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Eberhard Ritz

Publications and source records attributed to Eberhard Ritz.

141 records · Page 8Linked to original sources
PubMed2001

Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy?

There is convincing evidence for a specific BP-independent effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 +/- 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 +/- 5.1 yr) with baseline urinary albumin excretion rates (AER) >20 microg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 +/- 7.1 mmHg in the third week of placebo and 91.1 +/- 8.7 mm Hg on moxonidine). There was a significant (P< 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 microg/min (range, 15.9 to 117 microg/min) versus 29.0 (range, 9.03 to 85.8 microg/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for the finding.

Adult↗
PubMed2000

Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure.

High lipoprotein(a) (Lp(a)) serum concentrations and the underlying apolipoprotein(a) (apo(a)) phenotypes are risk factors for cardiovascular disease in the general population as well as in patients with renal disease. Lp(a) concentrations are markedly elevated in patients with end-stage renal disease. However, nothing is known about the changes of Lp(a) depending on apo(a) size polymorphism in the earliest stages of renal impairment. In this study, GFR was measured by iohexol technique in 227 non-nephrotic patients with different degrees of renal impairment and was then correlated with Lp(a) serum concentrations stratified according to low (LMW) and high (HMW) molecular weight apo(a) phenotypes. Lp(a) increased significantly with decreasing GFR. Such an increase was dependent on apo(a) phenotype. Only renal patients with HMW apo(a) phenotypes expressed higher median Lp(a) concentrations, i.e., 6.2 mg/dl at GFR >90 ml/min per 1.73 m2, 14.2 at GFR 45 to 90 ml/min per 1.73 m2, and 18.0 mg/dl at GFR <45 ml/min per 1.73 m2. These values were markedly different when compared with apo(a) phenotype-matched control subjects who had a median level of 4.4 mg/dl (ANOVA, linear relationship, P < 0.001). In contrast, no significant differences were observed at different stages of renal function in patients with LMW apo(a) phenotypes when compared with phenotype-matched control subjects. The elevation of Lp(a) was independent of the type of primary renal disease and was not related to the concentration of C-reactive protein. Multiple linear regression analysis found that the apo(a) phenotype and GFR were significantly associated with Lp(a) levels. Non-nephrotic-range proteinuria modified the association between GFR and Lp(a) levels. In summary, an increase of Lp(a) concentrations, compared with apo(a) phenotype-matched control subjects, is seen in non-nephrotic patients with primary renal disease even in the earliest stage when GFR is not yet subnormal. This change is found only in subjects with HMW apo(a) phenotypes, however.

Adult↗
PubMed2000

Opposing effects of angiotensin II on muscle and renal blood flow under euglycemic conditions.

Angiotensin II (Ang II) enhances insulin sensitivity in humans, and this is associated with a paradoxical increase in skeletal muscle blood flow. It is unclear whether these effects are mediated via subtype 1 receptors of Ang II, because these receptors are thought to mediate vasoconstriction. Insulin-stimulated glucose uptake (euglycemic clamp technique) and leg muscle blood flow (plethysmography) were measured in nine healthy male volunteers (mean age, 24 +/- 2 yr) on three occasions using a double-blind, placebo-controlled study design. The subjects were allocated in random order to (1) placebo premedication per os plus placebo infusion, (2) placebo premedication per os plus infusion of 5 ng Ang II/kg per min, and (3) premedication with 300 mg of the angiotensin II-1-receptor antagonist irbesartan per os plus infusion of 5 ng Ang II/kg per min. In addition, GFR and effective renal plasma flow were assessed using the steady-state inulin- and paraaminohippurate clearance. Insulin sensitivity (i.e., M value) and muscle blood flow after infusion of Ang II (9.3 +/- 1.8 mg/kg per min; 17.7 +/- 2.1 ml/100 g per min) were significantly higher than after placebo infusion (7.2 +/- 1.6 mg/kg per min, P: < 0.02; 13.5 +/- 1.8 ml/100 g per min, P: < 0.01). In contrast, after premedication with irbesartan, they were not significantly different (7.5 +/- 1.7 mg/kg per min; 14.3 +/- 1.9 ml/100 g per min) as compared with placebo infusion. Mean GFR and effective renal plasma flow were significantly lower (P: < 0.01), and renal vascular resistance was significantly higher (P: < 0.01) with Ang II infusion as compared with the placebo infusion study. Premedication with irbesartan almost completely blocked the vasoconstrictive effect of Ang II on renal vasculature. Under hyperinsulinemic euglycemic conditions, infusion of Ang II has opposing effects on regional arterial blood flow, i.e., an increase in skeletal muscle blood flow, but vasoconstriction of renal vasculature. Both effects are antagonized by blockade of subtype 1 Ang II receptors.

