Faculty Bibliography

OBJECTIVE:Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. METHODS:Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. RESULTS:= 0.004). CONCLUSION/CONCLUSIONS:In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.

OBJECTIVES/OBJECTIVE:Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing. METHODS:Using 2017-2020 USRDS and Medicare claims, patients were identified as taking obesogenic medications if prescribed anticonvulsants, antidepressants, antidiabetics, anti-inflammatories, antipsychotics, and/or antihypertensives known to cause weight gain for ≥30 days in their first hemodialysis year. Ordinal logistic and Cox regression with inverse probability of treatment weighting were used to quantify obesogenic medications' association with body mass index (BMI) and listing, respectively. RESULTS:Among 271 401 hemodialysis initiates, 63.5% took ≥1 obesogenic medication. For those in underweight, normal weight, overweight, and class I, II, and III categories, 54.3%, 58.4%, 63.1%, 66.5%, 68.6%, and 68.8% took ≥1, respectively. Number of obesogenic medications was associated with increased BMI; use of one was associated with 13% increased odds of higher BMI (aOR [adjusted odds ratio] 1.14; 95%CI: 1.13-1.16; p < 0.001), use of three was associated with a 55% increase (aOR 1.55; 95%CI: 1.53-1.57; p < 0.001). Any use was associated with 6% lower odds of transplant listing (aHR [adjusted hazard ratio] 0.94; 95%CI: 0.92-0.96; p < 0.001). Within each BMI category, obesogenic medication use was associated with lower listing likelihood. CONCLUSIONS:Obesogenic medication use is common in ESKD patients-particularly those with obesity-and is associated with lower listing likelihood. Whenever possible, non-obesogenic alternatives should be chosen for ESKD patients attempting weight loss to achieve transplant listing.

BACKGROUND:Prior to kidney transplantation (KT) most patients have an elevated parathyroid hormone (PTH). However, the impact of PTH on post-KT mortality and graft loss is unclear. We quantified the association between PTH levels measured at transplant and adverse post-KT outcomes. STUDY DESIGN/METHODS:A prospective longitudinal cohort of 1,136 KT recipients from a single tertiary care center between 12/2008 and 2/2020. Pre-KT PTH levels were abstracted retrospectively. Adjusted multivariable Cox proportional hazards models were used to estimate the association between pre-KT PTH levels and mortality and death-censored graft loss (DCGL). RESULTS:Of 1,136 recipients, pre-KT PTH levels were ≤300pg/mL in 62.3% and >600pg/mL in 12.5%. Compared to those with a pre-KT PTH≤300pg/mL, patients with a pre-KT PTH>600pg/mL were more likely to be Black (51.4% vs. 34.6%) and have a longer dialysis vintage (4.8y vs. 1.7y) (p<0.001). Those with a pre-KT PTH>600pg/mL had a higher 10-year cumulative incidence of DCGL than those with PTH≤300pg/mL (31.7% vs. 15.4%, p<0.001). After adjusting for confounders, pre-KT PTH>600pg/mL was associated with a 1.76-fold increased risk of DCGL (95% CI: 1.16-2.65). The magnitude of this association differed by race (pinteraction=0.011) and by treatment (pinteraction=0.018). Among non-Black patients, a PTH>600pg/mL was associated with a 3.21-fold increased risk of DCGL compared to those with PTH≤300pg/mL (95%CI: 1.77-5.81). Among untreated patients, those with PTH>600pg/mL had a 2.54-fold increase in DCGL (95%CI: 1.44-4.47). There was no association between pre-KT PTH and mortality risk. CONCLUSIONS:PTH >600pg/mL prior to KT increased the risk of DCGL by 76%, demonstrating the importance of treating PTH prior to KT to prevent graft loss in a contemporary era with the introduction and widespread availability of medical therapy.

BACKGROUND:Kidney transplant recipients (KTRs) generate lower antibody responses to messenger RNA (mRNA)-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, yet precise mechanisms for this poor response remain uncertain. One potential contributor is suboptimal spike antigen (sAg) translation and expression owing to transplant immunosuppression, which might lead to insufficient exposure to develop humoral and/or cellular immune responses. METHODS:Within a single-arm clinical trial, 65 KTRs underwent ultrasensitive plasma sAg testing before, and 3 and 14 days after, the third mRNA vaccine doses. Anti-SARS-CoV-2 spike antibodies (anti-receptor binding domain [anti-RBD]) were serially measured at 14 and 30 days post-vaccination. Associations between sAg detection and clinical factors were assessed. Day 30 anti-RBD titer was compared among those with versus without sAg expression using Wilcoxon rank sum testing. RESULTS:Overall, 16 (25%) KTRs were sAg positive (sAg+) after vaccination, peaking at day 3. Clinical and laboratory factors were broadly similar in sAg(+) versus sAg(-) KTRs. sAg(+) status was significantly negatively associated with day 30 anti-RBD response, with median (interquartile range) 10.8 (<0.4-338.3) U/mL if sAg(+) versus 709 (10.5-2309.5) U/mL if sAg(-) (i.e., 66-fold lower; p = .01). CONCLUSION/CONCLUSIONS:Inadequate plasma sAg does not likely drive poor antibody responses in KTRs, rather sAg detection implies insufficient immune response to rapidly clear vaccine antigen from blood. Other downstream mechanisms such as sAg trafficking and presentation should be explored.

