End Stage Renal Disease as a Potential Risk Factor for Retinal Vein Occlusion.

End stage renal disease (ESRD) has been reported to be an important risk factor for systemic vascular disease. Retinal vein occlusion (RVO) is closely related with cardiovascular diseases; however, its association with ESRD had not been reported. The aim of the study was to investigate whether ESRD is a risk factor for RVO, including central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). This population-based study is based on the longitudinal data from Taiwan National Health Insurance Research Database. The study cohort comprised 5344 patients with diagnosis of ESRD on hemodialysis or peritoneal dialysis during the period from January 1996 to December 2011. For each ESRD patient, we selected 20 non-ESRD patients matched on age and sex. Each ESRD patient and his/her controls were followed from the initiation of renal dialysis until either the diagnosis of RVO or censorship. Kaplan-Meier method was used to compare the hazard of RVO between cohorts. Stratified Cox proportional hazard models were applied to estimate the hazard ratio (HR) adjusted by the comorbidities of RVO including diabetes mellitus (DM), hypertension, hypercholesteremia, and hypertriglyceridemia. After stratifying by DM status, the statistics were applied again to examine the associations among the DM cohort and non-DM cohort.The 16-year RVO cumulative incidence for ESRD cohort was 2-fold to the non-ESRD (1.01% vs 0.46%). After matching with age, sex, hypertension, and hypercholesteremia, the adjusted HR was 1.46 (95% confidence interval = 1.07-2.01, P value = 0.018). By further excluding patients with DM, the adjusted HR escalated to 2.43 (95% confidence interval = 1.54-3.83, P < 0.001). In contrast, there was no significant risk of ESRD on RVO in the DM patients (HR = 1.03). We conclude that among the non-DM patients, ESRD cases had significantly higher RVO rate than the non-ESRD, which indicates that ESRD maybe a potential risk factor for the development of RVO in nondiabetic patients.

Nonapnea sleep disorders and incident chronic kidney disease: a population-based retrospective cohort study.

Nonapnea sleep disorders (NASDs) are associated with an increased risk of stroke, diabetes, and hypertension. No longitudinal study has yet examined the association between NASD and chronic kidney disease (CKD) by using epidemiologic study methods. To test this hypothesis, we examined the effect of NASD on the incidence of CKD in a large population-based retrospective cohort study. Based on a retrospective cohort study of a general population sample of 128 to 436 patients in the Taiwan National Health Insurance Research Database from January 1, 1998 to December 31, 2001, 42 to 812 NASD patients were followed up for 10.2 ±â€Š3.12 years, and additional 85 to 624 individuals had no NASD at baseline. The International Classification of Diseases, Ninth Revision, Clinical Modification was used to identify the diagnosis of disease. Cox proportional hazard regression models were used to assess the association between NASD and subsequent CKD risk. The incidence rate of CKD was significantly higher in the NASD cohort than in the comparison cohort (2.68 vs 1.88 per 1000 person-years, respectively). After we adjusted for age, sex, and comorbidities, the risk of developing CKD was significant for patients with NASD (adjusted hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 1.05-1.22; P < 0.01). Among different types of NASDs, patients with sleep disturbance associated disorders had a 14% increased risk of developing CKD (95% CI = 1.03-1.26; P < 0.01), whereas patients with insomnia had a 13% increased risk of subsequent CKD (95% CI = 1.02-1.25; P < 0.05) compared with the non-NASD cohort. Kaplan-Meier survival analysis indicated that the CKD-free rate was 1% lower in the NASD cohort than in the comparison cohort (log-rank test, P < 0.0001). Our study provides evidence that patients with NASD have an increased risk of developing subsequent CKD compared with patients without NASD; men, elderly people, and patients with concomitant comorbidities are at the greatest risk.

High-dialysate-glucose-induced oxidative stress and mitochondrial-mediated apoptosis in human peritoneal mesothelial cells.

Human peritoneal mesothelial cells (HPMCs) are a critical component of the peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs can contribute to complications in peritoneal dialysis. Compelling evidence has shown that high-dialysate glucose is a key factor causing functional changes and cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by high-dialysate glucose, particularly the role of mitochondria in the maintenance of HPMCs. HPMCs were incubated at glucose concentrations of 5 mM, 84 mM, 138 mM, and 236 mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs to high-dialysate glucose resulted in substantial apoptosis with cytochrome c release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage. High-dialysate glucose induced excessive reactive oxygen species production and lipid peroxidation as well as oxidative damage to DNA. Mitochondrial fragmentation, multiple mitochondrial DNA deletions, and dissipation of the mitochondrial membrane potential were also observed. The mitochondrial dysfunction and cell death were suppressed using NAC. These results indicated that mitochondrial dysfunction is one of the main causes of high-dialysate-glucose-induced HPMC apoptosis.

