Alkaline Phosphatases Account for Low Plasma Levels of Inorganic Pyrophosphate in Chronic Kidney Disease

Audrey Laurain; Isabelle Rubera; Christophe Duranton; Frank Rutsch; Yvonne Nitschke; Elodie Ray; Sandor Vido; Antoine Sicard; Georges Lefthériotis; Guillaume Favre

doi:10.3389/fcell.2020.586831

Alkaline Phosphatases Account for Low Plasma Levels of Inorganic Pyrophosphate in Chronic Kidney Disease

Front Cell Dev Biol. 2020 Dec 3:8:586831. doi: 10.3389/fcell.2020.586831. eCollection 2020.

Authors

Audrey Laurain^{1

2

3}, Isabelle Rubera², Christophe Duranton², Frank Rutsch⁴, Yvonne Nitschke⁴, Elodie Ray⁵, Sandor Vido³, Antoine Sicard^{1

3}, Georges Lefthériotis^{1

2

5}, Guillaume Favre^{1

2

3}

Affiliations

¹ Faculty of Medicine, Côte d'Azur University, Nice, France.
² UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France.
³ Nephrology Department, University Hospital, Nice, France.
⁴ Department of General Pediatrics, Muenster University Children's Hospital, Muenster, Germany.
⁵ Department of Vascular Medicine and Surgery, University Hospital, Nice, France.

Abstract

Introduction: 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_i) 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.

Patients and methods: 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_i, the renal fractional excretion of PP_i (FePP_i), nucleoside triphosphate hydrolase (NPP) and ALP activities in plasma. Correlations and comparisons were assessed with non-parametric tests.

Results: Low PP_i was found in patients on dialysis [1.11 (0.88-1.35), p = 0.004], in early KTR [0.91 (0.66-0.98), p = 0.0003] and in late KTR [1.16 (1.07-1.45), p = 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/cm², p < 0.05]. ALP activity was augmented in patients on dialysis [113 (74-160), p = 0.01] and in early KTR [120 (84-142), p = 0.002] compared to controls [64 (56-70) UI/L]. The activity of NPP and FePP_i were not different between groups. ALP activity was negatively correlated with PP_i (r = -0.49, p = 0.001).

Discussion: Patients on dialysis and KTR have low plasma levels of PP_i, which are partly related to high ALP activity, but neither to low NPP activity, nor to increased renal excretion of PP_i. Further work is necessary to explore comprehensively the purinergic system in chronic kidney disease.

Keywords: alkaline phosphatase activity; hemodialysis; kidney transplant; mineral and bone disorder (CKD-MBD); purinergic mechanisms; pyrophosphate.