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A Kurtz

Publications and source records attributed to A Kurtz.

At least 181 records · Page 10Linked to original sources
PubMed1992

Insulin-like growth factor I: a modulator of erythropoiesis in uraemic patients?

Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.

Adult↗
PubMed1991

Structure-function correlations in erythropoietin formation and oxygen sensing in the kidney.

The kidney is the main site of erythropoietin (EPO) formation. Oxygen sensing in the kidney itself plays a major role in the control of EPO synthesis. By in situ hybridization it has been established that the EPO-producing cells are situated in the interstitium of the cortical labyrinth, but they have not been precisely identified. Morphological findings provide new insights into the location and mechanism of oxygen sensing in the kidney. In addition to causing an increase in the number of cells containing EPO messenger RNA, anemia provokes structural changes exclusively in the cortical labyrinth. Specifically, the fibroblasts become enlarged and show increased activity of 5'-nucleotidase, and the S1 segment of the proximal tubule shows similar alterations as in various models of hypoxia. Thus, structures that are situated in the close vicinity of the EPO-producing cells appear to be sensitive to decreased oxygen delivery.

Anemia↗
PubMed1991

Oxygen-dependent erythropoietin production by the isolated perfused rat kidney.

In this study we have investigated the role of oxygen delivery and of classic second messengers on erythropoietin production by the isolated perfused rat kidney. We found that the rat kidney was capable of de novo synthesis of erythropoietin. The erythropoietin production rate was inversely related to the oxygen pressure in the perfusate and increased from 0.17 to 1.85 U erythropoietin h-1 g kidney-1 when arterial PO2 was lowered from 500 mmHg to 30 mmHg. Addition of forskolin (10 microM) and 8-bromo-cGMP (100 microM) to the perfusate elicited significant effects on the renal vascular resistance, but had no significant effect on erythropoietin production. Hypoxia-induced erythropoietin formation, however, was blocked by calmidazolium (1 microM) and W-7 (10 microM), two structurally different putative calmodulin antagonists. Calmidazolium and W-7 had no effect on other functional parameters of the isolated perfused rat kidney such as flow rate, glomerular filtration rate or sodium reabsorption. Our findings suggest that the oxygen-sensing mechanism that controls renal erythropoietin production is primarily located in the kidney itself. A calcium/calmodulin-dependent cellular reaction could be involved in the signal transduction process.

Animals↗
PubMed1991

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells.

In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na+/H+ antiport, amiloride (1 mM) and ethylisopropylamiloride (EIPA, 50 microM), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na+]e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 microM). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the denovo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloride-sensitive transport process, presumably the Na+/H+ exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.

Amiloride↗
PubMed1991

Serial immunoreactive erythropoietin levels in autologous blood donors.

The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 +/- 1.1 g per dL (143 +/- 11 g/L) (mean +/- SD) before the first donation to 11.7 +/- 0.7 g per dL (117 +/- 7 g/L) on Day 22 (p less than or equal to 0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per microL (median, 32 x 10(9)/L [range, 5-95 x 10(9)/L]) to 93,800 (16,800-194,900) per microL (median, 94 x 10(9)/L [range, 17-195 x 10(9)/L]) on Day 28 (p less than or equal to 0.01). Plasma EPO concentration was 17.8 +/- 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 +/- 15.5 mU/mL), third (38.0 +/- 14.5 mU/mL), and fourth (36.1 +/- 11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO.

Adult↗
PubMed1991

A controlled study of psychoanalytic treatment of brittle diabetes.

The study compared two equivalent groups of 11 diabetic children with grossly abnormal blood glucose profiles necessitating repeated admissions to a hospital. Patients in the treatment group were offered an intensive inpatient treatment program including psychoanalytic psychotherapy three to four times a week, which took place on the hospital ward and lasted an average of 15 weeks. The intervention was highly effective in improving the diabetic control of the children, and this was maintained at a 1 year follow-up. Patients in the comparison group, who were offered only inpatient medical intervention, returned to their prehospitalization level of metabolic control within a period of 3 months from discharge.

Adolescent↗
PubMed1991

Differential response of renin secretion to vasoconstrictors in the isolated perfused rat kidney.

