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Eberhard Ritz

Publications and source records attributed to Eberhard Ritz.

At least 73 records · Page 4Linked to original sources
PubMed2004

No aggravation of renal injury in apolipoprotein E knockout mice (ApoE(-/-)) after subtotal nephrectomy.

BACKGROUND: There is substantial experimental evidence that various forms of dyslipidaemia aggravate the course of renal failure and that reversal of dyslipidaemia ameliorates progression of renal failure. The apolipoprotein E knockout mouse (ApoE(-/-)) is an established model of accelerated atherogenesis. We investigated whether the course of renal disease after uninephrectomy (UNX) and subtotal nephrectomy (SNX) is altered in ApoE(-/-) mice compared with their genetic controls. METHODS: Ten-week-old, male ApoE(-/-) mice (body weight 25+/-2 g) were subjected either to sham operation (sham), UNX or SNX. C57BL/6 sham, UNX and SNX mice served as controls (body weight 26+/-3 g). The food intake of ApoE(-/-) and C57BL/6 mice was kept identical by a pair-feeding protocol. After 12 weeks, mean arterial blood pressure and heart rate were measured in awake resting mice, the kidneys were perfusion fixed and analysed using quantitative histological methods, immunohistochemistry and RT-PCR. RESULTS: At baseline, the sham ApoE(-/-) mice had significantly higher (P<0.05) serum cholesterol and triglycerides than the controls. In parallel, mean arterial blood pressure was significantly elevated in sham ApoE(-/-) mice compared with controls (137+/-15 vs 116+/-4 mmHg; P<0.05). In the sham groups, the glomerulosclerosis index was significantly higher in the ApoE(-/-) mice (1.05+/-0.14 vs 0.57+/-0.07; P<0.05), whereas the tubulointerstitial damage score was comparable (0.06+/-0.04 vs 0.04+/-0.02; n.s.). After SNX there was a significant increase in glomerulosclerosis index, but no difference could be detected between ApoE(-/-) and controls (1.75+/-0.16 vs 1.61+/-0.01, n.s.). The same was true for the tubulointerstitial damage index. CONCLUSIONS: Despite some glomerulosclerosis and elevated mean arterial blood pressure at baseline, no acceleration of progression of renal disease was found in this genetic model of hyperlipoproteinaemia. This observation suggests that despite the known spontaneous histological changes in untouched kidneys, however, the presence of hyperlipidaemia in the ApoE(-/-) mouse does not cause more severe progression in the present models of moderate renal disease.

Animals↗
PubMed2004

High prevalence and poor control of hypertension in primary care: cross-sectional study.

OBJECTIVE: To report: (1) on the background, design and methods of the Hypertension and Diabetes Risk Screening and Awareness (HYDRA) study, (2) on the point prevalence of hypertension in primary care and (3) on the proportion of treated, controlled, and uncontrolled hypertension. DESIGN: Cross-sectional point prevalence study. SETTING: Representative nationwide sample of 1912 primary care practices in Germany. PARTICIPANTS: A total of 45,125 unselected primary care attendees. MAIN OUTCOME MEASURES: Prevalence of hypertension based on doctor's diagnosis, self-reported diagnosis, and blood pressure (BP) measurements. RESULTS: A total of 39% of all patients and 67% of patients aged 60 years or older, respectively, were diagnosed by their doctors as having hypertension. Eighty-four percent of diagnosed patients were on antihypertensive medication, 57% of which were rated by the physician as well controlled. When hypertension was defined as either current BP levels > or = 140/90 mmHg and/or current antihypertensive medication, the total point prevalence increased to 50%, while treatment and control rates (BP < 140/90 mmHg) dropped to 64 and 19%, respectively. CONCLUSIONS: Extrapolation of these findings to the entire primary care patient population seen in the over 20 000 primary care practices in Germany suggests that on an average day, over 700,000 patients with elevated BP are seen by primary care physicians, but that only around 132,000 of these patients are well controlled. Thus, this study not only documents the enormous burden of hypertensive patients in the primary health system, but also highlights the alarming lack of BP control in the vast majority of hypertensive patients.

