Biomedical subjects

Jürgen Bommer

Publications and source records attributed to Jürgen Bommer.

12 recordsLinked to original sources

PubMed2005

Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl.

BACKGROUND: Patients with secondary hyperparathyroidism often require therapy that provides long-term control of parathyroid hormone concentrations without increasing calcium and phosphorus concentrations. Cinacalcet modulates the calcium-sensing receptor on the parathyroid gland to reduce secretion of parathyroid hormone and lower serum calcium, phosphorus and calcium-phosphorus product in haemodialysis patients. METHODS: Dialysis patients with secondary hyperparathyroidism [parathyroid hormone (PTH) level > or =300 pg/ml] who were enrolled in one of four phase 2 placebo-controlled studies were eligible to enroll in an open-label extension study in which all patients received cinacalcet. For this extension study, cinacalcet was initiated at 30 mg in all patients and the dose was escalated to a maximum of 180 mg once daily if PTH concentrations were >250 pg/ml. Use of concomitant vitamin D sterols and phosphate binders was not restricted. RESULTS: The analysis of all patients (n = 59) completing 100 weeks of cinacalcet treatment showed long-term control of PTH and calcium-phosphorus product. Approximately 55% achieved a PTH concentration < or =300 pg/ml at the week-100 study visit, and approximately 60% had at least a 30% reduction in PTH from baseline. Serum calcium, phosphorus and the calcium-phosphorus product did not increase during the study. Concomitant vitamin D sterol and phosphate binder therapy remained stable. Cinacalcet was safe and generally well tolerated at doses up to 180 mg/day. CONCLUSIONS: In this long-term study, cinacalcet effectively sustained reductions in PTH for up to 3 years without increasing concentrations of serum calcium, phosphorus or calcium-phosphorus product.

Adult↗

PubMed2005

Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density.

BACKGROUND: Calcium-based phosphate binders may induce tissue calcification, and little is known about their effects on bone density. We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography. METHODS: Seventy-two adult haemodialysis patients were randomized to treatment with calcium carbonate (CC) or sevelamer (SEV) for 2 years. Electron beam CT scans were performed at baseline and at 6, 12 and 24 months. Serum phosphorus, calcium, calcium x phosphorus product and intact parathyroid hormone (iPTH) were measured and other routine laboratory tests were also carried out. RESULTS: The average calcium x phosphorus product was similar in the two treatment groups. However, patients receiving CC had significantly lower average iPTH (P<0.01), were more likely to have hypercalcaemic episodes (P = 0.03) and had significantly greater increases in coronary artery (CC median 484, P<0.0001, SEV median 37, P = 0.3118, between-group P = 0.0178) and aortic (CC median 610, P = 0.0003, SEV median 0, P = 0.5966, between-group P = 0.0039) calcification scores. The CC group also had a significant decrease in trabecular bone density (CC median -6%, P = 0.0049, SEV median +3%, P = 0.0296, between-group P = 0.0025). However, there was no significant difference in cortical bone density between the two groups. CONCLUSIONS: This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients. In addition, it suggests that it is also associated with decreased trabecular bone density. However, this latter finding requires confirmation by a study specifically devoted to this issue.

Adult↗

PubMed2005

Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. METHODS: This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N= 307) and patients (N= 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001. RESULTS: Many patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P= 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg(2)/dL(2), P= 0.0001), PTH (1.01 per 100 pg/dL, P= 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P= 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P= 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P= 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration. CONCLUSION: This study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area.

Calcium↗

PubMed2004

Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis.

UNLABELLED: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.

Aged↗

PubMed2004

Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.

