Len Usvyat

Periodontal disease adversely affects the survival of patients with end-stage renal disease

Periodontal disease is associated with cardiovascular disease and is thought to accelerate systemic atherosclerosis. Here we examined the relationship between periodontitis and cardiovascular disease mortality in outpatients on hemodialysis using a retrospective analysis of 168 adult patients in New York City and North Carolina. During 18 months of follow-up, cardiovascular disease and all-cause mortality were determined from a centralized dialysis registry. One hundred patients had mild or no periodontal disease but the remaining 68 had moderate-to-severe disease defined as 2 or more teeth with at least 6 mm of inter-proximal attachment loss. At baseline, the proportion of males was significantly lower in the moderate-to-severe group. Compared with mild or no periodontal disease, moderate-to-severe disease was significantly associated with death from cardiovascular causes. Adjustment for age, gender, center and dialysis vintage, smoking status, and history of diabetes mellitus or hypertension did not diminish the strength of this association. Our findings suggest a need for larger studies to confirm this connection, along with intervention trials to determine if treating periodontitis reduces cardiovascular disease mortality in dialysis patients.

Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome.

Intradialytic hypotension (IH) is a frequent complication of hemodialysis (HD) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30 mmHg decrease in systolic blood pressure to <90 mmHg. Risk factors were assessed by logistic regression and hospitalization by Poisson regression. Time to death and first hospitalization were assessed using Kaplan–Meier analysis in patients completing >20 HD treatments. We studied IH in 44,801 treatments (Tx) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0–100% Tx) and dialysis facility (11.1–25.8% Tx). 25.1% of patients had no IH (0% Tx) and 16.2% had IH on >35% Tx. Increased IH frequency was associated with age, female gender, diabetes, Hispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly Tx, lower pre‐HD systolic blood pressure, higher difference between prescribed and achieved post‐HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival (P = 0.036), and more frequent and longer hospitalization (P = 0.04, P = 0.002, respectively) than patients without IH. In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH, decreased mortality, and decreased hospitalization.

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.

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.

Relationship between adiposity and cardiovascular risk factors in prevalent hemodialysis patients.

OBJECTIVE Increased body mass index (BMI) is associated with reduced all-cause and cardiovascular (CV) mortality in hemodialysis (HD) patients, whereas CV risk increases with BMI in the general population. In the general population, obesity is associated with inflammation, decreased high-density lipoprotein (HDL) cholesterol, increased low-density lipoprotein (LDL) cholesterol, and triglycerides (TGs), all risk factors for CV disease. Low-density lipoprotein cholesterol does not predict CV risk in HD, whereas increased C-reactive protein and interleukin-6 (IL-6), low HDL and apolipoprotein (apo) AI, and increased fasting TGs do predict risk. Renal failure is associated with dyslipidemia and inflammation in normal-weight patients. We hypothesized that the effects of obesity may be obscured by renal failure in HD. METHODS We explored the relationship between adipose tissue pools and distribution, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (measured by magnetic resonance imaging) and measures of inflammation (C-reactive protein, IL-6, ceruloplasmin, and alpha1 acid glycoprotein), HDL and LDL cholesterol, total TGs, apo AI, apo B, apo CII (an activator of lipoprotein lipase), apo CIII (an inhibitor of lipoprotein lipase), and the adipokines, leptin and adiponectin, in 48 patients with prevalent HD. RESULTS AND CONCLUSIONS Total TG concentrations were positively correlated with VAT controlled for age, sex, and weight. Both apo CII and apo CIII were correlated only with VAT. Adiponectin was inversely correlated with VAT, and leptin was positively associated with SAT. C-reactive protein and alpha1 acid glycoprotein were weakly associated with SAT, whereas ceruloplasmin was strongly associated with VAT according to multiple regression analysis. In contrast, apo B, LDL, apo AI, HDL, and IL-6 were not correlated with any measure of body composition, potentially mitigating the effects of obesity in HD.