Adult↗
PubMed2000

Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats.

ABSTRACT.: A potential role of the sympathetic nervous system in progression of renal failure has received little attention. This study examined whether nonhypotensive doses of moxonidine, an agent that reduces sympathetic activity, affects glomerulosclerosis, urine albumin excretion, and indices of renal handling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Sprague Dawley rats were SNX or sham-operated (control). SNX rats were either left untreated or treated with moxonidine in a dose (1.5 mg/kg body wt per d) that did not modify telemetrically monitored 24-h BP. Glomerular and renal morphology were evaluated by quantitative histology, immunohistochemistry, and in situ hybridization. Urine albumin excretion rate was analyzed by enzyme-linked immunosorbent assay, and kidney angiotensin II and NE content were measured using HPLC, (3)H-NE uptake, and release. Body and kidney weight and BP were not significantly different between SNX with or without moxonidine. The glomerulosclerosis index was significantly lower in moxonidine-treated (0.88 +/- 0.09) compared with untreated (1.55 +/- 0.28) SNX rats, as was the index of vascular damage (0.32 +/- 0.14 versus 0.67 +/- 0.16). The number of proliferating cell nuclear antigen-positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in controls and moxonidine-treated SNX rats. The same was true for urine albumin excretion rate. Renal angiotensin II tissue concentration was not affected by moxonidine. In untreated SNX rats, renal nerve stimulation and exogenous NE induced an increase in isolated kidney perfusion pressure (102 +/- 21 versus 63 +/- 8 mmHg). Renal endogenous NE content was significantly lower in SNX rats than in controls (86 +/- 14 versus 140 +/- 17 pg/mg wet weight). Cortical uptake of [(3)H]-NE was not different, but cortical NE release was significantly higher in SNX rats than in controls. Reduced function of presynaptic inhibitory alpha-adreno-receptors is unlikely because an alpha(2)-adrenoceptor antagonist increased NE release. At subantihypertensive doses, moxonidine ameliorates renal structural and functional damage in SNX animals, possibly through central inhibition of efferent sympathetic nerve traffic. In kidneys of SNX rats, indirect evidence was found for increased activity of a reduced number of nerve fibers.

Albuminuria↗
PubMed2000

Retinoic acid reduces glomerular injury in a rat model of glomerular damage.

ABSTRACT.: In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n = 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol, i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 +/- 4.8 mmHg; anti-Thy1.1/RA, 87.5 +/- 2. 5 mmHg; P < 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P < 0. 02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 +/- 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 +/- 4.4; P < 0.02; control/vehicle, 69 +/- 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 +/- 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 +/- 0.5, P < 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 +/- 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 +/- 0.8 cells were proliferating cell nuclear antigen-positive (P < 0.002; control, 2.2 +/- 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1. 1/RA-treated group, compared with the anti-Thy1.1/control group (P < 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P < 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.

Albuminuria↗
PubMed2000

Endothelin A receptor blockade prevents capillary/myocyte mismatch in the heart of uremic animals.

In the heart of uremic animals and patients, the number of capillaries per volume of myocardium is reduced. Immunohistochemical studies demonstrated increased cardiac endothelin-1 (ET-1) expression in the left ventricle of uremic animals. Therefore, whether treatment with a selective ET(A)-receptor antagonist prevented such capillary-myocyte mismatch was investigated. Twenty-four h after subtotal nephrectomy, rats were left untreated or started on treatment with the ET(A)-receptor antagonist LU 135252 (20 mg/kg per d) and with the angiotensin-converting enzyme (ACE) inhibitor trandolapril (0.3 mg/kg per d), respectively. BP was monitored by telemetry. Myocardial capillary length density was analyzed by stereologic techniques that avoid anisotropy artifacts. In addition, cardiac ET-1 protein and mRNA were measured using immunohistochemistry, in situ hybridization, and quantitative reverse transcription-PCR. Changes in cardiac ET(A)-and ET(B)-PCR. receptor mRNA were measured using reverse transcription-PCR. Fifteen wk after subtotal nephrectomy, significantly reduced left ventricular capillary length density (3307 +/- 535 mm/mm(3)) was found compared with sham-operated controls (3995 +/- 471 mm/mm(3)); this was also seen in animals that were treated with trandolapril (3503 +/- 533 mm/mm(3)) but not in animals that were treated with LU 135252 (3800 +/- 303 mm/mm(3)). The results support a role of ET-1 in the genesis of left ventricular capillary/myocyte mismatch in uremia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Do AV fistulas contribute to cardiac mortality in hemodialysis patients?