Mycelia glycoproteins from Cordyceps sobolifera ameliorate cyclosporine-induced renal tubule dysfunction in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sorbolifera has been used in Traditional Chinese Medicine for improving the renal function. Cyclosporine A (CsA) is an important immunosuppressive agent in the prevention of renal allograft rejection, but long-term usage of CsA could lead to chronic nephrotoxicity and renal graft failure. The study was aimed to investigate whether the mycelia glycoproteins of Cordyceps sobolifera (CSP) exert prevention effects on CsA-induced nephrotoxicity. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly assigned into four groups (n=6 per group): normal saline (control group), CSP group, CsA group, and CSP-CsA group (CsA combined treatment with CSP). Glomerular and tubular functions were assessed and histological studies were performed. RESULTS: CSP, prepared by hot water extraction, ethanol precipitation and membrane dialysis, was found to be composed of three glycoproteins with average molecular weights of 543, 31, and 6.3 kDa, respectively. CsA impaired urea clearance and creatinine clearance were significantly improved by concomitant administration of CSP. TUNEL histochemical stain revealed that CSP significantly decreased CsA-induced apoptosis in renal tubular cells. The reducing effect of caspase-3 activation by CSP was suggested through the over-expression of the anti-apoptosis protein Bcl-2 in renal tubule cells. In assessment of CSP protection of renal tubule function, we found that CSP restored CsA induced magnesium wasting by increasing the magnesium reabsorption channels TRMP6 and TRMP7. CONCLUSION: The results suggested that CSP had a significant suppressive activity on CsA-induced apoptosis and protective activity against nephron loss possibly via its restoring activity by increasing the magnesium reabsorption channels TRMP6 and TRMP7 on CsA induced magnesium wasting.

Linkage of some trace elements, peripheral blood lymphocytes, inflammation, and oxidative stress in patients undergoing either hemodialysis or peritoneal dialysis.

BACKGROUND: Changes in essential trace elements may affect the inflammatory and immunological state of patients on hemodialysis (HD) or peritoneal dialysis (PD). Therefore, we aimed to determine trace element content and markers of oxidative stress, inflammation, and immune status in HD and PD patients and to assess the relationships among these parameters. METHODS: Patients on either HD (n = 20) or PD (n = 20) and age-, sex-, body mass index-matched healthy individuals (n = 20) were enrolled in the study. The trace elements zinc, copper, selenium, and iron; markers of oxidative stress thiobarbituric acid reactive substances (TBARS) and protein carbonyl levels; activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase; percentages of CD3 T lymphocytes and the subsets CD4 and CD8; the CD4/CD8 ratio; and C-reactive protein (CRP) were measured. RESULTS: All dialysis patients had low levels of albumin and hemoglobin. Significantly decreased percentages of CD3 and CD4 T lymphocytes and increased levels of CRP, TBARS, and carbonyl compounds were observed in HD patients. HD patients also had elevated erythrocyte SOD, lower GPx and catalase activities, and decreased levels of Se, Zn, and Fe in comparison to PD patients and healthy subjects. In addition, CRP was positively associated with TBARS and carbonyl levels, but was significantly inversely associated with Zn and Se levels. Positive correlations were found between T lymphocyte CD3 and CD4 percentages and Zn, Se, and Fe levels. CONCLUSIONS: There were significant decreases in T lymphocyte-related immunological regulation and increased inflammation and oxidative stress in dialysis patients. Essential trace element status was independently related to immune status, inflammation, and oxidative damage.

Ocular toxicity of intravitreal indocyanine green.

We report 6 cases of indocyanine green (ICG)-related ocular toxicity after intravitreal ICG usage. Five cases had preoperative diagnosis of macular hole, 1 case had preoperative rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy. All cases received vitrectomy, ICG-assisted internal limiting membrane (ILM) peeling and air-fluid exchange. All eyes had residual ICG left at the end of surgery. Patients were followed up with indirect ophthalmoscopy, visual acuity, color fundus photography, fluorescein angiography, and ocular coherence tomography. Circular foveal retinal pigment epithelium atrophy larger than the area of macular hole and surrounding cuff was noted in 4 of 5 cases with preoperative macular hole. The other eye with preoperative diagnosis of macular hole had shallow anterior chamber and low intraocular pressure lasting for 1 week postoperatively. Diffuse retinal pigment epithelial atrophy was noted in the eye with preoperative proliferative vitreoretinopathy. Four eyes demonstrated optic atrophy postoperatively. Ocular toxicity caused by ICG may present as pigment epithelial atrophy, which is characteristically larger than the previous area of macular hole and surrounding cuff. Disc atrophy, retinal toxicity, and ocular hypotony were also observed in some cases. To prevent toxicity, residual ICG and ICG-stained ILM must be removed as completely as possible.

Retinal toxicity of intravitreal tissue plasminogen activator: case report and literature review.

OBJECTIVE: To present the clinical picture of retinal toxicity of commercial tissue plasminogen activator (tPA). DESIGN: Case report and literature review. METHODS: Two successive intravitreal injections of tPA (50 micro g) 3 days apart with gas tamponade were given to treat a 49-year-old man with submacular hemorrhage. The adverse consequences of this treatment were monitored. A literature review of retinal toxicity of commercial tPA in animals was also done. MAIN OUTCOME MEASURES: Retinal findings, electroretinograph (ERG) and visual acuity testing. RESULTS: Diffuse pigmentary alterations sparing the posterior pole, poor visual acuity after the absorption of submacular hemorrhage, reduced scotopic and photopic ERG A- and B-waves were noted. CONCLUSIONS: This is the first reported case of retinal toxicity of commercial tPA in humans that resembles the descriptions of tPA-mediated retinal toxicity in animal models. The dosage of intravitreal tPA (between 50 and 100 micro g) may be toxic to the human retina.