Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients

Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

肾间质纤维化与动脉病变可预测慢性肾脏病患者的肾功能丢失，但目前尚无无创评估间质纤维化与血管病变的手段。本研究旨在明确磷钙代谢标志物是否与慢性肾脏组织学改变相关，并可对其进行预测。本回顾性研究纳入了129例具备可获取移植肾活检标本的肾移植受者，分析了磷钙代谢标志物及血清钙化倾向（T50）与慢性肾脏组织学改变（间质纤维化与血管病变）的关联及其预测价值。甲状旁腺激素（PTH）、T50及维生素D水平与间质纤维化独立相关。PTH升高与间质纤维化程度加重呈正相关（r=0.29，P=0.001），而T50与维生素D则发挥保护作用（分别为r=-0.20，P=0.025、r=-0.23，P=0.009）。与之相反，成纤维细胞生长因子23（FGF23）与克洛托素（Klotho）仅与间质纤维化存在弱相关（P=0.045），而血钙与血磷酸盐水平则无此关联。PTH、维生素D及T50可预测重度间质纤维化（曲线下面积（AUC）分别为0.73、0.72与0.68），但并未提升肾功能预测效能。PTH、FGF23及T50可轻度预测轻度间质纤维化（AUC分别为0.63、0.63与0.61），但同样未提升肾功能预测效能。T50随动脉病变程度加重而降低（r=-0.21，P=0.038）。T50预测显著血管病变的判别效能一般（AUC=0.61）。综上，本研究证实，在肾移植受者中，PTH、维生素D及T50与间质纤维化及血管病变的相关性独立于肾功能水平。尽管存在上述关联，但在肾移植受者中，除血管病变领域T50或具有一定临床价值外，矿物质代谢指标在纤维化预测方面并未展现出优于估算肾小球滤过率（eGFR）与蛋白尿的效能，亦未为其带来额外预测价值。