Search PubMed⌕ Search

Biomedical subjects

Eberhard Ritz

Publications and source records attributed to Eberhard Ritz.

At least 109 records · Page 6Linked to original sources
PubMed2003

Reversal of glomerulosclerosis after high-dose enalapril treatment in subtotally nephrectomized rats.

Interventions to block the renin-angiotensin system (RAS) halt the progression of renal lesions in renal damage models. It has recently also been reported that established glomerulosclerosis can be reversed by pharmacologic blockade of the RAS. It was the aim of this study to confirm that high doses of angiotensin-converting enzyme (ACE) inhibitors reverse established glomerulosclerosis and to extend the findings by providing quantitative information on glomerular geometry, podocytes and other glomerular cells, renal vessels and tubulointerstitial tissue. Male Sprague Dawley rats were subjected to subtotal surgical renal ablation (SNX) (n = 27) or sham operation (n = 31) and fed using a pair-feeding protocol. Eight weeks after surgery, rats were either sacrificed or allocated to two arms: enalapril treatment (48 mg/kg body wt per day administered in the drinking fluid for 4 wk) or no treatment. Renal morphology was evaluated after 8 or 12 wk, respectively, by stereology in tissue fixed by pressure-controlled perfusion. Both systolic BP and albumin excretion rate were significantly higher in SNX compared with sham-operated controls. They were significantly reduced in SNX after delayed enalapril treatment. The glomerulosclerosis (GSI), tubulointerstitial (TII), and vascular (VI) damage indices were significantly higher in all SNX groups than in sham-operated controls. At the end of the experiment (12 wk after SNX) GSI, TII, and VI were significantly lower in SNX with delayed enalapril treatment (0.77 +/- 0.18, 0.63 +/- 0.19 and 0.43 +/- 0.16, respectively) compared with untreated SNX (1.64 +/- 0.14, 1.16 +/- 0.34 and 0.67 +/- 0.29, respectively). GSI, TII, and VI were also significantly lower in SNX with delayed enalapril treatment compared with SNX sacrificed without treatment 8 wk after SNX. The same was true for glomerular volume. The number of podocytes was not affected by SNX, but podocyte volume was increased. Both indices remained unaffected by treatment. The numbers of cells within the mesangium and endothelial cells per glomerulus were significantly lower in SNX after delayed enalapril treatment compared with untreated SNX. These results strongly suggest regression of preexisting lesions, i.e., glomerular, tubular, and vascular remodeling as well as reversal of glomerular hypertrophy by ACE inhibitor treatment. The study confirms that high-dose ACE inhibitor treatment causes partial reversal of glomerular as well as interstitial lesions in subtotally nephrectomized rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Beta1-adrenergic blockade augments pulsatile PTH secretion in humans.

Pulsatile peptide hormone secretion provides efficient control of specific end organ functions. To test the hypothesis that sympathetic neuronal activity drives synchronous pulsatile PTH release from the parathyroid glands, we investigated the acute effects of beta1-adrenergic receptor blockade on PTH secretion patterns in a single-blinded study in nine healthy adults. Plasma PTH levels were determined at 1-min intervals. After a 75-min baseline period, seven subjects received a continuous intravenous infusion of the short-acting beta1-adrenergic receptor blocker esmolol for 105 min. After a 30-min washout period, esmolol was infused for another 30 min. Two additional subjects were randomized to receive solvent infusions. PTH secretion characteristics were analyzed by multiparameter deconvolution analysis, and the orderliness of plasma PTH fluctuations by Approximate Entropy statistics. BP slightly decreased during esmolol infusion, whereas heart rate, ionized calcium, phosphate, magnesium, and plasma and urine catecholamines remained unchanged. Esmolol increased mean plasma PTH by 33 +/- 8% (P < 0.01), due to a preferential increase in the pulsatile PTH secretion component (+129 +/- 44%, P < 0.02). The increased pulsatile PTH secretion was mediated by an augmented PTH burst mass (+117 +/- 42%, P < 0.01), whereas burst frequency remained unchanged. The regularity of PTH fluctuations was not affected by the beta-adrenergic blockade. The effects were reproducible during the second esmolol infusion. The authors conclude that the sympathetic nervous system has a modulating effect on pulsatile PTH secretion. Selective beta-1 adrenergic blockade acutely increases plasma PTH by augmenting the mass of hormone secreted per burst, but it does not alter the rhythmicity of pulsatile PTH release.

