Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges
Authors: Zoccali Carmine , Ortiz Alberto , Blumbyte Inga Arune , Rudolf Sarina , Beck-Sickinger Annette G , Malyszko Jolanta , Spasovski Goce , Carriazo Sol , Viggiano Davide , Kurganaite Justina , Sarkeviciene Vaiva , Rastenyte Daiva , Figurek Andreja , Rroji Merita , Mayer Christopher , Arici Mustapha , Martino Gianvito , Tedeschi Gioacchino , Bruchfeld Annette , Spoto Belinda , Rychlik Ivan , Wiecek Andrzej , Okusa Mark , Remuzzi Giuseppe , Mallamaci Francesca ,   CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target), Capasso Giovambattista , Andrade Alexandre , Bachmann Maie , Bumblyte Inga , Covic Adrian Constantin , Delgado Pilar , Endlich Nicole , Engvig Andreas , Fouque Denis , Franssen Casper , Frische Sebastian , Garneata Liliana , Gesualdo Loreto , Giannakou Konstantinos , Goumenos Dimitrios , Kartal Ayşe Tuğba , Mani Laila-Yasmin , Marti Hans-Peter , Mayer Christopher , Nielsen Rikke , Pešić Vesna , Rroji (Molla) Merita , Sakkas Giorgos , Spasovski Goce , Stevens Kate , Vazelov Evgueniy , Viggiano Davide , Zacharia Lefteris , Ferreira Ana Carina , Malyszko Jolanta , Hoorn Ewout , Figurek Andreja , Unwin Robert , Wagner Carsten , Wanner Christoph , Bruchfeld Annette , Pepin Marion , Wiecek Andrzej , Nitsch Dorothea , Fridolin Ivo , Hafez Gaye , Romeo Maria José Soler , Barbieri Michelangela , Batinić Bojan , Carrasco Laura , Carriazo Sol , Gansevoort Ron , Martino Gianvito , Raso Francesco Mattace , Nistor Ionut , Ortiz Alberto , Paolisso Giuseppe , Rastenytė Daiva , Stefan Gabriel , Tedeschi Gioacchino , Massy Ziad , Bikbov Boris , Endlich Karl Hans , Godefroy Olivier , Chillon Jean-Marc , Kossioni Anastassia , Kurganaite Justina , Perico Norberto , Remuzzi Giuseppe , Grodzicki Tomasz , Trepiccione Francesco , Zoccali Carmine , Arici Mustafa , Blankestijn Peter , Eckardt Kai-Uwe , Fliser Danilo , Jiménez Eugenio Gutiérrez , Konig Maximilian , Rychlik Ivan , Deleidi Michela , Reusz George 
Published: November 2021

ABSTRACT
Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut–brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system.