Kidney Transplant Candidates Research Articles

Abstract 4133846: Even Mild Increase in Pulmonary Arterial Pressure Following Kidney Transplantation is Associated with Increased Mortality

Background: In end-stage renal disease (ESRD), elevated systolic pulmonary artery pressure (sPAP) is common, attributed to post-capillary pulmonary hypertension (PH) and associated with adverse outcomes. Kidney transplantation (KT) may mitigate ESRD-PH. We aimed to profile sPAP trajectory in a national cohort of ESRD patients pre- and post-KT, and link findings to clinical outcome. Methods: We analyzed retrospectively all patients within the Veterans Affairs Healthcare System undergoing KT between 2000-2019 with sPAP recorded pre- and post-KT by echocardiography. PH was defined by >35mmHg. Patients were assigned to one of the following groups: Never PH, New PH post-KT, Resolved PH post-KT, and Persistent PH. Spline curve and Kaplan-Meier analyses were used to test the association of sPAP or PH group with all-cause mortality, adjusted for age and sex. Results: From 631 patients (median 62 [IQR 58-65]yr; 97% male), there were 231 (36.6%), 184 (29.2%), 133 (21.1%), and 83 (13.1%) patients in the Persistent PH, Never PH, Resolved PH, and New PH groups, respectively. Never PH, Resolved PH and New PH had, overall, similar cardiopulmonary comorbidities ( Tab. 1 ). By contrast, Persistent PH had the highest rate of congestive heart failure, atrial fibrillation, and impaired diastolic relaxation assessed by E/E’. Creatinine post-KT, indicative for graft function, was stable in Never PH, Resolved PH and Persistent PH, but significantly increased in New PH. Of all groups, Resolved PH was associated with the most favorable survival rate (HR 0.73 [95%CI 0.51-1.05], p=0.087). New PH and Persistent PH were associated with a 51% (HR=1.51 [95%CI 1.06-2.15], p=0.023) and 37% (HR=1.37 [95%CI 1.03-1.82], p=0.029; referent group for all: Never PH) increase in adjusted mortality risk post-KT ( Fig. 1a ). Overall, we observed 21% (HR=1.21 [95%CI 1.11-1.31], p<0.001) increase in mortality hazard adjusted for age, sex and baseline sPAP, per 10mmHg increment increase in sPAP from pre-KT to post-KT whereas a 10mmHg sPAP decrease was associated a 17% decrease in mortality (HR=0.83 [95%CI 0.76-0.90], p<0.001) ( Fig. 1b ). Conclusion: These data suggest that PH is common post-KT and includes a sizeable group of patients without PH pre-KT. Increased PAP or failure for PH to resolve post-KT were independently associated with mortality. Overall, these data warrant prospective studies in sex-balanced cohorts that use PH to stratify KT candidacy and PAP as a longitudinal biomarker of graft function post-KT.

Coronary artery disease screening in renal transplant candidates: insights from a large prospective cohort

Abstract Background There is currently no specific consensus regarding the screening strategy for CAD in renal transplant candidates. Purposes To describe in renal transplant candidates 1/ Strategies and results of CAD screening and 2/ renal and cardiovascular outcomes in this population Methods All patients registered on kidney transplant waiting list in our tertiary centre were classified into no screening for CAD (unscreened), screened, or with prior CAD. Unscreened was defined as no ischemia or anatomic testing while on waiting list or within the year prior to listing. Screening was considered as "positive" when it led to diagnostic of obstructive CAD (stenosis > 50%). Primary outcome was a composite outcome defined as [death or unplanned revascularization]. Primary outcome and renal transplant were analysed using multivariable Cox model. Results From 2005 to 2023, 3248 patients were registered as candidates for kidney transplantation, 228 (7.0%) patients had a history of CAD, 1987 (61.2%) patients were screened for CAD and 1033 (31.8%) were unscreened. Initial screening investigation were mainly stress cardiovascular MRI (33.7%), stress TTE (27.7%) or myocardial perfusion imaging (26.4%). Among screened patients, 133 (6.7%) patients had a positive screening for obstructive CAD. Within 4.7 [1.2 – 7.2] years, using patients with a negative screening as a reference, patients with positive screening and known CAD were less likely to receive renal transplant (aHR 0.70 [0.53 ; 0.93] and 0.64 [0.49 ; 0.84] respectively), while patients without screening were similarly transplanted (aHR 1.01 [0.89 ; 1.15]). Patients without screening or with a prior history of CAD were at higher risk of primary outcome compared with patients with negative screening (aHR 1.49 [1.16; 1.91]) and aHR 1.97 [1.48; 2.62] respectively), along with patients on dialysis at registration (1.37 [1.13; 1.66]), diabetic patients (1.79 [1.47; 2.18]) and smokers (1.25 [1.03; 1.53]). Age was an interaction factor between unscreening and primary outcome, as there was no association in younger patients (aHR 1.21 [0.81; 1.81]). Conclusion Among candidates for kidney transplantation, 2 out of 3 patients underwent non-invasive testing for obstructive CAD resulting in less than 10 % of positive cases. Positive testing and history of CAD were associated with a lower opportunity for kidney transplantation compared with negative testing or absence of screening. Nonetheless, absence of screening was associated with a higher risk of [death + unplanned revascularization], especially in older patients.Central illustration

