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.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite substantial growth in the population of older adults with kidney disease, there remains a lack of evidence to guide clinical care for this group. The Kidney Disease and Aging Research Collaborative (KDARC) conducted a Delphi study to build consensus on research priorities for clinical geriatric nephrology. STUDY DESIGN/METHODS:Asynchronous modified Delphi study. SETTING & PARTICIPANTS/METHODS:Clinicians and researchers in the US and Canada with clinical experience and/or research expertise in geriatric nephrology. OUTCOME/RESULTS:Research priorities in geriatric nephrology. ANALYTICAL APPROACH/METHODS:In the first Delphi round, participants submitted free-text descriptions of research priorities considered important for improving the clinical care of older adults with kidney disease. Delphi moderators used inductive content analysis to group concepts into categories. In the second and third rounds, participants iteratively reviewed topics, selected their top 5 priorities, and offered comments used to revise categories. RESULTS:Among 121 who were invited, 57 participants (47%) completed the first Delphi round and 48 (84% of enrolled participants) completed all rounds. After 3 rounds, the 5 priorities with the highest proportion of agreement were: 1) Communication and Decision-Making about Treatment Options for Older Adults with Kidney Failure (69% agreement), 2) Quality of Life, Symptom Management, and Palliative Care (67%), 3) Frailty and Physical Function (54%), 4) Tailoring Therapies for Kidney Disease to Specific Needs of Older Adults (42%), and 5) Caregiver and Social Support (35%). Health equity and person-centricity were identified as cross-cutting features that informed all topics. LIMITATIONS/CONCLUSIONS:Relatively low response rate and limited participation by private practitioners and older clinicians and researchers. CONCLUSIONS:Experts in geriatric nephrology identified clinical research priorities with the greatest potential to improve care for older adults with kidney disease. These findings provide a roadmap for the geriatric nephrology community to harmonize and maximize the impact of research efforts.

KEY POINTS:In frail kidney transplant (KT) candidates with obesity, unintentional weight loss preceding KT evaluation is associated with lower chance of listing. In frail candidates with obesity, both unintentional and intentional weight loss is associated with higher waitlist mortality. Results suggest that in frail candidates with obesity, careful supervision of weight loss prior to KT should be considered, emphasizing strategies to preserve muscle mass and function. BACKGROUND:Unintentional weight loss, a hallmark of frailty, predicts worse post–kidney transplantation (KT) outcomes. However, weight loss in candidates with obesity is often recommended to enhance transplant eligibility. We tested whether pre-evaluation weight change is associated with listing/waitlist mortality, considering intentionality and frailty. METHODS:) enrolled in a prospective multicenter cohort study. We estimated the association between pre-evaluation weight change (stable, gain, unintentional/intentional loss) with chance of listing/waitlist mortality using Cox proportional hazards/competing-risks models. RESULTS:Among candidates with obesity, 48% had stable weight, 17% had weight gain, 16% had unintentional weight loss, and 20% had intentional weight loss over the year before evaluation. Among frail candidates with obesity, stable weight was associated with a 27% lower chance of listing (adjusted hazard ratio [aHR], 0.73; 95% confidence intervals [CI], 0.55 to 0.96), weight gain with a 47% lower chance of listing (aHR, 0.53; 95% CI, 0.34 to 0.80), and unintentional weight loss with a 48% lower chance of listing (aHR, 0.52; 95% CI, 0.32 to 0.84) compared with nonfrail candidates with stable weight. However, in frail candidates with obesity, intentional weight loss was not associated with a significantly lower chance of listing compared with nonfrail candidates with stable weight. In addition, among frail candidates with obesity, stable weight (adjusted subhazard ratio [aSHR], 1.72; 95% CI, 1.01 to 2.90), unintentional weight loss (aSHR, 2.78; 95% CI, 1.23 to 6.27), and intentional weight loss (aSHR, 2.26; 95% CI, 1.05 to 4.85) were associated with higher waitlist mortality compared with nonfrail candidates with stable weight. Among nonfrail candidates, no associations were observed for weight change and frailty status with either chance of listing or waitlist mortality. CONCLUSIONS:Among frail candidates with obesity, unintentional pre-KT weight loss is associated with a lower chance of listing; however, any weight loss is associated with higher waitlist mortality. Our findings suggest that frail candidates with obesity may benefit from clinician supervision of pre-KT weight loss.

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.