The Long-Term Study of Urinary Biomarkers of Renal Injury in Spontaneously Hypertensive Rats
Metadatos
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Montoro Molina, Sebastián; Quesada Miñarro, Andrés; O'Valle Ravassa, Francisco Javier; Martín Morales, Natividad; De Gracia, María del Carmen; Rodríguez Gómez, Isabel María; Osuna Ortega, Antonio; Vargas Palomares, José FélixEditorial
Karger
Materia
Spontaneously hypertensive rats Aminopeptidases Klotho Dipeptidyl peptidase-4 Biomarkers Renal injury
Fecha
2021-07-08Referencia bibliográfica
Montoro-Molina S... [et al.]. The Long-Term Study of Urinary Biomarkers of Renal Injury in Spontaneously Hypertensive Rats. Kidney Blood Press Res 2021;46:502-513. doi: [10.1159/000516843]
Patrocinador
Instituto de Salud Carlos III PI13/02743 PI13/02384 PI18/01715; Red de Investigacion Renal REDinREN "FEDER una manera de hacer Europa" RD16/0009/0033Resumen
Background: The age-related increase in blood pressure in
spontaneously hypertensive rats (SHRs) is associated to cardiac
hypertrophy, heart failure, and renal injury. Here, we investigated
for the first time the urinary enzymatic activities
of glutamil aminopeptidase (GluAp), alanyl aminopeptidase
(AlaAp), dipeptidyl peptidase-4 (DPP4), and Klotho urinary
levels, proteins that are strongly expressed in the kidney, as
early biomarkers of renal injury in SHRs. Methods: Male SHR
and Wistar Kyoto (WKY) rats were studied from 2 to 8 months
old. Systolic blood pressure (SBP), the heart rate (HR), metabolic
variables, and urinary markers were measured monthly.
At the end of the study, a histopathological evaluation of
the kidney was performed. Results: Kidneys of SHR did not develop signs of relevant histopathological changes, but
showed increased glomerular area and cellularity. Plasma
creatinine was decreased, and creatinine clearance was augmented
in SHR at the end of the study. Urinary excretion of
Klotho was higher in SHR at 5 and 8 months old, whereas
plasma Klotho levels were similar to WKY. GluAp, AlaAp, and
DPP4 urinary activities were increased in SHR throughout
the time-course study. A positive correlation between glomerular
area and cellularity with creatinine clearance was
observed. Urinary GluAp, AlaAp, DPP4, and Klotho showed
positive correlations with SBP. Conclusions: GluAp, AlaAp,
DPP4, and Klotho in the urine are useful tools for the evaluation
of renal damage at early stages, before the whole histopathological
and biochemical manifestations of renal disease
are established. Moreover, these observations may represent
a novel and noninvasive diagnostic approach to
assess the evolution of kidney function in hypertension and
other chronic diseases.