BACKGROUND:Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS:Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: < 0.001) but not cognitive impairment. CONCLUSIONS:Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

Transplantation remains the gold-standard treatment for pediatric end-stage kidney disease. While living donor transplant is the preferred option for most pediatric patients, it is not the right choice for all. For those who have the option to choose between deceased donor and living donor transplantation, or from among multiple potential living donors, the transplant clinician must weigh multiple dynamic factors to identify the most optimal donor. This review will cover the key considerations when choosing between potential living donors and will propose a decision-making algorithm.

OBJECTIVE:Lung transplants from donors with hepatitis C (HCV D+) have excellent outcomes, but these organs continue to be declined. We evaluated whether (1) being listed to consider and (2) accepting versus declining HCV D+ offers provided a survival benefit to lung transplant candidates. METHODS:Using the Scientific Registry of Transplant Recipients, we identified all adult (≥18 years) lung transplant candidates 2016-2021 and compared waitlist mortality between those willing versus not willing to consider HCV D+ offers using competing risk regression. We identified all candidates offered an HCV D+ lung that was later accepted and followed them from offer decision until death or end-of-study. We estimated adjusted mortality risk of accepting versus declining an HCV D+ lung offer using propensity-weighted Cox regression. RESULTS:From 2016 to 2021, we identified 21,007 lung transplant candidates, 33.8% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 17% lower risk of waitlist mortality (subhazard ratio, 0.83; 95% confidence interval, 0.75-0.91, P < .001). Over the same period, 665 HCV D+ lung offers were accepted after being declined a total of 2562 times. HCV D+ offer acceptance versus decline was associated with a 20% lower risk of mortality (adjusted hazard ratio, 0.80; 95% confidence interval, 0.66-0.96, P = .02). CONCLUSIONS:Considering HCV D+ lung offers was associated with a 17% lower risk of waitlist mortality, whereas accepting versus declining an HCV D+ lung offer was associated with a 20% lower risk of mortality. Centers and candidates should consider accepting suitable HCV D+ lung offers to optimize outcomes.

BACKGROUND:Recent data suggest patients with graft failure had better access to repeat kidney transplantation (re-KT) than transplant-naive dialysis accessing first KT. This was postulated to be because of better familiarity with the transplant process and healthcare system; whether this advantage is equitably distributed is not known. We compared the magnitude of racial/ethnic disparities in access to re-KT versus first KT. METHODS:Using United States Renal Data System, we identified 104 454 White, Black, and Hispanic patients with a history of graft failure from 1995 to 2018, and 2 357 753 transplant-naive dialysis patients. We used adjusted Cox regression to estimate disparities in access to first and re-KT and whether the magnitude of these disparities differed between first and re-KT using a Wald test. RESULTS:Black patients had inferior access to both waitlisting and receiving first KT and re-KT. However, the racial/ethnic disparities in waitlisting for (adjusted hazard ratio [aHR] = 0.77; 95% confidence interval [CI], 0.74-0.80) and receiving re-KT (aHR = 0.61; 95% CI, 0.58-0.64) was greater than the racial/ethnic disparities in first KT (waitlisting: aHR = 0.91; 95% CI, 0.90-0.93; Pinteraction = 0.001; KT: aHR = 0.68; 95% CI, 0.64-0.72; Pinteraction < 0.001). For Hispanic patients, ethnic disparities in waitlisting for re-KT (aHR = 0.83; 95% CI, 0.79-0.88) were greater than for first KT (aHR = 1.14; 95% CI, 1.11-1.16; Pinteraction < 0.001). However, the disparity in receiving re-KT (aHR = 0.76; 95% CI, 0.72-0.80) was similar to that for first KT (aHR = 0.73; 95% CI, 0.68-0.79; Pinteraction = 0.55). Inferences were similar when restricting the cohorts to the Kidney Allocation System era. CONCLUSIONS:Unlike White patients, Black and Hispanic patients with graft failure do not experience improved access to re-KT. This suggests that structural and systemic barriers likely persist for racialized patients accessing re-KT, and systemic changes are needed to achieve transplant equity.

BACKGROUND/UNASSIGNED:The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30-35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. METHODS/UNASSIGNED:We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. RESULTS/UNASSIGNED: < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%). CONCLUSIONS/UNASSIGNED:In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.