Preemptive Living Donor Kidney Transplantation Research Articles

Preemptive living donor kidney transplantation: Access, fate, and review of the status in Egypt.

Preemptive living donor kidney transplantation (PLDKT) is recommended as the optimal treatment for end-stage renal disease. To assess the rate of PLDKT among patients who accessed KT in our center and review the status of PLDKT in Egypt. We performed a retrospective review of the patients who accessed KT in our center from November 2015 to November 2022. In addition, the PLDKT status in Egypt was reviewed relative to the literature. Of the 304 patients who accessed KT, 32 patients (10.5%) had preemptive access to KT (PAKT). The means of age and estimated glomerular filtration rate were 31.7 ± 13 years and 12.8 ± 3.5 mL/min/1.73 m2, respectively. Fifty-nine patients had KT, including 3 PLDKTs only (5.1% of total KTs and 9.4% of PAKT). Twenty-nine patients (90.6%) failed to receive PLDKT due to donor unavailability (25%), exclusion (28.6%), regression from donation (3.6%), and patient regression on starting dialysis (39.3%). In multivariate analysis, known primary kidney disease (P = 0.002), patient age (P = 0.031) and sex (P = 0.001) were independent predictors of achievement of KT in our center. However, PAKT was not significantly (P = 0.065) associated with the achievement of KT. Review of the literature revealed lower rates of PLDKT in Egypt than those in the literature. Patient age, sex, and primary kidney disease are independent predictors of achieving living donor KT. Despite its non-significant effect, PAKT may enhance the low rates of PLDKT. The main causes of non-achievement of PLDKT were patient regression on starting regular dialysis and donor unavailability or exclusion.

Pre-emptive living donor kidney transplantation: A public health justification to change the default.

OPINION article Front. Public Health, 17 March 2023Sec. Health Economics Volume 11 - 2023 | https://doi.org/10.3389/fpubh.2023.1124453

Clinical Significance of De Novo Donor Specific Antibody Based on the Type of Kidney Transplantation

Preemptive living donor kidney transplantation (P-LDKT) has shown a better prognosis than nonpreemptive living donor KT (NP-LDKT) or deceased donor KT (DDKT). However, association between KT type and de novo donor specific antibody (dnDSA) is uncertain. We retrospectively analyzed 1114 patients who underwent KT between 1994 and 2020. We investigated the clinical significance of dnDSA based on KT type. Mean follow-up duration was 131.5 ± 89.5 months. Mean age of recipients, mismatched number of human leukocyte antigens and incidence of delayed graft function were significantly higher in DDKT group than P-LDKT and NP-LDKT groups. There were no significant differences of incidence of dnDSA and acute rejection within 1 year among them. Death-censored graft survival rate was significantly lower in all groups with dnDSA than without dnDSA, respectively. In positive dnDSA, NP-LDKT and DDKT groups tended to be lower in the death-censored graft survival compared to P-LDKT and there was a significant interaction between type of KT and dnDSA (P = .010). Independent risk factors were acute rejection within 1 year (hazard ratio [HR], 4.341; 95% CI, 1.758-10.720; P = .001), dnDSA positivity (HR, 3.170; 95% CI, 1.364-7.371; P = .007), and eGFR at 12 months after KT (HR, 3.701; 95% CI 2.049-6.686; P < .001). There was no significant difference of incidence of dnDSA based on KT type, but allograft survival was poor in all recipients with dnDSA. NP-LDKT and DDKT with dnDSA showed poor prognosis compared to P-LDKT with dnDSA. Therefore, continuous and rigorous surveillance of DSA needs among NP-LDKT and DDKT.

Ravulizumab in Preemptive Living Donor Kidney Transplantation in Hereditary Atypical Hemolytic Uremic Syndrome.

