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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 91 records · Page 5Linked to original sources
PubMed2000

Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure.

BACKGROUND: An excessive rate of cardiac death is a well-known feature of renal failure. Coronary heart disease is frequent and the possibility has been raised that the natural history of the coronary plaque is different in uraemic patients. We assessed the morphology of coronary arteries in patients with end-stage renal failure and compared them with coronary arteries of matched non-uraemic control patients. METHODS: Fifty-four cases were identified at autopsy who met the inclusion criteria: cases, end-stage renal disease (n=27); controls, non-renal patients with coronary artery disease (n=27). At autopsy all three coronary arteries were prepared at corresponding sites for investigations: (i) qualitative analysis (after Stary), (ii) quantitative measurements of intima and media thickness (by planimetry), (iii) immunohistochemical analysis of the coronary plaques and (iv) X-ray diffraction of selected calcified plaques. RESULTS: Qualitative analysis of the coronary arteries showed significantly more calcified plaques of coronary arteries in patients with end-stage renal failure. Plaques of non-uraemic patients were mostly fibroatheromatous. Media thickness of coronary arteries was significantly higher in uraemic patients (187+/-53 microm vs 135+/-29 microm in controls) and intima thickness tended to be higher (158+/-38 microm vs 142+/-31 microm) but this difference was not statistically significant. Plaque area (4.09+/-1. 50 mm(2) vs 4.39+/-0.88 mm(2)) was comparable in both groups. Lumen area, however, was significantly lower in end-stage renal patients. Immunohistochemical analysis of the cellular infiltrate in coronary arteries showed no major differences in these advanced plaques of uraemic and non-uraemic subjects. CONCLUSION: Coronary plaques in patients with end-stage renal failure are characterized by increased media thickness and marked calcification. In contrast to the previous opinion the most marked difference compared to non-uraemic controls does not concern the size, but the composition of the plaque. Deposition of calcium within the plaques may contribute to the high complication rate in uraemic patients.

Aged↗
PubMed2000

The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. For the Collaborative Study Group.

BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal disease in the developed world. Angiotensin-converting enzyme inhibitors have been demonstrated to be renoprotective in type I diabetes and are now the standard of care for both hypertensive and non-hypertensive type I diabetic patients with any level of proteinuria. The role of blockade of the renin-angiotensin system in type II diabetic patients is not defined. The Collaborative Study Group has initiated the Irbesartan Type II Diabetic Nephropathy Trial (IDNT), studying the effect of the angiotensin II receptor antagonist irbesartan on progression of renal disease and mortality in type II diabetic patients with overt nephropathy and hypertension. Here we report the study design and baseline patient characteristics. METHODS: To qualify, hypertensive type II patients, age 30-70 years, must have a 24 h urinary protein excretion of >900 mg and a serum creatinine 90-265 micromol/l (1.0-3. 0 mg/dl) in women and 110-265 micromol/l (1.2-3.0 mg/dl) in men. Three treatment arms include irbesartan, placebo and amlodipine, with every attempt made to achieve similar blood pressure levels in all treatment arms. A total of 1650 patients will be enrolled utilizing approximately 225 clinics worldwide. The primary outcome measure is time to event to the composite end-point of doubling of serum creatinine, end-stage renal disease or death. The secondary outcome measure is time to composite end-point of fatal or non-fatal cardiovascular events. The average length of patient follow-up is expected to be approximately 36 months. RESULTS: The baseline characteristics of the study subjects are: age 59+/-8 years, duration of diabetes 15+/-9 years, height 168+/-11 cm (5 ft 6 in), weight 87+/-19 kg (192 lb), body mass index 31+/-7 kg/m(2), blood pressure 156+/-18 mmHg/85+/-11 mmHg, serum creatinine 150+/-53 micromol/l (1.7+/-0.6 mg/dl), creatinine clearance 66+/-34 ml/min and 24 h urine protein 4.0+/-3.5 g/day.

Adult↗
PubMed2000

G(-699)/C polymorphism in the bradykinin-1 receptor gene in patients with renal failure.

