Faculty Bibliography

INTRODUCTION/BACKGROUND:A comprehensive geriatric assessment (CGA) tailored to the chronic kidney disease (CKD) population would yield a more targeted approach to assessment and care. We aimed to identify domains of a CKD-specific CGA (CKD-CGA), characterize patterns of these domains, and evaluate their predictive utility on adverse health outcomes. METHODS:We used data from 864 participants in the Chronic Renal Insufficiency Cohort aged ≥55 years and not on dialysis. Constituents of the CKD-CGA were selected a priori. Latent class analysis informed the selection of domains and identified classes of participants based on their domain patterns. The predictive utility of class membership on mortality, dialysis initiation, and hospitalization was examined. Model discrimination was assessed with C-statistics. RESULTS:The CKD-CGA included 16 domains: cardiovascular disease, diabetes, five frailty phenotype components, depressive symptoms, cognition, five kidney disease quality-of-life components, health literacy, and medication use. A two-class latent class model fit the data best, with 34.7% and 65.3% in the high- and low-burden of geriatric conditions classes, respectively. Relative to the low-burden class, participants in the high-burden class were at increased risk of mortality (aHR = 2.09; 95% CI: 1.56, 2.78), dialysis initiation (aHR = 1.63; 95% CI: 1.06, 2.52), and hospitalization (aOR = 2.00; 95% CI: 1.38, 2.88). Model discrimination was the strongest for dialysis initiation (C-statistics = 0.86) and moderate for mortality and hospitalization (C-statistics = 0.70 and 0.66, respectively). CONCLUSION/CONCLUSIONS:With further validation in an external cohort, the CKD-CGA has the potential to be used in nephrology practices for assessing and managing geriatric conditions in older adults with CKD.

BACKGROUND:Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades, but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment. METHODS:Using the SRTR and Medicare claims data, we identified 5,094 adults (age≥18) treated with cinacalcet or parathyroidectomy for SHPT prior to receiving KT between 2007-2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics. RESULTS:Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure or death. However, compared to patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (aHR=0.56, 95%CI: 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (pinteraction=0.039). Among patients on maintenance dialysis therapy for ≥3 years prior to KT (n=3,477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (aHR=0.43, 95%CI: 0.24-0.79). CONCLUSIONS:Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 years. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18-64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59-3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33-0.41 and aHR = 0.31, 95% CI: 0.24-0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.

PURPOSE OF REVIEW:Clinicians treating end-stage kidney disease (ESKD) and kidney transplant patients face unique challenges in their care because of the high burden of frailty in these patients. Frailty has gained significant attention by medical and surgical specialties for risk stratification in the past decades. This review highlights the importance of measuring frailty in kidney transplant candidates and recipients. RECENT FINDINGS:Emerging data support that frailty is present even at younger ages among patients undergoing dialysis, transplant evaluation, or transplantation. It is estimated that 18.8% of younger (18-64 years) candidates, 25.2% of older (≥65 years) candidates, 14.3% of younger recipients, and 20.8% of older recipients are frail. Additionally, frailty is dynamic and subject to change pretransplantation and posttransplantation. Although many patients and clinicians are aware of the importance of measuring frailty, further studies addressing the need for interventions to reduce frailty burden are needed. SUMMARY:Frailty is independently associated with many adverse outcomes in ESKD and kidney transplant populations. Given the growing number of ESKD and kidney transplant patients, it is pivotal to expand the utility of frailty measurement in clinical practice, recognize the burden of frailty, and identify appropriate interventions to mitigate the adverse effects of frailty.

BACKGROUND:Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. METHODS:To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8). RESULTS:Among KT candidates, global cognitive impairment (18-34 years: 11.1%; 35-49 years: 14.0%; 50-64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18-34 years: 1.1%; 35-49 years: 3.0%; 50-64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18-34 years: 9.1%; 35-49 years: 6.1%; 50-64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18-34 years: 1.4%; 35-49 years: 1.4%; 50-64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1-year post-KT across all ages (18-34 years: 1.7%; 35-49 years: 3.4%; 50-64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18-34 years: .0%; 35-49 years: 1.9%; 50-64 years: 2.4%; ≥65 years: 3.5%). CONCLUSION/CONCLUSIONS:Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community-dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age.

BACKGROUND & AIMS:Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology. METHODS:Included were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; 'frail' = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness). RESULTS:Of 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol-associated liver disease (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in 'other' (P < .001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12-2.09), NAFLD (OR 1.64, 95% CI 1.18-2.29) and 'other' (OR 1.58, 95% CI 1.06-2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01-1.94) and 'other' (OR 1.59; 95% 1.05-2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03-1.06), but aetiology was not (P > .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term). CONCLUSIONS:Frailty is more common in patients with ALD, NAFLD and 'other' aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.