Frequencies or Absolute Numbers? Cluster Analysis of Frequencies and Absolute Numbers of B-Cell Subsets in Dialysis Patients Who Are Candidates for Kidney Transplantation Reveals Different Profiles.

Background: Detailed characterization of B cells in dialysis patients who are candidates for kidney transplant is still lacking, with little information on how dialysis duration and modality impact B cell subsets. Methods: Cluster analysis of flow cytometry determined the frequencies and absolute numbers of B-cell subsets and divided the cohort of 78 candidates into two distinct clusters, one with shorter and one with longer dialysis duration. Results: The immune profiles of the clusters differed depending on whether frequencies or absolute counts were considered. In long-term dialysis patients, the frequency of total memory, double negative and marginal zone B cells increased, while the frequency of naive and regulatory B cells decreased. This pattern was reversed in short-term dialysis patients, with a decrease in memory and an increase in naive and regulatory populations. The B subset number decreased significantly in long-term dialysis patients, while it increased significantly in short-term dialysis patients. The dialysis modality affected the frequency-based subset immune profiles. Conclusions: It is important to determine whether the evaluation is based on frequencies or absolute numbers. The different distribution of B cell subsets in the clusters, in terms of frequencies and absolute numbers, was influenced by dialysis duration. Modality and age only influenced the frequencies.

SMART-2D: a novel scoring system to predict non diagnostic exercise stress echocardiography in renal transplant candidates

Abstract Background Exercise stress echocardiography (ESE) is often used for pre-renal transplant risk stratification. Nearly 20% of ESE may be non-diagnostic, resulting in delays to transplant and increased healthcare cost. A simple, reliable tool for predicting non-diagnostic ESE may streamline assessment. Methods Retrospective analysis of 898 kidney transplant candidates between 2013-2020 who underwent exercise stress echocardiography for pre-transplant cardiovascular assessment was performed. The cohort was separated into a derivation and validation set. Multivariable logistic regression identified predictors of non-diagnostic ESE. Covariates associated with non-diagnostic ESE (p<0.10) on univariate analysis were included in the multivariable model. From this model, only variables with p<0.05 were included for score development. Model discrimination was assessed by area under the receiver operating curve (AUROC). Results Non-diagnostic ESE occurred in 17% (151/898). Predictors of non-diagnostic study formed the scoring system: 1 point for female sex, 2 points for BMI >40, 1 point for age >55, Heart Rate<55 4 points, <65 3 points and <75 2 points. LV Hypertrophy was assigned 2 points, Type 1 Diabetes 3 points and Type 2 diabetes 1 point, LV Dysfunction was assigned 2 points. This scoring system had excellent discriminative ability (derivation AUROC 0.80, validation AUROC 0.81). A score of 8 or more had a specificity of 97% and a positive likelihood ratio of 9.4 for non-diagnostic ESE. A score of <8 had a negative predictive value of 86%. Patients with Non-Diagnostic ESE had longer time to transplantation (695 vs 636 days), and more investigations performed (43.05% vs 17.94%, p<0.001) and less likely to receive a renal transplant (OR 0.47, p<0.001). Conclusion Non diagnostic ESE in pre-transplant assessment causes significant delays to patient care. A simple clinical scoring system may identify patients likely to have non-diagnostic ESE and can be utilised to identify patients who may benefit from alternative risk-stratification investigations.

