Abstract
Sirtuins have become important players in renal damage in hypertension and diabetes, but their value as biomarkers is poorly assessed. The aims of the study were to evaluate the levels of sirtuin1 (SIRT1), and two miRNAs that regulate SIRT1 expression in hypertensive patients with incipient renal damage with and without diabetes. We quantified urinary SIRT1 and claudin 1 (CLDN1) mRNA and miR34-a and miR-200a levels by quantitative real-time polymerase chain reaction (RT-qPCR) from patients and in cultured podocytes treated with high glucose and angiotensin II. Western blot and fluorescence analyses were also performed. We found decreased SIRT1 levels in patients with increased urinary albumin excretion (UAE), the lowest with diabetes presence, and a strong association with UAE, discriminating incipient renal damage. In vitro experiments also showed SIRT1 overall decreases in podocyte cultures under treatment conditions. In urine samples, miR-34a was reduced and miR-200a increased, both related to UAE levels. However, both miRNAs were generally increased in podocyte cultures under high glucose and angiotensin-II treatment. These results show a significant urinary SIRT1 decrease in albuminuric hypertensive patients, strongly associated with albuminuria, suggesting that SIRT1 could be a potential and non-invasive method to assess incipient renal damage in hypertensive patients.
Highlights
Hypertension and diabetes mellitus (DM) are high prevalent diseases that often affect organ structure and microvasculature, as occur with the kidney, becoming leading causes of renal injury [1,2,3]
The analysis shows how decreased levels of SIRT1 in diseased patients are inversely correlated to urinary albumin excretion (UAE) levels
We observed this reduction in human podocyte cultures placed in high glucose (HG) milieu and angiotensin II (Ang II) treatments
Summary
Hypertension and diabetes mellitus (DM) are high prevalent diseases that often affect organ structure and microvasculature, as occur with the kidney, becoming leading causes of renal injury [1,2,3]. A progressive decrease in glomerular filtration rate (GFR) and/or an increase in urinary albumin excretion (UAE) are common features of renal damage [4,5]. UAE is a well-established prognostic marker in cardiovascular and renal diseases, widely used in clinical practice [6,7]. UAE measurement as a risk marker for the development of chronic kidney disease or end-stage renal disease remains controversial [8,9]. At structural level, during injury, the glomerulus and renal tubule are greatly compromised, subjected to morphological and molecular alterations [10,11,12]. Evaluation of lesions is invasively assessed by renal biopsy; alternative options have emerged based on the research for damage biomarkers in a patient’s urine [16,17,18]
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