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Published on: May 26, 2023
Urinary podocyte-associated molecules and albuminuria in hypertension
Javier Perez-Hernandez1,2, Maria D Olivares1,2, Elena Solaz2,3
1Genomic and Genetic Diagnosis Unit.
Insights
Hypertension damages kidney podocytes, indicated by increased urinary albumin excretion (UAE). Early glomerular injury in hypertensive patients shows decreased podocyte mRNA and increased protein levels, with nephrin as a key marker.
Area of Science:
- Nephrology
- Diabetology
- Hypertension Research
Background:
- Hypertension is a leading cause of chronic kidney disease.
- Podocyte injury is a critical factor in the progression of kidney damage.
- Urinary albumin excretion (UAE) is an early indicator of glomerular damage.
Purpose of the Study:
- To analyze hypertension-induced podocyte damage in diabetic and nondiabetic individuals.
- To investigate the relationship between urinary albumin excretion (UAE) and podocyte-specific molecules (mRNA and protein).
- To identify early markers of glomerular injury in hypertensive patients.
Main Methods:
- Sixty-four hypertensive patients (30 with diabetes) with eGFR > 60 ml/min/1.73m² were studied.
- Urinary albumin excretion (UAE) was measured using nephelometry (albumin/creatinine ratio).
- Podocyte-specific mRNA and protein levels (nephrin, CD2AP, podocalyxin, aquaporin-1) were assessed via real-time PCR and western blot.
Main Results:
- Increased UAE (>30 mg/g) was observed in 14 nondiabetics and 20 diabetics.
- Diabetics with increased UAE showed low nephrin and CD2AP mRNA; nondiabetics showed low nephrin mRNA only.
- Increased UAE correlated with higher podocyte protein levels (nephrin, CD2AP, podocalyxin) and lower mRNA levels.
Conclusions:
- Elevated UAE in hypertensive patients is associated with increased urinary podocyte proteins and decreased podocyte mRNA expression.
- Podocyte-specific mRNA phenotype and increased nephrin levels serve as valuable markers for early glomerular injury.
- These findings highlight potential biomarkers for monitoring kidney health in hypertensive populations.
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.
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