Association of Urine Biomarkers of Kidney Tubule Injury and Dysfunction With Frailty Index and Cognitive Function in Persons With CKD in SPRINT.

RATIONALE & OBJECTIVE: The associations of the glomerular markers of kidney disease, estimated glomerular filtration rate (eGFR) and albuminuria, with frailty and cognition are well established. However, the relationship of kidney tubule injury and dysfunction with frailty and cognition is unknown. STUDY DESIGN: Observational cross-sectional study. SETTING & PARTICIPANTS: 2,253 participants with eGFR<60mL/min/1.73m2 in the Systolic Blood Pressure Intervention Trial (SPRINT). EXPOSURE: Eight urine biomarkers: interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-3-like protein 1 (YKL-40), monocyte chemoattractant protein 1 (MCP-1), α1-microglobulin (A1M), ß2-microglobulin (B2M), and uromodulin (Umod). OUTCOME: Frailty was measured using a previously validated frailty index (FI), categorized as fit (FI≤0.10), less fit (0.100.21). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). ANALYTICAL APPROACH: Associations between kidney tubule biomarkers with categorical FI were evaluated using multinomial logistic regression with the fit group as the reference. Cognitive function was evaluated using linear regression. Models were adjusted for demographic, behavioral, and clinical variables including eGFR and urine albumin. RESULTS: Three of the 8 urine biomarkers of tubule injury and dysfunction were independently associated with FI. Each 2-fold higher level of urine KIM-1, a marker of tubule injury, was associated with a 1.22 (95% CI, 1.01-1.49) greater odds of being in the frail group. MCP-1, a marker of tubulointerstitial fibrosis, was associated with a 1.30 (95% CI, 1.04-1.64) greater odds of being in the frail group, and A1M, a marker of tubule reabsorptive capacity, was associated with a 1.48 (95% CI, 1.11-1.96) greater odds of being in the frail group. These associations were independent of confounders including eGFR and urine albumin, and were stronger than those of urine albumin with FI (1.15 [95% CI, 0.99-1.34]). Higher urine B2M, another marker of tubule reabsorptive capacity, was associated with worse cognitive scores at baseline (ß: -0.09 [95% CI, -0.17 to-0.01]). Urine albumin was not associated with cognitive function. LIMITATIONS: Cross-sectional design, and FI may not be generalizable in other populations. CONCLUSIONS: Urine biomarkers of tubule injury, fibrosis, and proximal tubule reabsorptive capacity are variably associated with FI and worse cognition, independent of glomerular markers of kidney health. Future studies are needed to validate these results among other patient populations.

Changes of a frailty index based on common blood and urine tests during a hospital stay on geriatric wards predict 6-month and 1-year mortality in older people.

BACKGROUND: We aimed to evaluate the abilities of a 21-item frailty index based on laboratory blood and urine tests (FI-Lab21) assessed at different points in time, ie, at admission to hospital (FI-Lab21admission) and before discharge from hospital (FI-Lab21discharge), and the change of the FI-Lab21 during the hospital stay to predict 6-month and 1-year mortality in hospitalized geriatric patients. METHODS: Five hundred hospitalized geriatric patients aged ≥65 years were included in this analysis. Follow-up data were acquired after a period of 6 months and 1 year. RESULTS: The FI-Lab21admission and FI-Lab21discharge scores were 0.33±0.15 and 0.31±0.14, respectively (P<0.001). The FI-Lab21admission and FI-Lab21discharge both predicted 6-month and 1-year mortality (areas under the receiver operating characteristic curves: 0.72, 0.72, 0.77, and 0.75, respectively, all P<0.001). The predictive abilities for 6-month and 1-year mortality of the FI-Lab21admission were inferior compared with those of the FI-Lab21discharge (all P<0.05). Patients with a reduction in or stable FI-Lab21 score during the hospital stay revealed lower 6-month and 1-year mortality rates compared with the persons whose FI-Lab21 score increased during the hospital stay (all P<0.05). After adjustment for age, sex, and FI-Lab21admission, each 1% decrease in the FI-Lab21 during the hospital stay was associated with a decrease in 6-month and 1-year mortality of 5.9% and 5.3% (both P<0.001), respectively. CONCLUSION: The FI-Lab21 assessed at admission or discharge and the changes of the FI-Lab21 during the hospital stay emerged as interesting and feasible approaches to stratify mortality risk in hospitalized geriatric patients.

Operationalizing a frailty index using routine blood and urine tests.

BACKGROUND: Uncomplicated frailty instruments are desirable for use in a busy clinical setting. The aim of this study was to operationalize a frailty index (FI) from routine blood and urine tests, and to evaluate the properties of this FI compared to other frailty instruments. MATERIALS AND METHODS: We conducted a secondary analysis of a prospective cohort study on 306 patients aged ≥65 years hospitalized on geriatric wards. An FI comprising 22 routine blood parameters and one standard urine parameter (FI-Lab), a 50-item FI based on a comprehensive geriatric assessment (FI-CGA), a combined FI (FI-combined [items from the FI-Lab + others from the FI-CGA]), the Clinical Frailty Scale, rule-based frailty definition, and frailty phenotype were operationalized from data obtained during patients' hospital stays (ie, before discharge [baseline examination]). Follow-up data were obtained up to 1 year after the baseline examination. RESULTS: The mean FI-Lab score was 0.34±15, with an upper limit of 0.74. The FI-Lab was correlated with all the other frailty instruments (all P<0.001). The FI-Lab revealed an area under the receiver-operating characteristic curve (AUC) for 6-month and 1-year mortality of 0.765 (0.694-0.836) and 0.769 (0.706-0.833), respectively (all P<0.001). Each 0.01 increment in FI-Lab increased the risk (adjusted for age and sex) for 6-month and 1-year mortality by 7.2% and 7.1%, respectively (all adjusted P<0.001). When any of the other FIs (except the FI-combined) were also included in the models, each 0.01 increment in FI-Lab score was associated with an increase in the risk of 6-month and 1-year mortality by 4.1%-5.4% (all adjusted P<0.001). CONCLUSION: The FI-Lab showed key characteristics of an FI. The FI-Lab can be applied as a single frailty measure or in combination with/in addition to other frailty instruments.

Association between low-grade albuminuria and frailty among community-dwelling middle-aged and older people: a cross-sectional analysis from I-Lan Longitudinal Aging Study.

Frailty is characterized by decreased physiological reserve and increased vulnerability to atherosclerosis and subsequent mortality. Recently, low-grade albuminuria has been proposed as an atherosclerotic risk factor. We aimed to investigate the relationship between low-grade albuminuria and frailty by using cross-sectional data among community-dwelling middle-aged and older people. Totally, 1,441 inhabitants of I-Lan County with normal urinary albumin excretion (urine albumin to urine creatinine ratio [UACR] <30 mg/g) were enrolled (677 men; mean age 63 ± 9 years, range from 50 to 91 years old). Assessment of frailty was based on the 'Fried frailty phenotype' criteria, including weight loss, grip strength, exhaustion, slowness and low physical activity. The study population was stratified into quartiles according to UACR levels. Age, body mass index, hypertension, diabetes, systolic blood pressure, insulin resistance, fasting glucose and high-sensitivity C-reactive protein levels were increased with the increment of UACR (P for trend <0.05). The prevalence of prefrailty/frailty and its components increased across the UACR quartiles. A multivariate stepwise logistic regression analysis revealed that UACR was independently associated with the likelihood of prefrailty/frailty (odds ratio 1.13, 95% CI 1.01-1.27). In conclusion, low-grade albuminuria is associated with the increased prevalence of prefrailty/frailty.