Narrative Review: Clinical Implications and Assessment of Frailty in Patients With Advanced CKD. Kidney international reports Frailty is a multidimensional clinical syndrome characterized by low physical activity, reduced strength, accumulation of multiorgan deficits, decreased physiological reserve, and vulnerability to stressors. Frailty has key social, psychological, and cognitive implications. Frailty is accelerated by uremia, leading to a high prevalence of frailty in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) as well as contributing to adverse outcomes in this patient population. Frailty assessment is not routine in patients with CKD; however, a number of validated clinical assessment tools can assist in prognostication. Frailty assessment in nephrology populations supports shared decision-making and advanced communication and should inform key medical transitions. Frailty screening and interventions in CKD or ESKD are a developing research priority with a rapidly expanding literature base. 10.1016/j.ekir.2023.12.022

Elucidating the causal nexus and immune mediation between frailty and chronic kidney disease: integrative multi-omics analysis. Renal failure BACKGROUND:Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous. METHODS:Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999-2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells' mediating roles in the FI-CKD relationship. RESULT:Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD. CONCLUSION:Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population. 10.1080/0886022X.2024.2367028

Effect of Frail Phenotype on Cardiorenal Risk and Healthcare Utilization in Older Patients with Chronic Kidney Disease. Cardiorenal medicine INTRODUCTION:Limited data have addressed frailty's role in cardiorenal risk among older adult patients with chronic kidney disease (CKD). We investigated whether frailty could predict major renal and cardiovascular events, healthcare utilization, and mortality in these patients. METHODS:We conducted a prospective cohort enrolling patients aged ≥75 years with a stable estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The frailty phenotype consists of shrinking, low activity, exhaustion, weakness, and slowness, scored 0 to 5. The primary composite renal outcome was a ≥25% decrease in eGFR concurrent with CKD stage progression or dialysis initiation. Secondary outcomes included major adverse cardiovascular events (MACE), emergency room (ER) visits, all-cause mortality, and hospitalization. Using multivariate Cox models with/without competing risk analyses, we explored frailty's impact on these outcomes. RESULTS:Among 203 older CKD patients (mean age: 81.6 ± 5.0 years, female: 40.9%, diabetes: 33.0%, body mass index: 24.9 ± 3.7 kg/m2), 67.9% were frail. Over 3.47 years, 38.9% faced composite renal outcomes; 13.3%, MACE; 15.3%, mortality; and more than half utilized healthcare. Every one-point frailty elevated renal outcome risk by 28.0% (HR: 1.28, 95% confidence interval [CI]: 1.03-1.59) and significantly increased secondary outcomes (MACE [HR: 1.43, 95% CI: 0.99-2.08], hospitalization [HR: 1.24, 95% CI: 1.06-1.46], unexpected ER visit [HR: 1.20, 95% CI: 1.03-1.39], and mortality [HR: 1.51, 95% CI: 1.06-2.16]). Results were consistent across subgroups and competing risk analysis. CONCLUSION:In CKD patients aged ≥75 years, frailty was associated with progressive kidney disease, increased mortality, and healthcare utilization. 10.1159/000541807