Faculty Bibliography

BACKGROUND:Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS:We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS:Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS:Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

BACKGROUND:Hyperparathyroidism persists in many patients after kidney transplantation. The purpose of this study was to evaluate the association between post-transplant hyperparathyroidism and kidney transplantation outcomes. METHODS:We identified 824 participants from a prospective longitudinal cohort of adult patients who underwent kidney transplantation at a single institution between December 2008 and February 2020. Parathyroid hormone levels before and after kidney transplantation were abstracted from medical records. Post-transplant hyperparathyroidism was defined as parathyroid hormone level ≥70 pg/mL 1 year after kidney transplantation. Cox proportional hazards models were used to estimate the adjusted hazard ratios of mortality and death-censored graft loss by post-transplant hyperparathyroidism. Models were adjusted for age, sex, race/ethnicity, college education, parathyroid hormone level before kidney transplantation, cause of kidney failure, and years on dialysis before kidney transplantation. A Wald test for interactions was used to evaluate the risk of death-censored graft loss by age, sex, and race. RESULTS:> .05). There was no association between post-transplant hyperparathyroidism and mortality. CONCLUSION/CONCLUSIONS:The risk of graft loss was significantly higher among patients with post-transplant hyperparathyroidism when compared with patients without post-transplant hyperparathyroidism.

BACKGROUND:Prior studies have demonstrated racial disparities in the severity of secondary hyperparathyroidism among dialysis patients. Our primary objective was to study the racial and socioeconomic differences in the timing and likelihood of parathyroidectomy in patients with secondary hyperparathyroidism. METHODS:We used the United States Renal Data System to identify 634,428 adult (age ≥18) patients who were on maintenance dialysis between 2006 and 2016 with Medicare as their primary payor. Adjusted multivariable Cox regression was performed to quantify the differences in parathyroidectomy by race. RESULTS:Of this cohort, 27.3% (173,267) were of Black race. Compared to 15.4% of White patients, 23.1% of Black patients lived in a neighborhood that was below a predefined poverty level (P < .001). The cumulative incidence of parathyroidectomy at 10 years after dialysis initiation was 8.8% among Black patients compared to 4.3% among White patients (P < .001). On univariable analysis, Black patients were more likely to undergo parathyroidectomy (adjusted hazard ratio = 1.83; 95% confidence interval, 1.74-1.93). This association persisted after adjusting for age, sex, cause of end-stage renal disease, body mass index, comorbidities, dialysis modality, and poverty level (adjusted hazard ratio = 1.35; 95% confidence interval, 1.27-1.43). Therefore, patient characteristics and socioeconomic status explained 26% of the association between race and likelihood of parathyroidectomy. CONCLUSION/CONCLUSIONS:Black patients with secondary hyperparathyroidism due to end-stage renal disease are more likely to undergo parathyroidectomy with shorter intervals between dialysis initiation and parathyroidectomy. This association is only partially explained by patient characteristics and socioeconomic factors.

BACKGROUND/UNASSIGNED:The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. OBJECTIVES/UNASSIGNED:We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. DESIGN/UNASSIGNED:We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. METHODS/UNASSIGNED:Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. RESULTS/UNASSIGNED: = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. CONCLUSION/UNASSIGNED:telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.

BACKGROUND:Frailty is common and associated with poor outcomes among kidney transplant (KT) recipients. While frailty improves in the first 3 months post-KT with restored kidney function, longer-term trajectories are likely to plateau/decline due to aging and other stressors (eg, immunosuppression). We evaluated longer-term post-KT trajectories of the physical frailty phenotype (PFP) and its components in adult patients at 2 centers. METHODS:PFP components were measured at admission, 1, 3, 6 months, 1 year, and annually thereafter post-KT. We used adjusted mixed-effects models to describe repeated measures of continuous components (weight, gait speed, grip strength, activity) and generalized estimating equations to quantify longitudinal, binomial response patterns (PFP; exhaustion). RESULTS:Among 1 336 recipients (mean age = 53) followed for a median of 1.9 years (interquartile range [IQR] = 0.1-3.2), likelihood of frailty declined in the first 2.5 years post-KT (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI]: 0.95, 0.98), but increased after 2.5 years post-KT (aOR = 1.03, 95% CI: 1.00, 1.05). In the first 2.5 years post-KT, recipients demonstrated increases in weight (0.4 lbs/month, 95% CI: 0.3, 0.5), grip strength (0.2 kg/month, 95% CI: 0.1, 0.2), and activity (23.9 kcal/month, 95% CI: 17.5, 30.2); gait speed remained stable (-0.01 s/month, 95% CI: 0.01, 0.003). Additionally, likelihood of becoming exhausted declined post-KT (OR = 0.99, 95% CI: 0.98, 1.00). After 2.5 years post-KT, recipients demonstrated decreased grip strength (-0.07 kg/month, 95% CI: -0.12, -0.01) and activity (-20 kcal/month, 95% CI: -32.3, -8.2); they had stable weight (-0.003 lbs/month, 95% CI: -0.17, 0.16), gait speed (-0.003 s/month, 95% CI: -0.02, 0.01), and likelihood of becoming exhausted (OR = 1.01, 95% CI: 0.99, 1.02). CONCLUSION:Despite frailty improvements in the first 2.5 years, recipients' frailty worsened after 2.5 years post-KT. Specifically, they experienced gains in strength, activity, and exhaustion in the first 2.5 years post-KT, but declined in strength and activity after 2.5 years post-KT while experiencing persistent slowness. Clinicians should consider monitoring recipients for worsening frailty after 2.5 years despite shorter-term improvements.

