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Clin J Am Soc Nephrol. 2018 Nov 5. pii: CJN.07670618. doi: 10.2215/CJN.07670618. [Epub ahead of print]

Fostering Innovation in Symptom Management among Hemodialysis Patients: Paths Forward for Insomnia, Muscle Cramps, and Fatigue.

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Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, University of North Carolina Kidney Center, Chapel Hill, North Carolina;
Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, North Carolina.
American Institutes for Research, Washington, D.C.
Division of Nephrology, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia.
University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington.
Harborview Medical Center, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota.
College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.
Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
Renal Section, Medicine Service Line, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; and.
Punta Gorda, Florida.


Individuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes. Moreover, patients on hemodialysis have identified symptom management as a key area for research and innovation, prioritizing symptom alleviation over other health outcomes such as mortality and biochemical indices. Despite the importance of symptoms to patients, there has been little research explicitly geared toward improving patient symptoms, and therefore minimal innovation in symptom management. In general, the physiologic underpinnings of symptoms are poorly understood, hampering the development of targeted therapies. In fact, there have been few drugs or devices approved by the US Food and Drug Administration for the indication of improving any patient-reported outcomes for patients on hemodialysis. Recognizing this gap in innovation, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to first prioritize symptoms for the development of therapeutic interventions, and then identify near-term actionable research goals for the prioritized physical symptoms of insomnia, muscle cramps, and fatigue. This paper summarizes the pathophysiology of the three prioritized symptoms, identifies key knowledge gaps, acknowledges factors that challenge development of new therapies, and offers the nephrology community actionable research goals for insomnia, muscle cramps, and fatigue.


ESKD; ESRD; chronic dialysis; dialysis; end stage kidney disease; hemodialysis; kidney disease


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