Constance C F M J Baaten1,2, Marieke Sternkopf3, Tobias Henning3, Nikolaus Marx4, Joachim Jankowski3,5, Heidi Noels1,2. 1. Institute for Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany hnoels@ukaachen.de cbaaten@ukaachen.de. 2. Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. 3. Institute for Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany. 4. Department of Internal Medicine I, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany. 5. Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
Abstract
BACKGROUND: Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings. METHODS: To help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function. RESULTS: We included 73 studies in the systematic review to assess CKD's overall effect on platelet function in patients; 11 of them described CKD's effect on ex vivo platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ex vivo; ex vivo analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects. CONCLUSIONS: Overall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.
BACKGROUND: Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings. METHODS: To help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function. RESULTS: We included 73 studies in the systematic review to assess CKD's overall effect on platelet function in patients; 11 of them described CKD's effect on ex vivo platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ex vivo; ex vivo analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects. CONCLUSIONS: Overall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.
Authors: D Tàssies; J C Reverter; A Cases; G Escolar; N Villamor; J López-Pedret; R Castillo; A Ordinas Journal: Am J Hematol Date: 1995-11 Impact factor: 10.047
Authors: Constance C F M J Baaten; Jonas R Schröer; Jürgen Floege; Nikolaus Marx; Joachim Jankowski; Martin Berger; Heidi Noels Journal: Clin J Am Soc Nephrol Date: 2021-11-08 Impact factor: 8.237
Authors: Lucas B Cofer; Qandeel H Soomro; Yuhe Xia; Elliot Luttrell-Williams; Khrystyna Myndzar; David M Charytan; Jeffrey S Berger Journal: Kidney Int Rep Date: 2022-08-04