In clinical trials, harms (i.e., adverse events) are often reported by simply counting the number of people who experienced each event. Reporting only frequencies ignores other dimensions of the data that are important for stakeholders, including severity, seriousness, rate (recurrence), timing, and groups of related harms. Additionally, application of selection criteria to harms prevents most from being reported. Visualization of data could improve communication of multidimensional data. We replicated and compared the characteristics of 6 different approaches for visualizing harms: dot plot, stacked bar chart, volcano plot, heat map, treemap, and tendril plot. We considered binary events using individual participant data from a randomized trial of gabapentin for neuropathic pain. We assessed their value using a heuristic approach and a group of content experts. We produced all figures using R and share the open-source code on GitHub. Most original visualizations propose presenting individual harms (e.g., dizziness, somnolence) alone or alongside higher level (e.g., by body systems) summaries of harms, although they could be applied at either level. Visualizations can present different dimensions of all harms observed in trials. Except for the tendril plot, all other plots do not require individual participant data. The dot plot and volcano plot are favored as visualization approaches to present an overall summary of harms data. Our value assessment found the dot plot and volcano plot were favored by content experts. Using visualizations to report harms could improve communication. Trialists can use our provided code to easily implement these approaches.

Kidney transplant (KT) recipients with delirium, a preventable surgical complication, are likely to reap cognitive benefits from restored kidney function, but may be more vulnerable to longer-term neurotoxic stressors post-KT (i.e., aging, immunosuppression). In this prospective cohort study, we measured delirium (chart-based), global cognitive function (3MS), and executive function (Trail Making Test Part B minus Part A) in 894 recipients (2009-2021) at KT, 1/3/6-months, 1-year, and annually post-KT. Dementia was ascertained using linked Medicare claims. We described repeated measures of cognitive performance (mixed effects model) and quantified dementia risk (Fine & Gray competing risk) by post-KT delirium. Of 894 recipients, 43(4.8%) had post-KT delirium. Delirium was not associated with global cognitive function at KT (difference = -3.2 points, 95%CI: -6.7, 0.4) or trajectories post-KT (0.03 points/month, 95%CI: -0.27, 0.33). Delirium was associated with worse executive function at KT (55.1 s, 95%CI: 25.6, 84.5), greater improvements in executive function <2 years post-KT (-2.73 s/month, 95%CI: -4.46,-0.99), and greater decline in executive function >2 years post-KT (1.72 s/month, 95%CI: 0.22, 3.21). Post-KT delirium was associated with over 7-fold greater risk of dementia post-KT (adjusted subdistribution hazard ratio = 7.84, 95%CI: 1.22, 50.40). Transplant centers should be aware of cognitive risks associated with post-KT delirium and implement available preventative interventions to reduce delirium risk.

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = _0.09 0.13_0.18 ). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = _1.00 1.45_2.13 ); however, importantly, this seemingly protective tendency disappeared (aOR = _0.47 0.73_1.12 ) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = _2.39 4.26_7.92 for mTORi+tacrolimus; _2.34 5.54_15.32 for mTORi-only; and _6.78 10.25_15.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = _0.81 1.54_2.98 for MMF + mTORi; and _0.81 1.51_2.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.

BACKGROUND:Cognitive impairment is common among persons with chronic kidney disease (CKD) due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differs by PA. METHODS:We leveraged 3,223 participants (aged≥60years) enrolled in National Health and Nutrition Examination Survey (NHANES,2011-2014), with at least one measure of objective cognitive function (immediate recall [CERAD-WL], delayed recall [CERAD-DR], verbal fluency [AF], executive function/processing speed [DSST], global [average of 4 tests]) or self-perceived memory decline [SCD]. We quantified the association between CKD stage (no CKD: eGFR≥60 mL/min/1.73m2 and albuminuria(ACR)<30 mg/g; stage G1-G3: eGFR≥60mL/min/1.73m2 and ACR≥30mg/g or eGFR 30-59mL/min/1.73m2; stage G4-G5: eGFR<30mL/min/1.73m2) and cognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally-representative estimates. We tested whether associations differed by physical activity (Global Physical Activity Questionnaire, high PA≥600MET*min/week vs. low PA<600MET*min/week) using a Wald test. RESULTS:Among NHANES participants, 34.9% had CKD stageG1-G3, 2.6% had stageG4-G5, and 50.7% had low PA. CKD stageG4-G5 was associated with lower global cognitive function (difference = -0.38SD, 95%CI:-0.62,-0.15). This association differed by PA (pinteraction = 0.01). Specifically, among participants with low PA, those with CKD stageG4-G5 had lower global cognitive function (difference = -0.57SD, 95%CI: -0.82,-0.31) compared to those without CKD. Among those with high PA, no difference was found (difference = 0.10SD, 95%CI:-0.29,0.49). Similarly, CKD stage was only associated with immediate recall, verbal fluency, executive function, and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. CONCLUSIONS:CKD is associated with lower objective cognitive function among those with low, but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines.

BACKGROUND:Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared to the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥ 65) ESRD patients differed if they were treated for SHPT. METHODS:Using the United States Renal Data System (USRDS) and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006-2016. SHPT treatment was defined as use of vitamin D analogs, phosphate binders, calcimimetics, or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time varying exposure. RESULTS:Of 189 433 older ESRD adults, 92% had a claims diagnosis of SHPT, and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared to 11 cases per 100 person-years among untreated patients. Compared to untreated SHPT patients, the risk of dementia was 42% lower (aHR = 0.58, 95% CI: 0.56-0.59) among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (pinteraction = 0.02) and race (pinteraction ≤ 0.01) with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having greatest reduction in dementia risk. CONCLUSION/CONCLUSIONS:Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for treatment of SHPT in older ESRD patients.