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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 217 records · Page 12Linked to original sources
PubMed1998

Optimal haemoglobin during treatment with recombinant human erythropoietin.

The optimal target haemoglobin during treatment with recombinant human erythropoietin (r-HuEPO) is still controversial. The impact of haemoglobin on cardiovascular function or survival, on physical performance and on medical rehabilitation have to be taken into consideration. Although currently there is no solid evidence to show that haemoglobin beyond that recommended by the ad hoc committee of the National Kidney Foundation improves survival, sound theoretical arguments can be offered for this proposition, particularly in cardiac patients. It is sensible to individualize the target haemoglobin and to avoid rapid correction of anaemia.

Anemia↗
PubMed1998

Cardiovascular abnormalities in ageing and in uraemia--only analogy or shared pathomechanisms?

The analogies between the effects of ageing and of uraemia on the function and the structure of central elastic arteries and of the heart are striking. Qualitatively similar changes are seen in pulse contour, pulse wave velocity, and impedance and also similar structural abnormalities with wall thickening, diminished elastin, and increased collagen content. The altered 'Windkessel' function of central arteries in age and uraemia is one factor contributing to left ventricular hypertrophy.

Aged↗
PubMed1998

The drama of the continuous increase in end-stage renal failure in patients with type II diabetes mellitus.

Type II diabetes mellitus has become the leading cause of end-stage renal failure in many countries of Western Europe. In all European countries, even in those with a relatively low prevalence of diabetic nephropathy, the number of patients with type II diabetes mellitus admitted for renal replacement therapy has recently increased continuously. Survival and medical rehabilitation of patients with type II diabetes on renal replacement therapy is significantly worse than in non-diabetic patients. It is obvious that in order to stem the tide, intense efforts are necessary (i) to inform the medical community about the renal risk of type II diabetes and the striking effectiveness of preventive measures, (ii) to provide better care for diabetic patients, and (iii) to reduce the high prevalence of diabetes in the population by modification of the Western life style.

Diabetes Mellitus, Type 2↗
PubMed1998

Regulation of intestinal vitamin D receptor expression in experimental uraemia: effects of parathyroidectomy and administration of PTH.

In this study, the effects of PTH on binding of [3H]-1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and on vitamin D receptor (VDR) mRNA concentration were assessed in intestinal mucosa of subtotally nephrectomized rats (Nx) and in intestinal mucosa of sham-operated rats with normal kidney function (Intact). Intestinal 1,25(OH)2D3 binding capacity of Intact remained unchanged (i) after parathyroidectomy (PTx), (ii) after administration of PTH for up to 6 days, and (iii) after PTx and subsequent administration of PTH (n = 4 experiments). In contrast, PTx of subtotally nephrectomized animals (Nx-PTx) decreased 1,25(OH)2D3 binding capacity from 757 +/- 95 fmol/mg protein in Nx to 417 +/- 42 in Nx-PTx (P < 0.01, n = 5). PTH administration had no effect on intestinal 1,25(OH)2D3 binding capacity in Nx. However, PTH administration to Nx-PTx resulted in re-elevation of 1,25(OH)2D3 binding capacity to a level (790 +/- 113 fmol/mg protein) which was comparable to Nx. Kd-values remained unaltered under all experimental conditions. The intestinal VDR mRNA concentration (normalized to beta-actin mRNA) was decreased, on average, by 23% in Nx-PTx (P < 0.05 versus Nx). In further experiments, 1,25(OH)2D3 was administered to Nx-PTx. This resulted in upregulation of 1,25(OH)2D3 binding capacity as compared to vehicle-treated Nx-PTx (562 +/- 90 fmol/mg protein versus 249 +/- 32, P < 0.01). The latter results could indicate that PTH-mediated stimulation of residual renal 1,25(OH)2D3 production was involved in PTH-mediated up-regulation of intestinal 1,25(OH)2D3 binding capacity in Nx-PTx. To rule out this possibility, PTH was administered to totally nephrectomized and parathyroidectomized rats (TNx-PTx). Since PTH caused an approximately 80% increase (P < 0.05) in intestinal 1,25(OH)2D3 binding capacity under those experimental conditions a mediator role of 1,25(OH)2D3 could be excluded. Functional significance of decreased intestinal 1,25(OH)2D3 binding capacity in Nx-PTx as compared to Nx was demonstrated by significantly lower 1,25(OH)2D3-mediated stimulation of intestinal 25(OH)D3-24-hydroxylase activity in Nx-PTx (209 +/- 68 pmol/mg protein) than in Nx (385 +/- 81, P < 0.01). The modulation of intestinal 1,25(OH)2D3 binding capacity was not correlated with changes in calcium, phosphate or 1,25(OH)2D3 serum concentrations under our experimental conditions. Taken together, intact parathyroid gland function was required to maintain adequate intestinal VDR expression in experimental uraemia (but not in normal animals). The mechanism of the modulation of intestinal VDR by PTH remains to be elucidated although an indirect effect of PTH on VDR expression in intestinal mucosa seems most likely.