Optimal survival analyses with prevalent and incident patients.

Period-prevalent cohorts are often used for their cost-saving potential in epidemiological studies of survival outcomes. Under this design, prevalent patients allow for evaluations of long-term survival outcomes without the need for long follow-up, whereas incident patients allow for evaluations of short-term survival outcomes without the issue of left-truncation. In most period-prevalent survival analyses from the existing literature, patients have been recruited to achieve an overall sample size, with little attention given to the relative frequencies of prevalent and incident patients and their statistical implications. Furthermore, there are no existing methods available to rigorously quantify the impact of these relative frequencies on estimation and inference and incorporate this information into study design strategies. To address these gaps, we develop an approach to identify the optimal mix of prevalent and incident patients that maximizes precision over the entire estimated survival curve, subject to a flexible weighting scheme. In addition, we prove that inference based on the weighted log-rank test or Cox proportional hazards model is most powerful with an entirely prevalent or incident cohort, and we derive theoretical formulas to determine the optimal choice. Simulations confirm the validity of the proposed optimization criteria and show that substantial efficiency gains can be achieved by recruiting the optimal mix of prevalent and incident patients. The proposed methods are applied to assess waitlist outcomes among kidney transplant candidates.

Prognostic value of dobutamine stress echocardiography for the long-term outcomes in kidney transplant candidates.

Cardiovascular disease is a primary cause of morbidity and mortality in kidney transplant (KT) candidates. Dobutamine stress echocardiography (DSE) is an effective noninvasive modality for evaluating coronary artery disease with high accuracy. However, long-term data in KT candidates are still lacking. This study aims to assess the prognostic value of DSE in predicting long-term outcomes in KT candidates. This study retrospectively included consecutive KT candidates who underwent preoperative DSE between 2007 and 2017 at Siriraj Hospital, Bangkok, Thailand. Normal DSE was characterized by the absence of wall motion abnormalities both at rest and during stress. The primary endpoint was all-cause mortality. Univariable and multivariable analyses were conducted to determine predictors of all-cause mortality, with a P value of <0.05 considered statistically significant. Among 269 patients (mean age 51 years, 58% male), 34 (12.6%) had abnormal DSE results, and 63 (23%) underwent kidney transplantation after DSE. During a median follow-up period of 7.6 (4.5, 10.1) years, 129 (48%) patients died. Patients with abnormal DSE had a significantly higher mortality rate than those with normal DSE (73.5% vs. 44.2%, P=0.003). Univariable analysis demonstrated that male gender [hazard ratio (HR) 1.50, 95% confidence interval (CI): 1.04-2.16, P=0.03], resting systolic blood pressure (HR 1.006, 95% CI: 1.00-1.01, P=0.04), abnormal DSE (HR 1.95, 95% CI: 1.25-3.05, P=0.003), higher delta wall motion score index (HR 2.57, 95% CI: 1.24-5.35, P=0.01), abnormal stress left ventricular end-systolic volume (HR 2.05, 95% CI: 1.11-3.82, P=0.02), and post-KT status (HR 0.48, 95% CI: 0.30-0.79, P=0.004) were associated with mortality. In the multivariable analysis, male gender and abnormal DSE were independent predictors of mortality [adjusted HR (aHR) 1.65, 95% CI: 1.06-2.20, P=0.02 and aHR 1.88, 95% CI: 1.20-2.93, P=0.006, respectively], while post-KT status emerged as an independent predictor of better outcomes (aHR 0.47, 95% CI: 0.29-0.77, P=0.003). In KT candidates, preoperative assessment with DSE provides valuable prognostic information for long-term outcomes, particularly regarding all-cause mortality.

Dietary Restriction, Socioeconomic Factors, Access to Kidney Transplantation, and Waitlist Mortality.

Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT. In our two-center prospective cohort study (2014-2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors. At evaluation, 18% of KT candidates felt extremely bothered by dietary restrictions. Those who felt extremely bothered were less likely to be listed for KT (adjusted hazard ratio [aHR]=0.75, 95% confidence interval [CI]: 0.64-0.87); this association did not differ by neighborhood-level socioeconomic factors. Overall, the burden of dietary restrictions was not associated with waitlist mortality (p=0.62). However, among candidates living in high food insecurity neighborhoods, those who felt extremely bothered had higher waitlist mortality (adjusted subhazard ratio [aSHR]=2.07, 95% CI: 1.14-3.75, p[interaction]=0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access. The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs.

