Urinary podocyte-associated molecules and albuminuria in hypertension

J Hypertens. 2018 Aug;36(8):1712-1718. doi: 10.1097/HJH.0000000000001747.

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / urine
  • Adult
  • Aged
  • Albuminuria / urine*
  • Aquaporin 1 / genetics
  • Aquaporin 1 / urine
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / urine
  • Diabetes Mellitus / urine*
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / metabolism
  • Hypertension / urine*
  • Kidney Diseases / etiology
  • Kidney Diseases / urine*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / urine
  • Middle Aged
  • Podocytes / metabolism*
  • Podocytes / pathology
  • RNA, Messenger / urine
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / urine

Substances

  • AQP1 protein, human
  • Adaptor Proteins, Signal Transducing
  • CD2-associated protein
  • Cytoskeletal Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Sialoglycoproteins
  • nephrin
  • podocalyxin
  • Aquaporin 1