Cristina Marelli

Oral active vitamin D is associated with improved survival in hemodialysis patients

Injection of active vitamin D is associated with better survival of patients receiving chronic hemodialysis. Since in many countries oral active vitamin D administration is the most common form of treatment for secondary hyperparathyroidism we determined the survival benefit of oral active vitamin D in hemodialysis patients from six Latin America countries (FME Register as part of the CORES study) followed for a median of 16 months. Time-dependent Cox regression models, after adjustment for potential confounders, showed that the 7,203 patients who received oral active vitamin D had significant reductions in overall, cardiovascular, infectious and neoplastic mortality compared to the 8,801 patients that had not received vitamin D. Stratified analyses found a survival advantage in the group that had received oral active vitamin D in 36 of the 37 strata studied including that with the highest levels of serum calcium, phosphorus and parathyroid hormone. The survival benefit of oral active vitamin D was seen in those patients receiving mean daily doses of less than 1 microg with the highest reduction associated with the lowest dose. Our study shows that hemodialysis patients receiving oral active vitamin D had a survival advantage inversely related to the vitamin dose.

Body Composition and Survival in Dialysis Patients: Results from an International Cohort Study

BACKGROUND AND OBJECTIVES High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan-Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression. RESULTS In 37,345 hemodialysis patients, median (25th-75th percentile) LTI and FTI were 12.2 (10.3-14.5) and 9.8 (6.6-12.4) kg/m(2), respectively. Median (25th-75th percentile) follow-up time was 266 (132-379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th-90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P<0.001). Survival was best with LTI between 15 and 20 kg/m(2) and FTI between 4 and 15 kg/m(2) (probability of death during follow-up: <5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P<0.001 at low LTI-low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P<0.001 at low LTI-high FTI). CONCLUSIONS This large international study indicates best survival in patients with both LTI and FTI in the 10th-90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.

Influenza A(H1N1)v pandemic in the dialysis population: first wave results from an international survey

Abstract Background. After the first cases of influenza A(H1N1)v in Mexico and the USA became public, Fresenius Medical Care established a case-based reporting of cases for all of its dialysis clinics located in Europe, Middle East, Africa and Latin America. This paper aims to describe mortality rates of patients on dialysis and to assess the risk profiles. Methods. The survey was developed in Lotus Notes with a secure browser-based form. The form was open to 602 Fresenius Medical Care clinics located in Europe, Middle East, Africa and Latin America. Results. As of 3 September 2009, 306 cases have been reported by 85 clinics located in Argentina, Chile, Brazil, UK and Spain. The mean age was 52.7 ± 17.7 years. The majority of cases (70.6%) were from 20- to 44-year-old and 45- to 64-year-old subgroups. Moreover, 35.3% had no associated comorbidity, 20.3% had two and 4.6% three comorbidities, with heart disease being the most frequent. Fever was the most common symptom, present in 94.4% of the cases, followed by cough (78.8%) and muscle and joint pain (69.3%). Eighty-seven percent were treated with antiviral agents, the majority with oseltamivir. One hundred and three patients (34%) were admitted to hospital because of influenza. Pneumonia was reported for 69 cases, out of which 52 patients belonged to a high-risk group. Mortality rate of all the patients (confirmed, probable and suspected cases) was around 5%. Conclusion. End-stage renal disease patients should be included in first ranks of the priority list for the influenza A (H1N1)v vaccine, as already advocated by some healthcare authorities.

Interdialytic weight gain, systolic blood pressure, serum albumin, and C-reactive protein levels change in chronic dialysis patients prior to death

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.

The MONitoring Dialysis Outcomes (MONDO) initiative

Background: Systematic collection and analysis of global hemodialysis patient data may help to improve patient outcomes. Methods: The MONitoring Dialysis Outcomes (MONDO) initiative comprises data from eight dialysis providers worldwide. Data are combined into one repository. Extensive procedures are employed to merge data across countries and providers. Results: The MONDO database comprises longitudinal data of currently 128,000 hemodialysis patients from 26 countries on five continents. Here we report data from 62,345 incident hemodialysis patients. We found lower catheter rates in South-East Asia and Australia, lower hemoglobin levels in South-East Asia, and a higher prevalence of diabetes in North America. Longitudinal analyses suggest that there is a decline in interdialytic weight gain and serum phosphorus and an increasing neutrophil-to-lymphocyte ratio before death in all regions studied. Conclusions: While organizationally lean and low-cost, MONDO is the largest global dialysis database initiative to date, with a particular focus on high longitudinal data density and geographical diversity.

