Javier Perez-Hernandez1,2, Maria D Olivares1,2, Elena Solaz2,3, Fernando Martinez2,3, Sergio Martínez-Hervas4,5, Gernot Pichler2, Felipe J Chaves1,5, Josep Redon2,3,6, Raquel Cortes1,2. 1. Genomic and Genetic Diagnosis Unit. 2. Research Group of Cardiometabolic and Renal Unit, INCLIVA Biomedical Research Institute. 3. Internal Medicine Unit, Hospital Clínico Universitario. 4. Service of Endocrinology and Nutrition, Hospital Clínico Universitario, Valencia. 5. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Institute of Health Carlos III, Minister of Health, Barcelona. 6. CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Minister of Health, Madrid, Spain.
Abstract
OBJECTIVE: Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. PATIENTS AND METHODS: Sixty-four hypertensive patients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR. Likewise, protein podocyte-specific molecules were measured by western blot using specific antibodies. RESULTS: Fourteen nondiabetics and 20 diabetics had increased UAE greater than 30 mg/g. In individuals with increased EUA, the mRNA expression of nephrin and CD2AP was low in diabetics, whereas only nephrin mRNA in nondiabetics. No differences were observed in podocalyxin and aquaporin-1 mRNA levels. Concerning the protein values, in both nondiabetic and diabetic patients, nephrin, CD2AP and podocalyxin were increased in patients with increased UAE, with no differences in aquaporin-1. A significant positive relationship was observed between log UAE and nephrin protein values, and an inverse association observed with mRNA. CONCLUSION: Hypertensive patients who had elevated UAE showed increased urinary excretion of podocyte-specific proteins coupled with a phenotype of decreased mRNA expression. The phenotype of podocyte-specific mRNA and the increment of nephrin can be used as a valuable marker of early glomerular injury.
OBJECTIVE:Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. PATIENTS AND METHODS: Sixty-four hypertensivepatients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR. Likewise, protein podocyte-specific molecules were measured by western blot using specific antibodies. RESULTS: Fourteen nondiabetics and 20 diabetics had increased UAE greater than 30 mg/g. In individuals with increased EUA, the mRNA expression of nephrin and CD2AP was low in diabetics, whereas only nephrin mRNA in nondiabetics. No differences were observed in podocalyxin and aquaporin-1 mRNA levels. Concerning the protein values, in both nondiabetic and diabeticpatients, nephrin, CD2AP and podocalyxin were increased in patients with increased UAE, with no differences in aquaporin-1. A significant positive relationship was observed between log UAE and nephrin protein values, and an inverse association observed with mRNA. CONCLUSION:Hypertensivepatients who had elevated UAE showed increased urinary excretion of podocyte-specific proteins coupled with a phenotype of decreased mRNA expression. The phenotype of podocyte-specific mRNA and the increment of nephrin can be used as a valuable marker of early glomerular injury.
Authors: Olga Martinez-Arroyo; Ana Ortega; Javier Perez-Hernandez; Felipe J Chaves; Josep Redon; Raquel Cortes Journal: Am J Physiol Renal Physiol Date: 2020-06-22