Cognitive disorders in patients with chronic kidney disease: specificities of clinical assessment.

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients.

Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy.

The coexistence of bleeding and thrombosis in patients with chronic kidney disease (CKD) is frequent and poorly understood. Mouse models are essential to understand complications of CKD and to develop new therapeutic approaches improving the health of patients. We evaluated the hemostasis in two models of renal insufficiency: adenine-diet and 5/6th nephrectomy (5/6Nx). Compared with 5/6Nx mice, mice fed with 0.25% adenine had more severe renal insufficiency and so higher levels of prothrombotic uremic toxins like indoxyl sulfate. More severe renal inflammation and fibrosis were observed in the adenine group, as demonstrated by histological and reverse transcription quantitative polymerase chain reaction experiments. Liver fibrinogen γ chain expression and level of plasma fibrinogen were increased only in adenine mice. In both CKD mouse models, tissue factor (TF) expression was increased in kidney and aorta extracts. Immunochemistry analysis of kidney sections showed that TF is localized in the vascular walls. Thrombin-antithrombin complexes were significantly increased in plasma from both adenine and 5/6Nx mice. Tail bleeding time increased significantly only in adenine mice, whereas platelet count was not significant altered. Finally, results obtained by intravital microscopy after laser-induced endothelial injury showed impaired platelet function in adenine mice and an increase in fibrin generation in 5/6Nx mice. To summarize, adenine diet causes a more severe renal insufficiency compared with 5/6Nx. The TF upregulation and the hypercoagulable state were observed in both CKD models. Bleeding tendency was observed only in the adenine model of CKD that recapitulates the whole spectrum of hemostasis abnormalities observed in advanced human CKD.

Access to kidney transplantation in European adults aged 75-84 years and related outcomes: an analysis of the European Renal Association-European Dialysis and Transplant Association Registry.

To what extent access to, and allocation of kidney transplants and survival outcomes in patients aged ≥75 years have changed over time in Europe is unclear. We included patients aged ≥75-84 years (termed older adults) receiving renal replacement therapy in thirteen European countries between 2005 and 2014. Country differences and time trends in access to, and allocation of kidney transplants were examined. Survival outcomes were determined by Cox regression analyses. Between 2005 and 2014, 1392 older adult patients received 1406 transplants. Access to kidney transplantation varied from ~0% (Slovenia, Greece and Denmark) to ~4% (Norway and various Spanish regions) of all older adult dialysis patients, and overall increased from 0.3% (2005) to 0.9% (2014). Allocation of kidney transplants to older adults overall increased from 0.8% (2005) to 3.2% (2014). Seven-year unadjusted patient and graft survival probabilities were 49.1% (95% confidence interval, 95% CI: 43.6; 54.4) and 41.7% (95% CI: 36.5; 46.8), respectively, with a temporal trend towards improved survival outcomes. In conclusion, in the European dialysis population aged ≥75-84 years access to kidney transplantation is low, and allocation of kidney transplants remains a rare event. Though both are increasing with time and vary considerably between countries. The trend towards improved survival outcomes is encouraging. This information can aid informed decision-making regarding treatment options.

The effect of differing kidney disease treatment modalities and organ donation and transplantation practices on health expenditure and patient outcomes.

The Effect of Differing Kidney Disease Treatment Modalities and Organ Donation and Transplantation Practices on Health Expenditure and Patient Outcomes (EDITH) aims to obtain information on long-term kidney transplant outcomes, long-term health outcomes of living kidney donors and detailed outcomes and costs related to the different treatment modalities of end-stage kidney disease. Nine partners from seven European Union countries will participate in this project.

Attainment of guideline targets in EURODOPPS haemodialysis patients: are differences related to a country's healthcare expenditure and nephrologist workforce?

