Conversion from Aranesp® to NESP® in dialysis patients-Exploration of dosing strategies and the feasibility of extending the dosing interval.

AIM: Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. METHODS: Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. RESULTS: Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. CONCLUSION: Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.

Left Atrial Remodeling Assessed by Cardiac MRI after Conversion from Conventional Hemodialysis to In-Centre Nocturnal Hemodialysis.

BACKGROUND: Left atrial (LA) volume is a well-established cardiovascular prognosticator in patients with end-stage renal disease. Although dialysis intensification is associated with left ventricular mass regression, there are limited data regarding LA remodeling. Using cardiac magnetic resonance imaging (CMR), we examined changes in LA size and function relative to ventricular remodeling and cardiac biomarkers after dialysis intensification. METHODS: In this prospective 2-centre cohort study, 37 patients receiving conventional hemodialysis (CHD, 4 h/session, 3×/week) were converted to in-centre nocturnal hemodialysis (INHD 7-8 h/session, 3×/week); 30 patients remained on CHD. CMR and biomarkers were performed at baseline and repeated at 52 weeks. RESULTS: After 52 weeks, there were no significant changes in the LA volumes or LA ejection fraction (EF) within either the CHD or INHD group, and no significant differences between the two groups. Correlations existed between changes in LA and LV end-diastolic volume index (EDVi, Spearman's r = 0.69, p < 0.001), LA and LV end-systolic volume index (ESVi, r = 0.44, p = 0.001), LAEF and LVEF (r = 0.28, p = 0.04), LA and RV EDVi (r = 0.51, p < 0.001), LA and RV ESVi (r = 0.29, p = 0.039), and LA ESVi and LV mass index (r = 0.31, p = 0.02). At baseline, indexed LA volumes positively correlated with NT-proBNP, whereas LAEF negatively correlated with NT-proBNP and Troponin I. After 52 weeks, changes in biomarker levels did not correlate with changes in LA volume or EF. CONCLUSION: There was no significant change in LA size or systolic function after conversion to INHD. The significant correlations between LA and ventricular remodeling and cardiac biomarkers suggest common underlying pathophysiologic mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00718848.

Global prevalence of protein-energy wasting in kidney disease: A meta-analysis of contemporary observational studies from the international society of renal nutrition and metabolism

Objective: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. Methods: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. Results: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. Conclusion: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies From the International Society of Renal Nutrition and Metabolism.

OBJECTIVE: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. METHODS: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. RESULTS: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. CONCLUSION: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Eating During Hemodialysis Treatment: A Consensus Statement From the International Society of Renal Nutrition and Metabolism.

Poor nutritional status and protein-energy wasting are common among maintenance dialysis patients and associated with unfavorable outcomes. Providing foods, meal trays, snack boxes, and/or oral nutritional supplements during hemodialysis can improve nutritional status and might also reduce inflammation, enhance health-related quality of life, boost patient satisfaction, and improve survival. Potential challenges include postprandial hypotension and other hemodynamic instabilities, aspiration risk, gastrointestinal symptoms, hygiene issues, staff burden, reduced solute removal, and increased costs. Differing in-center nutrition policies exist within organizations and countries around the world. Recent studies have demonstrated clinical benefits and highlight the need to work toward clear guidelines. Meals or supplements during hemodialysis may be an effective strategy to improve nutritional status with limited reports of complications in real-world scenarios. Whereas larger multicenter randomized trials are needed, meals and supplements during hemodialysis should be considered as a part of the standard-of-care practice for patients without contraindications.

First Report of Human Infection by Agromyces mediolanus, a Gram-Positive Organism Found in Soil.

We report the first human infection by a member of the Agromyces genus, a group of Gram-positive bacteria found in soil. A patient with a long-term venous catheter developed bacteremia due to a non-vancomycin-susceptible isolate of Agromyces mediolanus. Rapid identification was possible by matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Etiology of the protein-energy wasting syndrome in chronic kidney disease: a consensus statement from the International Society of Renal Nutrition and Metabolism (ISRNM).

Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW.

Left ventricular filling pressure by Doppler echocardiography in patients with end-stage renal disease.

