Showing papers by "Tilman B. Drüeke published in 2000"
TL;DR: Secondary hyperparathyroidism is a well known feature of chronic renal failure and is characterized by an increase in the synthesis and secretion of parathyroid hormone, mainly due to disturbances of calcium, phosphate, and vitamin D metabolism.
Abstract: Secondary hyperparathyroidism is a well known feature of chronic renal failure. It is characterized by an increase in the synthesis and secretion of parathyroid hormone (PTH), mainly due to disturbances of calcium, phosphate, and vitamin D metabolism. Our understanding of the mechanisms by which the
160 citations
TL;DR: HCl-oxLDL are as potent as Cu-ox LDL to induce high rates of apoptosis in monocytes through a caspase-dependent pathway and the resistance of differentiated THP-1 cells to oxLDL-induced apoptosis is compatible with the hypothesis that mature macrophages have prolonged survival and thereby enhance the atherogenic process.
51 citations
TL;DR: It is suggested that hyperparathyroidism is associated with a compensatory increase in apoptosis, possibly favored by a diminished Bcl-2/Bax ratio.
45 citations
TL;DR: Observations suggest that inactivating defects within the VDR gene do not commonly contribute to the primary pathogenesis of severe refractory hyperparathyroidism in uremia.
Abstract: Most chronic renal failure patients with severe refractory hyperparathyroidism harbor at least one monoclonal parathyroid tumor, but the specific acquired genetic defects that confer this clonal selective advantage remain poorly understood. Somatic inactivation of the vitamin D receptor (VDR) gene could contribute to clonal outgrowth, because a parathyroid cell containing this lesion would have an impaired response to the antiproliferative influence of 1,25-dihydroxyvitamin D3. Furthermore, diminished expression of VDR protein has been described in uremia-associated parathyroid tumors. Therefore, to assess VDR gene inactivation’s potential pathogenetic role in this disease, we rigorously analyzed the VDR gene in 59 parathyroid tumors surgically resected from uremic patients. First, Southern blotting and/or PCR analyses of 29 tumor samples from 14 genetically informative patients revealed no allelic losses at the VDR locus. Next, direct DNA sequencing of all VDR splice junctions, associated intronic sequen...
45 citations
TL;DR: Because of its relatively low sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx, but it is very useful in locating the remaining parathyroid gland in case of reoperation.
Abstract: Background. The place of parathyroid gland imaging by [ 99m Tc](technetium)-sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism remains a matter of debate. The purpose of the present study was (i) to assess its value with respect to plasma intact parathyroid hormone (iPTH) levels and to surgical parathyroidectomy (PTx), and (ii) to explore the possibility of suppressing parathyroid [ 99m Tc]-sestamibi uptake by calcitriol. Methods. In a first cross-sectional, static study 52 chronic haemodialysis (HD) patients with plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a [ 99m Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second longitudinal, dynamic study 14 chronic HD patients with advanced secondary hyperparathyroidism received short-term calcitriol treatment in an attempt to suppress [ 99m Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given intravenously for 2 weeks, 2 μg after each haemodialysis session. Scintigraphy was carried out before and at the end of this inhibition test. Results. [ 99m Tc]-Sestamibi scan led to imaging of one or more (maximum three) parathyroid glands in most, but not all, HD patients with plasma iPTH values > 600 pg/ml. Based on surgical findings, overall sensitivity of [ 99m Tc]-sestamibi scan in correctly locating parathyroid glands was only 50%, whereas specificity was 100%. In contrast, its sensitivity was 100% in locating single glands in the subgroup of five patients with recurrent hyperparathyroidism. The calcitriol inhibition test showed suppression of [ 99m Tc]-sestamibi uptake by at least one parathyroid gland in eight patients (57%), with complete suppression in five of them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to calcitriol was not predictive of suppressible [ 99m Tc]-sestamibi uptake in the individual case, although mean iPTH was markedly higher in patients with non-suppressible parathyroid glands. Conclusion. Because of its relatively low sensitivity the [ 99m Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx. However, it is very useful in locating the remaining parathyroid gland(s) in case of reoperation. The novel calcitriol inhibition test of [ 99m Tc]-sestamibi uptake could help to better distinguish parathyroid glands with non-suppressible, autonomous activity from glands whose activity might be amenable to long-term suppression.
