The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network

Jonathan P Troost; Anne Waldo; Noelle E Carlozzi; Shannon Murphy; Frank Modersitzki; Howard Trachtman; Patrick H Nachman; Kimberly J Reidy; David T Selewski; Emily G Herreshoff; Tarak Srivastava; Keisha L Gibson; Vimal K Derebail; Jen Jar Lin; Sangeeta Hingorani; Alessia Fornoni; Fernando C Fervenza; Kamalanathan Sambandam; Ambarish M Athavale; Jeffrey B Kopp; Heather N Reich; Sharon G Adler; Larry A Greenbaum; Katherine M Dell; Gerald Appel; Chia-Shi Wang; John Sedor; Frederick J Kaskel; Richard A Lafayette; Meredith A Atkinson; John C Lieske; Christine B Sethna; Matthias Kretzler; Michelle A Hladunewich; Kevin V Lemley; Elizabeth Brown; Kevin E Meyers; Crystal A Gadegbeku; Lawrence B Holzman; Jonathan Ashley Jefferson; Katherine R Tuttle; Pamela Singer; Marie C Hogan; Daniel C Cattran; Laura Barisoni; Debbie S Gipson; Nephrotic Syndrome Study Network

doi:10.1093/ckj/sfz092

The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network

Clin Kidney J. 2019 Aug 5;13(4):597-606. doi: 10.1093/ckj/sfz092. eCollection 2020 Aug.

Authors

Jonathan P Troost¹, Anne Waldo¹, Noelle E Carlozzi², Shannon Murphy³, Frank Modersitzki⁴, Howard Trachtman⁵, Patrick H Nachman⁶, Kimberly J Reidy⁷, David T Selewski⁸, Emily G Herreshoff¹, Tarak Srivastava⁹, Keisha L Gibson³, Vimal K Derebail³, Jen Jar Lin¹⁰, Sangeeta Hingorani¹¹, Alessia Fornoni¹², Fernando C Fervenza¹³, Kamalanathan Sambandam¹⁴, Ambarish M Athavale¹⁵, Jeffrey B Kopp¹⁶, Heather N Reich¹⁷, Sharon G Adler¹⁸, Larry A Greenbaum¹⁹, Katherine M Dell²⁰, Gerald Appel²¹, Chia-Shi Wang¹⁹, John Sedor²², Frederick J Kaskel⁷, Richard A Lafayette²³, Meredith A Atkinson²⁴, John C Lieske¹³, Christine B Sethna²⁵, Matthias Kretzler²⁶, Michelle A Hladunewich¹⁷, Kevin V Lemley²⁷, Elizabeth Brown²⁸, Kevin E Meyers²⁹, Crystal A Gadegbeku³⁰, Lawrence B Holzman³¹, Jonathan Ashley Jefferson³², Katherine R Tuttle^{33

34}, Pamela Singer²⁵, Marie C Hogan¹³, Daniel C Cattran³⁵, Laura Barisoni^{36

37}, Debbie S Gipson¹; Nephrotic Syndrome Study Network

Affiliations

¹ Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
² Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA.
³ University of North Carolina Kidney Center at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Medicine, Division of Nephrology, New York University Langone Health, New York, NY, USA.
⁵ Department of Pediatrics, Division of Nephrology, New York University Langone Health, New York, NY, USA.
⁶ Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, MN, USA.
⁷ Department of Pediatrics, Division of Nephrology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.
⁸ Department of Pediatrics, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA.
⁹ Section of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO, USA.
¹⁰ Division of Pediatric Nephrology, Brenner Children's Hospital, Wake Forest University, Winston-Salem, NC, USA.
¹¹ Department of Pediatrics, Division of Nephrology, Seattle Children's Hospital and University of Washington, Seattle, WA, USA.
¹² Department of Medicine, Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL, USA.
¹³ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
¹⁴ Department of Internal Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, USA.
¹⁵ Division of Nephrology, Core Faculty, Internal Medicine Residency Program, John H. Stroger Jr. Hospital of Cook County, Chicago, IL, USA.
¹⁶ Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁷ Department of Medicine, Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
¹⁸ Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, CA, USA.
¹⁹ Department of Pediatrics, Division of Pediatric Nephrology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
²⁰ Center for Pediatric Nephrology, Cleveland Clinic Children's and Case Western Reserve University, Cleveland, OH, USA.
²¹ Division of Nephrology, Columbia University Medical Center, New York, NY, USA.
²² Department of Nephrology, Cleveland Clinic, Cleveland, OH, USA.
²³ Department of Medicine, Division of Nephrology, Stanford University, Stanford, CA, USA.
²⁴ Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁵ Pediatric Nephrology, Cohen Children's Medical Center of New York, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
²⁶ Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
²⁷ Division of Nephrology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
²⁸ Department of Pediatrics, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²⁹ Department of Pediatrics, Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³⁰ Division of Nephrology, Temple University School of Medicine, Philadelphia, PA, USA.
³¹ Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³² Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA, USA.
³³ Providence Health Care, Providence Medical Research Center, Spokane, WA, USA.
³⁴ Nephrology Division, Kidney Research Institute and Institute for Translational Health Sciences, University of Washington, Seattle, WA, USA.
³⁵ Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada.
³⁶ Department of Pathology, Division of Nephrology, Duke University, Durham, NC, USA.
³⁷ Department of Medicine, Division of Nephrology, Duke University, Durham, NC, USA.

Abstract

Background: Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS).

Methods: FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied.

Results: There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P = 0.02) and mobility (-4.2, P = 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P = 0.009) and anxiety (-2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03).

Conclusions: PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.

Keywords: PROMIS; focal segmental glomerulosclerosis; nephrotic syndrome; patient-reported outcomes; prospective cohort study; proteinuria; remission.

Grants and funding

K23 DK118189/DK/NIDDK NIH HHS/United States