Adolescent↗
PubMed2004

Beneficial Effects of Estrogens on Indices of Renal Damage in Uninephrectomized SHRsp Rats.

Renal diseases tend to be less severe among premenopausal female patients, compared with male patients. Experimental data on the effects of estrogens on renal damage are controversial, and potential underlying mechanisms have not been fully clarified. Three-month-old, female, uninephrectomized (UNX), sham-operated or ovariectomized (OVX) SHRsp rats were left untreated or received either 17beta-estradiol 3-benzoate (25 micro g/d) or estriol (0.02 mg/d) daily. After 3 mo, indices of renal damage (glomerulosclerosis index and tubulointerstitial damage index) and glomerular geometric parameters were investigated. The expression of desmin, TGF-beta, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors alpha and beta in the glomeruli and tubulointerstitium was immunohistochemically evaluated. Estradiol and estriol did not significantly affect kidney weights or BP. Estradiol and estriol caused significant reductions in albuminuria (vehicle-treated UNX/OVX animals, 25.4 +/- 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 +/- 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 +/- 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol- and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 +/- 0.16; estriol-treated UNX/OVX animals, 0.21 +/- 0.12; P < 0.05), compared with vehicle-treated animals (1.46 +/- 0.09); the tubulointerstitial damage index exhibited a similar pattern. The mean glomerular volume was significantly less in estrogen-treated animals. UNX/OVX animals demonstrated significantly greater expression of TGF-beta and endothelin-1 in immunohistochemical, in situ hybridization, and reverse transcription-PCR assays. This increase was abrogated by estriol but not estradiol. Similarly, significantly higher glomerular and tubulointerstitial expression of proliferating cell nuclear antigen and collagen IV was observed in UNX/OVX animals, and expression was decreased by estriol but not estradiol. It was concluded that, in the UNX model of spontaneous renal damage, glomerular lesions and glomerular hypertrophy were reduced by estriol but less consistently by estradiol. In parallel, loss of podocytes, evidence of podocyte injury (i.e., desmin expression), and expression of mediator systems of glomerular damage were decreased, pointing to a major renoprotective action of estriol.

Animals↗
PubMed2004

Increased infarct size in uremic rats: reduced ischemia tolerance?

In patients with renal failure, myocardial infarction (MI) is more frequent and the rate of death from acute MI is very high. It has been argued that ischemia tolerance of the heart is reduced in uremia, but direct evidence for this hypothesis has not been provided. It was the purpose of this study (1) to ligate the left coronary artery and to measure the nonperfused area (risk area: total infarction plus penumbra) as well as the area of total infarction in subtotally nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and (2) to examine the effects of potential confounders such as BP, sympathetic overactivity, and salt retention. The left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. For visualizing perfused myocardium, lissamine green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (triphenyltetrazolium chloride stain) were assessed in sections of the left ventricle using image analysis. Groups of SNX rats also received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high salt diet or low salt diet (1.58% versus 0.015%). In surviving animals, the nonperfused area at risk (as the proportion of total left ventricular area), presumably determined by the geometry of vascular supply, was similar in sham-operated and SNX animals (0.38 +/- 0.13 versus 0.45 +/- 0.09; NS). In contrast, the infarcted area, given as a proportion of the nonperfused risk area, was significantly (P < 0.003) higher in SNX (0.68 +/- 0.09) compared with sham-operated (0.51 +/- 0.11) rats and was not altered by any of the above interventions. The finding that a greater proportion of nonperfused myocardium undergoes total necrosis is consistent with the hypothesis of reduced ischemia tolerance of the heart in renal failure. The findings could explain the high rate of death from MI in patients with impaired renal function.

Animals↗
PubMed2004

Reversal of glomerular lesions involves coordinated restructuring of glomerular microvasculature.

