Sirimongkolchaiyakul Ornatcha, Wesseling-Perry Katherine, Gales Barbara, Markovic Daniela, Elashoff David, Ramos Georgina, Pereira Renata C, Hanudel Mark R, Salusky Isidro B
Department of Pediatrics David Geffen School of Medicine at the University of California Los Angeles CA USA.
Department of Pediatrics, Faculty of Medicine Vajira Hospital Navamindrahiraj University Bangkok Thailand.
JBMR Plus. 2022 Apr 8;6(4):e10601. doi: 10.1002/jbm4.10601. eCollection 2022 Apr.
Congenital diseases of the kidney and urinary tract (CAKUT) and glomerulonephritis are the main causes of chronic kidney disease (CKD) in children. Although renal osteodystrophy (ROD) and indices of mineral metabolism have been characterized in dialyzed children, the impact of primary kidney disease on ROD is unknown. We performed a cross-sectional study of bone biopsies performed in 189 pediatric dialysis patients aged 12.6 ± 5.4 years. Patients were classified into three groups according to primary kidney disease: CAKUT ( = 82), hereditary ( = 22), or glomerular disease ( = 85). Serum concentrations of calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 25(OH) vitamin D were measured at the time of biopsy. Fibroblast growth factor 23 (FGF23) levels were measured in a subset of 59 patients. Levels of calcium, phosphate, PTH, and 25(OH) vitamin D were similar across groups. CAKUT patients had higher serum ALP and lower C-terminal FGF23 levels. Bone turnover and bone volume parameters did not differ across groups. However, osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid maturation time (OMT) were highest in the CAKUT group and lowest in the hereditary group. Multiple regression analysis revealed that calcium, phosphate, ALP, and PTH were independently associated with OV/BV and osteoid thickness (O.Th). PTH was an independent factor affecting bone formation rate. The relationship between CKD etiology and bone histomorphometric variables was abrogated after adjustment for biochemical parameters in the multivariable models. Overall, bone histology differed according to CKD etiology in the unadjusted analysis; however, this association could not be confirmed independently of biochemical parameters. Although CAKUT patients had a greater mineralization defect with elevated serum ALP levels, longitudinal studies will be needed to elucidate mediation pathways that might be involved in the complex interplay of CKD-mineral bone disease (MBD). © 2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
先天性肾脏和尿路疾病（CAKUT）以及肾小球肾炎是儿童慢性肾脏病（CKD）的主要病因。尽管已经对接受透析治疗的儿童的肾性骨营养不良（ROD）和矿物质代谢指标进行了特征描述，但原发性肾脏疾病对ROD的影响尚不清楚。我们对189名年龄为12.6±5.4岁的儿科透析患者进行的骨活检进行了一项横断面研究。根据原发性肾脏疾病将患者分为三组：CAKUT（n = 82）、遗传性疾病（n = 22）或肾小球疾病（n = 85）。在活检时测量血清钙、磷、碱性磷酸酶（ALP）、甲状旁腺激素（PTH）和25（OH）维生素D的浓度。在59名患者的亚组中测量成纤维细胞生长因子23（FGF23）水平。各组之间钙、磷、PTH和25（OH）维生素D的水平相似。CAKUT患者的血清ALP较高，而C末端FGF23水平较低。各组之间的骨转换和骨体积参数没有差异。然而，类骨质体积（OV/BV）、类骨质表面（OS/BS）和类骨质成熟时间（OMT）在CAKUT组中最高，在遗传性疾病组中最低。多元回归分析显示，钙、磷、ALP和PTH与OV/BV和类骨质厚度（O.Th）独立相关。PTH是影响骨形成率的独立因素。在多变量模型中对生化参数进行调整后，CKD病因与骨组织形态计量学变量之间的关系被消除。总体而言，在未调整的分析中，骨组织学根据CKD病因不同而有所差异；然而，这种关联不能独立于生化参数得到证实。尽管CAKUT患者存在更大的矿化缺陷且血清ALP水平升高，但仍需要进行纵向研究以阐明可能参与CKD-矿物质骨病（MBD）复杂相互作用的介导途径。© 2022作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版。
