Occult hepatitis C virus infection among haemodialysis patients

Background and study aims

Hepatitis C virus (HCV) infection is a severe problem among patients on maintenance haemodialysis who are at particular risk for blood-borne infections because of prolonged vascular access and potential for exposure to contaminated equipment. Occult hepatitis C virus infection (OCI) is defined as the presence of HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) in the absence of detectable HCV antibody or HCV RNA in the serum. In this study, we aimed to investigate the existence of occult hepatitis C virus infection in PBMCs of haemodialysis (HD) patients in one center. Moreover, we tried to link the condition to risk factors associated with HCV infection in those patients.

The natural history of atherosclerosis: an ecologic perspective

Virologic findings reported in recent atherosclerosis literature may have profound implications. To assess them, we have viewed atherosclerosis in a broad biologic context and against a background of environmental, behavioral, and social change. Reasonable grounds exist, we believe, for regarding atherosclerosis as a chronic, low-grade infectious macroangiopathy which is aggravated by hypercholesterolemia and other recognized risk factors. There are probably multiple infective pathogens and transmission routes. The putative agents that initiate atherosclerosis might include ubiquitous viruses that produce clinically unapparent infections in many animal species. Pathways for their transmission to humans may include the food chain and contaminated water. Food-chain transmission may have been largely responsible for the parallel increases of meat consumption and mortality from coronary heart disease in the United States during the middle third of the century. It provides a hypothetical basis for considering thermal intervention as a heretofore unrecognized factor that may actually best account for the surprising reversal of climbing heart disease mortality rates. Improved sanitation and food hygiene as well as improvements in diet, lifestyle, and medical care may have shaped the downward mortality curve. The virus hypothesis may reconcile apparent epidemiologic conflicts and elucidate the natural history of atherosclerosis.     

Microbiota That Affect Risk for Shigellosis in Children in Low-Income Countries

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17–0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8–220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.–induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.     

Peripheral blood mononuclear cell CD62L and CD11a expression and soluble interstitial cell adhesion molecule-1 levels following infused isoproterenol in hypertension

OBJECTIVES : Increasingly, studies indicate that alterations in leukocyte and endothelial cell adhesion molecules may enhance atherosclerotic processes in human hypertension. beta-adrenergic receptor activation has long been implicated in the aetiology and/or maintenance of hypertension and also has significant effects on leukocyte and endothelial adhesion molecules. This study therefore examined the effects of hypertension on peripheral blood mononuclear cell CD62L and CD11a expression and circulating soluble interstitial cell adhesion molecule (ICAM)-1 (sCD54) levels following infusion of the non-specific beta-adrenergic agonist isoproterenol. DESIGN : In the setting of a General Clinical Research Center, 15 hypertensive and 20 normotensive subjects underwent an infusion of isoproterenol consisting of two sequential 15 min fixed-order doses of 20 and 40 ng/kg per min. Flow cytometry was used to quantify lymphocyte and monocyte populations and adhesion molecules, and ELISA was used to quantify sCD54 levels. RESULTS : As expected, isoproterenol led to a significant increase in the number of circulating lymphocytes (P < 0.001) and monocytes (P < 0.01). The number of circulating CD3+CD8+CD62Llow T cytotoxic cells increased following isoproterenol (P < 0.001) and this increase was greater in hypertensives than in normotensives (P < 0.05). Isoproterenol led to a decrease in surface density of CD62L (P < 0.001) and an increase in surface density of CD11a (P < 0.001) in all subjects. Hypertensives had a significantly lower CD62L density (P = 0.01) and higher CD11a density on lymphocytes (P = 0.002) compared to normotensives. sCD54 levels were unchanged following isoproterenol but were elevated in hypertensives (P < 0.05). CONCLUSIONS : A beta-adrenergic-induced environment of increased CD62Llow/CD11ahigh leukocytes, coupled with existing endothelial CD54 activation, could support basic atherosclerotic processes of increased peripheral blood mononuclear cell-endothelial adhesion in hypertension.     

Predictors of renal replacement therapy and mortality in children with chronic kidney disease

Objectives:

To study the epidemiology of chronic kidney disease (CKD) in children, and to look for risk factors to predict renal replacement therapy (RRT) and mortality.