There is increasing evidence from both human and experimental studies that at least partial reversal of glomerulosclerosis can be achieved by glomerular remodeling. This requires substantial changes in glomerular architecture, specifically of glomerular capillaries. It was the purpose of the present study to characterize the stereologic and topologic characteristics of glomerular capillaries when partial reversal of glomerular lesions is achieved by high-dose angiotensin-converting enzyme inhibitor treatment. Sham-operated male Sprague-Dawley rats were compared with subtotally nephrectomized (SNX) rats. The latter were kept untreated for 8 wk and subsequently randomly divided into one group that was continued without treatment and another group that was treated with enalapril (48 mg/kg body wt per d administered in the drinking fluid for 4 wk). Renal morphology was evaluated after 8 or 12 wk, respectively, by stereologic techniques after pressure-controlled perfusion fixation. In SNX rats at 8 and particularly at 12 wk, the glomerulosclerosis index was significantly higher than in sham-operated rats. At 12 wk, it was lower in rats that had been treated for 4 wk with enalapril compared with untreated SNX rats, suggesting partial reversal of glomerular lesions. This was associated with a decrease in mean glomerular volume and mean glomerular tuft volume, a reduced number of capillaries per glomerulus, and reduced total length of capillaries per glomerulus but without any significant change in the length of individual capillaries. The numerical capillary density (Euler number density) as an index of topologic complexity did not change. The total capillary surface area per glomerulus was strikingly increased after subtotal nephrectomy and partially reversed after enalapril. This was accounted for primarily by fewer capillaries without any change in diameter. In parallel, the number of endothelial cells per glomerulus was strikingly increased after subtotal nephrectomy and decreased with enalapril treatment, but endothelial cell volume remained elevated. The study shows harmonious coordinate remodeling of the entire glomerulus during regression of glomerular lesions after subtotal nephrectomy. Proportionate reduction of glomerular volume and capillary number without change of individual capillary length were found. The numerical capillary density of the tuft therefore remained unchanged.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Vascular calcification: a stiff challenge for the nephrologist: does preventing bone disease cause arterial disease?

There has been an explosion of interest in vascular calcification in the last 5 years. Four key "germinal" findings have fallen onto very fertile soil. First, on the background of an increasing cardiovascular disease burden it has been found that at least cross-sectionally, and in a limited fashion prospectively, achieved dialysis plasma phosphate levels are linked to all-cause and cardiovascular mortality. Second, there are increasing reports of calcific uremic arteriolopathy in Australia and the United States. Third, we know know that the mechanical properties of the carotid artery, and the aorta, have a profound influence on survival for dialysis patients. Vascular calcification itself (as assessed by x-ray films and ultrasound) has been linked to aortic stiffness. Fourth, increasing numbers of studies are showing extremely extensive coronary artery calcification (CAC) in dialysis patients, even at a young age. From these apparently unlinked observations the following assertion has been posited-that in the widespread (over) use of calcium-containing oral phosphate binders (OPB) to prevent uremic osteodystrophy in our dialysis population we have unwittingly accelerated widespread uremic vasculopathy and thereby contributed to premature cardiovascular mortality. It is the purpose of this article to discuss vascular calcification (and particularly CAC) in dialysis patients as we understand it today. We will review the published series, with special reference to the Sevelamer Treat to Goal trial and also discuss the new Kidney Disease Outcome Quality Initiative (K-DOQI) guidelines on the use of phosphate binders in chronic kidney disease.

Bone Diseases↗
PubMed2004

Atherosclerosis in dialyzed patients.

In the recent HEMO study, the most common cause of death in dialyzed patients was ischemic heart disease. In Europe there are regional differences, but the mortality due to cardiovascular disease is also very high. The long-lasting controversy whether the high incidence and prevalence of atherosclerotic manifestations (particularly ischemic heart disease) may be explained by known risk factors, or non-traditional risk factors are also involved seems to be partially solved with the increasing evidence that the latter hypothesis is true. Thus, together with classic risk factors such as hypertension, dyslipidemia and diabetes, other situations such as microinflammation, increased concentration of asymmetrical dimethyl-L-arginine, disturbed phosphate metabolism and anemia may represent important risk factors for accelerated atherosclerosis in dialyzed patients.