BACKGROUND: Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEpo), darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo. This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia. METHODS: In this multicentre, prospective, open-label study, 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [intravenous (i.v.), n = 900 or subcutaneous (s.c.), n = 602]. Subjects receiving rHuEpo two (n = 408, 27%) or three times (n = 884, 59%) a week were switched to darbepoetin alfa once a week, and those receiving rHuEpo once a week (n = 210, 14%) were switched to darbepoetin alfa once every 2 weeks. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations of 10-13 g/dl for 24 weeks. RESULTS: Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks. The overall mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was +0.10 g/dl [95% confidence interval (CI) 0.04+/- 0.17]. The mean haemoglobin concentration increased by 0.19 g/dl (95% CI 0.11+/-0.27) in subjects receiving i.v. darbepoetin alfa, and was unchanged (-0.02 g/dl; 95% CI -0.12 to 0.07) in patients treated with s.c. darbepoetin alfa. Subjects with baseline haemoglobin < 11 g/dl experienced a clinically relevant increase in mean haemoglobin concentration of 0.67 g/dl (95% CI 0.56+/-0.77) from baseline to the evaluation period. The mean weekly i.v. and s.c. darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week (95% CI 19.02+/-20.87) and 21.6 microg/week (95% CI 20.36+/- 22.94), respectively. Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects. CONCLUSIONS: Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated. Moreover, administration of darbepoetin alfa by both the i.v. and s.c. route is associated with stable haemoglobin concentrations.

Adult↗

PubMed2004

Health-related quality of life in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Health-related quality of life (HRQOL), a validated system of measuring patients' physical, mental, and social well-being, can be of particular use in populations with chronic conditions, such as end-stage renal disease (ESRD). METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS) has used the Kidney Disease Quality of Life Short Form (KDQOL-SF) to measure ESRD patients' self-assessment of functioning and well-being, as measured by 3 component scores: physical component summary (PCS, 4 subscales), mental component summary (4 subscales), and kidney disease component summary (11 subscales). Several DOPPS studies examined HRQOL's associations with mortality and hospitalization by country, ethnicity (United States only), and in comparison with serum albumin levels; international variations in HRQOL of ESRD patients were also evaluated. RESULTS: Lower scores for all 3 summary scores were strongly associated with higher risk of death and hospitalization; these measures, especially PCS, may better identify patients at risk for death and hospitalization than serum albumin level. Japanese patients reported a greater burden of kidney disease but higher physical functioning than patients in Europe or the United States; many other significant regional differences in HRQOL were found. In the United States, all summary scores were significantly associated with mortality risk, regardless of ethnicity. Compared with whites, blacks had higher scores for all 3 summary scores, Asians and Hispanics had higher PCS scores, and Native Americans had lower mental component summary scores. CONCLUSION: Among ESRD patients, HRQOL displays an important predictive power for adverse events. Identifying effective interventions to improve the HRQOL of patients with ESRD should be viewed as a valued health care goal.

Humans↗

PubMed2004

Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Experimental and some clinical data suggest that metabolic acidosis contributes to poor nutritional status, a strong predictor for mortality in hemodialysis patients. However, recent cross-sectional studies indicate that severe predialysis metabolic acidosis is associated with a greater normalized protein catabolic rate (nPCR) and greater serum albumin levels. Given this controversy, we analyzed data from the Dialysis Outcomes and Practice Pattern Study (DOPPS) for associations between predialysis serum bicarbonate and albumin concentrations, nPCR, and patient risk for mortality and hospitalization. METHODS: Data from more than 7,000 representative and randomly selected hemodialysis DOPPS patients from France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States were analyzed. Serum bicarbonate (total CO2 ) levels predialysis were corrected to the midweek interdialytic interval. RESULTS: The midweek predialysis serum bicarbonate level averaged 21.9 mEq/L (mmol/L) and correlated inversely with nPCR, serum albumin, and serum phosphorus values. Before and after adjusting for 15 comorbidities, nutrition, and equilibrated Kt/V, a U-curve best represented the association between predialysis serum bicarbonate level and risk for mortality or hospitalization. Patients with midweek predialysis serum bicarbonate levels of 20.1 to 21.0 mEq/L (mmol/L) faced the lowest risk for mortality, whereas those with bicarbonate levels of 21.1 to 22.0 mEq/L faced the lowest risk for hospitalization. Both high (>27 mEq/L) and low (< or =17 mEq/L) serum bicarbonate levels were associated with increased risk for mortality and hospitalization. CONCLUSION: Moderate predialysis acidosis seems to be associated with better nutritional status and lower relative risk for mortality or hospitalization than is observed in patients with normal ranges of midweek predialysis serum bicarbonate concentration (approximately 24 mEq/L) or severe acidosis (<16 mEq/L).