BACKGROUND: Bradykinin is thought to have protective effects on the progression of renal failure. Of particular interest, it has been reported that one polymorphism in the promoter region of the human kinin B1-receptor gene which is associated with higher activity, is less frequently found in patients with end-stage renal failure. The present study was performed to independently confirm these results. DESIGN: Cross-sectional study on 376 healthy controls, 262 non-diabetic dialysis patients and 175 patients with type 1 diabetes >/=10 years and microalbuminuria (of whom 21 were dialysis-dependent) and 334 patients with type 2 diabetes >/=10 years and nephropathy (of whom 61 were dialysis-dependent). METHODS: Genotyping was performed by polymerase chain reaction, followed by restriction enzyme analysis. RESULTS: All groups were in Hardy Weinberg equilibrium. The study showed no significant difference in the frequency of the C-allele between controls (0.093) and non-diabetic dialysis patients (0.095). No significant difference in C-allele frequency was observed between controls and patients with type 1 diabetes and microalbuminuria (0.092) or patients with type 2 diabetes and nephropathy (0.099). CONCLUSION: In large cohorts of patients with non-diabetic end-stage renal disease and diabetic renal disease with and without end-stage renal failure, no change in the frequency of the C-699 allele of the B-1-receptor gene was found.

Adult↗
PubMed2000

Glial cell line-derived neurotrophic factor (GDNF) is expressed in the human kidney and is a growth factor for human mesangial cells.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent neurotrophic factor in vitro and in vivo. GDNF is essential for nephrogenesis and the highest expression of GDNF is found in the developing kidney. Increased plasma GDNF levels have recently been documented in patients with chronic renal failure; the source and role of this increase, however, remain unclear. No data are available about the expression of GDNF in human adult kidney or human adult mesangial cell (HMC) cultures. We hypothesized that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor in the pathogenesis of glomerulosclerosis. METHODS: To address this hypothesis, we first investigated (by RT-PCR) the expression of GDNF mRNA and the mRNAs of the GDNF receptors Ret and GFRalpha-1 in (i) adult human renal cortex and medulla and (ii) in HMC in culture. The results were compared to the expression of these molecules in different developmental stages of the rat kidney. We found that both GDNF and its receptors were expressed in human adult kidney and HMC. Since this finding implicates a role for GDNF beyond nephrogenesis, i.e. in renal physiology/pathophysiology, we investigated the effect of GDNF on HMC growth, i.e. (i) cellular protein synthesis as an index of hypertrophy ([(3)H]methionine incorporation), (ii) DNA synthesis ([(3)H]thymidine incorporation) and cell proliferation (cell numbers) as indices of hyperplasia, and (iii) extracellular matrix synthesis, i.e. collagenous and non-collagenous extracellular proteins ([(3)H]proline incorporation into the collagenase-sensitive and -insensitive fraction). HMC cultures were used as a surrogate model for the development of glomerulosclerosis. RESULTS: GDNF induced a biphasic growth stimulatory effect in HMC with stimulation at the lowest concentration used (2 ng/ml) but had no effect at higher concentrations (20 and 50 ng/ml). In contrast, cellular protein synthesis and extracellular matrix synthesis were significantly and dose-dependently increased by GDNF. CONCLUSIONS: These results suggest that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor for mesangial cells and might thus be a player in the pathogenesis of glomerulosclerosis.

Aging↗
PubMed2000

Capillary/myocyte mismatch in the heart in renal failure--a role for erythropoietin?

BACKGROUND: Chronic renal failure is characterized by remodeling of the heart with left ventricular hypertrophy (increasing oxygen demand) and capillary deficit leading to capillary/myocyte mismatch (decreasing oxygen supply). Erythropoietin (Epo) has known angiogenic properties causing endothelial cell activation, migration and sprouting, mediated at least in part via the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway. In uraemic cardiac hypertrophy the presence of diminished capillary supply implies that capillary growth does not keep pace with development of hypertrophy. To investigate whether this was due to a deficit of the angiogenic hormone Epo we examined whether Epo levels are altered and whether an increase in haematocrit by administration of rhEpo influences capillary supply, i.e. capillary/myocyte mismatch in experimental renal failure. METHOD: Male Spraque-Dawley rats were either subjected to partial renal ablation or sham operation. Only modest amounts of renal tissue were removed so that the rats were not anemic. Subgroups of rats received either human (rh)Epo alone or in combination with unspecific antihypertensive treatment (dihydralazine plus furosemide) in order to control the Epo induced rise in blood pressure. Capillary supply was measured stereologically as capillary length per volume myocardium using the orientator method. RESULTS: Capillary length density was reduced by approximately 25% after partial renal ablation (3237+/-601 vs 4293+/-501 mm/mm(3) in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620+/-828 mm/mm(3)) compared to partial ablation alone. CONCLUSION: The study shows that lack of Epo does not cause, or contribute to, the deficit of capillary growth in the hypertrophied left ventricle of rats with renal failure. In addition, a rise in haematocrit is not accompanied by beneficial effects on alterations of cardiovascular structure in experimental renal failure.

Animals↗
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↗