Faculty Bibliography

BACKGROUND:Frailty predicts adverse post-kidney transplant (KT) outcomes, yet the impact of frailty assessment on center-level outcomes remains unclear. We sought to test whether transplant centers assessing frailty as part of clinical practice have better pre- and post-KT outcomes in all adult patients (≥18 years) and older patients (≥65 years). METHODS:In a survey of US transplant centers (11/2017-4/2018), 132 (response rate = 65.3%) centers reported their frailty assessment practices (frequency and specific tool) at KT evaluation and admission. Assessment frequency was categorized as never, sometime, and always; type of assessment tool was categorized as none, validated (for post-KT risk prediction), and any other tool. Center characteristics and clinical outcomes for adult patients during 2017-2019 were gleaned from the transplant national registry (Scientific Registry of Transplant Recipients). Poisson regression was used to estimate incidence rate ratios (IRRs) of waitlist outcomes (waitlist mortality, transplantation) in candidates and IRRs of post-KT outcomes (all-cause mortality, death-censored graft loss) in recipients by frailty assessment frequency. We also estimated IRRs of waitlist outcomes by type of assessment tool at evaluation. All models were adjusted for case mix and center characteristics. RESULTS:Assessing frailty at evaluation was associated with lower waitlist mortality rate (always IRR = 0.91,95%CI:0.84-0.99; sometimes = 0.89,95%CI:0.83-0.96) and KT rate (always = 0.94,95%CI:0.91-0.97; sometimes = 0.88,95%CI:0.85-0.90); the associations with waitlist mortality rate (always = 0.86,95%CI:0.74-0.99; sometimes = 0.83,95%CI:0.73-0.94) and KT rate (always = 0.82,95%CI:0.77-0.88; sometimes = 0.92,95%CI:0.87-0.98) were stronger in older patients. Furthermore, using validated (IRR = 0.90,95%CI:0.88-0.92) or any other tool (IRR = 0.90,95%CI:0.87-0.93) at evaluation was associated lower KT rate, while only using a validated tool was associated with lower waitlist mortality rate (IRR = 0.89,95%CI:0.83-0.96), especially in older patients (IRR = 0.82,95%CI:0.72-0.93). At admission for KT, always assessing frailty was associated with a lower graft loss rate (IRR = 0.71,95%CI:0.54-0.92) but not with mortality (IRR = 0.93,95%CI:0.76-1.13). CONCLUSIONS:Assessing frailty at evaluation is associated with lower KT rate, while only using a validated frailty assessment tool is associated with better survival, particularly in older candidates. Centers always assessing frailty at admission are likely to have better graft survival rates. Transplant centers may utilize validated frailty assessment tools to secure KT access for appropriate candidates and to better allocate health care resources for patients identified as frail, particularly for older patients.

OBJECTIVES:The COVID-19 pandemic significantly affected the provisions of health services to necessary but deprioritised fields, such as transplantation. Many programmes had to ramp-down their activity, which may significantly affect transplant volumes. We aimed to pragmatically analyse measures of transplant activity and compare them by a country's income level and cumulative COVID-19 incidence (CCI). DESIGN, SETTING AND PARTICIPANTS:From June to September 2020, we surveyed transplant physicians identified as key informants in their programmes. Of the 1267 eligible physicians, 40.5% from 71 countries participated. OUTCOME:Four pragmatic measures of transplant activity. RESULTS:Overall, 46.5% of the programmes from high-income countries anticipate being able to maintain >75% of their transplant volume compared with 31.6% of the programmes from upper-middle-income countries, and with 21.7% from low/lower-middle-income countries (p<0.001). This could be because more programmes in high-income countries reported being able to perform transplantation/s (86.8%%-58.5%-67.9%, p<0.001), maintain prepandemic deceased donor offers (31.0%%-14.2%-26.4%, p<0.01) and avoid a ramp down phase (30.9%%-19.7%-8.3%, p<0.001), respectively. In a multivariable analysis that adjusted for CCI, programmes in upper-middle-income countries (adjusted OR, aOR=0.47, 95% CI 0.27 to 0.81) and low/lower-middle-income countries (aOR 0.33, 95% CI 0.16 to 0.67) had lower odds of being able to maintain >75% of their transplant volume, compared with programmes in high-income countries. Again, this could be attributed to lower-income being associated with 3.3-3.9 higher odds of performing no transplantation/s, 66%-68% lower odds of maintaining prepandemic donor offers and 37%-76% lower odds of avoiding ramp-down of transplantation. Overall, CCI was not associated with these measures. CONCLUSIONS:The impact of the pandemic on transplantation was more in lower-income countries, independent of the COVID-19 burden. Given the lag of 1-2 years in objective data being reported by global registries, our findings may inform practice and policy. Transplant programmes in lower-income countries may need more effort to rebuild disrupted services and recuperate from the pandemic even if their COVID-19 burden was low.

BACKGROUND:Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood. METHODS:A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. RESULTS:In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 [calculated as weight in kilograms divided by height in meters squared]; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median [interquartile range], 41.1 [20.5-72.4) vs 18.5 [10.7-31.8] days; P < .001). CONCLUSION:CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m² ) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.

Background/UNASSIGNED:COVID-19-associated mucormycosis (CAM) is a recently emerging entity. There is a lack of reports of CAM in organ transplant recipients. Methods/UNASSIGNED:We conducted a multicenter (n = 18) retrospective research in India during November 2020 to July 2021. The purpose of this study was to explore the clinical spectrum, outcome and risk factors for mortality of CAM in kidney transplant recipients (KTRs). Results/UNASSIGNED:= 0.05] was associated with mortality. The median follow-up of the study was 60 (35-60) d. Conclusions/UNASSIGNED:We describe the largest case series of CAM in KTRs. Morality in pulmonary CAM is extremely high. Severe COVID-19 pose extra risk for the development of CAM and associated mortality. Our report will help in better understanding the conundrum and management of CAM.

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using Scientific Registry of Transplant Recipients data from all prevalent liver transplant candidates from 2010 to 2020, we used a bias-corrected Kaplan-Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20-46) days-over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

BACKGROUND:Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS:A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS:Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION/CONCLUSIONS:Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.