Animals↗
PubMed1998

Low-salt diet downregulates plasma but not tissue kallikrein-kinin system.

The kallikrein-kinin system (KKS) is involved in the regulation of blood pressure and in the sodium and water excretion. In humans, the KKS is divided functionally into a plasma KKS (pKKS) generating the biologically active peptide bradykinin and into the tissue (glandular) KKS (tKKS) generating the active peptide kallidin. The objective of this study was to examine the effect of a low-NaCl diet on the concentration of both pKKS and tKKS in plasma and urine in 10 healthy volunteers. After a 4-day low-NaCl diet, the urinary sodium and chloride excretions had decreased from 234 to 21.2 mmol/24 h and from 198 to 14.6 mmol/24 h, respectively. The plasma levels of ANG I, aldosterone, and angiotensin converting enzyme (ACE) significantly increased from 50.4 to 82.8 pg/ml, from 129 to 315 pg/ml, and from 46.4 to 59.8 U/ml, respectively, demonstrating the physiological adjustment to the low-salt diet. In plasma, the levels of bradykinin and plasma kallikrein had significantly decreased from 13.7 to 7.57 pg/ml and 14.4 to 7.13 U/ml, respectively. However, the levels of high-molecular-weight kininogen (HMW kininogen) remain unchanged (101 vs. 112 microg/ml, not significant). Contrary to plasma kallikrein, the plasma levels of tissue kallikrein increased (0.345 vs. 0.500 U/ml; P < 0.01). The plasma kallidin levels, however, did not change (64.7 vs. 68.6 pg/ml, not significant). This can be explained by a simultaneous decrease in the plasma low-molecular-weight kininogen (LMW kininogen) levels (89.9 vs. 44.4 microg/ml; P < 0.05). As in plasma, we find increased urinary concentrations of renal (tissue) kallikrein (23.3 to 42.8 U/24 h; P < 0.05) that contrast with, and are presumably counterbalanced by, urinary LMW kininogen levels (77.0 vs. 51.8 microg/24 h; P < 0.05). Consequently, in urine low-NaCl diet caused no significant change in either bradykinin or kallidin (9.2 vs. 10.8 microg/24 h, and 10.9 vs. 10.3 microg/24 h). It is concluded that the stimulation of the renin-angiotensin system on a low-NaCl diet is associated with a decrease in pKKS (bradykinin and plasma kallikrein) but not in tissue and renal KKS. Although tissue kallikrein is increased, there is no change in kallidin, as LMW kininogen in plasma and urine is decreased. These data suggest a difference in the regulation of pKKS and tKKS by low-salt diet.

Adult↗
PubMed1998

Relationship between hypertension and renal function and its therapeutic implications in the elderly.

The kidney is an important target of hypertension-induced organ damage. Recent long-term observation studies have documented that in individuals, without primary chronic renal disease, a very significant relationship exists between hypertension and impaired renal function, elderly hypertensives having a particularly worse prognosis. The hallmark of hypertensive renal injury is thought to be a progressive increase in intrarenal vascular resistance. The alterations in renal hemodynamics are accentuated in elderly patients with essential hypertension, pointing to a greater vulnerability of the senescent kidney to superimposed injury such as high blood pressure. Treatment of elevated blood pressure in the elderly therefore not only reduces cardiovascular morbidity and mortality, but also reduces the incidence of renal failure as a consequence of hypertension-induced damage.

Aging↗
PubMed1998

Hypertension in the transplanted patient.

Hypertension is a common finding after renal transplantation, and it has a variety of underlying mechanisms. One reason is the type of immunosuppressive therapy, with a higher prevalence of hypertension in cyclosporine-treated patients. Cyclosporine interferes with several humoral and neural systems which are involved in blood pressure regulation such as the renin-angiotensin system, endothelins, nitric oxide, prostaglandins and the sympathetic nervous system. Other pathomechanisms for posttransplant hypertension are uncontrolled renin secretion of the native kidneys, polycythemia, recurrence of renal disease in the graft and renal failure. Renal transplant artery stenosis is a potentially treatable cause of post-transplant hypertension and several techniques such MRT angiography, Doppler sonography and conventional angiography are available. The diagnosis and treatment of hypertension are of high importance in general for the transplanted patient, and especially for the long-term prognosis of graft function.