Longitudinal Changes in Body Composition in Patients After Initiation of Hemodialysis Therapy: Results From an International Cohort

OBJECTIVE In patients with advanced kidney disease, metabolic and nutritional derangements induced by uremia interact and reinforce each other in a deleterious vicious circle. Literature addressing the effect of dialysis initiation on changes in body composition (BC) is limited and contradictory. The aim of this study was to evaluate changes in BC in a large international cohort of incident hemodialysis patients. METHODS A total of 8,227 incident adult end-stage renal disease patients with BC evaluation within the initial first 6 months of baseline, defined as 6 months after renal replacement therapy initiation, were considered. BC, including fat tissue index (FTI) and lean tissue index (LTI), were evaluated by Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany). Exclusion criteria at baseline were lack of a BCM measurement before or after baseline, body mass index (BMI) < 18.5 kg/m(2), presence of metastatic solid tumors, treatment with a catheter, and prescription of less or more than 3 treatments per week. Maximum follow-up was 2 years. Descriptive analysis was performed comparing current values with the baseline in each interval (delta analysis). Linear mixed models considering the correlation structure of the repeated measurements were used to evaluate factors associated with different trends in FTI and LTI. RESULTS BMI increased about 0.6 kg/m(2) over 24 months from baseline. This was associated with increase in FTI of about 0.95 kg/m(2) and a decrease in LTI of about 0.4 kg/m(2). Female gender, diabetic status, and low baseline FTI were associated with a significant greater increase of FTI. Age > 67 years, diabetes, male gender, high baseline LTI, and low baseline FTI were associated with a significant greater decrease of LTI. CONCLUSIONS With the transition to hemodialysis, end-stage renal disease patients presented with distinctive changes in BC. These were mainly associated with gender, older age, presence of diabetes, low baseline FTI, and high baseline LTI. BMI increases did not fully represent the changes in BC.

Assessment of a five-year survival on hemodialysis in Brazil: a cohort of 3,082 incident patients

Brazil has the third largest contingent of patients on maintenance hemodialysis (HD) worldwide. However, little is known regarding survival rate and predictors of mortality risk in that population, which are the purposes of this study. A total of 3,082 patients incident on HD, from 2000 to 2004, at 25 dialysis facilities distributed among 7 out of 26 states of Brazil were followed-up until 2009. Patients were 52 ± 16 years-old, 57.8% men, and 20.4%, diabetics. The primary outcome was all causes of mortality. Data were censored at five years of follow-up. The global five-year survival rate was 58.2%. In the Cox proportional model, variables associated with risk of death were: age (hazard ratio - HR = 1.44 per decade, p < 0.0001), diabetes (HR = 1.51, p < 0.0001), serum albumin (HR = 0.76 per g/dL, p = 0.001), creatinine (HR = 0.92 per mg/dL, p < 0.0001), and phosphorus (HR = 1.06 per mg/dL, p = 0.04). The present results show that the mortality rate on HD in this Brazilian cohort was relatively low, but the population is younger and with a lower prevalence of diabetes than the ones reported for developed countries.

Monitoring dialysis outcomes across the world--the MONDO Global Database Consortium

Background/Aims: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. Methods: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. Results: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. Conclusion: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

Relationship of Neutrophil-to-Lymphocyte Ratio and Serum Albumin Levels with C-Reactive Protein in Hemodialysis Patients: Results from 2 International Cohort Studies

Background/Aim: The neutrophil-to-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is an inexpensive and readily available parameter, which may serve as a surrogate for inflammation markers, such as C-reactive protein (CRP). The aim of this study was to determine the utility of NLR in the prediction of elevated CRP levels in hemodialysis (HD) patients. Methods: We analyzed 43,272 HD patients from 2 distinct cohorts within the Monitoring Dialysis Outcomes research collaboration in whom contemporaneous measurements of neutrophil and lymphocyte counts, serum albumin and CRP levels were available. Logistic regression was used to determine the relationship of trichotomized NLR (<2.5, 2.5-5 and >5.0) and albumin levels (<3.1, 3.1-4.0 and >4.0 g/dl) with elevated CRP levels (>10.0, >20.0 and >30.0 mg/l). Congruence of the prediction models was examined by comparing the regression parameters and by cross-validating each regression equation within the other cohort. Results: We found that NLR >5.0 vs. <2.5 (cohort 1: OR 2.3; p < 0.0001 and cohort 2: OR 2.0; p < 0.0001) was associated with CRP levels >10.0 mg/l. Stepwise increase in odds ratio for CRP >10.0 mg/l was observed with the combination of high NLR and low albumin levels (NLR >5.0 and albumin <3.1) (cohort 1: OR 7.6; p < 0.0001 and cohort 2: OR 11.9; p < 0.0001). Cross-validation of the 2 regression models revealed a predictive accuracy of 0.68 and 0.69 in the respective cohorts. Conclusion: This study suggests that NLR could serve as a potential surrogate marker for CRP. Our results may add to diagnostic abilities in settings where CRP is not measured routinely in HD patients. NLR is easy to integrate into daily practice and may be used as a marker of systemic inflammation.

Hemodialysis outcomes in a global sample of children and young adult hemodialysis patients: the PICCOLO MONDO cohort

Background The aim of this study was to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort. Methods The Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0–30 years from 2000 to 2012 in four regions: Asia, Europe, North America and South America. The study sample was categorized into pediatric (≤18 years old) and young adult (19–30 years old) groups based on the age at dialysis initiation. Results For those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region. Conclusions The PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation.