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E Ritz

Publications and source records attributed to E Ritz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Receptors for advance glycation end-products (AGE) - expression by endothelial cells in non-diabetic uraemic patients.

BACKGROUND: Cellular actions of advanced glycation end-products (AGE) are mediated by a receptor for AGE (RAGE), a novel integral membrane protein. Immunohistochemical studies show only low-level RAGE antigen expression in endothelial cells. Design. It was the purposes of the study to compare expression of RAGE antigen by endothelial cells in non-diabetic uraemic patients (n=8) with non-uraemic controls (n=11). Samples of arterial tissue were obtained at the time of renal transplantation (in uraemic patients) and abdominal surgery (in controls). RAGE antigen was visualized using guinea-pig anti-RAGE IgG and PAP technique. RESULTS: Marked staining for RAGE was noted in endothelial cells, both arterial endothelium and endothelium of vasa vasorum of normoglycaemic uraemic patients, but was not demonstrable in endothelial cells of large arteries and only faintly expressed in vasa vasorum of non-uraemic individuals. CONCLUSION: Normal endothelial cells do not constitually express RAGE antigen; in contrast it is expressed by arterial and capillary endothelial cells of uraemic patients. The observation is of note in view of the putative role of AGE of causing atherosclerotic and non-atherosclerotic vascular lesions.

Adult↗
PubMed1996

Albuminuria in normotensive and hypertensive individuals attending offices of general practitioners.

OBJECTIVE: To investigate the rate of albumin excretion and the prevalence of albuminuria in hypertensive individuals relative to the normotensive population, and to clarify the quantitative importance of confounding variables. DESIGN AND METHODS: We examined the morning urines of all consecutive non-diabetic and diabetic hypertensive patients (n = 631; 371 women, 260 men) attending the offices of five general practitioners in a circumscribed geographical area during a 4-month period. To obtain a normotensive control population, all consecutive visitors (n = 375; 217 women, 158 men) were also examined. Urinary albumin excretion was assessed by kinetic nephrelometry in morning urine samples. RESULTS: The median albumin excretion rate was 4.3 micrograms/ml (range 1.9-112) in normotensive individuals; 3.4 micrograms/ml (1.9-1440) in hypertensive and 3.6 micrograms/ml (1.9-2790) in diabetic patients (n = 189; 115 women, 74 men). The overall prevalence of albuminuria above 20 micrograms/ml was 4% in normotensive individuals, 10% in hypertensive patients and 17% in diabetic patients. The proportion of patients with higher-grade albuminuria (> 50 micrograms/ml) was 1% among the normotensive subjects aged below 60 years and 2% in those aged above 60 years; the respective values in hypertensive patients were 3 and 6% and in diabetic patients 8 and 13%. The multivariate regression analysis showed a significant correlation between albuminuria and smoking (P < 0.0001), the presence of hypertension (P < 0.001), the current level of systolic blood pressure (P < 0.01) and age (0.031), but not sex or body mass index. CONCLUSIONS: The present study confirms a higher prevalence of albuminuria above 20 micrograms/ml in individuals with primary hypertension and diabetes mellitus compared with that in normotensive subjects, despite similar median albumin excretion rates. However, the excess of prevalence is moderate. Smoking, advanced age and current level of systolic blood pressure are the important determinants.

Adult↗
PubMed1996

Cardiac structure and function in renal disease.

Cardiac death secondary to ischaemia, but not necessarily associated with coronary lesions, is the leading cause of death in uraemic patients. This article reviews recent findings that demonstrate abnormalities of cardiac structure which have a bearing on ischaemia tolerance. These abnormalities comprise the following: (1) left ventricular hypertrophy not fully explained by increased mean arterial pressure, (2) interstitial fibrosis and (3) abnormalities of myocardial microvasculature, i.e. capillary rarefaction and arteriolar-wall thickening.

Endomyocardial Fibrosis↗
PubMed1996

Renal 31-phosphorus-magnetic resonance spectral changes in experimental uremia.

