Faculty Bibliography

BACKGROUND:Cognition is a research priority for people living with chronic kidney disease (CKD), but identification of critical research questions is lacking. This study aimed to determine which cognition-related research questions are most important to CKD stakeholders. METHODS:A modified Delphi technique with 3 survey rounds was used. The study sample included 3 panels (People with lived CKD experience, Researchers, and Clinicians) recruited through international patient and kidney research networks, kidney societies, and snowball sampling with email invitations. Survey rounds were distributed electronically through REDCap. In Round 1 (October 2021-May 2022), respondents contributed three important research questions regarding cognition in CKD (free text). After deduplication and qualitative synthesis, respondents ranked the importance of these questions on a nine-point Likert scale in Round 2 (Feb-April 2023). Questions with mean and median ratings of >7 by at least two respondent panels or rated critically important by the 'lived experience' panel were re-ranked in Round 3 ( Aug-Sept 2023) and assessed for consensus to identify the final list of priority research questions. RESULTS:Respondents (n=152) identified 125 and 44 discrete questions after Rounds 1 and 2, respectively. The final shortlist included 27 questions in 8 categories. The most critical research question identified was "What factors prevent cognitive impairment in people receiving dialysis?" Overall, respondents prioritized questions focusing on prevention and treatment of cognitive impairment. Scores between the panels were significantly different for 16 questions. Those with lived CKD experience prioritized quality of life, researchers emphasized developing interventions to mitigate cognitive impairment, and clinicians prioritized the effect of CKD treatment on cognitive impairment. CONCLUSIONS:Through an established consensus methodology involving key stakeholder groups, we identified 27 critical research questions about cognition in CKD. These questions should guide future study design and outcome selection.

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.

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.

Central body fat distribution affects kidney function. Abdominal fat measurements using computed tomography (CT) may prove superior in assessing body composition-related kidney risk in living kidney donors. This retrospective cohort study including 550 kidney donors aimed to determine the association between CT-measured abdominal fat areas and kidney function before and after donor nephrectomy. Donors underwent glomerular filtration rate measurements (¹²⁵I-Iothalamate, mGFR) before and 3 months after donation. Linear regression analyses with body surface area (BSA)-standardized and crude mGFR were performed to assess the association of height-indexed tomographic fat measurements with kidney function. In age-, and sex-adjusted analyses higher levels of total abdominal, visceral, subcutaneous, and intramuscular adipose tissue index were significantly associated with lower mGFR levels before donation (BSA-standardized mGFR: visceral adipose tissue index: Βeta=-0.11, p < 0.001, subcutaneous: Βeta=-0.10, p < 0.001, intramuscular: Βeta=-1.18, p < 0.001, total abdominal: Βeta=-0.07, p < 0.001). Higher tomographic abdominal fat is associated with lower BSA-standardized mGFR after donation and a greater decrease in mGFR between screening and 3 months post-donation. This study shows that CT-measured abdominal fat area is associated with kidney function before and after living kidney donation.

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.

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.

With the growth of the older adult population, the number of older adults waitlisted for and undergoing kidney and liver transplantation has increased. Transplantation is an important and definitive treatment for this population. We present a contemporary review of the unique preoperative, intraoperative, and postoperative issues that patients older than 65 y face when they undergo kidney or liver transplantation. We focus on geriatric syndromes that are common in older patients listed for kidney or liver transplantation including frailty, sarcopenia, and cognitive dysfunction; discuss important considerations for older transplant recipients, which may impact preoperative risk stratification; and describe unique challenges in intraoperative and postoperative management for older patients. Intraoperative challenges in the older adult include using evidence-based best anesthetic practices, maintaining adequate perfusion pressure, and using minimally invasive surgical techniques. Postoperative concerns include controlling acute postoperative pain; preventing cardiovascular complications and delirium; optimizing immunosuppression; preventing perioperative kidney injury; and avoiding nephrotoxicity and rehabilitation. Future studies are needed throughout the perioperative period to identify interventions that will improve patients' preoperative physiologic status, prevent postoperative medical complications, and improve medical and patient-centered outcomes in this vulnerable patient population.