Epigenetic mechanisms and kidney diseases.

In recent years, molecular research has brought to light a series of mechanisms involved in the regulation of gene function without altering the DNA sequence. These mechanisms are described with the term "epigenetics" and include modifications in the structure of the human genome, leading to heritable and potentially reversible changes in gene expression. There is now increasing evidence suggesting that several characteristic features of chronic kidney disease such as hyperhomocysteinemia, subclinical inflammation, increased oxidative stress and others may affect the human epigenome. In addition, animal studies have suggested a possible link between nutrition and environmental exposure during the periconceptional period and epigenetic changes in the expression of major genes implicated in kidney organogenesis; these changes result in a diminished number of nephrons in the developing kidney, which predisposes to an increased risk for hypertension and chronic kidney disease in future life. The understanding of the role of epigenetic phenomena in the pathogenesis of chronic kidney disease opens new avenues for future therapeutic strategies, through the development of pharmaceutical agents that target directly with the changes in the human epigenome. Such epigenetic drugs are already in clinical use for the treatment of cancer as well as under investigation for the use in other diseases. This review will summarize the existing data on the link between epigenetic mechanisms and chronic uremic milieu, as well as the promising results of ongoing research in the field of epigenetic drugs that could represent additional options in our therapeutic armamentarium for patients with chronic kidney disease.

Cost-effectiveness of losartan in diabetic nephropathy: a Greek perspective.

BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease (ESRD), which involves substantial economic burden. The primary objective of this study was to estimate the potential effect of losartan on the costs associated with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary aim was to approximate the direct health care cost of renal replacement therapy (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical data were derived from the RENAAL study. All costs were calculated from the perspective of the Greek social insurance system, in 2003 euros. Future costs were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity analyses were performed. RESULTS: The reduction in the number of ESRD days over 3.5 years in patients treated with losartan reduced ESRD-related costs by 3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net cost savings increase thereafter, increasing to 2,686.48 euros per patient over a period of 4.0 years. The results were robust under a wide range of plausible assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per patient. The total economic burden of RRT for the year 2003 has been estimated at 304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of patients with diabetic nephropathy in Greece with losartan is cost-effective, as it leads to important savings for the social insurance system by slowing the progression to ESRD.

Prevalence, awareness, treatment and control of hypertension in employees of factories of Northern Greece: the Naoussa study.

The objective of this study was to examine the prevalence and the levels of awareness, control, and treatment of hypertension in workers, technicians and clerks of factories of the city of Naoussa. A total of 1976 employees in 19 units were examined. From those, 1937 (1045 men and 892 women), 15-73 years of age, were included in the analysis. Every employee was examined twice with 1 week's interval between the two examinations. Analysis was performed using the 140/90 mmHg hypertension threshold. In every visit, three blood pressure (BP) measurements were taken with at least 1-min interval between them. In the analysis only the average BP of the second clinic visit was used. In total, hypertension prevalence was 30.5% (32.1% for men and 28.7% for women respectively, P=0.10). The levels of awareness, treatment, and control of hypertension in hypertensive patients were 18.6%, 11.8%, and 2.2%, respectively. The levels of awareness and treatment differed significantly between men and women (13.4 vs 25.4%, P<0.001 and 9.6 vs 14.8%, P<0.05), but there was no difference in the levels of control (1.5 vs 3.1%, P=0.18). Hypertension prevalence, awareness, and treatment differed also between patients <45 and > or =45 years of age (22.0 vs 53.2%, P<0.001, 9.7 vs 28.4%, P<0.001 and 6.5 vs 17.7%, P<0.001, respectively). In conclusion, the prevalence of hypertension in our study's population is high, while the levels of awareness, treatment, and control are disappointing and should be significantly improved. There is also a difference in awareness and treatment in favour of women compared to men and in favour of patients >/=45 years of age compared to those <45 years of age.