Female↗
PubMed1998

Nephroprotection of an ET(A)-receptor blocker (LU 135252) in salt-loaded uninephrectomized stroke-prone spontaneously hypertensive rats.

The present study was designed to assess whether the orally active and highly specific endothelin A (ET(A)) receptor antagonist LU 135252 affects progressive renal dysfunction in a hypertensive rat model of renal damage, ie, the uninephrectomized (UNX) stroke-prone spontaneously hypertensive rat (SHRsp). The animals were examined on a normal salt (0.25%) diet and, to sensitize the kidney to hypertensive injury, also on a high salt (3%) diet. Stereological methods were used to quantify indices of glomerulosclerosis, vascular damage, and tubulointerstitial damage. Treatment with LU 135252 (100 mg/kg body wt) did not affect systolic blood pressure (BP) in animals on a normal salt diet during the whole period of the experiment (18 weeks) or in salt-loaded animals until week 10; subsequently, BP was slightly but significantly lower in salt-loaded UNX-SHRsp given LU 135252. Between weeks 6 and 12, 40% of the untreated UNX-SHRsp on a high salt diet, but none on a standard salt diet, died; such mortality was completely prevented by LU 135252. Indices of renal damage were more abnormal in salt-loaded UNX-SHRsp compared with UNX-SHRsp on a normal salt diet. Development of glomerulosclerosis and tubulointerstitial and vascular damage in UNX-SHRsp on high salt was completely prevented by LU 135252. The respective indices were no longer significantly different from those of salt-loaded sham-operated SHRsp controls. In the less severely damaged kidneys of UNX-SHRsp on normal salt, treatment with LU 135252 tended to ameliorate the indices, but the difference was not statistically significant. The results document a role of the ET system, specifically of ET(A) receptors, in the development of progressive renal injury in salt-loaded UNX-SHRsp. LU 135252 completely prevented death and renal damage resulting from salt loading.

Animals↗
PubMed1998

Effects of acute ACE inhibition on pulsatile renin and aldosterone secretion and their synchrony.

Pulsatile (burstlike) secretion of renin and aldosterone is positively coupled with a short time lag of about 10 to 20 minutes. We investigated how acute interruption of the renin-angiotensin-aldosterone axis, ie, acute angiotensin-converting enzyme (ACE) inhibition, alters the pattern of renin and aldosterone secretion. Eight healthy men (mean age, 22+/-1 years) were studied while on standardized salt intake. They were allocated on 2 occasions in random order to injection of placebo or 1.25 mg of the ACE inhibitor enalaprilat. Blood samples were obtained every 10 minutes for 24 hours for measurement of plasma renin and aldosterone concentrations. The hormone concentration profiles were analyzed using a multiparameter deconvolution technique; basal (tonic) and pulsatile hormone secretion was assessed. The regularity of pulsatile hormone secretion was analyzed using approximate entropy (ApEn). Cross-correlation and cross-ApEn analysis of renin and aldosterone secretion were performed to assess synchrony. Acute ACE inhibition caused an immediate burst of renin release and, in addition, significantly (P<0.01) increased 24-hour pulsatile and total renin secretion. It did not affect basal (nonpulsatile) renin secretion. The amplitude of renin bursts and the mass of hormone secreted per burst were significantly (P<0.01) increased, whereas the burst frequency (ie, number of secretory events) was unchanged. ApEn analysis revealed significantly (P<0.05) more regular renin secretion after ACE inhibition. In contrast, neither basal nor pulsatile aldosterone secretion was affected by administration of enalaprilat. Cross-ApEn analysis documented not only a maintained pattern of reproducibility (ie, synchrony) but also greater conditional regularity between pulsatile renin and aldosterone secretions with acute ACE inhibition. However, the quantitative strength of hormone coupling (assessed by cross-correlation analysis) was markedly diminished by enalaprilat treatment. The present findings suggest that the renin-angiotensin-aldosterone axis may not be completely uncoupled by acute ACE inhibition or that pulsatile renin and aldosterone secretion is driven by a common signal generator that is unaffected by ACE inhibition. In addition, a background basal and pulsatile aldosterone secretion not regulated by the renin-angiotensin axis may exist.

Adult↗
PubMed1998

Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease.

Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of FF were not uniform, and a small but consistent increase of urinary albumin/creatinine ratio was observed. An additional 20 volunteers were subjected to the smoking arm of the study for statistical evaluation of the GFR change in patients. The difference between the change of GFR between all volunteers (n = 35) and patients (n = 7) was significant (P < 0.005). It is concluded that the known effects of smoking and nicotine on the sympathetic nervous system and on systemic hemodynamics are accompanied by significant acute changes in renal hemodynamics and albuminuria. These findings are of interest because of the known effects of smoking on progression of renal disease.

Adult↗
PubMed1998

Altered instantaneous and calcium-modulated oscillatory PTH secretion patterns in patients with secondary hyperparathyroidism.

The relative contributions of increased parathyroid cell mass and altered control mechanisms of parathyroid hormone (PTH) secretion in secondary hyperparathyroidism are still controversial. In this study, endogenous pulsatile PTH secretion was analyzed by the multiparameter deconvolution technique to differentiate alterations in cell mass-dependent (PTH burst mass) and regulation-dependent (frequency, synchrony, calcium responsiveness) PTH release in uremic patients. PTH concentration versus time profiles were obtained in 13 uremic and 16 healthy adults under baseline conditions and during acute hypo- and hypercalcemia. Plasma PTH half-life was increased in patients compared with control subjects (4.7+/-1.9 versus 2.6+/-0.1 min, P < 0.005). The baseline PTH secretion rate was elevated eightfold in the patients as a result of an increased PTH mass secreted per burst (17.1+/-4.7 versus 2.0+/-0.4 pM, P = 0.0001), higher burst frequency (8.0+/-0.3 versus 6.8+/-0.3 h(-1), P < 0.01), and a higher tonic secretion rate (343+/-99 versus 30+/-4 pM/h, P = 0.0001). Acute hypocalcemia elicited an immediate, frequency- and amplitude-mediated selective increase in the pulsatile secretory component, which was fractionally weaker in patients (+595%) than control subjects (+1755%, P < 0.001). The acceleration and the amplification of PTH bursts were 35 and 60% lower in the patient group. Acute hypercalcemia suppressed total PTH secretion by 79% in control subjects but only by 63% in patients (P < 0.002). PTH burst frequency was reduced during hypercalcemia by 30% in control subjects, but remained unchanged in patients. In conclusion, uremic hyperparathyroidism is mediated by a marked increase in glandular secretion, but also by reduced PTH elimination. The increased spontaneous PTH burst frequency and the blunted responsiveness to changes in Ca2+ indicate partial uncoupling of hyperplastic parathyroid glands from the physiologic regulatory mechanisms that direct pulsatile PTH release.

Adolescent↗
PubMed1998

1,25(OH)2-vitamin D3 reduces spontaneous and hypocalcemia-stimulated pulsatile component of parathyroid hormone secretion.

To investigate the effects of 1,25(OH)2-vitamin D3 (1,25(OH)2D3) on pulsatile parathyroid hormone (PTH) release, minute-to-minute intact PTH secretion was examined in nine healthy adults under baseline conditions and during hypocalcemia (sodium citrate clamp) before and after 5 d of oral 1,25(OH)2D3 treatment (1 microgram/d). In addition, acute effects of 1,25(OH)2D3 were examined by a single intravenous bolus of 2 micrograms of 1,25(OH)2D3. Pulsatile and tonic PTH secretion rates were calculated by the multiparameter deconvolution technique. During baseline, 68% of circulating PTH was attributable to tonic, and 32% to pulsatile, secretion. During induction of hypocalcemia, a selective increase in pulsatile secretion (+1100%), mediated by a combined increase in burst frequency and burst mass, was observed. During the subsequent steady-state hypocalcemic period, burst frequency and mass decreased and tonic secretion increased to 3 times the baseline level. Intravenous 1,25(OH)2D3 did not affect the temporal pattern of PTH secretion. In contrast, oral 1,25(OH)2D3 decreased baseline plasma PTH by 30% without a detectable change in Ca2+. This suppression was accounted for mainly by a decrease in PTH burst frequency. During hypocalcemia induction, a significantly lower (30%) increase in burst mass occurred compared with the pretreatment study. During steady-state hypocalcemia, PTH burst mass (-45%) and pulsatile (-50%) and total (-35%) secretion rate were lower than before treatment. In conclusion, acute hypocalcemia selectively increases pulsatile PTH release by stimulating both burst frequency and mass via a Ca2+ rate-sensitive mechanism. Oral 1,25-(OH)2D3 suppresses pulsatile baseline PTH release and reduces the pulsatile secretory capacity of the parathyroids during a hypocalcemic stimulus.

Administration, Oral↗
PubMed1998

Myocyte/capillary mismatch in the heart of uremic patients.

