Cystatin C- and Creatinine-based Estimated GFR Differences: Prevalence and Predictors in the UK Biobank.

Rationale & Objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study Design: Cohort study. Setting & Participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical Approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

Estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine may differ substantially within an individual. Although most clinicians are aware that creatinine is influenced by muscle mass, there are additional numerous lifestyle and health characteristics that may affect serum concentrations of either biomarker. Our analyses of 468,969 individuals in the UK Biobank identified independent predictors of large differences between eGFR based on cystatin C and eGFR based on creatinine, which may inform the interpretation of discrepant eGFR values within an individual. We developed models that may be implemented at a population level to help health systems identify individuals who are likely to have large differences between eGFR based on cystatin C and eGFR based on creatinine and thus should be prioritized for cystatin C testing.

Frequency of Screening for Colorectal Cancer by Predicted Life Expectancy Among Adults 76-85 Years.

This study assesses whether colorectal cancer screening varied by predicted life expectancy in a national sample of Veterans Affairs patients aged 76 to 85 years.

Skeletal Muscle Health, Physical Performance, and Lower Urinary Tract Symptoms in Older Adults: the Study of Muscle, Mobility and Aging (SOMMA).

BACKGROUND: Lower urinary tract symptoms (LUTS) and mobility limitations are bidirectionally associated among older adults, but the role of skeletal muscle remains unknown. We evaluated cross-sectional associations of muscle health and physical performance with LUTS. METHODS: We used data from 377 women and 264 men age>70 years in the Study of Muscle, Mobility and Aging (SOMMA). LUTS and urinary bother were assessed using the LURN Symptom Index-10 (SI-10;higher=worse symptoms). Muscle mass and volume were assessed using D3-creatine dilution (D3Cr) and magnetic resonance imaging. Grip strength and peak leg power assessed upper/lower extremity physical performance. 400m walk, Short Physical Performance Battery (SPPB), and Four Square Step Test (FSST) assessed global physical performance. Mobility Assessment Tool-short form (MAT-sf) assessed self-reported mobility. We calculated Spearman correlation coefficients adjusted for age, BMI, multimorbidity, and polypharmacy, chi-square tests, and Fisher's Z-test to compare correlations. RESULTS: Among women, LURN SI-10 total scores were inversely correlated with FSST (rs=0.11,P=0.045), grip strength (rs=-0.15,P=0.006), and MAT-sf (rs=-0.18,P=0.001), but not other muscle and physical performance measures in multivariable models. LURN SI-10 was not associated with any of these measures among men. 44% of women in the lowest tertile of 400m walk speed versus 24% in the highest tertile reported they were at least "somewhat bothered" by urinary symptoms (P<0.001) whereas differences among men were not significant. CONCLUSIONS: Balance and grip strength were associated with LUTS severity in older women but not men. Associations with other muscle and physical performance measures varied by LUTS subtype but remained strongest among women.

Differential Associations of Cystatin C Versus Creatinine-Based Kidney Function With Risks of Cardiovascular Event and Mortality Among South Asian Individuals in the UK Biobank.

Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.

Trends in Healthcare Expenditures among Adults in the United States by Cancer Diagnosis Status, 2008-2016: A Cross-Sectional Study.

BACKGROUND: This study aims to assess trends in direct medical expenditures and indirect costs between adults with and without a prior cancer diagnosis from 2008 to 2016. METHODS: Nine years of data (2008-2016) from the Medical Expenditure Panel Survey (weighted N = 236,811,875) were used. The outcomes included medical expenditures (total expenditure, inpatient, office-based, medications, outpatient, dental, emergency room visits, home health, other) and health-related missed workdays. The predictor was prior cancer diagnosis. Covariates included demographic characteristics, comorbidities, and calendar year at time of survey completion. Two-part statistical modeling with a combination of binomial and positive distributions was used to estimate medical expenditures and missed workdays. Data were clustered into five timepoints: 2008 to 2009, 2010 to 2011, 2012 to 2013, 2014 to 2015, and 2016. RESULTS: Eleven percent of the sample (n = 25,005,230) had a prior cancer diagnosis. Compared with those without a prior cancer diagnosis, those with a prior cancer diagnosis had higher mean incremental total expenditures across all years. Between 2008 and 2016, the adjusted annual incremental total expenditures were $3,522 [95% confidence interval (CI), $3,072-$3,972]; office-based visits ($1,085; 95% CI, $990-$1180); inpatient hospitalizations ($810; 95% CI, $627-$992); outpatient appointments ($517; 95% CI, $434-$600); and medications ($409; 95% CI, $295-$523); and health-related missed workdays (0.75; 95% CI, 0.45-1.04) compared with adults without a prior cancer diagnosis. CONCLUSIONS: Adults with a prior cancer diagnosis had significantly increased healthcare expenditures and health-related missed workdays compared with those with no cancer diagnosis. IMPACT: Our findings highlight the need for increasing strategies to remedy the impact of increasing direct and indirect costs associated with cancer survivorship as the population grows and ages.