Kidney Transplant Candidates Research Articles

Neurocognitive disruption in pediatric kidney transplant candidates: Medical and sociodemographic factors

We evaluated the effects of kidney failure etiology, dialysis, and area deprivation index on the subdomains of neurocognitive functioning in pediatric kidney transplant candidates. The study included 78 pediatric kidney transplant candidates (47.4% male, 70.5% White, M.age = 11.77 years, and 51.3% patients have public insurance) who completed a pre-transplant neuropsychological evaluation between 1/1/2010 and 10/31/2022. Linear regression models were employed to complete data analyses. The mean scores of various neurocognitive functioning domains in pediatric kidney transplant candidates were significantly lower than in the general population (ps < .001). After adjusting for covariates, patients with congenital anomalies of the kidney and urinary tract (M = 87; 95% CI: 80–94) and other etiologies (M = 82; 95% CI: 76–89) had significantly lower processing speed compared to patients with nephrotic syndrome (M = 98; 95% CI: 89–107) (p = .02). Patients living in high-level deprivation neighborhoods showed significantly lower verbal skills (p = .01), working memory performance (p = .02), and full-scale IQ (p = .03) than patients living in median-level and low-level deprivation neighborhoods. Additionally, dialysis did not show significant association with neurocognitive domains ((ps ranged from .07 to .52).

A Multicenter Home-based Prehabilitation Intervention in Kidney Transplant Candidates.

Frailty is a modifiable risk factor for morbidity and mortality among kidney transplant (KT) candidates. We previously demonstrated that an 8-wk center-based exercise intervention is associated with improved frailty parameters in patients with advanced chronic kidney disease. This study aimed to adapt the intervention for home-based delivery and examine its feasibility, safety, and acceptability in a multicenter cohort of KT candidates. We conducted a prospective pilot study between January 2021 and November 2023 involving KT candidates from Mayo Clinic in Minnesota and Baylor St. Luke's Medical Center in Texas. Adults approved for KT who were (1) frail or prefrail by the Physical Frailty Phenotype and/or (2) had a Short Physical Performance Battery score ≤10 were enrolled. The exercise intervention consisted of an individualized exercise prescription provided by a Mayo Clinic exercise physiologist followed by 8 weekly phone calls. Feasibility was assessed via retention rates, adverse events were recorded, and acceptability was assessed via survey. Baseline characteristics of the 15 enrolled participants included a median age of 64 y, 73.3% were men, and 73.3% were of White race. Sixty percent of participants completed the intervention. No unanticipated adverse events occurred. Most participants strongly agreed that the exercise intervention was beneficial to their overall health. This pilot study demonstrates that a home-based 8-wk exercise intervention is a promising prehabilitation strategy in KT candidates and provides important preliminary data for future larger, randomized studies.

Frailty in kidney transplant recipients.

Kidney transplantation is the treatment of choice even for the elderly, as it improves quality of life and life expectancy, lowering the financial burden to the health care system compared to dialysis therapy. In Japan, kidney transplant recipients have become older due to the shift in demographics. Compared to community-dwelling elderly adults, elderly kidney transplant recipients undergoing immunosuppressive therapy have a higher risk of age-related outcomes including hospital readmissions, infections, dementia, malignancies, and fractures. In frailty, patients become vulnerable to adverse events after stressors due to a lack of physiologic reserve. Although it is often associated with aging, frailty can also occur in younger individuals with certain chronic illnesses or conditions including chronic kidney disease. Limited compensatory mechanisms result in functional impairment and adverse health outcomes, such as disability, falls, decreased mobility, hospitalization, and death. Although kidney transplant recipients can restore their kidney function after transplantation, most of them still have chronic kidney disease, as well as a gradual decline in graft function as a result of chronic allograft nephropathy. Wait-listed candidates for kidney transplantation with frailty are more likely to experience wait-list removal or death. Frailty at the time of transplantation is associated with complications after kidney transplantation such as delayed graft function, longer hospital stays, rehospitalizations, immunosuppression intolerance, surgical complications, and death. Nevertheless, kidney transplantation can be a viable intervention for frailty in dialysis patients.