1. We have examined whether an increase of renal vascular resistance is generally accompanied by an inhibition of renin secretion. The effects of vasoconstriction produced by angiotensin II (Ang II), arginine-vasopressin (AVP), and potassium (KCl) depolarization on vascular resistance and on renin release from isolated rat kidneys perfused at constant pressure of 100 mmHg were investigated. 2. Histological examination performed on some representative kidneys revealed that the tubular lumina of all segments within the cortex were patent and the brush borders of the proximal tubules were well preserved. The renal vasculature and the juxtaglomerular region appeared to be morphologically intact. By immunocytochemistry, renin-positive cells were found exclusively in the wall of the afferent arterioles. 3. Basal flow rate through isolated kidneys was 14.5 +/- 2.0 ml min-1 (g kidney weight (gkw))-1 (mean +/- S.E.M., n = 10). Under control conditions renin secretory rates were in the range of 30-40 (ng Ang I h-1) min-1 gkw-1. 4. Ang II (100 pM) caused a decrease of renal flow rate to 42 +/- 2% of control which was accompanied by a reduction of renin secretion rates by a factor of 4. 5. AVP (10 pM to 1 nM) reduced renal perfusate flow in a dose-dependent fashion to a minimum of 25 +/- 3% of control. The vasoconstrictor effect of AVP was paralleled by a concentration-dependent increase of renin secretory rates reaching a factor of maximally 5 when AVP was used at a concentration of 1 nM. The stimulatory effect of AVP on renin release could be mimicked by [deamino-Cys1, D-Arg8]-vasopressin (dDAVP), a vasopressin analogue with prevalent V2 receptor agonistic properties. In the presence of dDAVP (100 nM, 1 microM) renal flow rate reversibly increased by 8 and 12% of control values, respectively. 6. Depolarizing concentrations of KCl (30 mM) decreased perfusate flow to 20 +/- 4% of control. The vasoconstrictor effect of KCl was paralleled by an increase of the arterio-venous difference of perfusate renin activity to such an extent that the rate of renin release remained unaltered. 7. Our findings suggest that there exists no general inverse relationship between renal arteriolar resistance and renin secretion. Our study, moreover, does not support a functional role of potential operated calcium channels in the control of renin secretion. Finally, we conclude that V2 receptors are present on juxtaglomerular epithelioid cell membranes and mediate the stimulatory effect of AVP on renin release from isolated rat kidneys.

Angiotensin II↗
PubMed1991

Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy.

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.

Calcitriol↗
PubMed1991

Endothelial cells modulate renin secretion from isolated mouse juxtaglomerular cells.

Utilizing cocultures of mouse renal juxtaglomerular cells with bovine microvascular endothelial cells, we have examined whether endothelial cells exert direct influence on renin secretion from renal juxtaglomerular cells. In the presence of endothelial cells both spontaneous and forskolin (10 microM) or isoproterenol (10 microM) stimulated renin release were markedly attenuated. The stimulatory effect of the calmodulin antagonist calmidazolium (10 microM) on renin secretion was not altered by endothelial cells, whereas the stimulatory effect of ethylisopropylamiloride (50 microM) an inhibitor of sodium-proton exchange was enhanced in the presence of endothelial cells. Indomethacin (10 microM) and NG-monomethyl-l-arginine (NMMA) (1 mM) used to inhibit cyclooxygenase activity and production of endothelium-derived relaxing factor (EDRF) decreased spontaneous renin release in the presence of endothelial cells only, but had no effect on forskolin stimulated renin secretion. Endothelin (1 microM) inhibited cAMP stimulated renin release both in the absence and in the presence of endothelial cells. ATP (10 microM) which acts on both endothelial and juxtaglomerular cells via purinergic P2 receptors inhibited cAMP stimulated renin release only in the absence but not in the presence of endothelial cells. This modulatory effect of endothelial cells was no altered by indomethacin nor by NMMA. Taken together, our findings provide first evidence for a local control function of the endothelium on cAMP stimulated renin secretion from renal juxtaglomerular cells, which could in part be mediated by endothelin.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Determinants of renin secretion and renin synthesis in isolated mouse juxtaglomerular cells.

