Laurain Audrey, Rubera Isabelle, Duranton Christophe, Rutsch Frank, Nitschke Yvonne, Ray Elodie, Vido Sandor, Sicard Antoine, Lefthériotis Georges, Favre Guillaume
Faculty of Medicine, Côte d'Azur University, Nice, France.
UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France.
Front Cell Dev Biol. 2020 Dec 3;8:586831. doi: 10.3389/fcell.2020.586831. eCollection 2020.
Patients on dialysis and kidney transplant recipients (KTR) present the syndrome of mineral and bone disorders (MBD), which share common traits with monogenic calcifying diseases related to disturbances of the purinergic system. Low plasma levels of inorganic pyrophosphate (PP) and ectopic vascular calcifications belong to these two conditions. This suggests that the purinergic system may be altered in chronic kidney disease with MBD. Therefore, we perform a transversal pilot study in order to compare the determinants of PPi homeostasis and the plasma levels of PPi in patients on dialysis, in KTR and in healthy people.
We included 10 controls, 10 patients on maintenance dialysis, 10 early KTR 3 ± 1 months after transplantation and nine late KTR 24 ± 3 months after transplantation. We measured aortic calcifications, plasma and urine levels of PP, the renal fractional excretion of PP (FePP), nucleoside triphosphate hydrolase (NPP) and ALP activities in plasma. Correlations and comparisons were assessed with non-parametric tests.
Low PP was found in patients on dialysis [1.11 (0.88-1.35), = 0.004], in early KTR [0.91 (0.66-0.98), = 0.0003] and in late KTR [1.16 (1.07-1.45), = 0.02] compared to controls [1.66 (1.31-1.72) μmol/L]. Arterial calcifications were higher in patients on dialysis than in controls [9 (1-75) vs. 399 (25-526) calcium score/cm, < 0.05]. ALP activity was augmented in patients on dialysis [113 (74-160), = 0.01] and in early KTR [120 (84-142), = 0.002] compared to controls [64 (56-70) UI/L]. The activity of NPP and FePP were not different between groups. ALP activity was negatively correlated with PP ( = -0.49, = 0.001).
Patients on dialysis and KTR have low plasma levels of PP, which are partly related to high ALP activity, but neither to low NPP activity, nor to increased renal excretion of PP. Further work is necessary to explore comprehensively the purinergic system in chronic kidney disease.
透析患者和肾移植受者（KTR）存在矿物质和骨代谢紊乱综合征（MBD），其与嘌呤能系统紊乱相关的单基因钙化疾病具有共同特征。血浆无机焦磷酸盐（PP）水平降低和异位血管钙化属于这两种情况。这表明在伴有MBD的慢性肾脏病中嘌呤能系统可能发生改变。因此，我们进行了一项横断面初步研究，以比较透析患者、KTR和健康人群中PPi稳态的决定因素以及PPi的血浆水平。
我们纳入了10名对照者、10名维持性透析患者、10名移植后3±1个月的早期KTR以及9名移植后24±3个月的晚期KTR。我们测量了主动脉钙化、血浆和尿液中的PP水平、PP的肾分数排泄（FePP）、血浆中的核苷三磷酸水解酶（NPP）和碱性磷酸酶（ALP）活性。采用非参数检验评估相关性和进行比较。
与对照组[1.66（1.31 - 1.72）μmol/L]相比，透析患者[1.11（0.88 - 1.35），P = 0.004]、早期KTR[0.91（0.66 - 0.98），P = 0.0003]和晚期KTR[1.16（1.07 - 1.45），P = 0.02]的PP水平较低。透析患者的动脉钙化高于对照组[9（1 - 75）对399（25 - 526）钙积分/cm，P < 0.05]。与对照组[64（56 - 70）UI/L]相比，透析患者[113（74 - 160），P = 0.01]和早期KTR[120（84 - 142），P = 0.002]中的ALP活性增强。各组之间NPP活性和FePP无差异。ALP活性与PP呈负相关（r = -0.49，P = 0.001）。
透析患者和KTR的血浆PP水平较低，这部分与高ALP活性有关，但与低NPP活性和PP肾排泄增加均无关。有必要进一步开展工作以全面探究慢性肾脏病中的嘌呤能系统状况。