39 citations
TL;DR: A review of the value and the limitations of serum markers of bone formation and resorption in the diagnosis of the major types of renal osteodystrophy considers the hypothetical role of serum beta2-microglobulin and of some local mediators involved in the process of bone cell activation and inhibition.
36 citations
TL;DR: Patients continue to enter dialysis with a considerable cardiovascular burden, many having already suffered a stroke or myocardial infarction, and early corrective treatment may help to reduce the incidence of CVD and hence improve long-term outcome.
Abstract: Background: Cardiovascular disease (CVD) is a major cause of death in patients with chronic renal failure (CRF). It is well recognised that dialysis patients have a high burden of factors that predispose to CVD. What is less clear is the extent of this problem in the pre-dialysis patient. This is the subject of this review. Methods: The role of potentially correctable cardiovascular risk factors in pre-dialysis patients has been examined using published data. Results: Anaemia is a major cardiovascular risk factor in patients with CRF. Partial correction of renal anaemia with recombinant human erythropoietin leads to improvements in cardiac dysfunction in such patients, such as alleviation of left ventricular hypertrophy. Secondly, malnutrition and inflammation have also been recently identified as potentially correctable cardiovascular risk factors in these patients. Conclusions: Patients continue to enter dialysis with a considerable cardiovascular burden, many having already suffered a stroke or myocardial infarction. Many risk factors, including malnutrition and inflammation, account for the increased incidence of cardiovascular events. Anaemia is common in pre-dialysis patients, and early corrective treatment may help to reduce the incidence of CVD and hence improve long-term outcome.
32 citations
TL;DR: Subtotal parathyroidectomy provides the best conditions for successful reoperation in case of recurrent hyperparathyroidism and should become the surgical treatment of choice for secondary hyperparathiroidism.
31 citations
TL;DR: It is hypothesized that the characteristic deficit of T cell function and of cytokine and growth factor production may protect nude mice with chronic hypersecretion of human PTH from hypercalcemia and bone lesions and could be used for better understanding the relationship between cytokines and bone turnover.
Abstract: In athymic mice we have developed a model of long-term human PTH hypersecretion, using xenotransplantation of respectively parathyroid gland fragments obtained from patients with primary (1°) or secondary (2°) uremic hyperparathyroidism (HPT), and parathyroid cells maintained in culture from patients with 2° uremic HPT. Both grafted parathyroid tissue fragments and cultured cells induced prolonged and marked secretion of human intact PTH (iPTH) in nude mice. Despite extremely high plasma iPTH levels, hypercalcemia or hypophosphatemia was not observed. Moreover, PTH secretion was not significantly modified by low-calcium, high-phosphate diet for 3 weeks. Four mice which had a mean plasma human iPTH level of 237±152 pg/ml for more than 9 months and 4 age-matched, sham-grafted control mice with undetectable human iPTH levels underwent bone histomorphometry examination. No difference was found between the two groups with respect to active bone resorption surface or number of osteoclasts/ mm2. We hypothesize that the characteristic deficit of T cell function and of cytokine and growth factor production may protect nude mice with chronic hypersecretion of human PTH from hypercalcemia and bone lesions. We suggest that this strain of mice could be used for better understanding the relationship between cytokines and bone turnover.
23 citations
TL;DR: Although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events.
Abstract: Background.Renal transplant recipients have an increased incidence of cardiovascular disease, but less data exist about cerebrovascular atherosclerosis. In this study, we assessed the prevalence of carotid lesions as evaluated by B-mode ultrasonography in a group of renal transplant recipients, and
22 citations
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