Kidney Transplant Candidacy in a Patient with Recurrent Infection: Balancing Improved Quality of Life vs. Potential Infection Risk

Kidney Transplant Candidacy in a Patient with Recurrent Infection: Balancing Improved Quality of Life vs. Potential Infection Risk

Cancer Screening and Cancer Treatment in Kidney Transplant Recipients.

As the population ages and post-transplant survival improves, pretransplant and post-transplant malignancy are becoming increasingly common. In addition, rapid advances in cancer therapies and improving outcomes prompt us to rethink pretransplant cancer-free wait time and screening strategies. Although kidney transplant recipients (KTRs) are at higher risk of developing cancer, epidemiological data on how to best screen and treat cancers in KTRs are incomplete. Thus, current recommendations are still largely on the basis of studies in the general population, and their validity in KTRs is uncertain. Kidney transplant candidates without prior cancer should be evaluated for latent malignancies even in the absence of symptoms. Conversely, individuals with a history of malignancy require thorough monitoring to detect potential recurrences or de novo malignancies. When treating KTRs with cancer, reducing immunosuppression can enhance antitumor immunity, yet this also increases the risk of graft rejection. Optimal treatment and immunosuppression management remains undefined. As the emergence of novel cancer therapies adds complexity to this challenge, individualized risk-benefit assessment is crucial. In this review, we discuss up-to-date data on pretransplant screening and cancer-free wait time, as well as post-transplant cancer screening, prevention strategies, and treatment, including novel therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies.

Medical Mistrust Predicts Lower Likelihood of Wait-Listing in Kidney Transplant Candidates

Medical Mistrust Predicts Lower Likelihood of Wait-Listing in Kidney Transplant Candidates

Kidney Transplant Candidates with Reduced Ejection Fraction: Risky Business or Not?

Kidney Transplant Candidates with Reduced Ejection Fraction: Risky Business or Not?

Barriers to Obesity Management in Kidney Transplant Candidates

Barriers to Obesity Management in Kidney Transplant Candidates

Preemptive Registration in Hispanic Kidney Transplant Candidates: When Is Early Not Early Enough?

Preemptive Registration in Hispanic Kidney Transplant Candidates: When Is Early Not Early Enough?

BMI in Pediatric Kidney Transplant Candidates: Association with Neurodevelopmental Outcomes

BMI in Pediatric Kidney Transplant Candidates: Association with Neurodevelopmental Outcomes

Accuracy of Myocardial Perfusion Imaging (MPI) in Predicting Post-transplant Cardiovascular Events among Asymptomatic Diabetic Kidney Transplant Candidates

Accuracy of Myocardial Perfusion Imaging (MPI) in Predicting Post-transplant Cardiovascular Events among Asymptomatic Diabetic Kidney Transplant Candidates

Coronary Plaque Characteristics in Patients With Chronic Kidney Failure: Impact on Cardiovascular Events and Mortality.

In patients with coronary artery disease, coronary plaques with high-risk features and low-attenuation plaque burden are independent measures associated with major adverse cardiovascular events (MACEs). Patients with chronic kidney failure may have different coronary artery disease characteristics. The aim was to assess the association of coronary plaque characteristics and coronary artery disease extent with MACE and all-cause mortality in patients with chronic kidney failure. Potential kidney transplant candidates who underwent coronary computed tomography angiography as part of the cardiac screening program before kidney transplantation were included. We evaluated high-risk plaques and diameter stenosis semiqualitatively and quantified coronary artery calcium score and plaque burden (percentage atheroma volume). In 484 patients with chronic kidney failure and few or no symptoms of coronary artery disease (mean age, 53±12 years; 62% men; 32% on dialysis), 56 (12%) patients suffered MACE and 69 (14%) patients died during a median follow-up of 4.9 years. High-risk plaques were present in 39 (70%) patients with MACE. Median calcified plaque burden was 3.7% in patients with MACE versus 0.2% in patients without MACE. The median low-attenuation plaque burden was 0.3% versus 0.03%, respectively. In semiqualitative analyses, the presence of high-risk plaque and a higher coronary artery calcium score were associated with increased risk of MACE (hazard ratio (HR), 2.0 [95% CI, 1.0-3.7]; P=0.040; HR, 1.2 [95% CI, 1.0-1.3]; P=0.014), respectively. Neither were associated with all-cause mortality. In quantified analysis, increasing levels of both calcified and low-attenuation plaque burdens were associated with risk of MACE (HR, 2.6 [95% CI, 1.8-3.7]; P<0.001; HR, 2.6 [95% CI, 1.5-4.5]; P=0.001 [per variable doubling, respectively]) and all-cause mortality (HR, 1.6 [95% CI, 1.2-2.1]; P=0.002; HR, 1.8 [95% CI, 1.1-3.0]; P=0.028, respectively). In patients with chronic kidney failure, calcified and low-attenuation plaque burdens were independently associated with MACE and all-cause mortality, while high-risk plaques and coronary artery calcium score were only associated with MACE. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01344434.

