Troost Jonathan P, Waldo Anne, Carlozzi Noelle E, Murphy Shannon, Modersitzki Frank, Trachtman Howard, Nachman Patrick H, Reidy Kimberly J, Selewski David T, Herreshoff Emily G, Srivastava Tarak, Gibson Keisha L, Derebail Vimal K, Lin Jen Jar, Hingorani Sangeeta, Fornoni Alessia, Fervenza Fernando C, Sambandam Kamalanathan, Athavale Ambarish M, Kopp Jeffrey B, Reich Heather N, Adler Sharon G, Greenbaum Larry A, Dell Katherine M, Appel Gerald, Wang Chia-Shi, Sedor John, Kaskel Frederick J, Lafayette Richard A, Atkinson Meredith A, Lieske John C, Sethna Christine B, Kretzler Matthias, Hladunewich Michelle A, Lemley Kevin V, Brown Elizabeth, Meyers Kevin E, Gadegbeku Crystal A, Holzman Lawrence B, Jefferson Jonathan Ashley, Tuttle Katherine R, Singer Pamela, Hogan Marie C, Cattran Daniel C, Barisoni Laura, Gipson Debbie S
Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA.
Clin Kidney J. 2019 Aug 5;13(4):597-606. doi: 10.1093/ckj/sfz092. eCollection 2020 Aug.
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).
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.
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).
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.
了解临床结局与患者报告结局（PROs）之间的关系，将有助于支持局灶节段性肾小球硬化（FSGS）新疗法的临床护理及未来临床试验设计。
纳入肾病综合征研究网络中年龄≥8岁的FSGS患者，完成患者报告结局测量信息系统中与健康相关生活质量（HRQoL）的PRO测量（儿童：总体健康、活动能力、疲劳、疼痛干扰、抑郁、焦虑、压力及同伴关系；成人：身体功能、疲劳、疼痛干扰、睡眠障碍、心理健康、抑郁、焦虑及社会满意度），测量在基线及长达5年的纵向随访期间进行。使用线性混合效应模型确定所研究的8名儿童及8名成人中，哪些人口统计学、临床及实验室特征与PROs相关。
共纳入45名儿童及114名成人FSGS患者，这些患者至少进行了一次PRO评估，总计519次患者访视。儿童多变量分析发现，水肿与总体健康（-7.6分，P = 0.02）及活动能力（-4.2，P = 0.02）相关，报告症状的数量与更严重的抑郁（每个症状-2.7，P = 0.009）及焦虑（-2.3，P = 0.02）相关，过去6个月内急诊就诊次数与更差的活动能力（每次就诊-2.8，P < 0.001）及疲劳（-2.4，P = 0.03）相关。成人多变量分析发现，报告症状的数量与所有八项患者报告结局测量信息系统测量指标中更差的功能相关，急诊就诊次数与更差的疲劳、疼痛干扰、睡眠障碍、抑郁、焦虑及社会满意度相关。在多变量分析中，疾病严重程度的实验室指标（即蛋白尿、估算肾小球滤过率及血清白蛋白）不能预测PROs，但儿童完全缓解及更好的疼痛干扰评分除外（+9.3，P < 0.03）。
PROs为FSGS患者提供了关于HRQoL的重要信息，这些信息不能仅通过检查基于实验室的疾病指标来获取。然而，关键在于测量工具要能体现患者的体验，FSGS临床试验可能会受益于对患者内部变化更敏感的疾病特异性测量工具。