Altered renal cellular phosphate (Pi) homeostasis may be involved in disturbed regulation of 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3] production in chronic renal failure. To assess cytoplasmic concentrations of P(i) and other phosphate metabolites in uremia, phosphorus-magnetic resonance spectroscopy (31P-MRS) studies were carried out in vivo in rat remnant kidney. Five-sixths-nephrectomized animals (Nx, n = 8, serum creatinine 1.28 +/- 0.18 mg/ dl) and sham-operated control animals (n = 8) were pair-fed a high-phosphate diet (1.6% phosphate, 1.0% calcium) for 19 days. In both remnant and intact kidneys, 31P-magnetic resonance spectra displayed six major peaks: phosphomonoesters (PME), P(i), phosphodiesters, and adenosine triphosphate (ATP)-gamma, -alpha, and -beta. Phosphocreatine was absent. The relative intensity of the renal gamma ATP signal was comparable between the remnant kidney in Nx and the sham-operated kidney in control animals and was, therefore, used as the internal standard to assess the P(i)/gamma ATP ratio. The P(i)/gamma ATP ratio was significantly (p < 0.05) increased in the remnant kidney as compared to the sham-operated control kidney (0.97 +/- 0.24 in Nx vs. 0.75 +/- 0.12 in sham-operated controls; means +/- SE). Similarly, the PME/gamma ATP ratio was significantly increased in Nx (p < 0.01), whereas the relative intensities of other phosphate metabolite signals were not altered in Nx. Mean serum 1,25(OH)2D3 concentrations were 62 pg/ml for Nx and 93 for sham-operated controls (p < 0.05); mean serum phosphate levels were 4.35 mmol/l for Nx and 2.61 for sham-operated controls (p < 0.01). The pH in the remnant kidneys was 7.20 +/- 0.06 (mean +/- SE, n = 8), whereas the pH in intact kidneys was 7.29 +/- 0.05 (n = 8, p < 0.05). To examine the contribution of blood cells to 31P-magnetic resonance spectra, an exchange transfusion with a fluorocarbonated oxygen carrier (to a final hematocrit of 8%) was carried out, while animals (n = 5) were monitored by MRS. This did not significantly change the relative intensities of phosphate metabolite peaks, indicating that blood phosphorus did not measurably contribute to the renal P(i) signal. The data suggest that intrarenal P(i) concentration is elevated in renal failure. This could inhibit 25-hydroxyvitamin D3-1 alpha-hydroxylase activity and thus have some relevance for pathogenesis of renal hyperparathyroidism.

Animals↗
PubMed1996

Abnormal expression and regulation of vitamin D receptor in experimental uremia.

The low concentration of the biologically active metabolite of vitamin D, namely 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), is critical to the pathogenesis of secondary hyperparathyroidism in chronic renal failure. The actions of 1,25(OH)2D3 are mediated through binding to a cellular receptor protein, the vitamin D receptor (VDR). In order to further investigate expression and regulation of VDR in uremia, we measured specific [3H]-1,25(OH)2D3 binding capacity and VDR mRNA concentration in intestinal mucosa and in parathyroid glands of subtotally nephrectomized rats (Nx) and compared Nx to sham-operated rats with normal kidney function (Intact). Intestinal [3H]-1,25(OH)2D3 binding capacity in short-term Nx (6-10 days after nephrectomy) was 663 +/- 114 fmol/mg protein; it was 517 +/- 34 in Intact (p = 0.06, n = 6 experiments). Intestinal VDR mRNA concentration was comparable between Nx and Intact. Specific 1,25(OH)2D3 binding capacity in parathyroid glands was higher in Nx (195 +/- 9 fmol/mg protein) than in Intact (116 +/- 14 fmol/mg protein, n = 5, p < 0.05). The affinity of the VDR for 1,25(OH)2D3 (KD) did not change in Nx. The 1,25(OH)2D3 binding capacity in intestinal mucosa of more long-term uremic animals (14-16 weeks after subtotal Nx) was 519 +/- 32 fmol/mg protein versus 349 +/- 31 in Intact (n = 3, p < 0.01). Parathyroid VDR was 171 +/- 9 fmol/mg protein in long-term Nx and 125 +/- 3 in Intact (p < 0.01). These results were confirmed when 1,25(OH)2D3 binding capacity in uremic rats with hereditary polycystic kidney disease was compared to control rats with normal kidney function (757 +/- 54 fmol/mg protein versus 495 +/- 59 in intestinal mucosa, p < 0.05; 273 +/- 48 versus 104 +/- 27 in parathyroid glands, p < 0.05). In parallel to changes in intestinal 1,25(OH)2D3 binding capacity, 1,25(OH)2D3-mediated stimulation of intestinal 25(OH)D3-24-hydroxylase activity was significantly higher in long-term subtotally Nx (1.43 +/- 0.06 pmol 24,25-dihydroxyvitamin D3/mg protein) than in sham-operated normal rats (1.04 +/- 0.10, p < 0.05). Administration of 1,25(OH)2D3 to sham-operated normal rats resulted in an increase of 1,25(OH)2D3 binding capacity by 20-40% in intestinal mucosa and by 40-50% in parathyroid glands. In contrast, 1,25(OH)2D3 caused down-regulation of mean 1,25(OH)2D3 binding capacity in short-term Nx by 38% in intestinal mucosa (p < 0.01) and by 43% in parathyroid glands (p < 0.01). In long-term Nx, mean 1,25(OH)2D3 binding capacity was reduced by 20% in intestinal mucosa (p < 0.05) and by 22% in parathyroid glands (p < 0.01). After prolonged exposure to 1,25(OH)2D3 for 6 weeks, intestinal 1,25(OH)2D3 binding capacity was markedly down-regulated in uremic rats (43% versus vehicle-treated animals p < 0.05). Taken together, our results provide evidence for abnormal expression and regulation of VDR in experimental uremia. This may be relevant for responsiveness to 1,25(OH)2D3 in renal insufficiency.

