Aldosterone, hypertension, and beyond

Aldosterone, a mineralocorticoid hormone, has a well-known function on water balance and blood pressure homeostasis. Recently, its role in metabolic syndrome, insulin resistance, and obesity has come into a spotlight. Aldosterone induces inflammation and oxidative stress that are attenuated by mineralocorticoid receptor blockers such as spironolactone. Aldosterone exerts its effects via the epithelial sodium channel by non-genomic pathways, including serum and glucocorticoid kinase 1, neural precursor cell-expressed developmentally downregulated [gene 4] protein, and K-Ras, and genomic pathways via epigenetic mechanisms. Beyond regulating epithelial sodium channel, aldosterone induces cardiac hypertrophy, endothelial dysfunction, podocyte injury, and fibrosis. This opens new horizons for mineralocorticoid receptor antagonists and novel therapeutic targets such as serum-glucocorticoid regulated kinase 1

Association of interleukin-10, interferon-gamma, transforming growth factor-beta, and tumor necrosis factor-alpha gene polymorphisms with long-term kidney allograft survival

Single nucleotide polymorphisms within promoter or other regulatory sequences of cytokine genes mainly influence the level of production and secretion of proteins. A large amount of evidence has shown that cytokine gene variations alter graft survival length after kidney transplantation. We studied the association of gene polymorphisms in the interlekin-10 gene [IL10;-1082 G/A], interferon-gamma gene [IFNG; +874 T/A], transforming growth factor-beta gene [TGFB; +869 T/C], and tumor necrosis factor-alpha gene [TNFA;-308 A/G] with kidney allograft survival. The IL10 [-1082 G/A], IFNG [+874 T/A], TGFB [+869 T/C], and TNFA [-308 A/G] genotypes were determined in 32 kidney allograft recipients with graft rejection during the 1st posttransplant year and 52 without rejection in 5 posttransplant years, using allele-specific oligonucleotides-polymerase chain reaction method. The IFNG +874 A/T genotype showed a significantly higher frequency among kidney recipients of the rejection group than the control group [odds ratio, 2.64, 95% confidence interval, 1.03 to 6.74; P=.04]. Comparisons between the rejection and control groups in IL10 [-1082 G/A], IFNG [+874 T/A], TGFB [+869 T/C], and TNFA [-308 A/G] single nucleotide polymorphisms showed no significant difference. Based on the finding of this study, it seems polymorphisms in the genes that regulate IL-10, IFN-gamma, TGF-beta, and TNF-alpha cytokines do not play a major role in kidney allograft survival, and other potential factors in this regard should be considered

Glutathione, glutathione-related enzymes, and total antioxidant capacity in patients on maintenance dialysis

Oxidative stress due to overproduction of reactive oxygen species and impairment in antioxidant defense mechanisms have been suggested as possible factors contributing to the pathogenesis of atherosclerosis in patients with end-stage renal disease. We compared glutathione levels, glutathione peroxidase and glutathione reductase activities, and total antioxidant capacity between patients on hemodialysis and peritoneal dialysis and healthy individuals. Thirty patients receiving regular hemodialysis and 12 on continuous ambulatory peritoneal dialysis were recruited as well as 25 healthy volunteers. Diabetes mellitus, recent febrile or infectious episodes, and hospitalization during the past month were the exclusion criteria. Erythrocyte glutathione level, plasma activities of glutathione peroxidase and glutathione reductase, total antioxidant capacity were determined and compared between the three studied groups. Glutathione levels and glutathione peroxidase activity were markedly lower in the patient groups than in the controls. Conversely, higher activity of glutathione reductase and total antioxidant capacity were noted in the patients than in the controls. There were no significant differences between antioxidant markers of the patients on hemodialysis and peritoneal dialysis. Strong positive correlation were observed between total antioxidant capacity and uric acid in the patients [r = 0.59, P = .045 and r = 0.63, P = .03, respectively]. Although total antioxidant capacity of plasma is increased in patient on dialysis, depletion of glutathione as a key antioxidant component and disturbances in its related enzymes show oxidative stress. This condition may increase the risk of developing cardiovascular disease in patients with end-stage renal disease

Human herpesvirus-8 and kaposi sarcoma after kidney transplantation Mechanisms of tumor genesis

Human herpesviruses [HHVs] are able to escape from complete clearance by the immune system. Their ability to become latent is due to their delicate interferences with the immune system. This characteristic makes some of them known as important tumor viruses. Based on the prevalence of the seropositivity for the HHV-8, the world can be divided into 4 regions, one of which is the Middle East with a seroprevalence of 5% to 20%. The incidence of iatrogenic Kaposi sarcoma, a cancer linked with HHV-8 following organ transplantation, is 500 times higher than that in general population. In the Middle East, Kaposi sarcoma is the most common malignancy reported in kidney transplant recipients. In an immunocompromised host, the primary infection with HHV-8 presents with fever, hepatosplenomegaly, lymphoid hyperplasia, pancytopenia, and liver dysfunction. Occasionally, rapid-onset Kaposi sarcoma develops in association with apparent primary HHV-8 infection. In this article, the tumor genesis mechanism of HHV-8 in kidney transplant recipients was reviewed

Transplanted renal artery stenosis: a case report and review of literature

Transplant renal artery strenosis [TRAS] is a relatively frequent, potentially curable cause of refractory hypertension and allograft dysfunction and usually becomes apparent between 3 months and 2 years after transplantation. Depending on the hemodynamic significance of stenosis it can be treated conservatively or revascularization. Here we describe a case of TRAS which was treated successfully with angioplasty and stenting and then we will have a review on its etiology, natural history, diagnosis and therapy