The Long-Term Study of Urinary Biomarkers of Renal Injury in Spontaneously Hypertensive Rats

Kidney & Blood Pressure Research

Natividad Martín Morales¹  Francisco O’Valle¹  Rosemary Wangensteen²  Félix Vargas³  Isabel Rodríguez-Gómez³  Sebastián Montoro-Molina³  Andrés Quesada⁴  Antonio Osuna⁴  María del Carmen de Gracia⁴ 

[1] Departamento de Anatomía Patológica e Instituto de Biomedicina Regenerativa (IBIMER), Facultad de Medicina, Granada, Spain;

[2] Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain;

[3] Departamento de Fisiología, Facultad de Medicina, Granada, Spain;

[4] Servicio de Nefrología, Unidad Experimental, Hospital Virgen de las Nieves, Granada, Spain;

关键词: spontaneously hypertensive rats;    aminopeptidases;    klotho;    dipeptidyl peptidase-4;    biomarkers;    renal injury;   

DOI  :  10.1159/000516843

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown