Christian Tielemans

Use of phosphate-binding agents is associated with a lower risk of mortality

Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

COSMOS: the dialysis scenario of CKD–MBD in Europe

BACKGROUND Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. METHODS COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. RESULTS The haemodialysis population in Europe is an aged population (mean age 64.8±14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3±14.3 versus 66.0±13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. CONCLUSIONS The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

Twenty-four-Hour Blood Pressure and Heart Rate Patterns in Chronic Hemodialysis Patients

To test the assumption that the previously reported abnormal 24-hour blood pressure (BP) variations in hemodialysis (HD) patients might be due to associated complications of chronic renal failure, we recorded the 24-hour noninvasive BP and heart rate (HR) patterns in 14 carefully selected chronic HD patients. No of the patients suffered from orthostatic hypotension, and all were free of any previously reported associated condition known to affect the 24-hour BP profiles. The BP and HR profiles were quantitatively analyzed using the periodogram method. The results were compared those from 14 controls matched for age, sex, and casual BP. No difference could be found between the HD patients and the controls, either in the absolute and relative amplitudes of the 24-hour systolic BP and diastolic BP variations or in the timings and levels of their respective acrophases and nadirs (except for the timings of the second systolic BP and diastolic BP acrophases; P < 0.05). The absolute levels of the HR acrophases and nadirs were higher in the HD patients than in the controls (P < 0.05 and P < 0.01, respectively), while both the absolute and relative amplitudes of the 24-hour HR profiles and the relative values and timings of the HR acrophases and nadirs were similar in both groups. Consequently, the 24-hour HR pattern was similar in the HD patients than in the controls, except that the entire profile was shifted upward.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid, enhanced, and persistent protection of patients with renal insufficiency by AS02V-adjuvanted hepatitis B vaccine

The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02 with that of HB-AS04. In this phase III, open, randomized study, 151 hepatitis B vaccine-naïve pre-dialysis, peritoneal dialysis, and hemodialysis patients aged 15 years and older received three doses of HB-AS02 at 0, 1, and 6 months. Another 149 similar patients received four doses of HB-AS04 at 0, 1, 2, and 6 months, and all were followed up for 12 months. HB-AS02 elicited more rapid and persistent seroprotection than HB-AS04, with rates of 77 and 39%, respectively, 1 month after the second vaccine dose, and 94 and 79%, respectively, at 12 months. Superiority of HB-AS02 over HB-AS04 in anti-hepatitis B geometric mean concentrations was found at all time points. HB-AS02 was more reactogenic than HB-AS04, but adverse events were mainly transient, of mild to moderate intensity with no reportable vaccine-related serious events. We conclude that a three-dose primary course of HB-AS02 induced more rapid, enhanced, and persistent protection in patients with renal insufficiency than the licensed four-dose primary schedule of HB-AS04. This adjuvanted vaccine affords greater protection with reduced need for booster doses in patients at high risk of hepatitis B infection.

Influence of Body Mass Index on the Association of Weight Changes with Mortality in Hemodialysis Patients

BACKGROUND AND OBJECTIVES A high body mass index (BMI) is associated with lower mortality in patients undergoing hemodialysis. Short-term weight gains and losses are also related to lower and higher mortality risk, respectively. The implications of weight gain or loss may, however, differ between obese individuals and their nonobese counterparts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Current Management of Secondary Hyperparathyroidism: A Multicenter Observational Study (COSMOS) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007, with prospective data collection every 6 months for 3 years. Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality. Analyses were performed after patient stratification according to their starting BMI. RESULTS Among 6296 patients with complete data, 1643 died. At study entry, 42% of patients had a normal weight (BMI, 20-25 kg/m(2)), 11% were underweight, 31% were overweight, and 16% were obese (BMI ≥ 30 kg/m(2)). Weight loss or gain (<1% or >1% of body weight) was strongly associated with higher rates of mortality or survival, respectively. After stratification by BMI categories, this was true in nonobese categories and especially in underweight patients. In obese patients, however, the association between weight loss and mortality was attenuated (hazard ratio, 1.28 [95% confidence interval (CI), 0.74 to 2.14]), and no survival benefit of gaining weight was seen (hazard ratio, 0.98 [95% CI, 0.59 to 1.62]). CONCLUSIONS Assuming that these weight changes were unintentional, our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients. In addition, a patients BMI modifies the strength of the association between weight changes with mortality.

Effect of aluminum on porphyrin metabolism in hemodialyzed patients.

In patients with renal failure and on chronic hemodialysis, serum aluminum, serum delta-aminolevulinic acid, serum porphobilinogen and erythrocyte zinc protoporphyrin (ZPP) are significantly elevated, whereas erythrocyte delta-aminolevulinic acid dehydratase activity (ALAD, values in percent) is significantly reduced. The last two parameters (ZPP and ALAD) are statistically related to serum aluminum concentration (Al-S), but only the correlation between Al-S and ALAD remains statistically significant after standardization for the degree of renal insufficiency (expressed in terms of urea level). This study does not support the hypothesis that the retention of aluminum is responsible for the increase of ZPP in uremic patients on dialysis. The disturbances of porphyrin metabolism found in patients with renal failure and on chronic dialysis are not similar to those observed in porphyria cutanea tarda.

Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes

Background: Dialysis with complement-activating membranes is associated with leukopenia, which is related to an increased expression of adhesion molecules on leukocytes. Citrate chelates calcium and has been claimed to attenuate leukopenia. Methods: In this study, the effects of citrate anticoagulation on leukocyte and granulocyte counts, complement activation, and the expression of CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during hemodialysis with unmodified cellulose membranes. Standard heparin was compared to citrate in three different schedules: citrate was infused to obtain a concentration of either 7 or 10 mmol/l blood. CaCl2 was administered into the dialyzer outlet at 8.25 mmol Ca2+/h (citrate 10 mmol/l) or at 11 mmol Ca2+/h (citrate 7 and 10 mmol/l) to restitute the calcium levels in the blood returning to the patient. Results: The use of citrate at a high concentration (10 mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet and at the outlet bloodline; for CD11c a reduced upregulation was observed on granulocytes harvested from the inlet bloodline. No effects of citrate were observed on leukopenia, granulocytopenia, or complement activation. A positive correlation between the decrease in systemic ionized Ca2+ concentration and the increase in CD11b and CD11c expression was found. Conclusion: Citrate/CaCl2 administration affects leukocyte adhesion molecule expression in a dose-dependent way; however, no significant effect could be demonstrated on leukopenia and complement activation.

Continuous hemofiltration in severe sepsis: Is it beneficial?

S INCE ITS introduction by Kramer et al in 1977,29 continuous hemofiltration has seen a large development in the management of critically ill patients. I9 The primary advantage of this technique is to provide a smooth and continuous control of the volume status while avoiding the cardiovascular instability associated with intermittent hemodialysis.‘” Continuous blood purification techniques may facilitate the administration of high amounts of fluids required for parenteral nutrition or administration of blood products. These techniques may be more easily manageable than peritoneal dialysis, which is contraindicated in patients with previous abdominal procedures. Another practical issue is that hemofiltration techniques have allowed smaller community-based intensive care units to have access to renal support techniques, thus avoiding a routine transfer of patients with renal failure to a larger center with hemodialysis facilities. A further potential benefit of these continuous techniques is to remove a number of proinflammatory mediators that may be involved in the development of multiple organ failure. However, it should be borne in mind that hemofiltration could clear a large number of molecules from the circulation including mediators with more protective effects. Although it has been suggested that hemofiltration may have some beneficial effects in septic patients, data from experimental and clinical studies have been inconsistent and sometimes contradictory. Part of these discrepancies may be related to the wide variation in the technical conditions (type of technique, nature of the membrane, ultrafiltration rate, etc.). This article summarizes the data available today on the use of continuous hemofiltration techniques in severe sepsis (Table 1).

Immunogenicity and safety of an investigational AS02v-adjuvanted hepatitis B vaccine in patients with renal insufficiency who failed to respond or to maintain antibody levels after prior vaccination: results of two open, randomized, comparative trials

An investigational AS02(v)-adjuvanted hepatitis B (HB-AS02) was compared with a licensed conventional recombinant hepatitis B vaccine (HBVAXPRO™; Sanofi Pasteur MSD, Lyon, France) in pre-dialysis, peritoneal dialysis and hemodialysis patients aged ≥18 years who had failed either to respond to prior vaccination with a conventional hepatitis B vaccine (Study A; n=251) or to maintain protective antibody concentrations after prior hepatitis B vaccination (Study B; n=181). These were open, randomized, comparative trials. Mean (range) age was 65.9 (31-92) and 64.6 (29-92) years in the two studies, respectively. In Study A, two doses of HB-AS02 given one month apart were found to be superior to two doses of the licensed vaccine in terms of seroprotection rate (76.9% versus 37.6%) and anti-HBs geometric mean antibody concentration (GMC; 139.3 versus 6.9mIU/ml), with antibody concentrations ≥100mIU/ml in 61.1% and 15.4% of subjects in the two groups, respectively. In Study B, one month after administration of a single booster dose, seroprotection rates were 89.0% in the HB-AS02 group and 90.8% in the licensed vaccine group, 81.3% and 60.9% of subjects had antibody concentrations ≥100mIU/ml, and anti-HBs GMCs were 1726.8 and 189.5mIU/ml. HB-AS02 was found to be more reactogenic than the licensed vaccine. In summary, the investigational HB-AS02 vaccine induced higher seroprotection rates and anti-HBs GMCs than a licensed conventional hepatitis B vaccine in uremic patients who had failed to respond or to maintain protective antibody titers after prior hepatitis B vaccination.

Evaluation of surgical treatment of renal hyperparathyroidism by measuring intact parathormone blood levels on first postoperative day

Abstract. Intact parathormone (inPTH) has a short half-life. Its blood level on the first day after total parathyroidectomy and subcutaneous parathyroid implantation (PTX + G) should therefore allow an early diagnosis of missed residual parathyroid tissue. We tested this hypothesis in 72 uremic patients who were followed for 6 to 110 months after operation. Nine were reoperated for recurrence of the disease. Graft removal was successful in four patients who had post-PTX inPTH levels of 16 pg/ml or lower. In five patients, an overlooked parathyroid gland had to be resected. All of them had elevated post-PTX inPTH blood levels ranging from 72 to 791 pg/ml (upper normal limit 55 pg/ml). Three of these patients had presented with hypocalcemia after PTX. We conclude that the inPTH blood concentration on the first day after PTX allows more precise evaluation of the efficacy of the surgical procedure than the postoperative evolution of blood calcium levels. It is also useful for localizing the source of excessive PTH secretion (graft or overlooked gland) when the disease recurs.