients remain prednisone-free. We conclude that excellent 3-year patient and graft survival can be achieved without maintenance prednisone. With such a protocol, steroid-related side-effects are minimal