Left ventricular hypertrophy and systolic dysfunction predict mortality in patients with end-stage renal disease. However, the prognostic value of left ventricular filling pressure has remained uncertain in this population. We evaluated whether the early mitral inflow velocity to peak mitral annulus velocity (E/Em) ratio, an estimate of left ventricular filling pressure by tissue Doppler imaging, has significant additional prognostic value to conventional echocardiographic parameters and other clinical and biochemical parameters in 220 patients with end-stage renal disease. The E/Em ratio was elevated (>15) in 62% of the patients. Multivariate analysis showed that an elevated E/Em ratio had the highest correlation with left ventricular volume index, followed by loss of residual glomerular filtration rate, increasing age, worsening ejection fraction, and diabetes. During the median follow-up of 48 months, the E/Em ratio emerged as an independent predictor of all-cause mortality (adjusted hazard ratio: 1.027; 95% CI: 1.003 to 1.051; P=0.026) and cardiovascular death (adjusted hazard ratio: 1.033; 95% CI: 1.002 to 1.065; P=0.035) in the multivariable Cox regression analysis. In addition, the E/Em ratio added significant incremental prognostic value for all-cause mortality (P=0.035) and cardiovascular death (P=0.035) beyond the standard clinical, biochemical, and dialysis parameters and echocardiographic measurements. In conclusion, the E/Em ratio displayed important additional long-term prognostic information above and beyond that of left ventricular mass and systolic function. Our data suggest that left ventricular filling pressure should be estimated during echocardiographic examination for additional prognostication in patients with end-stage renal disease.

Prognostic value of C-reactive protein for heart disease in dialysis patients.

C-reactive protein (CRP) is considered to be the prototype marker of inflammation. In the general population, there are ample clinical and epidemiological data that indicate its usefulness both in predicting the prognosis for various forms of cardiovascular disease, and in monitoring response to treatment. There is also evolving evidence that CRP may be directly involved in the pathological disease process itself. In end-stage renal disease (ESRD) patients, cardiovascular disease remains the leading cause of morbidity and mortality, and is accounted for by a clustering of both traditional and non-traditional risk factors. Of these, inflammation is considered one of the important risk factors and is usually denoted by the presence of elevated CRP. However, since it is a non-specific inflammatory marker and acute-phase reactant, CRP may become elevated as a result of other dialysis-related (such as graft and fistula infections, bio-incompatible dialysis membrane or dialysate, endotoxin exposure and back filtration) and dialysis-unrelated factors (such as chronic infections and malnutrition). This raises an important question as to whether CRP serves as a useful prognostic biomarker in the dialysis population. This review provides an updated view of the use of CRP as a prognostic marker of cardiovascular disease in ESRD patients on maintenance dialysis.

Peak early diastolic mitral annulus velocity by tissue Doppler imaging adds independent and incremental prognostic value.

OBJECTIVES: The aim of this study was to ascertain if left ventricular mitral annulus velocities measured by tissue Doppler imaging (TDI) are more powerful predictors of outcome compared with clinical data and standard Doppler-echocardiographic parameters. BACKGROUND: Tissue Doppler imaging of basal or mitral annulus velocities provides rapid assessment of ventricular long axis function. But it is not known if TDI-derived velocities in systole and diastole add incremental value and are superior to the standard Doppler-echocardiographic measurements as a predictor of outcome. METHODS: The study population consisted of 518 subjects, 353 with cardiac disease and 165 normal subjects who had full Doppler two-dimensional-echocardiographic studies with measurement of mitral inflow velocities in early and late diastole, E-wave deceleration time (DT), peak systolic mitral annular velocity (Sm) early and late diastolic mitral annular velocity (Em and Am) by TDI, early diastolic flow propagation velocity, and standard chamber dimensions. All subjects were followed up for two years. The end point was cardiac death. RESULTS: Tissue Doppler imaging mitral annulus systolic and diastolic velocities were all significantly lower in the non-survivors (all p < 0.05) as was DT (p = 0.024). In the Cox model the best predictors of mortality were Em, Sm, Am, left ventricular ejection fraction, left ventricular mass, and left atrial diameter in systole (LADs). By backward stepwise analysis Em and LADs were the strongest predictors. After forcing the TDI measurements into the covariate model with clinical and mitral DT <0.16 s, Em provided significant incremental value for predicting cardiac mortality (p = 0.004). CONCLUSIONS: Mitral annulus velocity measured by TDI in early diastole gives incremental predictive power for cardiac mortality compared to clinical data and standard echocardiographic measurements. This easily available measurement adds significant value in the clinical management of cardiac patients.