Adrenergic beta-Antagonists↗
PubMed2003

Retinoid agonist isotretinoin ameliorates obstructive renal injury.

PURPOSE: Interstitial fibrosis is a major cause of end stage renal failure. Retinoids, which are involved in tissue repair and fibrosis, inhibit inflammatory and proliferative pathways. Therefore, we studied the dose dependent effects of the retinoid receptor agonist isotretinoin 13-cis retinoic acid in the unilateral ureteral obstruction model (UUO). MATERIALS AND METHODS: Sham operated control rats were compared with UUO rats treated with vehicle (UUO-Veh), or low (5 mg/kg body weight (UUO-LD) or high (25 mg/kg) (UUO-HD) dose isotretinoin. Kidneys were evaluated using reverse transcriptase-polymerase chain reaction and immunohistology 7 days after UUO. Renal injury and fibrosis were quantified by immunostaining and expression measurements of the genes involved in renal fibrosis. RESULTS: In UUO-Veh kidneys the interstitial area was expanded 5-fold but only 3-fold in UUO-HD and 3.5-fold in UUO-LD rats. Interstitial cell counts were 3-fold higher in UUO-Veh rats but significantly less in UUO-HD or UUO-LD animals. Tubular and interstitial cell proliferation was significantly higher in UUO-Veh rats compared with sham operated control plus vehicle animals but less so in UUO-LD and UUO-HD rats. In UUO-Veh rats interstitial infiltration by monocytes/macrophages was higher compared with unobstructed controls. It was significantly less after isotretinoin treatment. In UUO-Veh rats mRNA for procollagen I, and transforming growth factor-beta1 and II receptor was significantly increased. It was significantly less after treatment with isotretinoin. Fibronectin and collagen I immunostaining was also decreased by isotretinoin. CONCLUSIONS: Since isotretinoin limits proliferation, inflammation and fibrosis after UUO, retinoids should be further investigated as potentially promising therapeutic agents for renal disease.

Animals↗
PubMed2003

Renal damage in the SHR/N-cp type 2 diabetes model: comparison of an angiotensin-converting enzyme inhibitor and endothelin receptor blocker.

SUMMARY: The pathomechanisms that cause renal damage in diabetes have not been completely clarified. Treatment with angiotensin-converting enzyme inhibitors (ACE-i) is highly effective but fails to completely prevent end-stage renal disease. The effects of ET(A)-receptor blockers (ET(A)-RB) on renal damage are controversial and have rarely been investigated in type 2 diabetes. We compared the influence of the selective ET(A)-RB LU135252 and the ACE-i Trandolapril on renal structure in the SHR/N-cp rat model of type 2 diabetes. Three-month-old male SHR/N-cp rats were left untreated or received daily either Trandolapril or LU135252. The experiment was terminated after 6 months. The glomerulosclerosis index; tubulointerstitial damage index; and glomerular geometry, glomerular cell number, and capillary density were investigated. Proliferating cell nuclear antigen and desmin expression of podocytes, renal mRNA expression of endothelin (ET-1) and transforming growth factor-beta, blood pressure, and urine albumin excretion were measured. The glomerulosclerosis index was significantly higher in untreated diabetic animals than in the groups that were treated with ACE-i and ET(A)-RB. There were analogous changes in tubulointerstitial damage index. Treatment with either substance comparably lowered urinary albumin excretion in diabetic SHR/N-cp. Podocyte and endothelial cell numbers per glomerulus decreased in untreated diabetic animals; this was prevented by the ACE-i but not by the ET(A)-RB. Glomerular capillary length density was lower in SHR/N-cp, and this was normalized by ACE-i only. Increased expression of desmin and proliferating cell nuclear antigen expression of podocytes in the SHR/N-cp was abrogated by ACE-i but not by ET(A)-RB. Treatment with ACE-i or ET(A)-receptor antagonist resulted in less structural and functional alterations, but the ET(A)-RB was inferior to the ACE-i. This is particularly the case for podocyte changes pointing to angiotensin II-dependent pathomechanisms.

