Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling.

Kidney is a major route of xenobiotic excretion, but the accuracy of preclinical data for predicting in vivo clearance is limited by species differences and non-physiologic 2D culture conditions. Microphysiological systems can potentially increase predictive accuracy due to their more realistic 3D environment and incorporation of dynamic flow. We used a renal proximal tubule microphysiological device to predict renal reabsorption of five compounds: creatinine (negative control), perfluorooctanoic acid (positive control), cisplatin, gentamicin, and cadmium.

Technology Transfer of the Microphysiological Systems: A Case Study of the Human Proximal Tubule Tissue Chip.

The adoption of a new technology into basic research, and industrial and clinical settings requires rigorous testing to build confidence in the reproducibility, reliability, robustness, and relevance of these models. Tissue chips are promising new technology, they have the potential to serve as a valuable tool in biomedical research, as well as pharmaceutical development with regards to testing for efficacy and safety. The principal goals of this study were to validate a previously established proximal tubule tissue chip model in an independent laboratory and to extend its utility to testing of nephrotoxic compounds.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity.

Association of Muscle Endurance, Fatigability, and Strength With Functional Limitation and Mortality in the Health Aging and Body Composition Study.

Background: Mobility limitation is highly prevalent among older adults and is central to the loss of functional independence. Dynamic isokinetic muscle fatigue testing may reveal increased vulnerability to disability and mortality beyond strength testing.

Methods: We studied community-dwelling older adults enrolled in the Health Aging and Body Composition study (age range: 71-82) free of mobility disability and who underwent isokinetic muscle fatigue testing in 1999-2000 (n = 1,963).

Longitudinal association between serum leptin concentration and glomerular filtration rate in humans.

Background: Obesity is a risk factor for decline in glomerular filtration rate (GFR). One proposed mechanism leading to glomerulopathy is an increase in leptin levels. However, the association between leptin and GFR has never been demonstrated.

Creatinine clearance, walking speed, and muscle atrophy: a cohort study.

Background: Chronic kidney disease is associated with malnutrition and inflammation. These processes may lead to loss of skeletal muscle and reduced physical performance. Associations of kidney function with muscle composition and longitudinal measures of physical performance are unknown.

Serum phosphate is associated with aortic valve calcification in the Multi-ethnic Study of Atherosclerosis (MESA).

Objectives: This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC).

Background: Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease.

Association between physical performance and all-cause mortality in CKD.

In older adults, measurements of physical performance assess physical function and associate with mortality and disability. Muscle wasting and diminished physical performance often accompany CKD, resembling physiologic aging, but whether physical performance associates with clinical outcome in CKD is unknown. We evaluated 385 ambulatory, stroke-free participants with stage 2-4 CKD enrolled in clinic-based cohorts at the University of Washington and University of Maryland and Veterans Affairs Maryland Healthcare systems.

A prospective study of frailty in nephrology-referred patients with CKD.

Background: Frailty is a construct developed to characterize a state of reduced functional capacity in older adults. However, there are limited data describing the prevalence or consequences of frailty in middle-aged patients with chronic kidney disease (CKD).

Study Design: Observational study.