Health-related quality of life in different stages of renal failure

Measures of health-related quality of life (HRQoL) have a significant predictive value on patient survival and hospitalizations, especially in patients with chronic kidney disease (CKD). In this review, some of the major studies performed in patients with different stages of renal failure are presented. The most used instrument for measuring HRQoL is the Short form health survey questionnaire (SF-36). Patients with predialysis CKD had higher SF-36 scores than a large cohort of hemodialysis (HD) or peritoneal dialysis (PD) patients, but lower scores than those reported for the adult population. Kidney transplantation offers better HRQoL than dialysis. Hemoglobin level predicted both physical and mental domain scores of the SF-36. HRQoL of HD and PD patients were compared in only a few studies, mostly because these studies are difficult to interpret. PD patients generally have lower comorbidity scores at the onset of end-stage renal disease (ESRD), independent of other factors influencing modality selection. Comorbid medical conditions are common in patients with ESRD, and are an important contributing factor to clinical outcomes and quality of life. Depression occurs in about 20-30% of dialysis patients. This is important because of the negative impact depression has on quality of life, but also because depression is now established as a factor that can significantly affect morbidity and mortality in ESRD patients. Sexual life satisfaction showed marked deterioration in all age groups. Patients aged over 65 scored significantly better than younger patients on dialysis stress scales, and were generally more satisfied with life. Longitudinal studies are needed to define periods at risk for decline in HRQoL during progression of CKD.     

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.     

Ocular and systemic factors associated with glaucoma in chronic kidney disease patients

The goal of this study was to examine, the relationship between chronic kidney disease (CKD) and glaucomatous optic disc neuropathy in a cohort of patients from the south-east Serbia and to determine whether limited screening for glaucoma in specific subgroups of patients with CKD is reasonable and justifiable. This cross-sectional study included 328 subjects with various stages of CKD. All patients had visited the Outpatient Department of the Nephrology Clinic, Clinical Center Nis, Serbia. All patients underwent routine ophthalmic examinations. Glaucoma diagnosis based on elevated intraocular pressure (IOP), the presence of excavation of the optic nerve head (C/D ratio), and characteristic glaucomatous visual field loss (MD—mean deviation, PSD—pattern standard deviation). CKD was defined as kidney damage or glomerular filtration rate (GFR) of <60 ml/min/1.73 m² for >3 months. A total number of 328 CKD patients, 33 (10.1 %) with primary open angle glaucoma and 28 (8.5 %) with ocular hypertension (OH), were included in the study. Patients with CKD and glaucoma had significantly higher mean values of C/D ratio (0.59), visual field mean deviations (dB)—MD (p < 0.001), and visual field pattern standard deviations (dB)—PSD (p < 0.001) than patients with CKD and OH. Stepwise multivariate linear regression analysis confirmed that the most significant factors related to IOP are age (p < 0.05), AHT (p = 0.01), and eGFR (p = 0.001). Multivariate regression analysis also confirmed that the most significant factors related to cup-to-disc ratio are number of years of smoking (p < 0.05), AHT, and sCr (p < 0.01). In conclusion, the prevalence of glaucoma among CKD patients in the cohort from south-east Serbia is 10.1 %. Patients with CKD and glaucoma, eGFR and current cigarette smoking are associated with IOP level, MD, and PSD of visual field and C/D ratio.     

Functional reactivity of cerebral capillaries.

The spatiotemporal evolution of cerebral microcirculatory adjustments to functional brain stimulation is the fundamental determinant of the functional specificity of hemodynamically weighted neuroimaging signals. Very little data, however, exist on the functional reactivity of capillaries, the vessels most proximal to the activated neuronal population. Here, we used two-photon laser scanning microscopy, in combination with intracranial electrophysiology and intravital video microscopy, to explore the changes in cortical hemodynamics, at the level of individual capillaries, in response to steady-state forepaw stimulation in an anesthetized rodent model. Overall, the microcirculatory response to functional stimulation was characterized by a pronounced decrease in vascular transit times (20%+/-8%), a dilatation of the capillary bed (10.9%+/-1.2%), and significant increases in red blood cell speed (33.0%+/-7.7%) and flux (19.5%+/-6.2%). Capillaries dilated more than the medium-caliber vessels, indicating a decreased heterogeneity in vessel volumes and increased blood flow-carrying capacity during neuronal activation relative to baseline. Capillary dilatation accounted for an estimated approximately 18% of the total change in the focal cerebral blood volume. In support of a capacity for focal redistribution of microvascular flow and volume, significant, though less frequent, local stimulation-induced decreases in capillary volume and erythrocyte speed and flux also occurred. The present findings provide further evidence of a strong functional reactivity of cerebral capillaries and underscore the importance of changes in the capillary geometry in the hemodynamic response to neuronal activation.     

