Adrian Guinsburg

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.

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.

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.

Dialysis Access as an Area of Improvement in Elderly Incident Hemodialysis Patients: Results from a Cohort Study from the International Monitoring Dialysis Outcomes Initiative

Background: Commencing hemodialysis (HD) using a catheter is associated with a higher risk of adverse outcomes, and early conversion from central-venous catheter (CVC) to arteriovenous fistula/graft (non-CVC) improves outcomes. We investigated CVC prevalence and conversion, and their effects on outcomes during the first year of HD in a multinational cohort of elderly patients. Methods: Patients ≥70 years from the MONDO Initiative who commenced HD between 2000 and 2010 in Asia-Pacific, Europe, North-, and South-America and survived at least 6 months were included in this investigation. We stratified by age (70-79 years [younger] vs. ≥80 years [older]) and compared access types (at first and last available date) and their changes. We studied the association between access at initiation and conversion, respectively, and all-cause mortality using Kaplan-Meier curve and Cox regression, and predicted the absence of conversion from catheter to non-CVC using adjusted logistic regression. Results: In 14,966 elderly, incident HD patients, survival was significantly worse when using a CVC at all times. In Europe, the conversion frequency from CVC to non-CVC was higher in the younger fraction. Conversion from non-CVC to CVC was associated with worsened outcomes only in the older fraction. Conclusion: These results corroborate the need for early HD preparation in the elderly HD population. Treatment of elderly patients who commence HD with a CVC should be planned considering aspects of individual clinical risk assessment. Differences in treatment practices in predialysis care specific to the elderly as a population may influence access care and conversion rate.

Nutritional Markers and Body Composition in Hemodialysis Patients

The aims of this study were to analyse body composition, to detect the presence of undernutrition, and to establish a relationship between undernutrition and the biological markers routinely used as indicators of nutritional status in hemodialysis (HD) patients (pts). We used a body composition monitor (BCM) that expresses body weight in terms of lean tissue mass (LTM) and fat tissue mass (FTM) independent of hydration status. From nine HD units, 934 pts were included. Undernutrition was defined as having a lean tissue index (LTI = LTM/height2) below the 10th percentile of a reference population. Biochemical markers and parameters delivered by BCM were used to compare low LTI and normal LTI groups. Undernutrition prevalence was 58.8% of the population studied. Low LTI pts were older, were significantly more frequently overhydrated, and had been on HD for a longer period of time than the normal LTI group. FTI (FTI = FTM/ height2) was significantly higher in low LTI pts and increased according to BMI. LTI was not influenced by different BMI levels. Albumin and C-reactive protein correlated inversely (r = −0.28). However neither of them was statistically different when considering undernourished and normal LTI pts. Our BCM study was able to show a high prevalence of undernutrition, as expressed by low LTI. In our study, BMI and other common markers, such as albumin, failed to predict malnutrition as determined by BCM.

Association between Heights of Dialysis Patients and Outcomes: Results from a Retrospective Cohort Study of the International MONitoring Dialysis Outcomes (MONDO) Database Initiative

Background: Tall people have improved metabolic profiles and better cardiovascular outcomes, a relationship inverted in dialysis patients. We investigated the relationship between height and outcomes in incident hemodialysis (HD) patients commencing treatment in an analysis of the international Monitoring Dialysis Outcomes (MONDO) database. Methods: In this retrospective cohort study, we included incident HD patients commencing treatment between January 1, 2006 and December 31, 2010 and investigated the association between height and mortality using the MONDO database. A 6-months baseline period preceded 2.5 years of follow-up, during which we recorded patient mortality. Patients were stratified in region-specific deciles of the respective database’s population (Asia Pacific, North and South America, and Europe) and we developed Cox-proportional hazard models (additionally adjusted for age, gender, post-dialysis weight, eKt/V, albumin, interdialytic weight gain, phosphorus, and predialysis systolic blood pressure) for each database. Results: We studied 23,353 patients (62 ± 15 years old, 42% female, body mass index 26 ± 6 kg/m2, height 165 ± 10 cm). We found a trend of increasing hazard ratio of death (HR) with increasing height for Asia Pacific, Europe, and South America. In the fully adjusted models, for South America, we found a trend of increasing HR without significance among deciles >5. In Europe, deciles 8–10 had significantly increased HR. No clear trend was found in North America. Conclusion: We found an increasing risk of death with increasing height in all regions, except North America. While the reasons remain unclear, further research may be warranted.