In this study we examined the effects of classic second messenger molecules on renin secretion and renin synthesis in primary cultures of mouse renal juxtaglomerular (JG) cells. Stimulation of cAMP formation by forskolin, inhibition of calmodulin by calmidazolium, and inhibition of Na+/H+ exchange by ethylisopropylamiloride enhanced renin secretion. Raising of intracellular cGMP by 8-bromo-cGMP and activation of protein kinase C by phorbol ester led to an inhibition of secretion. Renin synthesis was stimulated by forskolin. Calmidazolium, EIPA, 8-bromo-cGMP, and phorbol ester were without effect on basal renin synthesis. The data suggest that renin secretion is influenced by a number of transmembrane transduction systems which in their majority exert a negative control on renin secretion. Activation of adenylate cyclase appears to be a stimulatory control mechanism for both the secretion and the synthesis of renin. The findings suggest, moreover, that the second messenger controls of renin secretion and renin synthesis are not strictly linked in renal JG cells.

Animals↗
PubMed1990

Lack of direct evidence for a functional role of voltage-operated calcium channels in juxtaglomerular cells.

In this study we have examined the role of voltage-gated calcium channels in the regulation of calcium in juxtaglomerular cells. Using a combination of patch-clamp and single-cell calcium measurement we obtained evidence neither for voltage-operated calcium currents nor for changes of the intracellular calcium concentration upon acute depolarizations of the cell membrane. Increases of the extracellular concentration of potassium to 80 mmol/l depolarized the juxtaglomerular cells close to the potassium equilibrium potential, but did not alter the intracellular calcium concentration neither in patch-clamped nor in intact Furaester-loaded cells. Moreover, basal renin secretion from a preparation enriched in mouse juxtaglomerular cells and from rat glomeruli with attached juxtaglomerular cells was not inhibited when extracellular potassium was isoosmotically increased to 56 mmol/l. In mouse kidney slices, however, depolarizing potassium concentrations caused a delayed inhibition at 56 mmol/l and a delayed stimulation of renin secretion at 110 mmol/l. Taken together, our study does not provide direct evidence for a role of voltage-activated calcium channels in the regulation of calcium and renin secretion in renal juxtaglomerular cells.

Animals↗
PubMed1990

Serum immunoreactive erythropoietin of children in health and disease.

Serum immunoreactive erythropoietin (siEPO) was determined in cord serum from neonates (n = 97, gestational age 36-43 weeks), in healthy children from birth to adolescence (n = 260) and in children with haematological (n = 30), renal (n = 10) and congenital heart diseases (n = 70). In healthy children siEPO levels decreased after birth (geometric mean cord siEPO 35.6 mU/ml with 95% range of 17-56 mU/ml in eutrophic, nondistressed fetuses) and reached lowest values during the first 2 months (geometric mean siEPO 11.5 mU/ml). Thereafter siEPO levels increased slightly and were constant between 2 months and adolescence. The geometric mean siEPO for healthy children after birth was 18.8 mU/ml with 95% range of 7-47 mU/ml. These estimates were not significantly different from normal adult values. In newborns with fetal distress (n = 15) cord siEPO was significantly elevated (geometric mean 63.0 mU/ml; P less than 0.001). In children with haematological disease, siEPO and Hb concentration were inversely correlated (log siEPO (mU/ml) = 4.1-0.20 x Hb (g/dl); r = -0.62; P less than 0.0005). This relationship was significantly different in children with chronic renal failure (log siEPO (mU/ml) = 0.67 + 0.035 x Hb (g/dl); r = 0.50; P = 0.1). In children with heart disease the geometric mean siEPO was 19.2 mU/ml with 95% range 8-65 mU/ml for cyanotic (SaO2 less than 94%) and 17.7 mU/ml with 95% range of 12-36 mU/ml for acyanotic patients. In this group siEPO values were inversely correlated to the arterial oxygen content (log siEPO (mU/ml) = 1.61-2.04 x oxygen content (l/l); r = -0.28; P less than 0.02).

Adolescent↗
PubMed1990

Developmental regulation of mammary-derived growth inhibitor expression in bovine mammary tissue.