Albuminuria↗
PubMed2003

Effect of endothelin blockade on early cardiovascular remodeling in the one-clip-two-kidney hypertension of the rat.

BACKGROUND: In models of hypertension and of renal failure, pharmacological blockade of the ET(A) receptor has been shown to cause some inconsistent lowering of blood pressure (BP) and lesser left ventricular hypertrophy (LVH). The effects of ET(A) receptor blockade (ET(A)-RB) on vascular remodeling and their potential relation to BP lowering, have not been clarified. DESIGN: The experimental study in male Sprague-Dawley rats was designed to compare four experimental groups: (1) sham-operated controls (sham); (2) untreated rats with one-clip-two-kidney (1C-2K) renovascular hypertension; (3) 1C-2K rats treated with the ACE inhibitor (ACE-i) trandolapril (0.3 mg/kg b.w./day), and (4) 1C-2K rats treated with the ET(A)-RB LU-135252 (50 mg/kg b.w./day). BP was measured weekly by tail plethysmography. After 3 weeks, animals were sacrificed and cardiac, aortic and mesenteric artery morphology was evaluated using morphometric and stereological techniques. RESULTS: Systolic BP was significantly higher in 1C-2K rats compared to sham. BP was not significantly affected by ET(A)-RB, but was significantly lowered by the ACE-i. Despite no significant change in BP, ET(A)-RB treatment led to a significantly less volume density of the cardiac interstitium (sham 1.40 +/- 0.18, 1C-2K 2.66 +/- 0.56, 1C-2K + ACE-i 1.88 +/- 0.38, 1C-2K + ET(A)-RB 2.15 +/- 0.37%). In contrast, ET(A)-RB had no significant effect on left ventricular/body weight ratio (sham 2.85 +/- 0.26, 1C-2K 2.96 +/- 0.33, 1C-2K + ACE-i 2.54 +/- 0.22 and 1C-2K + ET(A)-RB 3.15 +/- 0.44 mg/g) or on wall thickness of intramyocardial arteries. CONCLUSIONS: The ET(A)-RB LU-135252 ameliorated the development of myocardial fibrosis in a short-term hyperreninemic normal salt model of experimental hypertension nearly as effectively as an ACE-i. This effect of LU-135252 is independent of systemic BP. In contrast to findings in other models, ET(A) receptor blockade had no significant effect on LVH or vascular remodeling. Only the ACE-i but not the ET(A)-RB prevented structural changes of small intramyocardial arteries and of the aorta.

Animals↗
PubMed2002

[Nephrology update. Kidney protection with antihypertensive drugs: I].