A 5-year single-center review of Strongyloides seropositivity in kidney transplant candidates in Central Texas

Introduction Strongyloides stercoralis is a soil-transmitted helminth that can lead to life-threatening hyperinfection in transplant recipients. Targeted screening based on social history alone may preclude a large proportion of seropositive patients. Our institution implemented universal screening for kidney transplant candidates. This study aimed to identify the prevalence and identify risk factors of transplant candidates. Methods This was a retrospective chart review of kidney transplant candidates who were Strongyloides seropositive using the Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) test. An equivocal Strongyloides serology was defined as 1.0 to 1.1 IV, a positive test as >1.1 IV, and a negative test as <1.0 IV. Results A total of 1653 patients underwent screening for Strongyloides, and 121 (7.3%) tested positive. Forty-seven patients (38.8%) who tested positive had no reported travel history to endemic areas, and 86% of patients originated from the United States. Forty-six patients (97.9%) who received a kidney transplant received treatment with ivermectin, and none developed disseminated disease or hyperinfection. Conclusions Among kidney transplant candidates screened for Strongyloides, 7.3% were seropositive and many reported no travel history to endemic areas, which highlights the significant prevalence of this parasite in Central Texas. Universal screening at our institution identified a substantial number of seropositive patients who might have otherwise been missed.

Tuberculosis in kidney transplant candidates and recipients.

Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

Pretransplant cardiac stress testing and transplant wait time in kidney transplantation candidates

ObjectiveRoutine screening for cardiovascular disease before kidney transplantation remains controversial. This study aims to compare cardiac testing rates in patients with end-stage renal disease, referred and not referred for transplantation,...

Trends in Patient Characteristics on the Japanese Waiting Lists for Deceased-Donor Kidney Transplantation. Are There no Eligibility or Ineligibility Criteria for Registration and Renewal?

BackgroundControversial issues in registering candidates for deceased-donor kidney transplantation (DDKT) comprise various factors, including age, life expectancy, and dialysis duration. We investigated patient characteristics on the waiting list and discussed suitable criteria in Japan, which has a long waiting period. MethodsThis study included 592 patients on the waiting list for DDKT at our institute between 1982 and 2023. We retrospectively reviewed patients’ medical charts and obtained their clinical information. Patient characteristics according to outcomes and eligibility criteria for applying for or renewing registration were investigated. No prisoners were used in the study, and the participants were neither coerced nor paid. ResultsApproximately 70%, 45%, and 14.5% of the registered patients were aged >60, >70, and 80 years, respectively. The number of patients aged ≥70 years gradually decreased over time. The median waiting periods of patients who underwent and interrupted DDKT were 13 and 7 years, respectively. Patients in their 70s with a >15-year dialysis period tended to have opportunities for DDKT. Living-donor kidney transplantation was performed in patients aged <60 years. Waiting patients were significantly younger and had a shorter dialysis duration. Advanced age at registration was associated with a significantly high risk of interruption. ConclusionsAdvanced age and longer dialysis periods were considered at registration because patients with these factors tended to experience interruptions despite the long waiting period and high cost. Although older patients can undergo DDKT, factors including surgical cost and risks are considered. Eligibility/ineligibility criteria should be established for DDKT waiting lists in Japan.