Predictors of Somatic Symptom Persistence in Patients With Chronic Kidney Disease (RU SOMACROSS)

在肾功能不全的早期阶段，十分之七的慢性肾脏病（CKD）患者会出现难以负担的持续性躯体症状（PSS）。尽管PSS在CKD中的患病率和与生活质量、疾病进展和死亡率的相关性，但其在很大程度上研究和治疗不足。PSS在早期CKD中的发病机制仍然知之甚少。因此，只有生物医学，治疗相关和心理社会因素的综合调查将解开病因机制，并确定可修改的预测PSS在CKD的早期阶段。这是我们的总体目标，以提高我们的理解如何PSS在CKD的发展和持续时间。首先，我们将在一个多变量预后预测模型中研究CKD患者PSS的生物心理社会预测因子及其相互作用。其次，我们的目标是确定不利的症状轨迹，并解开他们的关系，随着时间的推移与生物心理社会预测。第三，我们将实验性地测试症状感知的机制，并定性地探索症状发展的机制，重点关注新诊断的CKD患者。一项在基线、6个月和12个月进行评估的混合方法队列研究将在330例2-4期CKD患者中探索PSS的多变量预测因素。主要结局将是CKD特异性躯体症状负担。次要结局包括CKD特异性生活质量、一般躯体症状负担和功能。基于RU SOMACROSS的适应性生物心理社会工作模型的预测因子包括相关生物医学（包括表观遗传机制和生物标志物suPAR）、治疗相关（例如，副作用），和社会心理变量（例如，期望）。将使用纵向结构方程模型、潜在班级增长和交叉滞后面板分析。在嵌入式混合方法的研究中，实验研究将使用情感图片范式来测试负面情绪诱导对症状感知的影响，并检查调节剂。嵌入式定性研究将使用主题分析来探索患者在接受新的CKD诊断后出现躯体症状的内在机制。关注主观症状负担而不是客观疾病标志物将从根本上拓宽我们对CKD中PSS的认识。基于适应的生物心理社会RU SOMACROSS模型，我们将确定相关生物心理社会风险因素的相对影响，探索有前途的新变量，如表观遗传学改变，suPAR和患者的期望，并调查在CKD的PSS的发展和维持的相互作用。我们的研究结果将有助于RU SOMACROSS的主要目标，即确定各种疾病的PSS的风险因素和机制，并在第二个资助阶段为CKD的基于机制的定制干预措施的发展提供信息。

Seven out of ten patients with chronic kidney disease (CKD) experience burdensome persistent somatic symptoms (PSS) in early stages of renal dysfunction. Despite their prevalence and relevance for quality of life, disease progression, and mortality, PSS in CKD is largely under-researched and under-treated. The pathogenesis of PSS in early-stage CKD remains poorly understood. Thus, only an integrated investigation of biomedical, treatment-related and psychosocial factors will unravel aetiological mechanisms and identify modifiable predictors of PSS in early stages of CKD.It is our overall objective to improve our understanding of how PSS in CKD develop and persist over time. First, we will investigate biopsychosocial predictors and their interactions for PSS in CKD in a multivariate prognostic prediction model. Second, we aim to identify unfavourable symptom trajectories and unravel their relations with biopsychosocial predictors over time. Third, we will experimentally test mechanisms of symptom perception, and qualitatively explore mechanisms of symptom development focussing on patients newly diagnosed with CKD. A mixed methods cohort study with assessments at baseline, 6, and 12 months will explore multivariate predictors of PSS in 330 patients with CKD stages 2-4. The primary outcome will be CKD-specific somatic symptom burden. Secondary outcomes include CKD-specific quality of life, general somatic symptom burden, and functioning. Predictors based on the adapted biopsychosocial working model of RU SOMACROSS include relevant biomedical (including epigenetic mechanisms and the biomarker suPAR), treatment-related (e.g., side effects), and psychosocial variables (e.g., expectations). Longitudinal structural equation models, latent class growth and cross-lagged panel analyses will be used. In an embedded mixed methods approach, an experimental study will use an affective picture paradigm to test the effect of negative affect induction on symptom perception and examine moderators. The embedded qualitative study will use thematic analysis to explore intrapersonal mechanisms by which patients develop somatic symptoms after receiving a new diagnosis of CKD. Focussing on subjective symptom burden instead of objective disease markers will fundamentally broaden our knowledge on PSS in CKD. Based on the adapted biopsychosocial RU SOMACROSS model, we will identify the relative impact of relevant biopsychosocial risk factors, explore promising new variables such as epigenetic alterations, suPAR, and patients’ expectations, and investigate interactions in the development and maintenance of PSS in CKD. Our results will contribute to RU SOMACROSS’ main objective to identify risk factors and mechanisms of PSS across diseases and inform the development of mechanism-based tailored interventions in CKD in the second funding phase.