Pituitary adenylate cyclase-activating polypeptide deficiency associated with increased platelet count and aggregability in nephrotic syndrome

Journal of Thrombosis and Haemostasis : JTH
B EnemanE Levtchenko

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) was recently identified as an inhibitor of megakaryopoiesis and platelet aggregability. We studied PACAP levels in children with nephrotic syndrome (NS), which is associated with thrombocytosis, platelet hyperaggregability, and an increased risk of thrombosis. In four children with congenital NS (CNS) and 24 children with idiopathic NS (INS), plasma and urine levels of PACAP and ceruloplasmin were measured, as were platelet counts and platelet aggregation responses to collagen. In CNS patients, in vitro megakaryopoiesis and nuclear factor-κB expression in platelet lysates were also measured. All tests were performed during the nephrotic state and the non-nephrotic state. Urinary losses of PACAP and ceruloplasmin were observed during the nephrotic state, and disappeared during the non-nephrotic state. Plasma PACAP deficiency was more pronounced in CNS patients than in INS patients. Thrombocytosis was observed in all CNS patients and in 11 of 29 INS patients during the nephrotic state. During the PACAP-deficient state, in vitro megakaryopoiesis was increased for CNS patients, and this effect could be reversed by the addition of recombinant PACAP. Platelet hyperaggregabili...Continue Reading

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Citations

Aug 13, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Benedicte EnemanKathleen Freson
Mar 5, 2017·European Journal of Internal Medicine·A GiganteV Raparelli
Nov 12, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·James McCaffreyNicholas J A Webb
Feb 6, 2020·International Journal of Molecular Sciences·Denes TothDora Reglodi
Sep 9, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Shannon L CarpenterMichelle N Rheault
Dec 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ernest Y LeeGerard C L Wong

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