Dear editor, we here report the first case of successful living donor kidney transplantation using complement inhibition by ravulizumab in a 33-y-old woman suffering from hereditary atypical hemolytic uremic syndrome (aHUS). Atypical HUS is the prototype for complement-mediated diseases that typically present with acute renal failure, albuminuria, and hematological abnormalities.1 In 2018, our patient developed acute-on-chronic kidney failure and increasing albuminuria during her first pregnancy. A stable chronic kidney disease with elevated serum creatinine and albuminuria of unknown cause was already diagnosed in 2004 (Figure 1). Arterial hypertension was well controlled by angiotensin-converting enzyme inhibitors. After premature delivery because of kidney failure and albuminuria, we performed a kidney biopsy. We identified a double contour appearance of capillary walls as one hallmark of chronic thrombotic microangiopathy, thus confirming the diagnosis of aHUS. Interstitial fibrosis was estimated to be about 40%. We rapidly initiated complement inhibition with eculizumab, a C5 inhibitor.2 Although detection of a specific risk mutation is not essential to the clinical diagnosis of aHUS, 50% to 70% of patients show one or more of numerous known genetic alterations.3 In this case, genetic testing revealed a heterozygous variant in the complement factor H (CFH) gene (c.157C>T p.(Arg53Cys)). CFH is an essential inhibitory part of the complement cascade, accelerating the decay of the C3 convertase with >100 reported genetic mutations.4 Mutations in CFH correlate with early onset of disease and worse renal prognosis.4,5 In 2020, a phase 3 study on ravulizumab, a new anti-C5 antibody, demonstrated improved hematological and renal outcomes in aHUS.6 Ravulizumab was engineered from eculizumab but allows recycling of the antibody to expand the half-life compared with eculizumab.7 In consent with our patient, we switched from eculizumab to ravulizumab because of its time-saving infusion interval of once every 8 wk to support our young patient and mother of a small child continuing her university studies. Renal anemia and metabolic acidosis subsequently forced us to prepare our patient for kidney transplantation. Before eculizumab was introduced, renal transplantation of aHUS patients was challenging, and the renal prognosis was poor because of 50% to 90% recurrence rates. Patients with CFH mutations reached the highest relapse rates of thrombotic microangiopathy.8 As eculizumab demonstrated efficacy after kidney transplantation in aHUS and ravulizumab shares its mechanism, we expected noninferiority compared with eculizumab and continued ravulizumab treatment during transplantation, which was performed without shifting infusion intervals.9 In April 2021, the patient received kidney donation from her 30-y-old husband. S-creatinine and albuminuria rapidly declined after transplantation. Neither hematological parameters nor kidney biopsy 2 wk after transplantation revealed signs of thrombotic microangiopathy. Six months after transplantation, the patient presents with stable creatinine and no albuminuria. Given concerns of safety or on drug interactions, clinicians might hesitate to use ravulizumab in patients who progress to end-stage kidney disease and are candidates for living donation transplantation. Hence, patients might be deprived of the benefit from the extended half-life of this drug. To our knowledge, usage of ravulizumab has not been reported for patients undergoing renal transplantation. Thus, we provide first evidence for the efficacy of ravulizumab to prevent recurrence of aHUS in a genetically high-risk situation before and after renal transplantation.FIGURE 1.: Time course of the patient’s medical history depicting the course of serum creatinine (red circles), albuminuria (blue circles), duration of pregnancy (bright yellow square), time points of kidney biopsies (arrows pointing down), start of treatment with eculizumab (E) and ravulizumab (R), and time point of kidney transplantation (arrows pointing left and right).

Sex differences in the likelihood of pre-emptive living donor kidney transplantation, and outcomes after kidney transplantation in children and adolescents.

Data on sex-based disparities in children with kidney failure and outcomes after kidney transplantation are relatively sparse. This study examined the association between sex differences and the odds of receiving a pre-emptive living donor kidney transplantation, and post-transplant outcomes in children and adolescents. We studied all patients (aged <20years) who commenced kidney replacement therapy (KRT) between 2002 and 2017 using data from the ANZDATA Registry. Factors associated with graft loss and acute rejection after transplantation were assessed using multivariable Cox regression model. Differences in the odds of receiving a pre-emptive live donor transplant between sexes were assessed using adjusted logistic regression. Of the 757 children transplanted during the study period, 497 (65.7%) received a live donor kidney (163, 21.5% pre-emptive). In total, 168 (22.2%) patients experienced graft loss and 213 (28.1%) patients experienced a first episode of acute rejection during the median follow-up period of 6.9years (IQR 3.5-11.5years). There were no differences in the rates of graft loss or acute rejection by sex. Compared with boys, the adjusted hazard ratios (aHR) (95% confidence interval) for graft loss and acute rejection in girls were 0.97 (0.71-1.33) and 1.09 (0.82-1.44), respectively. Among children who received living donor kidney transplants, there were no sex differences in the odds of receiving a pre-emptive transplant (adjusted odds ratio (aOR) 0.90 (95% CI 0.56-1.45)). No sex differences were observed in the odds of receiving a pre-emptive living donor kidney transplant or outcomes after kidney transplantation.