Acidosis↗

PubMed2003

Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: We investigated whether indicators of health-related quality of life (HRQOL) may predict the risk of death and hospitalization among hemodialysis patients treated in seven countries, taking into account serum albumin concentration and several other risk factors for death and hospitalization. We also compared HRQOL measures with serum albumin regarding their power to predict outcomes. METHODS: We analyzed data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international, prospective, observational study of randomly selected hemodialysis patients in the United States (148 facilities), five European countries (101 facilities), and Japan (65 facilities). The total sample size was composed of 17,236 patients. Using the Kidney Disease Quality of Life Short Form (KDQOL-SFTM), we determined scores for three components of HRQOL: (1) physical component summary (PCS), (2) mental component summary (MCS), and (3) kidney disease component summary (KDCS). Complete responses on HRQOL measures were obtained from 10,030 patients. Cox models were used to assess associations between HRQOL and the risk of death and hospitalization, adjusted for multiple sociodemographic variables, comorbidities, and laboratory factors. RESULTS: For patients in the lowest quintile of PCS, the adjusted risk (RR) of death was 93% higher (RR = 1.93, P < 0.001) and the risk of hospitalization was 56% higher (RR = 1.56, P < 0.001) than it was for patients in the highest quintile level. The adjusted relative risk values of mortality per 10-point lower HRQOL score were 1.13 for MCS, 1.25 for PCS, and 1.11 for KDCS. The corresponding adjusted values for RR for first hospitalization were 1.06 for MCS, 1.15 for PCS, and 1.07 for KDCS. Each RR differed significantly from 1 (P < 0.001). For 1 g/dL lower serum albumin concentration, the RR of death adjusted for PCS, MCS, and KDCS and the other covariates was 1.17 (P < 0.01). Albumin was not significantly associated with hospitalization (RR = 1.03, P> 0.5). CONCLUSION: Lower scores for the three major components of HRQOL were strongly associated with higher risk of death and hospitalization in hemodialysis patients, independent of a series of demographic and comorbid factors. A 10-point lower PCS score was associated with higher elevation in the adjusted mortality risk, as was a 1 g/dL lower serum albumin level. More research is needed to assess whether interventions to improve quality of life lower these risks among hemodialysis patients.

Aged↗

PubMed2003

Health-related quality of life among dialysis patients on three continents: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Assessing health-related quality of life (HRQOL) can provide information on the types and degrees of burdens that afflict patients with chronic medical conditions, including end-stage renal disease (ESRD). Several studies have shown important international differences among ESRD patients treated with hemodialysis, but no studies have compared these patients' HRQOL. Our goal was to document international differences in HRQOL among dialysis patients and to identify possible explanations of those differences. METHODS: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational, international study of hemodialysis patients. We performed a cross-sectional analysis of DOPPS data from the United States, five countries in Europe (France, Germany, Italy, Spain, and the United Kingdom), and Japan. Linear mixed models were used to analyze differences in HRQOL, using the KDQOL-SFTM. Norm-based scores were used to minimize cultural response bias. Linear regression analysis was used to adjust for confounding factors. Other variables included demographic variables, comorbidities, primary cause of ESRD, complications of ESRD and treatment, and socioeconomic status. RESULTS: In all generic HRQOL subscales, patients on all three continents had much lower scores than their respective population norm values. Patients in the United States had the highest scores on the mental health subscale and the highest mental component summary scores. Japanese patients reported better physical functioning than did patients in the United States or Europe, but they also reported the greatest burden of kidney disease. Overall, these differences remained even after adjusting for possible confounders. CONCLUSION: On all three continents, ESRD and hemodialysis profoundly affect HRQOL. In the United States, the effects on mental health are smaller than in other countries. Japanese hemodialysis patients perceived that their kidney disease imposes a greater burden, but their physical functioning was significantly higher. Different distributions of socioeconomic factors and major comorbid conditions could explain little of this difference in physical functioning. Other possible factors, such as quality of dialysis and related health care, deserve careful study.