Diabetes has become the most common single cause of end-stage renal disease in many countries. The coexistence of diabetes mellitus and hypertension dramatically increases the risk of developing target organ complications including renal disease. There are good arguments that ESRD in the patient with diabetes is largely preventable with the interventions currently available. For type 2 diabetes the UK Prospective Diabetes Study Group Trial clearly documented that the frequency of microangiopathic sequelae can be diminished by glycaemic control and even more impressively by intensified antihypertensive treatment. An analysis of recent randomized long-term clinical trials that evaluated the rate of decline in renal function demonstrated that the lower the blood pressure within the range of normotensive values, the greater the preservation of renal function. Since the 1994 Working Group Report on Hypertension and Diabetes suggested a goal blood pressure of 130/80 mmHg should be achieved in patients with diabetes and/or renal insufficiency; lower blood pressure levels, i.e. less than 125/75 mmHg are recommended for patients with proteinuria > 1 g/d and renal insufficiency regardless of etiology. Antihypertensive regimens should include an ACE inhibitor or an AT1-receptor blocker in order to provide maximum renal benefits in diabetic and non-diabetic renal diseases. Such low blood pressure are virtually impossible to achieve with monotherapy. In most cases the combination of two and more antihypertensive drugs is necessary. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reduction and retarding the progression of renal disease.

Angiotensin Receptor Antagonists↗
PubMed2002

Renal dysfunction as a cardiovascular risk factor.

Indices of altered renal function (eg, microalbuminuria, increased serum creatinine concentration, or decrease in estimated creatinine clearance, particularly overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. These parameters should be routinely evaluated in the elderly and in high cardiovascular risk populations, particularly when hypertension is present. Hypertensive kidney damage should be prevented by early aggressive treatment of hypertensive patients with microalbuminuria. To avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used. Epidemiologic information suggests that renal and cardiovascular outcome run parallel in this segment of the population.

Antihypertensive Agents↗
PubMed2002

ATP release in human kidney cortex and its mitogenic effects in visceral glomerular epithelial cells.

BACKGROUND: In chronic renal failure the sympathetic nervous system is activated. Sympathetic cotransmitters released within the kidney may contribute to the progression of renal disease through receptor-mediated proliferative mechanisms. METHODS: In human renal cortex electrical stimulation induced adenosine 5'-triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release was measured. ATP release also was induced by alpha1- and alpha2-adrenergic agonists. [3H]-thymidine uptake was tested in human visceral glomerular epithelial cells (vGEC) and mitogen-activated protein kinase (MAPK42/44) activation in vGEC and kidney cortex. The involved P2-receptors were characterized pharmacologically and by RT-PCR. RESULTS: Sympathetic nerve stimulation and alpha-adrenergic agonists induced release of ATP from human kidney cortex. Seventy-five percent of the ATP released originated from non-neuronal sources, mainly through activation of alpha2-adrenergic receptors. ATP (1 to 100 micromol/L) and related nucleotides (1 to 100 micromol/L) increased [3H]-thymidine uptake. The adenine nucleotides ATP, ATPgammaS, ADP and ADPbetaS were about equally potent. UTP, UDP and alpha,beta-methylene ATP had no effect. ATP, ADPbetaS but not alpha,beta-methylene ATP activated MAPK42/44. ATP induced MAPK42/44 activation, and [3H]-thymidine uptake was abolished in the presence of the MAPK inhibitor PD 98059 (100 micromol/L). mRNA for P2X4,5,6,7 and P2Y1,2,4,6,11 were detected in human vGEC by RT-PCR. CONCLUSIONS: In human renal cortex, adrenergic stimulation releases ATP from neuronal and non-neuronal sources. ATP has mitogenic effects in vGEC and therefore the potential to contribute to progression in chronic renal disease. The pattern of purinoceptor agonist effects on DNA synthesis together with the mRNA expression suggests a major contribution of a P2Y1-like receptor.

Adenosine Triphosphate↗
PubMed2002

Cigarette smoke condensate aggravates renal injury in the renal ablation model.