Frailty and sarcopenia metabolomic signatures in kidney transplant candidates: the frailmar study

Abstract Sarcopenia and frailty are often overlooked in assessing kidney transplant (KT) candidates with chronic kidney disease (CKD), potentially leading to poor post-transplant outcomes. This study aimed to identify metabolites associated with frailty and sarcopenia in KT-candidates from the FRAILMAR study. Between June 2016 and June 2020, we evaluated frailty and sarcopenia in 173 KT-candidates using the Physical Frailty Phenotype and EGWSOP-2 criteria, respectively. Seventy-five metabolic markers from targeted pathways, previously linked to CKD, sarcopenia, or frailty, were measured in serum samples. These markers were analyzed using adjusted and weighted generalized linear models. Metabolomic data were integrated with multi-modal data, such as comorbidities, using a factor-based integration algorithm to identify metabolic phenotypes. Increased metabolites related to energy metabolism and essential amino acids were associated with frailty, mainly Krebs cycle intermediates. Sarcopenic KT-candidates showed lower levels of aromatic amino acids, lower protein/muscle metabolism, energy metabolism, and neurotransmission compared to non-sarcopenic patients. Unsupervised multi-modal integration revealed a high-risk metabolic phenotype characterized by the presence of sarcopenia, diabetes mellitus, and low body mass index, with alterations in branched-chain amino acids and high activity of lactate dehydrogenase enzyme. Frailty and sarcopenia are common among KT-candidates, and their metabolic status reveal notable disruptions in energy and amino acid metabolism. These findings highlight the value of a detailed metabolic assessment to more accurately evaluate patient health status prior to transplantation.

The evaluation of kidney transplant candidates prior to waitlisting: a scoping review

The evaluation of kidney transplant candidates prior to waitlisting: a scoping review

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 &gt;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&lt;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&lt;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.

Hospitalization and Hospitalized Delirium Are Associated With Decreased Access to Kidney Transplantation and Increased Risk of Waitlist Mortality.

Kidney transplant (KT) candidates often experience hospitalizations, increasing their delirium risk. Hospitalizations and delirium are associated with worse post-KT outcomes, yet their relationship with pre-KT outcomes is less clear. Pre-KT delirium may worsen access to KT due to its negative impact on cognition and ability to maintain overall health. Using a prospective cohort of 2374 KT candidates evaluated at a single center (2009-2020), we abstracted hospitalizations and associated delirium records after listing via chart review. We evaluated associations between waitlist mortality and likelihood of KT with hospitalizations and hospitalized delirium using competing risk models and tested whether associations differed by gerontologic factors. During a median of 1.8 years after listing, 735 (31.0%) candidates had ≥1 hospitalizations. Candidates with less education, frailty, depressive symptoms, and lower extremity function impairment were more likely to be hospitalized. Hospitalization was associated with higher waitlist mortality (aSHR = 3.65, 95% CI: 2.99-4.45) and a lower likelihood of KT (aSHR = 0.74, 95% CI: 0.66-0.84). Among candidates who were hospitalized, 80 (11%) had ≥1 delirium episodes. Candidates who were older, frail, and impaired in lower extremity function were more likely to have delirium, which was associated with higher waitlist mortality (aSHR = 4.87, 95% CI: 3.42-6.93) and a lower likelihood of KT (aSHR = 0.45, 95% CI: 0.27-0.74). The association between hospitalization and KT differed by candidate age (pinteraction<0.001), with those aged ≥65 having a 61% lower likelihood of KT. Hospitalization and delirium are associated with worse pre-KT outcomes and have serious implications on candidates' access to KT. Providers should work to reduce preventable instances of delirium.

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 &amp;gt; 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&amp;lt;0.10) on univariate analysis were included in the multivariable model. From this model, only variables with p&amp;lt;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 &amp;gt;40, 1 point for age &amp;gt;55, Heart Rate&amp;lt;55 4 points, &amp;lt;65 3 points and &amp;lt;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 &amp;lt;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&amp;lt;0.001) and less likely to receive a renal transplant (OR 0.47, p&amp;lt;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