Experiments indicate that capillary density is reduced in the hypertrophied left ventricle of rats with subtotal nephrectomy compared to control rats with similar BP and left ventricular hypertrophy, suggesting that in uremia, hypertrophying cardiomyocytes outgrow their capillary supply. No information on myocardial capillary supply in humans is currently available. The hearts of nine dialyzed patients, nine patients with essential hypertension, and 10 normotensive control subjects at postmortem were obtained. Subjects with stenosing coronary lesions and left ventricular pump failure were excluded. Special sampling procedures were used to exclude stereologic artefacts. Capillaries were specifically stained with ulex lectin and analyzed by stereologic techniques. Length density of myocardial capillaries (Lv; mm/mm3) was significantly (P < 0.001) lower in dialyzed patients (1483 +/- 238) than in patients with essential hypertension (1872 +/- 243) or in normotensive control patients (2898 +/- 456). In parallel, myocyte diameter and volume density of myocardial interstitial tissue were significantly (P < 0.001) increased in uremic patients compared to patients with essential hypertension and control patients, respectively. Diminished left ventricular capillary supply in renal failure must increase critical oxygen diffusion distance in the myocardium, thus exposing cardiomyocytes to the risk of hypoxia. It is unknown whether such reduced ischemia tolerance can be reversed by increasing oxygen supply (e.g., by reversing anemia).

Aged↗
PubMed1998

The genetics of renal tumors in end-stage renal failure differs from those occurring in the general population.

The genetics of renal cell tumors (RCT), which occur at a high frequency in patients with end-stage renal failure (ESRF), is not yet known. Using a fluorescence microsatellite assay and comparative genomic hybridization, 18 renal tumors obtained from nine patients with ESRF were analyzed for genetic alterations, which are known to be characteristic of common nonpapillary and papillary RCT in the general population. Deletion of chromosome 3p was detected in six nonpapillary tumors, whereas trisomies of 7 and 17 or 3, 8, and 16 were seen in four of 18 tumors. No alterations were found in four tumors, and another four tumors had unspecific changes. The fragile histidine triad (FHIT) gene is localized at the most common fragile site at chromosome 3p14.2. The FHIT and the p53 tumor suppressor gene are targets of different environmental agents. Because both toxic effect and genomic instability are implicated in the development of renal cysts in ESRF, the alteration of both genes in tumor cells was analyzed. No abnormal expression of the FHIT gene or mutation of the p53 gene were found. This study suggests that the genetics and also the morphology of some of the ESRF RCT differ from those known for RCT in the general population.

Acid Anhydride Hydrolases↗
PubMed1998

[Vitamin D receptor gene polymorphism and the rate of bone loss of the femur neck and lumbar spine in hemodialized patients with chronic renal failure].

It has been suggested that the vitamin D receptor (VDR) gene Bsml-polymorphism is a genetic determinant of bone metabolism. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 136 haemodialyzed patients. Lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1.25(OH)2D3, osteocalcin serum concentrations, bone alkaline phosphatase activity and intact 1, 84-PTH levels were measured. VDR genotype BB, Bb and bb were found in 24%, 46% and 30% of patients respectively. Initial BMD (g/cm2) of lumbar spine and femoral neck did not differ between genotypes, however the decrease of femoral neck BMD during 18 months of observation differ significantly (p < 0.02) between the particular genotype groups (femoral neck: BB -0.031 +/- 0.029; Bb -0.027 +/- 0.017; bb -0.017 +/- 0.019 g/cm2). Significantly lower serum level of 25OHD3 was found in patients with the BB genotype before and after 18 months of observation in comparison to the respective values obtained in bb genotype patients, (respectively, 21.0 +/- 16.8 ng/ml vs 30.8 +/- 17.9 ng/ml; p < 0.01 and 24.0 +/- 10.8 ng/ml vs 32.4 +/- 16.0 ng/ml; p < 0.02). BB genotype patients were also characterised by significantly lower serum level of 1.25(OH)2D3 both initially and after 18 month of the study (respectively in BB and bb patients 25.9 +/- 9.7 pg/ml vs 30.7 +/- 10.0 pg/ml; p < 0.02 and 18.4 +/- 12.3 pg/ml vs 24.3 +/- 13.0 pg/ml; p < 0.01). No significant differences were found in Ca, P, osteocalcin, iPTH serum concentrations and bone fraction of alkaline phosphatase activity between particular genotypes. Results from this study suggest that faster bone mineral loss and more exaggerated disturbances of vitamin D metabolism are present in haemodialyzed uraemic patients with BB than bb genotype of VDR.

Adult↗