Facilitators and barriers to living donor kidney transplantation

Facilitators and barriers to living donor kidney transplantation

Impact of technology-based interventions on linking potential kidney donors and transplant candidates: a scoping review.

Despite the demonstrated survival advantage in end-stage kidney disease (ESKD) patients of a preemptive living donor kidney transplantation (LDKT), there has been a decline in LDKT among African American and Hispanic populations. We performed a scoping review and summarized the evidence about the use of technology-based interventions (TBI) to not only increase knowledge and awareness of LDKT but also link living donors with transplant candidates. We evaluated 31 studies and characterized them into "transplant-candidate facing" TBI, "transplant donor facing" TBI, and "interactive websites" targeting both donors and candidates. For the patient-facing interventions, 60% of studies suggested an increased likelihood of linking possible donors and candidates. The donor-facing interventions showed an increase in donor awareness and 75% of these interventions suggested increasing donor-candidate linkage. This study also demonstrates that TBI (regardless of medium) that are accessible and customized to the specific target population can potentially increase linkage of donors to recipients and serve as effective guides to connect potential donors to transplant candidates.

Transplant social worker and donor financial assistance to increase living donor kidney transplants among African Americans: The TALKS Study, a randomized comparative effectiveness trial.

Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans' potential living kidney donors. African Americans (N=300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12months. Participants' mean age was 52years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12months, few (n=39, 13%) participants had a new donor activation event (35 [12%] new donor inquiries; 17 [6%] new donor evaluations; 4 [1%] LDKT). There were no group differences in donor activation events (subdistribution hazard ratio [95% CI]: 1.09 [0.51-2.30] for TALK SWI and 0.92 [0.42-2.02] for TALK SWI plus Financial Assistance compared to Usual Care, p=91). Alternative interventions to increase LDKT for African Americans on the waiting list may be needed. Trial registration: ClinicalTrials.gov (NCT02369354).

Quantifying lead time bias when estimating patient survival in preemptive living kidney donor transplantation.

Preemptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants during 1998-2017. Patients were transplanted preemptively (n=1435) or after receiving up to 6months of dialysis (n=712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated predialysis) using left-truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9mL/min per 1.73 m2 in the non-pre-emptive, and 9.6mL/min per 1.73 m2 in the preemptive group. In the matched cohort (n=1398), preemptive transplantation was not associated with a survival advantage hazard ratio (HR) for preemptive vs non-pre-emptive 1.12 (95% confidence interval [CI] 0.79-1.61). Accounting for lead time moved the point estimates toward a survival disadvantage for preemptive transplantation (eg, HR assuming 4mL/min per 1.73m2 /year eGFR decline, 1.21 [0.85, 1.73]), but in all cases the 95% CIs crossed 1. The optimal timing of preemptive living donor kidney transplantation requires further study.

Abstract P062: The Benefits of Preemptive Transplant Vary by Cause of End-stage Renal Disease

Introduction: Cardiovascular events, i.e. cardiac arrest and arrhythmia, are the leading cause of death among patients with end-stage renal disease (ESRD). Kidney transplantation (KT) reduces mortality and is the preferred treatment for ESRD. Generally, preemptive KT, especially with a living donor, reduces mortality over KT after dialysis initiation. Mortality reduction by preemptive KT may vary by cause of ESRD. Hypothesis: Decreased all-cause mortality after preemptive KT varies by cause of ESRD. Methods: We studied 56,927 adult living donor KT recipients from 2000 to 2017 using the Scientific Registry of Transplant Recipients. We compared all-cause mortality in preemptive living donor KT recipients to those who underwent living donor KT within a year of starting dialysis, stratifying by cause of ESRD. We estimated the adjusted hazard ratio (aHR) of mortality comparing KT with &lt;1 year on dialysis to preemptive KT recipients accounting for recipient and transplant factors using inverse probability weights. Results: Compared to recipients on &lt;1 year of dialysis, preemptive KT recipients were more often female, older, college educated, employed, and had higher BMI (all p&lt;0.001). The association between preemptive KT and post-KT mortality did vary by cause of ESRD (Figure 1). For example, among recipients with ESRD caused by type I diabetes, &lt;1 year on dialysis was associated with a higher hazard of mortality (aHR: 1.32 (1.17-1.50), p&lt;0.001). However, among recipients with ESRD caused by hypertension (p=0.1) or type II diabetes (p=0.3), there was not a statistically significantly difference in mortality comparing KT with &lt;1 year on dialysis vs. preemptive KT. Conclusions: Our findings suggest that for particular ESRD patients, like those with type I diabetes, early counseling regarding preemptive KT and finding a living donor are imperative. Future studies should assess whether expedited review of potential living donors for these patients reduces mortality in this population at high risk of cardiovascular events.

