2026-09-14T05:58:04Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1691292026-01-22T01:02:23Zcom_10366_128023com_10366_3947com_10366_3946com_10366_3823col_10366_128025

Blázquez Medela, Ana M. García Sánchez, Omar Blanco Gozalo, Víctor Quirós Luis, Yaremi Montero Gómez, María Josefa Martínez Salgado, José Carlos López-Novoa, José M. López Hernández, Francisco José 2026-01-21T12:11:01Z 2026-01-21T12:11:01Z 2014-08-22 Blázquez-Medela, A. M., García-Sánchez, O., Blanco-Gozalo, V., Quiros, Y., Montero, M. J., Martínez-Salgado, C., López-Novoa, J. M., & López-Hernández, F. J. (2014). Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats. PLoS ONE, 9(8). https://doi.org/10.1371/JOURNAL.PONE.0105988. PMID: 25148248; PMCID: PMC4141836. http://hdl.handle.net/10366/169129 10.1371/journal.pone.0105988 25148248 1932-6203 [EN]Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner. Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls). Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors. Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion. Junta de Castilla y León (Consejería de Educación,HUS02B06; Consejería de Sanidad,GRS80/A/06; and Excellence Group,GR-100); Instituto de Salud Carlos III(FIS,P081900,PI11/02278,PS0901067;and RETIC06/0016,RedinRen), and Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain. eng Public Library of Science Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Hypertension NGAL Urinary Excretion Rats Renal tubular alteration Hyperglycemia NG-Nitroarginine Methyl Ester Perfusion Kidney Tubules Acute-Phase Proteins Diabetes Mellitus Rats Animals Hyperglycemia Hypertension Lipocalins Blood Pressure 3209.90 Farmacología Experimental presión sanguínea proteínas de fase aguda lipocalinas perfusión túbulos renales animales hiperglucemia NG-nitroarginina metil éster ratas diabetes mellitus hipertensión Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://doi.org/10.1371/journal.pone.0105988 PLOS ONE 9 8 e105988