Evaluation of sirtuin 1 (SIRT1) levels in autosomal dominant polycystic kidney disease.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and the majority of patients have a PKD-1 or PKD-2 mutation. Sirtuin 1 (SIRT1) has roles in cellular aging, antioxidant activity, cellular proliferation. In an experimental study, inhibition of SIRT1 was found to delay renal cyst development in ADPKD. The purpose of this study is to determine the SIRT1 levels in ADPKD patients. To our knowledge, this is the first study that investigating blood and urine SIRT1 levels in ADPKD patients. METHODS: Sixty-seven patients with ADPKD and 34 control cases with normal renal functions and without renal cysts were included in this study. Serum and urine SIRT1 concentrations were determined by human enzyme-linked immunosorbent assay (ELISA) kit. 24-h urine samples were used for urine SIRT1 measurements. RESULTS: The urine SIRT1 levels were statistically significantly lower in ADPKD patients group (p < 0.001). Although blood SIRT1 levels of ADPKD patients were higher than control cases but there were no statistically significant difference between the groups in terms of blood SIRT1 levels. Urine SIRT1 levels (ß = 2.452, CI 95% 1.419-4.239, p = 0.001) were found an independent factor in multivariate regression analysis for ADPKD. CONCLUSIONS: Urine SIRT1 levels were lower in ADPKD patients than control group. The low urinary SIRT1 levels despite the similar blood SIRT1 levels might be due to the impaired metabolism of SIRT1 in ADPKD patients; this state might has a role in cyst development.

Decreased Urinary Levels of SIRT1 as Non-Invasive Biomarker of Early Renal Damage in Hypertension.

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.

Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis.

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (P=0.02) or healthy controls (P=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (P=0.029) and controls (P=0.001). A strong association was found between SIRT1 expression with anti-dsDNA in SLE and in patients with LN. In addition, histological features in LN biopsies were related with SIRT1, increasing its expression in proliferative forms. Finally, SIRT1 expression values showed a strong discriminatory power of renal injury in SLE. Our study demonstrated an altered urinary expression of SIRT1 and a strong association with disease activity in LN patients, being a valuable marker of renal injury. These results showed the role of the SIRT1 pathway in the SLE pathogenesis.