Genomes and Genes
Prevalence and Impact of Frailty among Dialysis Patients
Principal Investigator: Kirsten L Johansen
Abstract: DESCRIPTION (provided by applicant): Dr. Johansen was recently promoted to Professor of Medicine at the University of California, San Francisco (UCSF) with a long history of patient-oriented research (POR) focused on elucidating the degree of physical dysfunction among patients with chronic kidney disease, examining potential mechanisms for this dysfunction, and testing strategies to improve functioning in this population. Her overall career goals are to expand this line of research, becoming an internationally recognized investigator in this arena, and to increase her mentoring of junior investigators interested in POR. UCSF is a rich environment for training in POR, including an NIH-funded Clinical and Translational Sciences Institute (CTSI) offering a variety of opportunities, such as a K30-supported didactic training program in clinical research, a K12 (KL2) program, a Mentor Development program, which Dr. Johansen recently completed, as well as a Nephrology T32 that supports nephrology trainees in the pursuit of POR. This award would allow Dr. Johansen to reduce her clinical time in order to increase her POR and mentoring activities. The specific research to be supported under this award is an exploration of the prevalence and significance of frailty among patients new to dialysis. Frailty is a multidimensional construct reflecting a decline in health and functioning, initially observed in the elderly, that ultimately results in increased risk of disability, hospitalization, institutionalization, and death. We examined frailty in the USRDS Dialysis Morbidity and Mortality Study (DMMS) Wave 2 cohort and found that an extremely high proportion of incident ESRD patients, including many who were not elderly, met the criteria for frailty and that frailty was associated with greater risk of subsequent hospitalization and death. We recently completed data collection for a new USRDS special study, the Comprehensive Dialysis Study (CDS), in which 1,646 incident dialysis patients completed a questionnaire that asked about physical activity and functioning and health-related quality of life, providing the data needed for us to define a frailty phenotype based on low physical activity, poor physical functioning, and fatigue/exhaustion. We now propose to extend the investigation of frailty in ESRD by first determining the prevalence of frailty in this more modern dialysis cohort, then by capitalizing on the richness of the CDS data to delve deeper into the factors associated with frailty in this population and the relationship between frailty and ESRD process-related events and outcomes. We hypothesize that frailty is prevalent in this cohort and that frailty is independently associated with hospitalization and mortality as well as with ESRD-related outcomes such as type of vascular access and receipt of a transplanted kidney. Finally, we hypothesize that frailty is associated with depressed mood, post-dialysis fatigue, and sleep disturbance, all of which negatively affect quality of life in this population. It is hoped that these analyses will lead to better discrimination of dialysis patients at risk of adverse outcomes. Two new projects have been added to the revised application to address two of the components of the frailty phenotype: muscle wasting/weakness and physical inactivity. The first will extend Dr. Johansen's recent work evaluating the effects of oxidative stress on muscle fatigue to determine whether markers of oxidative stress are also associated with expression of proteins involved in the ubiquitin proteasome system, the major pathway of muscle catabolism. In addition, the muscle samples collected as part of Dr. Johansen's R21 project will also allow a preliminary assessment of whether short-term treatment with N-acetylcysteine, an anti-oxidant, is associated with reduced expression of catabolic proteins. In the second new project, Dr. Johansen will extend her previous work measuring physical activity in patients with ESRD to use pedometers as both an assessment tool and as a motivational tool in an intervention designed to increase physical activity in this population.
Funding Period: 2010-09-15 - 2015-08-31
more information: NIH RePORT
- Infection-related hospitalizations in older patients with ESRDLorien S Dalrymple
Medicine, University of California, Davis, Sacramento, CA 95817, USA
Am J Kidney Dis 56:522-30. 2010..Few studies have examined the full range of infections experienced by dialysis patients. The purpose of this study is to examine types, rates, and risk factors for infection in older persons starting dialysis therapy...
- Comparison of self-report-based and physical performance-based frailty definitions among patients receiving maintenance hemodialysisKirsten L Johansen
United States Renal Data System Nutrition Special Studies Center, University of California, San Francisco, CA Division of Nephrology, University of California, San Francisco, CA Nephrology Section, San Francisco VA Medical Center, University of California, San Francisco, CA Department of Epidemiology and Biostatistics, University of California, San Francisco, CA Electronic address
Am J Kidney Dis 64:600-7. 2014..A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility...