BACKGROUND: Cigarette smoking increases the risk of progression of diabetic and non-diabetic renal diseases. The mechanisms underlying the adverse effects of smoking are largely unknown. We examined the subtotally nephrectomized rat (i) to investigate whether components of cigarette smoke dissolved in acetone (cigarette smoke condensate) aggravate structural renal damage and (ii) to establish whether this provides an animal model that can be used to investigate potential pathomechanisms of cigarette smoke-induced renal damage. Since nicotine activates the sympathetic nerve system in humans, we investigated whether interference with this system modulates the effects of cigarette smoke condensate on the damaged kidney. METHODS: One group of Sprague-Dawley rats was subtotally nephrectomized (SNX). Acetone (SNX + solvent) or cigarette smoke condensate (SNX + cigarette) was applied daily to the oral mucosa. Another group of Sprague-Dawley rats was sham-operated and received the same treatments (sham + solvent, sham + cigarette). To investigate whether increased activity of the sympathetic nerve system is involved, the remnant kidney was denervated by microsurgical technique in one SNX + cigarette group. The control group for this intervention was a solvent-treated SNX group with denervated remnant kidney. Blood pressure (BP) was measured weekly by tail plethysmography. The experiment was terminated after 12 weeks. Structural renal damage was assessed by morphometric techniques (indices of glomerulosclerosis, tubulointerstitial and vascular damage) and urinary albumin and endothelin-1 excretion were measured. RESULTS: Indices of structural renal damage were increased in all SNX-groups. Treatment with cigarette smoke condensate further increased the indices of glomerulosclerosis and tubulointerstitial damage in SNX, but not sham-operated rats. This increase was completely prevented by renal denervation. No differences in systemic blood pressure were observed in the different SNX groups. Urinary albumin excretion went in parallel with the indices of glomerulosclerosis and tubulointerstitial damage and urinary endothelin-1 excretion was significantly increased in SNX + cigarette animals. CONCLUSION: These findings document that acetone soluble components in cigarette smoke aggravate glomerulosclerosis and tubulointerstitial damage in the renal ablation model. Renal injury induced by cigarette smoke condensate in this model is reversed by renal denervation. We conclude that cigarette smoke-induced renal damage is due, at least in part, to activation of the sympathetic nerve system.

Albuminuria↗
PubMed2002

Intraperitoneal protein injection in the axolotl: the amphibian kidney as a novel model to study tubulointerstitial activation.

BACKGROUND: A substantial body of experimental evidence suggests that protein loading causes activation of proximal tubular epithelial cells with consecutive interstitial fibrosis. These studies have mostly been performed using mammalian in vivo models of glomerular damage or tissue cultures of mammalian tubulointerstitial cells. The kidney of the axolotl contains not only closed nephrons, but also nephrons with ciliated peritoneal funnels called nephrostomes that have access to the peritoneal fluid. Injection of protein into the peritoneal cavity fails to expose closed nephrons to a protein load, but causes selective uptake and transient storage of proteins in tubular epithelial cells of nephrons with nephrostomes. The purpose of the present study was to determine whether (a) the axolotl kidney can be used as a model to assess protein uptake by tubular cells in vivo in the absence of glomerular damage, and (b) this is accompanied by any evidence of tubular epithelial cell activation and interstitial fibrosis. METHODS: Male and female axolotl (80 to 120 g of weight) were given a daily intraperitoneal injection of 1.5 mL endotoxin-free calf serum or saline as control. Kidneys were harvested after 4 or 10 days using perfusion fixation for light microscopy (fibrous tissue stain) and saline perfusion for immunohistochemistry (fibronectin, TGF-beta and collagen I). RESULTS: The findings document selective storage of protein and lipids, progressive with time, in proximal tubular epithelial cells of nephrons draining the coelomic cavity. In addition, progressive focal accumulation of fibrous tissue was noted around protein-storing tubules. Immunohistochemical staining demonstrated the presence of fibronectin and TGF-beta in the tubular epithelial cells and interstitial cells. CONCLUSION: The axolotl kidney provides a novel in vivo model to study tubulointerstitial activation and induction of interstitial fibrosis by protein loading. The findings are independent of alterations of glomerular function that may have potential confounding effects on peritubular hemodynamics, pO2, cell traffic, etc.

