Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Despite emerging studies on neighborhood-level risk factors for chronic kidney disease (CKD), our understanding of the causal links between neighborhood characteristics and CKD is limited. In particular, there is a gap in identifying modifiable neighborhood factors, such as the built environment, in preventing CKD, that could be targets for feasible place-based interventions. RECENT FINDINGS/RESULTS:Most published studies on neighborhood factors and CKD have focused on a single social attribute, such as neighborhood disadvantage, while research on the role of the built environment is more nascent. Early studies on this topic have yielded inconsistent results, particularly regarding whether food deserts are an environmental risk factor for CKD onset. International studies have shown that walkable neighborhoods - characterized by features such as urban design, park access, and green spaces - can be protective against both the onset and progression of CKD. However, these findings are inconclusive and understudied in the context of United States, where neighborhood environments differ from those in other countries. SUMMARY/CONCLUSIONS:Future research on modifiable neighborhood factors and CKD using advanced study designs and population-representative datasets can yield stronger evidence on potential causal associations and suggest feasible place-based interventions as strategies for preventing CKD. As an example, we demonstrated the potential of electronic health record-based studies to advance research in this area.

Developing real-world evidence from electronic health records (EHR) is vital to advance kidney transplantation (KT). We assessed the feasibility of studying KT using the Epic Cosmos aggregated EHR dataset, which includes 274 million unique individuals cared for in 238 U.S. health systems, by comparing it with the Scientific Registry of Transplant Recipients (SRTR). We identified 69,418 KT recipients transplanted between January 2014 and December 2022 in Cosmos (39.4% of all US KT transplants during this period). Demographics and clinical characteristics of recipients captured in Cosmos were consistent with the overall SRTR cohort. Survival estimates were generally comparable, although there were some differences in long-term survival. At 7 years post-transplant, patient survival was 80.4% in Cosmos and 77.8% in SRTR. Multivariable Cox regression showed consistent associations between clinical factors and mortality in both cohorts, with minor discrepancies in the associations between death and both age and race. In summary, Cosmos provides a reliable platform for KT research, allowing EHR-level clinical granularity not available with either the transplant registry or healthcare claims. Consequently, Cosmos will enable novel analyses to improve our understanding of KT management on a national scale.

BACKGROUND AND HYPOTHESIS/OBJECTIVE:Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. METHODS:To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. RESULTS:In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR = 1.04 [95% CI = 1.00-1.09]), slightly higher hazard of graft failure (HR = 1.09 [95% CI = 1.05-1.12]), and slightly lower mortality (HR = 0.93 [95% CI = 0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR = 1.42 [95% CI = 1.29-1.57]; interaction p < 0.001) and graft failure (HR = 1.24 [95% CI = 1.14-1.34]; interaction p = 0.003), and similar mortality (HR = 1.01 [95% CI = 0.94-1.08]; interaction p = 0.04). CONCLUSIONS:In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.

BACKGROUND:As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS/OBJECTIVE:To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS:We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS:Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION/CONCLUSIONS:Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

Frailty is a multi-system syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we aim to advance the clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address its common misconceptions; review the mechanisms and epidemiology of frailty in kidney disease; discuss challenges and limitations in frailty measurement; and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions. We further add to the literature in this topic by highlighting potential applications of frailty measurement in care of patients with kidney disease and conclude with our recommendations for future research related to this important syndrome.

The rise in the mean age of the global population has led to an increase in older kidney transplant (KT) patients. This demographic shift, coupled with the ongoing organ shortage, requires a nuanced understanding of which older adults are most suitable for KT. Recognizing the increased heterogeneity among older adults and the limitations of solely relying on chronological age, there is a need to explore alternative aging metrics beyond chronological age. In this review, we discuss the impact of older age on access to KT and postoperative outcomes. Emphasizing the need for a comprehensive evaluation that extends beyond chronological age, we explore alternative aging metrics such as frailty, sarcopenia, and cognitive function, underscoring their potential role in enhancing the KT evaluation process. Most importantly, we aim to contribute to the ongoing discourse, fostering an optimized approach to KT for the rapidly growing population of older adults.