Biomarker-based studies on the relevance of habitual phosphorus intake and dietary acid load during growth for endocrine and nephrological outcomes in adulthood

习惯性高磷摄入是否会导致长期的不良健康结果尚不清楚。到目前为止，没有人群数据可用于前瞻性检查肾磷酸盐排泄率，这些数据是通过多年来反复收集24小时尿液样本来确定的，用于无创评估膳食p摄入量。目前还缺乏研究来检验高和低潜在肾酸负荷（PRAL）对年轻成年期肾脏健康相关结局可能产生的长期影响。在本项目中，首先对1990年至2019年德国健康儿童和青少年P摄入量进行详细的长期趋势分析。该分析将基于以上期间从DONALD研究（德国多特蒙德）的3-17岁参与者中收集的7000多份24小时尿液样本中的磷排泄测量。儿童和青少年时期高磷摄入的潜在长期后果，将在成年后检查不同的肾脏健康相关结果。特别是，将分析特定的肾病和内分泌代谢结果，目的是评估儿童和青少年饮食中高磷摄入量与低磷摄入量的潜在重要性。成年DONALD参与者的肾功能将通过测量尿白蛋白排泄、肾小球滤过率、肌酐清除率、肾酸排泄能力和循环尿调素来检查。磷酸盐调节激素甲状旁腺激素、成纤维细胞生长因子23和a-Klotho将被额外测定，以及通过儿茶酚胺代谢物测量交感病理肾上腺素能活性。允许通过早期生活因素、社会经济地位、人体测量特征、代谢标志物以及其他潜在影响因素进行相关混淆。此外，还应检查所观察到的p摄入量与结果之间的至少部分关系是否也可以用习惯性的、相当高的膳食酸负荷来解释，通过重复收集24小时尿液样本的PRAL测量来量化-基于生物标志物。因此，还可以获得初步信息，说明报告中主要以植物为基础的、至少部分碱化的饮食（如地中海饮食或DASH饮食）对肾脏健康的益处是否可能是由习惯性减少饮食中的酸负荷引起的。

Whether a habitual high phosphorus(P)-intake may result in long-term adverse health outcomes is not yet clarified. Up do now, no population data are available on prospectively examined renal phosphate excretion rates determined in repeatedly – over years – collected 24-h urine samples for the non-invasive assessment of dietary P-intake. Studies are also lacking that examine possible long-term consequences of higher versus lower potential renal acid load (PRAL) for kidney health-relevant outcomes in young adulthood.In the current project, at first, a detailed long-term trend analysis of P intake in healthy children and adolescents in Germany between 1990 and 2019 shall be performed. This analysis will be based on measurements of phosphorus excretion in more than 7000 24-h urine samples collected from 3-17 years old participants of the DONALD study (Dortmund, Germany) during the above period.Potential long-term consequences of a high P-intake during childhood and adolescence will then be examined for different kidney health-relevant outcomes in adulthood. Particularly, specific nephrologic, and endocrine metabolic outcomes, will be analyzed with the aim to assess the prospective importance of higher vs. lower dietary P intake in children and youth. Kidney function in adult DONALD participants will be examined by measuring urinary albumin excretion, glomerular filtration rate, creatinine clearance, renal acid excretion capacity, and circulating uromodulin. The phosphate-regulating hormones parathyroid hormone, fibroblast growth factor 23, and a-Klotho will be additionally determined as well as sympathoadrenergic activity via catecholamine metabolite measurements.Relevant confounding through early life factors, socioeconomic status, anthropometric characteristics, metabolic markers, as well as further potential influencing factors will be allowed for. Additionally, it shall be examined whether at least parts of the observed relationships between P-intake and outcomes could be also explained by a habitual, rather high dietary acid load, quantified – biomarker-based – via PRAL measurements in repeatedly collected 24-h urine samples. Accordingly, preliminary information may be in addition obtained on whether kidney health benefits reported for mainly plant-based, at least partly alkalizing diets like the mediterranean or the DASH diet may be contributorily caused by a habitually reduced dietary acid load.