Anemia↗
PubMed2003

1,25-Dihydroxyvitamin D3 decreases podocyte loss and podocyte hypertrophy in the subtotally nephrectomized rat.

1,25(OH)(2)D(3) has antiproliferative effects and promotes cell differentiation. This consideration has provided the rationale for studies in subtotally nephrectomized rats showing that 1,25(OH)(2)D(3) interfered with glomerulosclerosis. The cellular mechanisms involved have remained obscure, however. It was the purpose of the present study to assess glomerular structure and cellular composition in subtotally nephrectomized (SNX) rats treated with nonpharmacological doses of 1,25(OH)(2)D(3). Male Sprague-Dawley rats were sham operated (sham) or underwent SNX under general anesthesia and received either solvent or 1,25(OH)(2)D(3) (3 ng.100 g body wt(-1).day(-1) sc). Blood pressure (BP) and albuminuria were measured. After 16 wk, the remnant renal tissue was perfusion fixed and morphometric and stereological measurements were carried out. The expression of proliferating cellular antigen (PCNA), cyclin-dependent kinase inhibitor p27, Wilms tumor gene (WT1), and desmin, a marker of early podocyte damage, was investigated by immunohistology. BP, serum creatinine, and urinary albumin excretion were significantly higher in SNX than in sham rats. Albuminuria was significantly lower in SNX+1,25(OH)(2)D(3) compared with SNX+solvent rats. Mean glomerular tuft volume was significantly higher in SNX+solvent (2.69 +/- 0.21 gx 10(6) microm(3)) than in sham rats (1.44 +/- 0.17 and 1.28 +/- 0.14 x 10(6) microm(3)); it was significantly (P < 0.05) lower in SNX+1,25(OH)(2)D(3) rats (1.81 +/- 0.16 x 10(6) microm(3)). The main finding was a significantly higher number of podocytes in SNX+1,25(OH)(2)D(3) (88 +/- 9) and sham (98 +/- 17) compared with SNX+solvent rats (81 +/- 8.7). In parallel, the increase in podocyte volume in SNX+solvent rats was abrogated by treatment with 1,25(OH)(2)D(3), and immunohistochemistry revealed less expression of desmin, PCNA, and p27, suggesting less podocyte injury and activation of the cyclin cascade. This study identifies the podocyte as an important target cell for the renoprotective action of 1,25(OH)(2)D(3). This notion is suggested by less evidence of podocyte injury, decreased podocytes loss, and abrogation of podocyte hypertrophy, findings that may also explain less pronounced albuminuria and glomerulosclerosis.

Animals↗
PubMed2003

The renal retinoid system: time-dependent activation in experimental glomerulonephritis.

Retinoids reduce renal damage in rat experimental glomerulonephritis. It is unknown, however, how local and systemic retinoid pathways respond to renal injury. We used a rat model of artificially induced acute anti-Thy1.1-nephritis (THY-GN). We examined the extrarenal and glomerular expression of the retinol (RoDH) and retinal (RalDH) dehydrogenases 1 and 2 as well as the expression of the retinoic acid (RAR) and retinoid X (RXR) receptor subtypes alpha, beta, and gamma. Furthermore, we investigated serum and glomerular retinoid concentration patterns. On days 3, 7, and 14, we compared nonnephritic rats (control group; CON) to THY-GN rats with respect to systolic blood pressure and glomerular cell count per cross section. Systolic blood pressure and glomerular cell count were significantly higher in THY-GN rats on days 7 and 14 (P < 0.001). We found a 60% reduction in expression levels for retinoid receptors and dehydrogenases in nephritic glomeruli on day 3, but a threefold increase on day 7 (P < 0.001 vs. CON). The same applies to RAR alpha protein. Hepatic expression of retinoid receptors was not influenced. On day 14, glomerular expression levels for retinoid receptors and retinoid-metabolizing enzymes had returned to a normal level, glomerular cell count being still increased. Administering 13-cis retinoic acid (isotretinoin) lowered blood pressure and glomerular cell count in nephritic rats but failed to influence the glomerular expression of retinoid receptors or retinoid-metabolizing enzymes. Our data document a stimulation of glomerular retinoid-synthesizing enzymes and expression of retinoid receptors in the early repair phase of THY-GN, suggesting activation of this system in acute renal disease.

