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

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.

Health-Related Quality of Life in Focal Segmental Glomerular Sclerosis and Minimal Change Disease: A Qualitative Study of Children and Adults to Inform Patient-Reported Outcomes

“…In summary, the findings presented are consistent with previous research in FSGS, MCD, and nephrotic syndrome that has demonstrated that while generic HRQOL J o u r n a l P r e -p r o o f measures capture important aspects of HRQOL, and that PROs can sensitively capture some outcomes in this population, the generic measures do not adequately capture the unique disease specific aspects of FSGS/MCD 16,[34][35][36] . These findings support our hypothesis that HRQOL measures for individuals with FSGS/MCD should incorporate both disease specific and generic HRQOL concepts.…”

“…In summary, the findings presented are consistent with previous research in FSGS, MCD, and nephrotic syndrome that has demonstrated that although generic HRQoL measures capture important aspects of HRQoL and that PROs can sensitively capture some outcomes in this population, the generic measures do not adequately capture the unique disease-specific aspects of FSGS/MCD. 16 , 33 , 34 , 35 These findings support our hypothesis that HRQoL measures for individuals with FSGS/MCD should incorporate both disease-specific and generic HRQoL concepts. Furthermore, the findings from this study suggest that the commonalities between HRQoL in FSGS and MCD, as well as the commonalities in HRQoL between adults and children, should allow for the development of an HRQoL PRO measure that can be used in children (aged ≥8 years) and adults, as well as in both disorders, and is appropriate for use supporting FDA-based labeling claims.…”

Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study

“…While the gene for ACE2 is on the X chromosome [ 30 ], studies of sex-based differences in kidney ACE2 expression and the relationships between ACE2 expression and kidney injury are limited. Accordingly, our goal was to study ACE2 expression in the NEPTUNE cohort [ 31 ] of FSGS and to compare relationships between ACE2 expression, clinical variables, and pathology in males and females.…”

“…We studied a well-characterized cohort of male and female subjects with FSGS [ 31 ]. We chose to study FSGS because clinical outcomes are dependent on sex: outcomes are better in females than males [ 23 , 32 ].…”

“…Our study has several strengths. The cohort is well characterized in terms of clinical variables, such as assessment of blood pressure, eGFR, proteinuria, and measures of IF and TA in kidney biopsy samples [ 31 , 63 ]. This allowed us to study the relationships between several variables and ACE2 expression, perhaps most importantly, histological assessment of kidney fibrosis.…”