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