Animals↗
PubMed1996

Changes in plasma phosphate levels influence insulin sensitivity under euglycemic conditions.

The euglycemic clamp technique is a useful tool to evaluate insulin-mediated glucose uptake. The plasma phosphate concentration decreases during euglycemic clamp studies. Because insulin-dependent glucose uptake is closely related to phosphate uptake, we investigated whether modulation of plasma phosphate levels in the range observed during clamp studies influences insulin sensitivity. We studied 11 healthy (phosphate-replete) male volunteers (mean age, 27.5 +/- 1.8 yr;, mean body mass index, 23.9 +/- 1.6 kg/m2) in a double blind placebo-controlled cross-over study. The volunteers received in random order on two occasions either an infusion of sodium chloride (sham infusion) or an infusion of sodium phosphate. Insulin sensitivity was assessed under euglycemic conditions (clamp technique). The mean plasma phosphate concentration decreased with sham infusion from 1.09 +/- 0.17 to 0.64 +/- 0.13 mmol/L, whereas it increased with phosphate infusion from 1.06 +/- 0.19 to 1.32 +/- 0.13 mmol/L. In all volunteers except one the glucose disposal rate (M-value) was higher after phosphate infusion (mean M-value, 10.4 +/- 1.5 mg/kg.min) than that after sham infusion (mean M-value, 9.4 +/- 1.5 mg/kg.min; P < 0.01, by Wilcoxon's test for paired samples). There were no significant differences in mean plasma glucose, sodium, insulin, or arterialized standard bicarbonate levels with the two infusion protocols. Mean plasma calcium, albumin-corrected calcium, and potassium levels, however, were all significantly (P < 0.05) lower after phosphate infusion than after sham infusion. The mean PTH level decreased with sham infusion from 28 +/- 9 to 20 +/- 6 ng/L, whereas it increased with phosphate infusion from 26 +/- 9 to 36 +/- 8 ng/L, whereas it increased with phosphate infusion from 26 +/- 9 to 36 +/- 8 ng/L. The difference between the two infusion protocols was statistically significant (P < 0.01). The data presented illustrate that plasma phosphate (and calcium) levels may be confounders that should be at least monitored, and possibly controlled for, when performing euglycemic clamp studies.

Adult↗
PubMed1996

Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma.

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.

Adolescent↗
PubMed1996

Control of pulsatile and tonic parathyroid hormone secretion by ionized calcium.

To investigate the effect of changes in ionized calcium on instantaneous PTH secretion, we examined seven young healthy volunteers by 1-min blood sampling under conditions of normo-, hypo-, and hypercalcemia. After a baseline period of 75 min, ambient ionized calcium was either increased or decreased by 0.2 mmol/L for 105 min by clamped infusion of calcium gluconate or sodium citrate. The characteristics of PTH secretion were analyzed by a deconvolution technique, accounting for subject-specific plasma PTH disappearance half-life, as measured during the first 15 min of calcium infusion (range, 2.04-2.93 min). The process regularity of pulsatile PTH secretion was evaluated by an approximate entropy statistic. Under baseline conditions, 32% of total PTH secretion was released in a pulsatile fashion, with a burst frequency of 6.9 +/- 0.8 h-1 and a PTH mass per burst of 2.6 +/- 0.9 pmol/L. The remaining 68% of total secretion was attributed to tonic hormone release. During the initial 30 min of induced hypocalcemia, pulsatile secretion increased by 1140%, whereas tonic secretion did not change. The preferential increase in pulsatile PTH secretion was mediated by a combined rise in burst frequency and mass released per burst. During subsequent steady state hypocalcemia, the tonic secretion rate increased (255% of baseline), whereas burst frequency and burst mass decreased (to 103% and 189% of the baseline values), restoring the baseline ratio of tonic to pulsatile PTH secretion. The regularity of PTH release increased during steady state hypocalcemia. During hypercalcemia, tonic secretion, burst mass, and burst frequency decreased by 75%, 82%, and 32%, respectively, and remained constant throughout the clamp period. We conclude that acute hypocalcemia elicits an immediate pulsatile and a delayed tonic secretory response of the parathyroid gland with increased regularity of PTH release. Acute hypercalcemia suppresses both the pulsatile and the tonic component of PTH secretion.

