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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 127 records · Page 7Linked to original sources
PubMed2000

Evaluation of clinical guidelines for the management of end-stage renal disease in europe: the EU BIOMED 1 study.

BACKGROUND: There are wide national and international variations in the management of patients with end-stage renal disease (ESRD). The aim of this study was to develop, harmonize, implement, and evaluate consensus-based clinical guidelines for the management of renal anaemia and renal bone disease in patients with ESRD, and for the prevention and management of cytomegalovirus disease in renal transplant recipients across six renal centres in Europe. METHODS: The trial was a prospective, multicentre, randomized balanced incomplete block design. Nephrologists from the six European renal units were randomized to develop and implement guidelines for two out of the three conditions and to act as a control for the third condition. Data were collected pre- (1 year) and post- (9 months) intervention on aspects of patient monitoring, management, and outcome. RESULTS: Eight hundred and twenty-nine dialysis patients from the six European dialysis centres were included in the study. Multivariate analysis (adjusting for case-mix and secular trends) showed a significant increase in the number of monitoring events in the guideline group compared with control group (6%, 95% CI, 1-11%). There was no concomitant increase in either appropriate management or the number of favourable patient outcomes. CONCLUSIONS: In the first European collaboration on renal guidelines, the introduction of the guidelines improved the monitoring of the patients, but did not improve patient management or outcome. This study suggests the potential for creating clinical guidelines with the aim of standardizing treatment protocols across international boundaries, and improving the quality of the medical care provided.

Adolescent↗
PubMed2000

Management of disturbed calcium metabolism in uraemic patients: 1. Use of vitamin D metabolites.

Chronic renal failure is characterized by diminished synthesis of, and resistance to, the active vitamin D metabolite 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3, calcitriol). Calcitriol results from the biotransformation of the precursor 25-hydroxy-vitamin D3 (25(OH)D3) to 1,25(OH)2D3. 25(OH)D3 is synthesized in the liver, and 1alpha-hydroxylase, the rate-limiting enzyme for its biotransformation into the most active metabolite, 1,25(OH)2D3, is located in the kidney. The regulation of 1alpha-hydroxylase in renal failure is not well known. Recent work indicates that, in contrast to previous opinion, 1alpha-hydroxylase is predominantly expressed not in the proximal tubule but in the distal tubule [1]. In vivo, the main stimulatory signal is presumably parathyroid hormone (PTH) and the main inhibitory signal hyperphosphataemia. Both signals are altered in renal failure. There is also evidence that the renal 1alpha-hydroxylase becomes substrate-dependent in patients with renal failure. This means that a higher concentration of the precursor 25(OH)2D3 will result in a higher rate of transformation into the active metabolite 1,25(OH)2D3 in renal patients. Calcitriol is not exclusively synthesized in the kidney, but may also be synthesized in extra-renal tissues, e.g. activated monocytes/macrophages [2], particularly in granuloma [3] as shown by anephric uraemic patients who develop hypercalcaemia and elevated calcitriol concentrations when sarcoidosis [4] or tuberculosis [5] supervenes. On the other hand, calcitriol is less effective in uraemia. This may be to some extent due to diminished expression of vitamin D receptors [6], particularly in parathyroid glands when they undergo nodular transformation [7], but there may also be resistance to calcitriol at the post-receptor level [8]. In a series of elegant experiments [9,10], calcitriol resistance has been related to disturbed genomic effects of active vitamin D because the interaction of the vitamin D receptor ligand complex with vitamin D-responsive elements (VDREs) upstream of vitamin D-regulated genes was disturbed by the action of low molecular weight substances in uraemia, which have not been completely characterized. The role of genetically determined polymorphisms of the vitamin D receptor in the genesis of disturbed calcium metabolism of renal failure is currently unclear.

Animals↗
PubMed2000

Early epoetin treatment in patients with renal insufficiency.

Historically, epoetin has been used to treat anaemia in patients already receiving renal replacement therapy. For many years, however, the results of early animal experiments raised considerable concern among nephrologists that disease progression would be accelerated if epoetin therapy were initiated in the predialysis phase of renal failure. In retrospect, it has become clear that the results of these early animal experiments were confounded by a concomitant and uncontrolled rise in blood pressure. In subsequent studies in rat models, antihypertensive treatment effectively prevented the adverse effect on disease progression. In addition, the results of several small observational studies and one large controlled study suggest that the glomerular filtration rate is not adversely affected in pre-dialysis patients treated with epoetin as long as blood pressure is well controlled. There are several observations, though not definitive, which suggest that disease progression may even be slower when anaemia is reversed. The benefits of early anaemia treatment with epoetin include increased exercise capacity and improved quality of life, cognitive function, and sexual function. Anaemia has also been identified as an important aetiological factor in the development of left ventricular hypertrophy. Whether pre-emptive treatment of anaemia is indicated in all pre-dialysis patients, or at least in those who develop progressive left ventricular hypertrophy, is currently under investigation.

Anemia↗
PubMed2000

Adult human mesangial cells (HMCs) express endothelin-B-receptors which mediate endothelin-1-induced cell growth.

