Berchtold Lena, Ponte Belen, Moll Solange, Hadaya Karine, Seyde Olivia, Bachtler Matthias, Vallée Jean-Paul, Martin Pierre-Yves, Pasch Andreas, de Seigneux Sophie
Service of Internal Medicine, Department of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland.
Service of Nephrology, Department of Internal Medicine Specialities, University Hospital of Geneva, Geneva, Switzerland.
PLoS One. 2016 Dec 30;11(12):e0167929. doi: 10.1371/journal.pone.0167929. eCollection 2016.
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.
肾间质纤维化和动脉病变可预测慢性肾脏病的功能丧失。目前尚无法对间质纤维化和血管病变进行无创评估。本研究的目的是确定钙磷标志物是否与肾脏慢性组织学改变相关并能够对其进行预测。在一项回顾性研究中,我们纳入了129例有可用移植肾活检标本的肾移植受者。我们分析了钙磷标志物和血清钙化倾向(T50)与慢性组织学改变(间质纤维化和血管病变)之间的关联及预测价值。甲状旁腺激素(PTH)、T50和维生素D水平与间质纤维化独立相关。PTH升高与间质纤维化严重程度增加相关(r = 0.29,p = 0.001),而T50和维生素D具有保护作用(分别为r = -0.20,p = 0.025和r = -0.23,p = 0.009)。相反,成纤维细胞生长因子23(FGF23)和Klotho仅与间质纤维化存在中等程度的相关性(p = 0.045),而钙和磷则无相关性。PTH、维生素D和T50是广泛纤维化的预测指标(曲线下面积[AUC]分别为0.73、0.72和0.68),但并未增加对肾功能的预测价值。PTH、FGF23和T50对低纤维化有中等程度的预测性(AUC分别为0.63、0.63和0.61),但也未增加对肾功能的预测价值。T50随动脉病变加重而降低(r = -0.21,p = 0.038)。T50在预测显著血管病变方面的鉴别性能中等(AUC为0.61)。总之,我们证明了PTH、维生素D和T50与肾移植受者的间质纤维化和血管病变相关,且独立于肾功能。尽管存在这些关联,但除了T50可能与之相关的血管病变外,矿物质代谢指标在预测肾移植受者的纤维化方面并不优于估算肾小球滤过率(eGFR)和蛋白尿,也没有附加价值。