Ambystoma↗
PubMed2002

Effect of antioxidant therapy with dl-alpha-tocopherol on cardiovascular structure in experimental renal failure.

BACKGROUND: Chronic renal failure is characterized by remodeling of the structure of the heart and the vasculature, for example, left ventricular hypertrophy, myocardial fibrosis, capillary/myocyte mismatch, as well as thickening of intramyocardial arteries and of peripheral arteries and veins. Furthermore, uremia is a state of increased oxygen stress. It was the purpose of this study to examine whether these findings are interrelated. METHODS: To investigate whether antioxidative therapy with dl-alpha-tocopherol (Toco; vitamin E) interferes with the development of abnormal cardiovascular structure in experimental renal failure, 28 male Sprague-Dawley rats were subjected to partial renal ablation (subtotal nephrectomy, SNX) or to sham operation (sham). SNX were either left untreated or received the antioxidant Toco (2 x 1500 IE/kg BW/week in the pellets). Blood pressure was measured using tail plethysmography. The experiment was terminated after 12 weeks. Heart and left ventricular weight were determined and the following parameters were measured using morphometry and stereology: volume densities of cardiomyocytes, capillaries and non-vascular interstitium; length density and total length of cardiac capillaries, wall thickness of intramyocardial arterioles and of the aorta. RESULTS: Systolic blood pressure and body weight were comparable in all groups. Treatment with Toco led to significantly increased plasma concentrations of Toco. Left ventricular weight and wall thickness of intramyocardial arteries were significantly higher in both SNX groups compared to sham controls. Volume density of the cardiac interstitial tissue was significantly higher in untreated SNX than in Toco treated SNX and sham control rats. Length density of capillaries was significantly lower in untreated SNX than in control rats; however, the values were significantly higher, and even higher than in sham controls, when SNX were treated with Toco. CONCLUSIONS: Treatment with the antioxidant dl-alpha-tocopherol prevented cardiomyocyte/capillary mismatch, and to some extent also myocardial fibrosis in rats with renal failure. The results point to a role of oxidative stress in the genesis of myocardial interstitial fibrosis and capillary deficit of the heart.

Animals↗
PubMed2002

Kidney and hypertension.

There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that "blood pressure goes with the kidney," a normotensive recipient of a kidney genetically programmed for hypertension (HT) will develop HT, while conversely hypertensive patients with renal failure receiving the kidney of a normotensive donor may develop normotension. Family studies showed higher BP values and more frequent HT in first degree relatives of patients with primary glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion that HT accelerates the loss of renal function has been proposed at the turn of the century, but definite evidence by observational and interventional studies has only been provided in the last two decades. The issue has been much confounded by the mistaken believe that damaged kidneys require higher BP values in order to function properly. The mechanisms of BP increase in renal disease comprise: salt retention, inappropriate activity of the renin-angiotensin system (RAS) and of the sympathetic nerve system as well as impaired endothelial cell-mediated vasodilatation. There is ample evidence both in primary renal disease (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT, RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers has BP-independent renoprotective effects. More recently, it has also been shown that blockade of the sympathetic nerve system has BP-independent effects on albuminuria and on glomerulosclerosis.

Humans↗
PubMed2002

Malignancy after renal transplantation.

Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression.

Adolescent↗
PubMed2002

Secondary hyperparathyroidism and its therapy as a cardiovascular risk factor among end-stage renal disease patients.

Secondary hyperparathyroidism (HPTH) was initially viewed as a disorder of the skeletal system; however, recent population-based data have associated markers of HPTH with an increased cardiovascular mortality among patients with end-stage renal disease (ESRD). This has stimulated much interest in further evaluating secondary HPTH as a cardiovascular disease risk factor, as well as the putative role of its therapy. This article explores the current state of scientific evidence concerning the pathophysiology of cardiovascular disease among the ESRD population and potential risk factors for its development, including markers of HPTH, and its therapies.

Animals↗