BACKGROUND: In the field of chronic kidney disease, global clinical practice guidelines have been developed and implemented with a view to improving patient care and outcomes. The attainment of international and European guideline targets for haemodialysis patients in European countries has not been audited recently. Hence, we sought to establish whether the attainment of the targets set out in guidelines and inappropriate care are similar across European countries and whether inter-country differences are related to disparities in national healthcare expenditures (as a percentage of gross domestic product) and/or the nephrologist workforce per capita. METHODS: EURODOPPS is the European part of an international, prospective study of a cohort of adult, in-centre, haemodialysed patients. For the current project, 6317 patients from seven European countries were included between 2009 and 2011. Data on laboratory test results and medication prescriptions were extracted from patient records, in order to determine the overall percentage of patients treated according to the international guidelines on anaemia, dyslipidaemia, metabolic acidosis and mineral bone disease. Data related to macroeconomic indices were collected from World Health Organization database and World Bank stats. RESULTS: Attainment of the targets set in international guidelines was far from complete; only 34.1% of patients attained their target blood pressure and 31.2% attained their target haemoglobin level. Overall, only 5% of the patients attained all of the studied guideline targets. We observed marked inter-country differences in levels of guideline uptake/application and the use of pharmacological agents. The levels of national healthcare expenditures and nephrologist workforce were not correlated with the percentage of patients on-target for ≥50% of the studied variables or with inappropriate care (except for anaemia). CONCLUSIONS: Our analysis of EURODOPPS data highlighted a low overall level of guideline target attainment in Europe and substantial differences between European countries. These inter-country differences did not appear to be linked to macroeconomic determinants.

The Addition of Vascular Calcification Scores to Traditional Risk Factors Improves Cardiovascular Risk Assessment in Patients with Chronic Kidney Disease.

BACKGROUND: Although a variety of non-invasive methods for measuring cardiovascular (CV) risk (such as carotid intima media thickness, pulse wave velocity (PWV), coronary artery and aortic calcification scores (measured either by CT scan or X-ray) and the ankle brachial index (ABI)) have been evaluated separately in chronic kidney disease (CKD) cohorts, few studies have evaluated these methods simultaneously. Here, we looked at whether the addition of non-invasive methods to traditional risk factors (TRFs) improves prediction of the CV risk in patients at different CKD stages. METHODS: We performed a prospective, observational study of the relationship between the outputs of non-invasive measurement methods on one hand and mortality and CV outcomes in 143 patients at different CKD stages on the other. During the follow-up period, 44 patients died and 30 CV events were recorded. We used Cox models to calculate the relative risk for outcomes. To assess the putative clinical value of each method, we also determined the categorical net reclassification improvement (NRI) and the integrated discrimination improvement. RESULTS: Vascular calcification, PWV and ABI predicted all-cause mortality and CV events in univariate analyses. However, after adjustment for TRFs, only aortic and coronary artery calcification scores were found to be significant, independent variables. Moreover, the addition of coronary artery calcification scores to TRFs improved the specificity of prediction by 20%. CONCLUSION: The addition of vascular calcification scores (especially the coronary artery calcification score) to TRFs appears to improve CV risk assessment in a CKD population.

Assessment of arterial stiffness for clinical and epidemiological studies: methodological considerations for validation and entry into the European Renal and Cardiovascular Medicine registry.

Epidemiological studies have highlighted the role of arterial stiffness as a risk factor for development of cardiovascular (CV) diseases. Moreover, aortic stiffness has been shown to be a significant predictive factor of all-cause and CV mortality in different populations including patients with end-stage renal disease. Pulse-wave velocity (PWV) is the most widely used technique to assess arterial stiffness. Although PWV can be measured on any artery or between any arterial sites, only carotid-to-femoral PWV, representing stiffness of the aorta and iliofemoral axes, has been shown to have predictive value for morbidity and mortality. The several available commercial devices differ according to the type of signal (pressure, distension, flow) or by recording both sites simultaneously or using ECG synchronization. It is also possible to directly measure arterial diameter changes during the cardiac cycle and link them to local pulse-pressure changes, which provides the pressure-diameter relationship and stress-strain relationship if arterial wall thickness is also measured. These techniques are based on high-precision vascular echo tracking or magnetic resonance imaging and applanation tonometry. This paper summarizes the basic principles of arterial haemodynamics and various methodologies to assess stiffness and the latest consensus recommendations for clinical applications.

The subxiphoid view cannot replace the apical view for transthoracic echocardiographic assessment of hemodynamic status.