Endothelin (ET) receptor antagonists are nephroprotective in renal damage models of the rat. It is unknown whether ET receptor antagonists are also beneficial in human renal diseases. Major differences exist between the ET systems in rats and humans, therefore this study was designed to characterize the ET receptors expressed on human adult mesangial cells (HMCs). HMCs cultures are a surrogate model for the development of glomerulosclerosis. Binding experiments with [125I]ET-1 in the presence or the absence of the test compounds [endothelin-1, -3 (ET-1, ET-3), sarafotoxin 6c (S6c), or BQ123] revealed an affinity (IC50 values) of 10.5 nm for ET-1 and 87.6 nm for ET-3. The affinities of the ET(B) agonist S6c and the ET(A) antagonist BQ123 were 85.9 nm and > 10 microm, respectively. Thus, the ET receptor on HMCs shows an ET(B)-like pharmacology, but in contrast to the classical ET(B)-receptor the affinities are low. No affinity for BQ123 up to > 10 microm excludes the presence of ET(A)-receptors. Functional studies using microfluorimetry (fura-2 method) showed comparable biphasic calcium signals induced by 10 nm ET-1, ET-3 and S6c. This effect could not be inhibited by BQ123, but by the ET(B) antagonist BQ788. Reverse transcriptase polymerase chain reaction (RT-PCR) studies under different culture conditions showed that both ET(A)- and ET(B)-receptor mRNAs are expressed in HMCs. The amount of ET(A)-receptor mRNA increased 2.7-fold and that of the ET(B)-receptor mRNA 7.1-fold after stimulation with 10% fetal calf serum (FCS). ET-1, ET-3 and S6c stimulated HMCs growth (ET-1 > S6c > ET-3), but the magnitude of the effect of ET-1 is lower than reported in rat mesangial cells (rat MCs). The effect on HMCs growth could be inhibited by BQ788, but not by BQ123. Our data provide evidence for the expression of ET(B)-receptors on HMCs that are functionally active. This finding differs from the ET receptor expression in rat MCs as reported by others.

Adult↗
PubMed2000

Smoking: a factor promoting onset and progression of diabetic nephropathy.

Although smoking was identified two decades ago as a factor promoting the onset and progression of nephropathy in Type 1 and then in Type 2 diabetes, its role has been largely neglected. More recently, it has been shown that smoking adversely affects renal haemodynamics and protein excretion even in subjects without renal disease. In addition, it impairs the prognosis for renal function in patients with non-diabetic renal disease. Recent studies have suggested the involvement of sympathetic activation, increased endothelin production, and impaired endothelial cell-dependent vasodilatation in the genesis of smoking-induced renal function impairement. Cessation of smoking apparently slows progression to renal failure, but the decision to stop smoking is difficult because of the high addictive potential of the habit. The challenge remains for diabetologists and nephrologists to motivate patients to stop smoking.

Diabetic Nephropathies↗
PubMed2000

The optimal target hemoglobin.

There is still controversy concerning the optimal target hemoglobin during treatment with recombinant human erythropoietin (rHuEPO). Some evidence suggests that hemoglobin concentrations higher than currently recommended lead to improvements in cognitive function, physical performance, and rehabilitation. At least in patients with advanced cardiac disease, however, one controlled trial failed to show a benefit from normalizing predialysis hemoglobin concentrations. In contrast, preliminary observations in three additional studies (albeit with limited statistical power) failed to show adverse cardiovascular effects from normalization of hemoglobin, but definite benefit with respect to quality of life, physical performance, and cardiac geometry. These observations are consistent with the notion that hemoglobin concentrations higher than those recommended by the National Kidney Foundation Dialysis Outcomes Quality Initiative Anemia Work Group are beneficial, at least in patients without advanced cardiac disease.

Anemia, Iron-Deficiency↗
PubMed1999

Differential regulation of transforming growth factor receptors by angiotensin II and transforming growth factor-beta1 in vascular smooth muscle.

Angiotensin II (Ang II) and transforming growth factor (TGF) beta1 play a role in vascular remodeling in hypertension. In this process they may interact on various levels, including that of receptor regulation. This consideration prompted the present study on transcriptional regulation of TGF-beta receptors by Ang II and TGF-beta in vascular smooth muscle cells. Transcriptional expression of the components of the TGF-beta system was demonstrated for TGF-beta and for TGF-beta receptors I, II, and III. As measured by quantitative reverse transcriptase polymerase chain reaction, TGF-beta mRNA increased about 2.4-fold in the presence of 40 pM exogenous TGF-beta. Ang II at 10(-6) M increased TGF-beta mRNA 2.5-fold compared to control cells (P<0.05). Ang II also significantly increased TGF-beta protein concentration in the supernatant of confluent vascular smooth muscle cells. Ang II caused the induction of TGF-beta, but short-term experiments showed TGF-beta receptor II mRNA to be differentially regulated by Ang II and TGF-beta; while TGF-beta caused a 40% decrease in TGF-beta receptor II mRNA after 4 h (P<0.05), Ang II caused an increase by about 70%. In contrast, both TGF-beta and Ang II increased TGF-beta receptor I mRNA to about 260% or 180% of controls (P<0.05). TGF-beta effects were abrogated by coincubation with a TGF-beta neutralizing antibody, and Ang II effects were abrogated by losartan, an AT-1 receptor antagonist. Coincubation of Ang II with the TGF-beta neutralizing antibody did not inhibit the effect of Ang II, indicating that the short-term effects of Ang II on the expression of the TGF-beta receptors are not mediated via TGF-beta. Furthermore, Ang II stimulated DNA synthesis even in the presence of the TGF-beta neutralizing antibody. In conclusion, this study indicates (a) that in vascular smooth muscle TGF-beta receptors are regulated on the RNA level by TGF-beta and Ang II, and (b) that Ang II dependent regulation of TGF-beta receptors is at least partially independent of endogenous TGF-beta. Stimulation of the transcriptional expression of TGF-beta receptors by Ang II may increase sensitivity of vascular smooth muscle cells to TGF-beta.

Angiotensin II↗