The cDNA for a previously described growth inhibitor, designated as mammary-derived growth inhibitor (MDGI) (Grosse, R., and P. Langen. 1989. In Handbook of Experimental Pharmacology. In press) has been cloned from a plasmid library which was derived from terminally differentiated bovine mammary gland. Sequencing of the cDNA showed an open reading frame coding for a protein of 133 amino acids. In six positions differences were found between the sequence determined from the cDNA and that determined previously by amino acid sequence analysis. Northern blot analysis revealed abundant MDGI mRNA in the terminally differentiated mammary gland, whereas in virgin gland, liver or pancreas transcripts were not expressed. By use of in situ hybridization technique transcription of MDGI in the developing bovine mammary gland was analyzed. Increasing amounts of MDGI mRNA were detected in the epithelial cells of embryonic mammary rudiment, in the epithelium of developing lobules and in terminal parts of ducts and lobuloalveolar epithelial cells of differentiated glands. There was a geographical gradient of MDGI mRNA concentration in bovine mammary gland reaching a maximum in the proximal parts of the tissue. An immunohistochemical analysis with different polyclonal and peptide directed antibodies against MDGI confirmed the in situ hybridization data with respect to the tissue-specific and differentiation-dependent MDGI expression in bovine mammary gland. The results suggest a close relationship between MDGI transcription and developmental processes in the normal bovine mammary gland.

Amino Acid Sequence↗
PubMed1990

Molecular mechanisms of renin release.

Renin secretion from renal juxtaglomerular cells is controlled by the intrarenal blood pressure, sodium chloride load of the organism, sympathetic nerve activity, and a number of hormones. The mechanisms by which these parameters exert their effects are not well understood. However, it is reasonable to assume that they act via signal transduction systems, implying the role of second messenger molecules in the control of renin secretion. This article summarizes present knowledge about the cellular mechanisms of renin secretion. Moreover, current concepts about the mechanisms by which the blood pressure and the sodium chloride load could influence renin secretion are discussed.

Angiotensin II↗
PubMed1990

Multiple site estimates of erythropoietin and renin in polycythemic kidney transplant patients.

The development of polycythemia after renal transplantation is a well known phenomenon and its etiology remains controversial. In particular, it is unknown whether inappropriate erythropoietin (EPO) production could be a reason. Utilizing a sensitive radioimmunoassay for EPO we have measured EPO concentrations in venous blood from native and grafted kidneys in three normocythemic and seven polycythemic patients. We found that (1) in our posttransplantation polycythemic patients there are inappropriately high systemic EPO levels, hence that posttransplantation polycythemia is related to EPO overproduction. (2) This high EPO production comes from the native kidneys. (3) There is a correlation between EPO and renin levels in the peripheral as well as in native and transplanted kidneys' venous samples.

Adult↗
PubMed1990

Role of excretory graft function for erythropoietin formation after renal transplantation.

To examine the role of renal excretory function for erythropoietin (EPO) formation we have determined the kinetics of plasma immunoreactive EPO (irEPO) in patients with end-stage renal disease undergoing renal allotransplantation (RTX). In 13 patients with immediate excretory graft function (imGF) and stable haemoglobin (Hb) concentrations (median Hb 9.5 g dl-1 and median irEPO 18 mU ml-1 before RTX) irEPO increased significantly on day 4 after RTX to a median value of 29 mU ml-1 and 2 days later reached a plateau of 34.4 +/- 3.3 mU ml-1 (mean +/- SD of daily median values during days 6-20). In patients with imGF having acute blood loss and subsequently receiving transfusions, irEPO responded in an inverse fashion to changes in Hb concentrations. In 12 patients with delayed graft function (dGF) (median Hb 8.8 g dl-1 and median irEPO 15 mU ml-1 before RTX) irEPO levels during the period of excretory failure remained either unchanged or displayed marked variations with peak values greatly exceeding those of patients with imGF. These variations were not related to changes in Hb concentrations and irEPO levels did not change following alterations in Hb concentrations. Upon recovery of excretory function irEPO approached the values found in patients with imGF. The results suggest that an intact excretory renal function is not a prerequisite for the capability to produce EPO, but correlates with the oxygen-dependent regulation of EPO formation.

Adolescent↗