Alcohol Oxidoreductases↗
PubMed2003

Asymmetric dimethylarginine, blood pressure, and renal perfusion in elderly subjects.

BACKGROUND: Reduced availability of nitric oxide (NO) is thought to contribute to the age-associated increase of renovascular tone and blood pressure. We assessed blood concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal hemodynamics, comparing young (n=24, 13 men, 25+/-1 years) and elderly (n=24, 13 men, 69+/-2 years) healthy subjects and elderly subjects with essential hypertension (n=24, 13 men, 70+/-2 years). METHODS AND RESULTS: Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P<0.05) and effective renal plasma flow (ERPF) significantly lower (P<0.05) in elderly (2.77+/-0.20 micromol/L, 125+/-10 mm Hg/mL per minute, 487+/-26 mL/min per 1.73 m2) than in young healthy subjects (1.30+/-0.11, 77+/-3, 654+/-18). Both ADMA levels and RVR were higher and ERPF lower in the hypertensive elderly subjects (3.53+/-0.23, 163+/-11, 427+/-19; P<0.05 versus both groups). In contrast, plasma concentrations of the biologically inactive stereoisomer symmetric dimethylarginine, l-arginine, and homocysteine were similar in the 3 groups studied. In the logistic regression analysis only ADMA was an independent determinant of both ERPF (P<0.001; r2=0.80) and RVR (P<0.002; r2=0.86). In addition, ADMA (P<0.002) and serum glucose (P<0.036) were independently related (r2=0.67) to the level of blood pressure. CONCLUSIONS: These results are compatible with the notion that accumulation of the endogenous NO synthase inhibitor ADMA in senescent individuals is involved in the decrease of renal perfusion and increase of blood pressure.

Adult↗
PubMed2003

Myocyte loss in early left ventricular hypertrophy of experimental renovascular hypertension.

Left ventricular hypertrophy (LVH) develops very early in experimental renovascular hypertension after clipping of one renal artery and is accompanied by a remodeling of cardiac structure which has not yet been investigated in detail. It was the aim of the present study to analyze changes in cardiomyocyte number and volume in LVH after 2 weeks of renovascular hypertension. Sprague-Dawley rats were subjected to clipping of the left renal artery (2K1C) or sham operation (sham). One group of 2K1C rats received antihypertensive treatment with dihydralazine. The experiment was terminated after 2 weeks. Hearts were investigated using stereological methods, electron microscopy, immunohistology for the proliferation marker proliferating cell nuclear antigen, the pro- and anti-apoptotic proteins Bax and Bcl-2 as well as the TUNEL technique. After 2 weeks, systolic blood pressure and relative left ventricular weight were significantly higher in untreated 2K1C animals than in sham and dihydralazine-treated 2K1C rats. Volume fraction of interstitial tissue and capillary length density were not different, whereas wall thickness of intramyocardial arteries was significantly higher in untreated 2K1C (5.12+/-0.7 micro m) than in sham (3.92+/-0.6 micro m) and in dihydralazine-treated 2K1C (3.91+/-0.7 micro m) rats. Cardiomyocyte diameter and volume were significantly higher in untreated 2K1C than in sham animals. The number of cardiomyocytes per left ventricle was significantly lower in untreated 2K1C rats (5.5+/-1.6 vs 3.9+/-6.9 x10(7)). Using immunohistochemistry, no direct evidence of apoptosis was found, but a relative higher expression of the anti-apoptotic protein bcl-2 expression was seen in untreated 2K1C than in sham animals. This may reflect a protective mechanism as a consequence of earlier occurring apoptosis. These observations document that experimental renovascular hypertension induces a rapidly developing LVH characterized by marked cardiac remodeling and substantial loss of cadiomyocytes.

Animals↗
PubMed2003

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

Adult↗