INTRODUCTION: This prospective study aimed to assess whether use of the subxiphoid acoustic window in transthoracic echocardiography (TTE) can be an accurate alternative in the absence of an apical view to assess hemodynamic parameters. METHODS: This prospective study took place in a teaching hospital medical ICU. Over a 4-month period, TTE was performed in patients admitted for more than 24 hours. Two operators rated the quality of parasternal, apical, and subxiphoid acoustic windows as Excellent, Good, Acceptable, Poor, or No image. In the subpopulation presenting adequate (rated as acceptable or higher) apical and subxiphoid views, we compared the left ventricular ejection fraction (LVEF), the ratio between right and left ventricular end-diastolic areas (RVEDA/LVEDA), the ratio between early and late mitral inflow on pulsed Doppler (E/A ratio), the aortic velocity time integral (Ao VTI), and the ratio between early mitral inflow and displacement of the mitral annulus on tissue Doppler imaging (E/Ea ratio). RESULTS: An adequate apical view was obtained in 80%, and an adequate subxiphoid view was obtained in 63% of the 107 patients included. Only 5% of patients presented an adequate subxiphoid view without an adequate apical view. In the subpopulation of patients with adequate apical and subxiphoid windows (n = 65), LVEF, E/A, and RVEDA/LVEDA were comparable on both views, and were strongly correlated (r > 0.80) with acceptable biases and precision. However, the Ao VTI and the E/Ea ratio were lower on the subxiphoid view than on the apical view (18 ± 5 versus 16 ± 5 cm and 9.6 ± 4.6 versus 7.6 ± 4 cm, respectively, P = 0.001 for both). CONCLUSIONS: An adequate TTE subxiphoid window was obtained in fewer than two thirds of ICU patients. In addition to the classic indication for the subxiphoid window to study the vena cava and pericardium, this view can be used to study right and left ventricular morphology and function, but does not provide accurate hemodynamic Doppler information. ICU echocardiographers should therefore record both apical and subxiphoid views to assess comprehensively the cardiac function and hemodynamic status.

[Renal and urinary tract disease national research program]. / Programme national de recherche sur les maladies du rein et des voies urinaires.

The National Institute of Health and Medical Research (Inserm), the Society of Nephrology, and the French Kidney Foundation recognized the need to create a National Research Program for kidney and urinary tract diseases. They organized a conference gathering 80 researchers to discuss the state-of-the art and evaluate the strengths and weaknesses of kidney and urinary tract disease research in France, and to identify research priorities. From these priorities emerged 11 of common interest: 1) conducting epidemiologic studies; 2) conducting large multicenter cohorts of well-phenotyped patients with blood, urine and biopsy biobanks; 3) developing large scale approach: transcriptomics, proteomics, metabolomics; 4) developing human and animal functional imaging techniques; 5) strengthening the expertise in renal pathology and electrophysiology; 6) developing animal models of kidney injury; 7) identifying nontraumatic diagnostic and prognostic biomarkers; 8) increasing research on the fetal programming of adult kidney diseases; 9) encouraging translational research from bench to bedside and to population; 10) creating centers grouping basic and clinical research workforces with critical mass and adequate logistic support; 11) integrating and developing european research programs.

Drug Insight: renal indications of calcimimetics.

Calcimimetics suppress the secretion of parathyroid hormone by sensitizing the parathyroid calcium receptor to serum calcium. Cinacalcet (Sensipar/Mimpara), Amgen Inc., Thousand Oaks, CA), the first-in-class calcimimetic agent approved for treatment of secondary hyperparathyroidism in dialysis patients, is, in association with higher dose of a calcium-based oral phosphate binder, a well-tolerated and effective alternative to standard treatments such as vitamin D derivatives in association with a non-calcium-based oral phosphate binder. Here, we present an overview of evidence in support of this assertion. We extend our discussion to encompass other indications for calcimimetics -- secondary hyperparathyroidism in predialysis chronic kidney disease patients, hypercalcemic hyperparathyroidism in renal transplant recipients, primary hyperparathyroidism, and hypercalcemia associated with parathyroid carcinoma -- as well as providing guidance on optimal usage of this drug.

Effects of oral vitamin C supplementation in hemodialysis patients: a proteomic assessment.

Evidence indicates that oxidative stress is present in dialysis patients, and is associated with vitamin C deficiency. Limited data are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in these patients. Moreover, there are no data available on plasma polypeptide fingerprints by proteome analysis before and after vitamin C supplementation. Therefore, we analyzed plasma samples from a prospective, randomized, open-labeled trial to assess the effects of oral vitamin C supplementation (250 mg three times per week), to define the plasma polypeptide pattern in hemodialysis patients. Our results reveal that more than 30 polypeptides show significant changes in the dialysis patients in comparison to controls with normal renal function, and that several polypeptides are affected/normalized by oral vitamin C supplementation. These results underline the remarkable potential for proteomics to recognize specific peptide profiles in different pathological situations, which might not be detected by classical methods.