Predictors of patient compliance during Class II division 1 malocclusion functional orthodontic treatment

ObjectivesTo determine factors that could predict Class II/1 malocclusion patient compliance during functional treatment.Materials and MethodsThe sample consisted of 77 subjects (aged 11–13 years; 47% girls) presenting with Class II/1 malocclusion. Inclusion criteria were distal molar relationship, overjet greater than 5 mm, and confirmed pubertal growth spurt. Removable functional appliances (62% Twin Block [TB], 38% Sander Bite Jumping [BJ]) with built-in maxillary expansion screws were used. Follow-up period was 1 year. Patients and parents independently filled out the Child Perception Questionnaire, Parental/Caregiver Perception Questionnaire, and Family Impact Scale to assess emotional and social well-being, oral symptoms, functional limitations, parental emotions, family activities, conflicts, and financial burden as possible predictors of compliance during treatment. Sex, overjet, and appliance type were also analyzed.ResultsThere were more noncompliant than compliant patients (55% vs 45%). Parental perception of altered emotional well-being of their children was the strongest predictor, increasing compliance odds 3.4 times (95% confidence interval [CI], 1.2–9.4; P = .017). Patients were 3.2 times (95% CI, 1.1–9.3; P = .033) more likely to cooperate with TB compared with BJ appliance. OJ ≥ 8 mm increased compliance odds 3.1 times (95% CI, 1.0–9.4; P = .044).ConclusionsParental perception of child''s emotional well-being alteration, severity of malocclusion, and type of appliance are major predictors of compliance. Psychosocial issues and oral function limitations reported by children and family impact are of negligible influence.     

Ocular melanoma: an overview of the current status

Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease.     

The partnership between renalase and ejection fraction as a risk factor for increased cardiac remodeling biomarkers in chronic heart failure patients

Abstract

Objective: Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse remodeling, which is seen in HF. We postulated the following aims: to investigate associations of renalase with biomarkers of cardiac remodeling: galectin-3, soluble suppression of tumorigenicity, (sST2), growth differentiation factor 15 (GDF-15) and syndecan-1, myocardial stretch (BNP) and cardio-renal axis (cystatin C) in HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) to determine whether renalase, in combination with left ventricular ejection fraction (LVEF), represents a risk factor for plasma elevation in biomarkers.

Methods: We classified HF patients (n?=?76) according to LVEF (preserved/reduced), applied a median plasma renalase (113?ng/mL) as a cut-off value (low/high) and created four subgroups of HF patients: HFpEF/low renalase (n?=?19), HFrEF/low renalase (n?=?19), HFrEF/high renalase (n?=?32) and HFpEF/high renalase (n?=?6). A control group (n?=?35) consisted of healthy volunteers.

Results: Plasma concentrations of evaluated biomarkers were determined using an ELISA technique and were highest in HF patients with reduced EF (p?<?.001, respectively), and renalase’s positive correlations were obtained relating to all biomarkers: galectin-3 (r?=?0.913; p?<?.001), sST2 (r?=?0.965; p?<?.001), GDF-15 (r?=?0.887; p?<?.001), syndecan-1 (r?=?0.922; p?<?.001), BNP (r?=?0.527; p?<?.001) and cystatin C (r?=?0.844; p?<?.001) and strong and negative correlation with LVEF (r?=??0.456, p?<?.001). Increased renalase, regardless of the EF (preserved/reduced), was shown to be an independent risk factor for an increase in all evaluated cardiac remodeling biomarkers, p?<?.001, respectively. However, increased renalase and reduced EF was the only independent risk factor for BNP and cystatin C elevation, p?<?.001, respectively. Results after multivariable adjustments (age/gender) were identical.

Conclusion: When elevated plasma renalase and HF are present, regardless of EF being reduced or preserved, that represents a significant risk factor for increase in cardiac remodeling biomarker plasma concentrations. However, only elevated renalase and reduced EF demonstrated significance as a risk factor for BNP and cystatin C plasma elevation. Renalase may be considered a promising molecule for the improved predictive abilities of conventional biomarkers and is worthy of further investigation.