Methods:

This is a retrospective cohort study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 2006 and 2014, where the files of 1,000 children with CKD were reviewed. We determined the effect of consanguinity and hypertension, and being a Saudi indigene on mortality and RRT. We compared children with congenital versus non-congenital causes of CKD.

Results:

The mean±standard deviation age at presentation was 4.9±4.3 years. The median duration of follow up was 1.5 (interquartile range [IQR]: 0.4-4.0) years. Only 9.7% of children received RRT, and 8.3% died. The underlying etiology for CKD was congenital in 537 children. The congenital CKD group presented at a younger age group (3.5±4.0 versus 6.6±3.9 years, p<0.0001), had more advanced stages of CKD (p<0.0001), higher rates of consanguinity (75.4% versus 47.1%, p<0.0001), and RRT (p<0.004) than children with non-congenital CKD. Risk factors for RRT among children with CKD include being a Saudi indigene (relative risk [RR]=1.49, 95% confidence interval (CI): 1.01-2.21), and hypertensive (RR=5.29, 95% CI: 3.54-7.91). The risk factor for mortality was hypertension (RR=2.46, 95% CI: 1.66-3.65).

Conclusion:

Congenital causes of CKD represent the main etiology of CKD in children living in the western province of Saudi Arabia. Significant risk factors for RRT include congenital CKD, Saudi nationality, and hypertension. Hypertension is also a predictor of mortality in children with CKD.Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health.1 Children with CKD who are on renal replacement therapy (RRT) have higher mortality rate, which is at least 30-fold higher than their age-matched peers.2 Epidemiological information on the incidence and prevalence of pediatric CKD in children is currently limited,3 particularly in developing countries. Furthermore, most of the available epidemiological data are from end-stage kidney disease (ESKD) registries, and information on the earlier stages of pediatric CKD is still lacking.4 The early stages of CKD in the pediatric population are in most cases asymptomatic, and are therefore under-diagnosed and under-reported.4 Direct comparisons of the incidence and prevalence rate of pediatric CKD are complex since each pediatric CKD registries uses different definition; some depend on the estimated glomerular filtration rate (eGFR), while others use serum creatinine levels. The incidence in Europe was consistent between 11-12 per million of the age-related population (pmarp) for CKD stages 3-5, and 8 pmarp for CKD stages 4-5.4 Data available on the exact prevalence of various kidney diseases in the Arab world is very limited. Most of the data come from small studies and are of limited generalizability.5 In Kuwait, the mean incidence was found to be as high as 38 pmarp, while the prevalence was as also high at 329 pmarp in 2003.6 An incidence of 11 pmarp and a prevalence of 51 pmarp has been reported in Jordanian children.7 The epidemiological data of CKD in children is very scarce in Saudi Arabia. One study from Asir reported that the mean annual incidence of CRF of 15.6 per million children, the mean annual incidence of ESRF is 9.2 per million children, and congenital anomalies of the urinary system constitute the most common cause of chronic renal failure (CRF).8 Another study from Jeddah reported similar results.9 All these studies enrolled a small number of children (less that 100). In the light of a limited data available regarding the epidemiology of CKD in children in Saudi Arabia, we performed a retrospective study to examine the risk factors for RRT and mortality among children with CKD.     

Calcium Antagonists in Patients with Type 2 Diabetes and Hypertension

Hypertension is twice as common in patients with diabetes compared to those without diabetes. It accounts for up to 75% of cardiovascular disease risk leading to the substantial increase in morbidity and mortality. Control of blood pressure in people with diabetes has been shown in randomized controlled trials to decrease cardiovascular risk and improve outcome especially in preventing stroke. A target blood pressure goal of <130/80 mm Hg is currently recommended for patients with diabetes. However, less than 1/3 of these patients achieve such a goal. This is in part due to the inherent difficulty in controlling blood pressure in these patients where hypertension is usually associated with increased salt sensitivity, volume expansion and isolated systolic hypertension. Therefore, patients with diabetes usually require multiple medications for optimal blood pressure control. Calcium channel antagonists have been shown in large clinical trials to be both safe and effective in controlling blood pressure in diabetic patients and will continue to play a major role in the management of hypertension in this population, particularly in the combination therapy that these patients usually require.