- Use of pedometers to increase physical activity among children and adolescents with chronic kidney diseaseAalia Akber
Department of Pediatrics, Division of Nephrology, Kaiser Oakland Medical Center, Oakland, CA, USA
Pediatr Nephrol 29:1395-402. 2014..Children and adolescents with chronic kidney disease (CKD) are inactive relative to their peers...
- Comparison of hospitalization rates among for-profit and nonprofit dialysis facilitiesLorien S Dalrymple
Departments of Medicine, Public Health Sciences, and, Biochemistry and Molecular Medicine, University of California, Davis, California, San Francisco Department of Veterans Affairs Medical Center, San Francisco, California, Departments of Medicine and, Epidemiology, and Biostatistics, University of California, San Francisco, California, United States Renal Data System Special Studies Center, Stanford, California, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, Department of Medicine, University of California Irvine, California
Clin J Am Soc Nephrol 9:73-81. 2014..This study examined whether dialysis facility profit status was associated with the rate of hospitalization in patients starting dialysis...
- Iron and infection in hemodialysis patientsJulie H Ishida
Division of Nephrology, Department of Medicine, University of California, San Francisco, California
Semin Dial 27:26-36. 2014..There is a need for further research on this topic, particularly in light of increased utilization of intravenous iron following implementation of the bundled ESRD reimbursement system. ..
- Determinants of hemodialysis-induced segmental wall motion abnormalitiesRuth F Dubin
Department of Medicine Nephrology, San Francisco VA Medical Center University of California, San Francisco, California, USA
Hemodial Int 18:396-405. 2014..Further studies are needed to determine the mechanism of this association and whether cardioprotective medications could ameliorate this adverse cardiac effect of hemodialysis...
- Frailty and dialysis initiationKirsten L Johansen
Division of Nephrology, Department of Medicine, University of California, San Francisco, California Nephrology Section, VA Medical Center, San Francisco, California
Semin Dial 26:690-6. 2013..Overall, there are no data to suggest that frail patients derive any benefit from early initiation of dialysis either in the form of improved survival or functional status...
- Association of segmental wall motion abnormalities occurring during hemodialysis with post-dialysis fatigueRuth F Dubin
Department of Medicine Nephrology, San Francisco VA Medical Center University of California, San Francisco, CA, USA
Nephrol Dial Transplant 28:2580-5. 2013..Post-dialysis fatigue (PDF) is a common, debilitating symptom that remains poorly understood. Cardiac wall motion abnormalities (WMAs) may worsen during dialysis, but it is unknown whether WMA are associated with PDF...
- Obesity and body composition for transplant wait-list candidacy--challenging or maintaining the BMI limits?Kirsten L Johansen
Department of Medicine, University of California San Francisco, San Francisco VA Medical Center, San Francisco, California 94121, USA
J Ren Nutr 23:207-9. 2013..Therefore, it is important to carefully examine the question of BMI limits to ensure that we are achieving the right balance and making the best use of donated kidneys...
- Frailty, dialysis initiation, and mortality in end-stage renal diseaseYeran Bao
Division of Endocrinology, University of California, San Francisco, CA 94143, USA
Arch Intern Med 172:1071-7. 2012....
- Longitudinal measures of serum albumin and prealbumin concentrations in incident dialysis patients: the comprehensive dialysis studyLorien S Dalrymple
Department of Medicine, University of California Davis School of Medicine, Sacramento, California, USA
J Ren Nutr 23:91-7. 2013..The outcomes of interest (dependent variables) were longitudinal measures of albumin and prealbumin concentrations, recorded at study entry and thereafter every 3 months for 1 year...
- Pedometer-assessed physical activity in children and young adults with CKDAalia Akber
Department of Pediatrics, Division of Pediatric Nephrology, University of California, San Francisco, San Francisco, California, USA
Clin J Am Soc Nephrol 7:720-6. 2012..The objectives of this study were to measure the level and correlates of physical activity in children and young adults with CKD and to determine the association of physical activity with physical performance and physical functioning...
- Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertensionRuth Dubin
Department of Medicine, Division Nephrology, University of California, San Francisco, California 94143 0532, USA
Hemodial Int 15:350-8. 2011..Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology...
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