Potential fistula-related problems which may impact on patient survival include high fistula flow with hyperkinetic circulation and cardiac failure, low fistula flow with the risks of underdialysis and fistula thrombosis, vascular access infection with local or systemic manifestations, and possibly induction and maintenance of a microinflammatory state (at least for synthetic grafts). All these complications are much more common with prosthetic grafts than with native arteriovenous (AV) fistulas. Fistula flow should be monitored (e.g., by duplex sonography) to guarantee adequate flow and permit preemptive intervention to avoid fistula thrombosis.

Arteriovenous Shunt, Surgical↗
PubMedDate not supplied

Cardiovascular abnormalities and hypertension in the elderly dialysis patient.

Elderly individuals comprise an ever-increasing proportion of patients on renal replacement therapy (RRT). As in younger patients, cardiovascular events are the major cause of death in the elderly on RRT, although the relative proportion succumbing to cardiovascular events is similar to that in young patients. An important observation is that the elderly are particularly likely to experience higher mortality if dialysis technique is suboptimal; they also experience particular benefit from successful renal transplantation. The latter observation has led to an "old for old" program in Europe.

Aged↗
PubMedDate not supplied

Congestive heart failure due to systolic dysfunction: the Cinderella of cardiovascular management in dialysis patients.

Cardiac disease is common in dialysis patients. Survival is poorest in the subgroup with systolic dysfunction (pump failure). Audits show that cardiovascular management of dialysis patients in general, and treatment of congestive heart failure (CHF) specifically, is generally not in agreement with recommendations based on evidence obtained from controlled trials, admittedly in nonrenal patients. The pathophysiology underlying CHF and the rationale underlying interventions are discussed in an effort to heighten awareness of this important clinical problem in the dialysis community.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Renal dysfunction: a novel indicator and potential promoter of cardiovascular risk.

Epidemiological studies have defined a number of risk factors predicting cardiovascular events, including hypertension, dyslipidaemia, diabetes mellitus and smoking. Renal dysfunction, however, has only recently been included among the strongest predictors of cardiovascular risk. The increment in risk is already apparent in the early stages of borderline renal dysfunction, for example low rates of albumin excretion (microalbuminuria) and minor decrease of creatinine clearance. The information is incomplete, but a number of potential mechanisms have been identified through which renal dysfunction may increase the cardiovascular risk. Great progress has been made in providing algorithms to detect patients at risk and to identify interventions to reduce the risk.

Albuminuria↗
PubMedDate not supplied

The clinical management of hyperphosphatemia.

As renal function declines in patients with end-stage renal disease (ESRD), excess dietary phosphorus accumulates in the bloodstream. Routine dialysis removes up to 70% of absorbed phosphorus; therefore, hyperphosphatemia is found in the majority of patients with ESRD. The consequences of this imbalance include secondary hyperparathyroidism and osteodystrophy. Recent studies have also documented that hyperphosphatemia can lead to soft-tissue and vascular calcification; the latter is strongly associated with cardiovascular disease and, thus, increased mortality and morbidity. The reduction of phosphorus levels is, therefore, an important therapeutic target in this patient group. Management of hyperphosphatemia using conventional phosphate binders is not always successful. However, emerging therapies aim to reduce the incidence of hyperparathyroidism, bone disease, and calcification in this patient population. In this article, the consequences of hyperphosphatemia are reviewed, and recent developments in the treatment of the condition are discussed.

Aluminum Hydroxide↗
PubMedDate not supplied

Mediators of inflammatory and ischemic renal damage: the role of neoangiogenesis.

Neoangiogenesis is at the forefront of research in a number of fields that are of interest to the nephrologist, ranging from the development of the kidney and glomerulus to microvascular injury and its repair. The molecular mechanisms have recently been elucidated to a considerable extent. They are relevant for understanding the link between endothelial cells and podocytes, which underlie the glomerular barrier function. For reasons poorly understood capillarogenesis is defective in renal failure.

Animals↗