Advantaged Outcomes of Pre-emptive Living Donor Kidney Transplantation and the Effect of Bias

Advantaged Outcomes of Pre-emptive Living Donor Kidney Transplantation and the Effect of Bias

Adequate Timing to Visit Transplant Center for Patient Intending Pre-Emptive Living–Donor Kidney Transplantation

Adequate Timing to Visit Transplant Center for Patient Intending Pre-Emptive Living–Donor Kidney Transplantation

Preemptive Living Donor Kidney Transplantation and Kidney Function at the Initial Hospital Visit: A Single-Center Case–Control Study

BackgroundStudies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. MethodsA single-center, case–control study was conducted to determine the clinical factors that lead to referral for PKT. ResultsBetween April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT−, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT−, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). ConclusionsOur results indicate that PKT should be performed within ∼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.

Barriers to Preemptive Living Donor Kidney Transplantation in The United States.

Barriers to Preemptive Living Donor Kidney Transplantation in The United States.

Effectiveness of Educational and Social Worker Interventions to Activate Patients' Discussion and Pursuit of Preemptive Living Donor Kidney Transplantation: A Randomized Controlled Trial

Many patients with chronic kidney disease (CKD) have difficulty becoming actively engaged in the pursuit of preemptive living donor kidney transplantation. The Talking About Live Kidney Donation (TALK) Study was a randomized controlled trial of the effectiveness of educational and social worker interventions designed to encourage early discussions and active pursuit of preemptive living donor kidney transplantation in patients with progressive CKD. We recruited participants with progressive CKD from academically affiliated nephrology practices in Baltimore, MD. Participants randomly received: (1) usual care (routine care with their nephrologists), the (2) TALK education intervention (video and booklet), or the (3) TALK social worker intervention (video and booklet plus patient and family social worker visits). We followed participants for 6 months to assess their self-reported achievement of behaviors reflecting their discussions about and/or pursuit of living donor kidney transplantation (discussions with family, discussions with physicians, initiating recipient evaluation, completing recipient evaluation, and identifying a potential living donor). We assessed outcomes through a questionnaire at 1-, 3-, and 6-months follow-up. Participants receiving usual care with their nephrologists (n = 44), TALK education (n = 43), and the TALK social worker (n = 43) were similar at baseline. TALK Study interventions improved participants' living donor kidney transplantation discussion and pursuit behaviors, with the social worker leading to greater patient activation (participants' predicted probability of achieving living donor kidney transplantation discussions, evaluations, or donor identification over 6 months): probabilities were 30% (95% CI, 20%-46%), 42% (95% CI, 33%-54%), and 58% (95% CI, 41%-83%), respectively, in the usual care, TALK education, and TALK social worker groups (P = 0.03). Our population was well educated and mostly insured, potentially limiting generalizability of our findings. TALK interventions improved discussion and active pursuit of living donor kidney transplantation in patients with progressive CKD and may improve their use of preemptive living donor kidney transplantation.

Preemptive Kidney Transplant From Deceased Donors: An Advantage in Relation to Reduced Waiting List

Background Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). Aim We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. Patients and Methods Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 ± 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. Results The types of donors in both groups were: non–heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 ± 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 ± 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 ± 0.2 in the preemptive group versus 1.7 ± 0.4 in the dialysis group ( P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. Conclusion PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.

Preemptive Living Donor Kidney Transplantation: Do the Benefits Extend to All Recipients?

Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients. We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months). Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37). With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.