Adult↗
PubMed1996

Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.

In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After perfusion fixation, heart and aorta were examined by stereological techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation.

BACKGROUND: Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. STUDY DESIGN: 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. METHODS: Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. RESULTS: SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. CONCLUSION: Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists interfere with development of glomerulosclerosis by mechanisms which are, at least in part, independent of systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental renal failure.

BACKGROUND: Experimental renal failure causes structural alterations of the kidney. It is still unresolved how these changes are modified by antihypertensive treatment. Purpose of the study. To examine the effects of different antihypertensive agents (ramipril, nifedipine, moxonidine) mainly on glomerular geometry, cell number, cell morphology, and capillarization, in a subtotal nephrectomy model of renal failure. MATERIAL AND METHODS: Sham-operated male SD rats and subtotally nephrectomized (SNX) ad libitum-fed rats were examined. Groups of 8-10 SNX rats were left untreated or were treated with ramipril (0.5 mg/kg b.w. per day), nifedipine (20 mg/kg b.w. per day) or moxonidine (10 mg/kg b.w.per day) respectively. After perfusion fixation the kidneys were examined using stereological techniques. RESULTS: Systolic blood pressure (by tail plethysmography) was 110+/-13 mm Hg in sham-op and 119+/-9 in SNX. It was effectively and comparably reduced below normal values by ramipril (89+/-11 mmHg), nifedipine (98+/-23 mmHg) and moxonidine (92+/-11 mmHg). The glomerulosclerosis index (SI) was significantly increased in SNX versus sham-op; it was similarly decreased by ramipril and moxonidine but less so by nifedipine. Vascular damage (preglomerular vessels) was reduced by all treatments whereas tubulointerstitial damage was signficantly reduced only by ramipril and moxonidine. Mean glomerular tuft volume was increased in SNX compared to sham-op. controls and was normalized only by ramipril treatment. Glomerular cells were differentially affected the three antihypertensive agents. After subtotal nephrectomy an increase in podocyte volume and mesangial cell number per glomerulus was noted. Nifedipine, and to a lesser extent ramipril, prevented mesangial cell hyperplasia. In contrast, only the ACE inhibitor ramipril, but not nifedipine or moxonidine prevented podocyte abnormalities, particularly podocyte hypertrophy. CONCLUSIONS: (i) Despite comparable reduction in systolic blood pressure, different classes of antihypertensive agents had diverse effects on renal damage in subtotally nephrectomized rat. This observation is consistent with specific, non-hemodynamic actions of anti-hypertensives. (ii) Glomerular and tubulointerstitial damage are prevented by treatment with ACE inhibitors and antisympathotonic agents, but not with the calcium antagonist nifedipine. In contrast, renal vascular changes were also prevented by nifedipine. (iii) Only ACE inhibitors effectively inhibited podocyte hypertrophy and mesangial cell hyperplasia. Whether the superior effect of ACE inhibitors on glomerulosclerosis is related to inhibition of glomerular growth and podocyte hypertrophy as well as preservation of podocyte structure, or whether these findings are merely a passive reflection of greater efficacy, remains unresolved.

Animals↗
PubMed1996

Why are lipids not predictive of cardiovascular death in the dialysis patient?

The rate of cardiovascular death, and specifically of cardiac death, in dialysis patient is excessive and comparable to that in the high-risk group of survivors of myocardial infarction. Yet, in patients on dialysis total cholesterol, LDL cholesterol, apolipoprotein B and other indicators of coronary risk--with the exception of lipoprotein(a)--are consistently higher in survivors than in those dying from cardiovascular causes, but at least in diabetic patients on dialysis, an extremely high-risk population, lipids are predictive of cardiac death. Malnutrition as a confounding factor might explain the inverse relation between lipid indicators and cardiac death in nondiabetic patients. Indirect arguments can be marshalled that malnutrition increases cardiac death as a consequence of low L-arginine levels and the ensuing diminished synthesis of NO.

Apolipoproteins B↗