D'Arrigo Graziella, Mallamaci Francesca, Pizzini Patrizia, Leonardis Daniela, Tripepi Giovanni, Zoccali Carmine
CNR-IFC, Reggio Cal, Italy.
Grande Ospedale Metropolitano, Reggio Cal, Italy.
Nephrol Dial Transplant. 2023 Mar 31;38(4):932-938. doi: 10.1093/ndt/gfac212.
Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) have been implicated in CKD progression in follow-up studies focusing on single measurements of individual biomarkers made at baseline only. The simultaneous relationship between the time trend of these biomarkers over the course of CKD and renal outcomes has never been tested.
We applied the joint model (JM) to investigate the longitudinal relationship between repeated measurements of CKD-MBD biomarkers and a combined renal endpoint (estimated glomerular filtration rate reduction >30%, dialysis or transplantation) in 729 stage 2-5 CKD patients over a 36-month follow-up.
In the survival submodel of the JM, the longitudinal series of parathyroid hormone (PTH) values was directly and independently related to the risk of renal events [hazard ratio (HR) (1 ln increase in parathyroid hormone (PTH) 2.0 (range 1.5-2.8), P < .001)] and this was also true for repeated measurements of serum phosphate [HR (1 mg/dl) 1.3924 (range 1.1459-1.6918), P = .001], serum calcium [HR (1 mg/dl) 0.7487 (range 0.5843-0.9593), P = .022], baseline fibroblast growth factor 23 [HR (1 pg/ml) 1.001 (range 1.00-1.002), P = .045] and 1,25-dihydroxyvitamin D [HR (1 pg/ml) 0.9796 (range 0.9652-0.9942), P = .006].
Repeated measurements of serum PTH, calcium and phosphate as well as baseline FGF23 and 1,25-dihydroxyvitamin D are independently related with the progression to kidney failure in a cohort of stage 2-5 CKD patients. This longitudinal study generates the hypothesis that interventions at multiple levels on MBD biomarkers can mitigate renal function loss in this population.
在仅对基线时单个生物标志物进行单次测量的随访研究中，慢性肾脏病 - 矿物质和骨代谢紊乱（CKD - MBD）的生物标志物与CKD进展有关。这些生物标志物在CKD病程中的时间趋势与肾脏结局之间的同步关系从未得到过检验。
我们应用联合模型（JM）来研究729例2 - 5期CKD患者在36个月随访期间CKD - MBD生物标志物的重复测量值与综合肾脏终点（估计肾小球滤过率降低>30%、透析或移植）之间的纵向关系。
在JM的生存子模型中，甲状旁腺激素（PTH）值的纵向序列与肾脏事件风险直接且独立相关[风险比（HR）（甲状旁腺激素（PTH）增加1 ln 2.0（范围1.5 - 2.8），P <.001）]，血清磷酸盐的重复测量也是如此[HR（1 mg/dl）1.3924（范围1.1459 - 1.6918），P =.001]，血清钙[HR（1 mg/dl）0.7487（范围0.5843 - 0.9593），P =.022]，基线成纤维细胞生长因子23[HR（1 pg/ml）1.001（范围1.00 - 1.002），P =.045]和1,25 - 二羟基维生素D [HR（1 pg/ml）0.9796（范围0.9652 - 0.9942），P =.006]。
在一组2 - 5期CKD患者中，血清PTH、钙和磷酸盐以及基线FGF23和1,25 - 二羟基维生素D的重复测量值与肾衰竭进展独立相关。这项纵向研究提出了一个假设，即对MBD生物标志物进行多层次干预可以减轻该人群的肾功能丧失。