Cost of Illness↗

PubMed2002

Bedside testing with the new CoaguChek Pro activated clotting time assay in dialysis.

The objective of this study was to assess the analytical performance of CoaguChek Pro activated clotting time (ACT) assay using 2 lots versus Hemochron Celite and glass ACT regarding ACT values and correlations versus heparin levels. Determinations were performed using 4 CoaguChek Pro meters and 1 Hemochron 801 meter. Samples were collected during hemodialysis before, after start of heparinization, and 2 h later. Agreement between CoaguChek Pro ACT and Hemochron Celite was good (r = 0.82, slope = 1.12) and moderate with Hemochron glass (r = 0.83, slope = 0.97). Agreement between both CoaguChek Pro lots was r = 0.98. Agreement between the activators, Hemochron Celite, and glass was r = 0.73. Correlation between CoaguChek Pro ACT and heparin concentration was r = 0.88 and 0.94; for Hemochron the correlation was r = 0.75 (Celite) and r = 0.73 (glass). CoaguChek Pro ACT is therefore suitable for monitoring heparin administration during dialysis.

Humans↗

PubMed2002

Pharmacokinetics of 5-fluorouracil and its catabolites determined by 19F nuclear magnetic resonance spectroscopy for a patient on chronic hemodialysis.

5-fluorouracil (5-FU), widely used for chemotherapy of colorectal carcinoma, requires intracellular anabolic conversion to cytotoxic nucleotides and exhibits a narrow therapeutic range with dose-dependent and concentration-dependent effects. 5-FU undergoes extensive metabolic degradation to several catabolites, which are excreted mainly by the kidneys. Alteration of the pharmacokinetics of 5-FU and its catabolites as a result of renal dysfunction might augment systemic toxicity. Because no data are available for patients with severe renal failure, the pharmacokinetic parameters of 5-FU and its catabolites were determined for a patient with colorectal carcinoma and end-stage renal disease on maintenance hemodialysis therapy. Plasma was analyzed by 19F nuclear magnetic resonance spectroscopy for the first 5-day treatment cycle (daily bolus injections of 5-FU for 5 days in combination with low-dose folinic acid). On days 1 and 5, the pharmacokinetic parameters for 5-FU (total area under the plasma concentration-time curve, terminal half-life, total plasma clearance, volume of distribution based on the terminal phase) and its initial catabolite dihydrofluorouracil (total area under the plasma concentration-time curve, terminal half-life) were in the ranges reported in the literature for patients with normal renal function, implying no need for primary dose adjustment. In contrast, the final 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) accumulated to a concentration of 276 micromol/L on day 5 (approximately twofold higher than expected from the literature) despite good removal by hemodialysis with extraction ratios of 0.6 to 0.85 over the filter membrane. Negative effects of FBAL or enhancement of 5-FU-related toxicity could not be judged in this individual case, but further study is warranted to determine the possible benefits of more intensive dialysis treatment.

Adenocarcinoma↗

PubMed2002

Prevalence and socio-economic aspects of chronic kidney disease.

The incidence and prevalence of end-stage renal disease (ESRD) are rising in Europe, the USA, and Japan. Prevalence is rising more steeply than incidence, due mostly to improved efficiency of treatment -patients are surviving longer. Hypertension and diabetes, the main causes of progression from chronic kidney disease (CKD) to ESRD, are becoming more frequent in the general population and make a large contribution to the rising incidence of ESRD. More effective therapies for other conditions have introduced new complications for patients with CKD, thereby also increasing the incidence of ESRD. Increased survival in the general population is reflected in the greater number of elderly people requiring care for ESRD. ESRD is a great economic burden and one that will increase as the incidence and prevalence of the disease increase. This needs to be considered when planning treatment. Prevention and early treatment of hypertension and diabetes will have the greatest impact on the future prevalence of ESRD and the costs associated with its treatment.

Chronic Disease↗