Comparison of Outcomes on Continuous Ambulatory Peritoneal Dialysis Versus Automated Peritoneal Dialysis: Results from a USA Database

♦ Background and Objective: Automated peritoneal dialysis (APD) is being increasingly used as an alternative to continuous ambulatory peritoneal dialysis (CAPD). However, there has been concern regarding reduced sodium removal leading to hypertension and resulting in a faster decline in residual renal function (RRF). The objective of the present study was to compare patient and technique survival and other relevant parameters between patients treated with APD and patients treated with CAPD. ♦ Methods: Data for incident patients were retrieved from the database of the Renal Research Institute, New York. Treatment modality was defined 90 days after the start of dialysis treatment. In addition to technique and patient survival, RRF, blood pressure, and laboratory parameters were also compared. ♦ Results: 179 CAPD and 441 APD patients were studied. Mean as-treated survival was 1407 days [95% confidence interval (CI) 1211 – 1601] in CAPD patients and 1616 days (95% CI 1478 – 1764) in APD patients. Adjusted hazard ratio (HR) for mortality was 1.31 in CAPD compared to APD (95% CI 0.76 – 2.25, p = NS). Unadjusted as-treated technique survival was lower in CAPD compared to APD, with HR 2.84 (95% CI 1.65 – 4.88, p = 0.002); adjusted HR was 1.81 (95% CI 0.94 – 3.57, p = 0.08). Peritonitis rate was 0.3 episodes/patient-year for CAPD and APD; exit-site/tunnel infection rate was 0.1 and 0.3 episodes/patient-year for CAPD and APD respectively (p = NS). ♦ Conclusions: Patient survival was not significantly different between APD and CAPD patients, whereas technique survival appeared to be higher in APD patients and could not be explained by differences in infectious complications. No difference in blood pressure control or decline in RRF was observed between the 2 modalities. Based on these results, APD appears to be an acceptable alternative to CAPD, although technique prescription should always follow individual judgment.

Anaphylaxis and Hypotension after Administration of Peginesatide

This letter describes serious adverse events (three fatal cardiorespiratory arrests and two grade 4 anaphylaxis and hypotension events) related to the administration of peginesatide during surveillance in patients undergoing dialysis. As a result, the drug was removed from the market.

Out of control: accelerated aging in uremia

Next to a high morbidity, patients with end-stage renal failure (ESRD) suffer from a complex spectrum of clinical manifestations. Both the phenotype of patients with ESRD as well as the pathophysiology of uremia show interesting parallels with the general aging process. Phenotypically, patients with ESRD have an increased susceptibility for both cardiovascular as well as infectious disease and show a reduction in functional capacity as well as muscular mass (sarcopenia), translating into a high prevalence of frailty also in younger patients. Pathophysiologically, the immune dysfunction, telomere attrition and the presence of low-grade inflammation in uremic patients also show parallels with the aging process. System models of aging, such as the homeodynamic model and reliability theory of Gavrilov may also have relevance for ESRD. The reduction in the redundancy of compensatory mechanisms and the multisystem impairment in ESRD explain the rapid loss of homeodynamic/homeostatic balance and the increased susceptibility to external stressors in these patients. System theories may also explain the relative lack of success of interventions focusing on single aspects of renal disease. The concept of accelerated aging, which also shares similarities with other organ diseases, may be of relevance both for a better understanding of the uremic process, as well as for the design of multidimensional interventions in ESRD patients, including an important role for early rehabilitation. Research into processes akin to both aging and uremia may result in novel therapeutic approaches.

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.

Seasonal Variations in Mortality, Clinical, and Laboratory Parameters in Hemodialysis Patients: A 5-Year Cohort Study

BACKGROUND AND OBJECTIVES Mortality varies seasonally in the general population, but it is unknown whether this phenomenon is also present in hemodialysis patients with known higher background mortality and emphasis on cardiovascular causes of death. This study aimed to assess seasonal variations in mortality, in relation to clinical and laboratory variables in a large cohort of chronic hemodialysis patients over a 5-year period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 15,056 patients of 51 Renal Research Institute clinics from six states of varying climates in the United States. Seasonal differences were assessed by chi-squared tests and univariate and multivariate cosinor analyses. RESULTS Mortality, both all-cause and cardiovascular, was significantly higher during winter compared with other seasons (14.2 deaths per 100 patient-years in winter, 13.1 in spring, 12.3 in autumn, and 11.9 in summer). The increase in mortality in winter was more pronounced in younger patients, as well as in whites and in men. Seasonal variations were similar across climatologically different regions. Seasonal variations were also observed in neutrophil/lymphocyte ratio and serum calcium, potassium, and platelet values. Differences in mortality disappeared when adjusted for seasonally variable clinical parameters. CONCLUSIONS In a large cohort of dialysis patients, significant seasonal variations in overall and cardiovascular mortality were observed, which were consistent over different climatic regions. Other physiologic and laboratory parameters were also seasonally different. Results showed that mortality differences were related to seasonality of physiologic and laboratory parameters. Seasonal variations should be taken into account when designing and interpreting longitudinal studies in dialysis patients.