Serum erythropoietin and parathyroid hormone concentrations in kidney transplant patients during acute graft rejection.
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Biomedical subjects
Publications and source records attributed to A Wiecek.
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Presence of elevated plasma levels of erythropoietin (EPO) has been reported both in polycythaemic and normocythaemic patients with chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate in what extent prolonged erythropoietin half-life time (T1/2EPO) is involved in the pathogenesis of elevated plasma EPO levels in patients with COPD. Seven normocythaemic patients (5 men and 2 women) with CODP and 6 healthy controls (4 males and 2 females) were examined. In all examined subjects half-life time of erythropoietin was determined after i.v. administration of EPO in a dose of 50 U/kg b.m. In COPD patients the T1/2EPO value was 5.98 +/- 0.67 hours and did not differ from that found in healthy controls (5.87 +/- 0.35 h). Results obtained in this study suggest participation of factors other than prolonged half-time of erythropoietin in the pathogenesis of polycythaemia in patients with COPD.
UNLABELLED: Water immersion (WI) is followed by hypoxemia and haemodilution, and induces alterations in renal haemodynamics (increase of tubular sodium load). These facts justified the performance of studies which aimed to assess the influence of WI on EPO secretion. Serum EPO and atrial natriuretic peptide (ANP) concentration and plasma renin activity (PRA) were estimated in 18 patients with essential hypertension (EH) and in 9 healthy subjects (HS) before, after two hours of WI and two hours after discontinued WI. WI was followed by a significant increase of plasma volume and decrease of PRA which were of similar magnitude in both examined groups. Patients with EH showed significantly higher basal levels of serum EPO (66.7 +/- 11.4 mU/ml in EH vs 20.0 +/- 3.4 mU/ml in HS) and ANP (110.6 +/- 15.4 pg/ml in EH vs 75.6 +/- 8.2 pg/ml in HS). WI was followed by significant increase of both EPO (by 34.0 +/- 8.9 mU/ml in EH and 17.0 +/- 5.4 mU/ml in HS) and ANP (by 106.9 +/- 19.2 pg/ml in EH and 149.4 +/- 16.9 pg/ml in HS). Only in EH a significant correlation was found between serum EPO level and MAP and post-WI natriuresis respectively. CONCLUSIONS: 1. Patients with EH are characterized by elevated basal serum levels of ANP and EPO. 2. Participation of the renin-angiotensin system and ANP in the regulation of EPO secretion could not be proven both in normotensive and hypertensive patients. 3. Involvement of EPO in the pathogenesis of EH seems to be likely.
The relationship between sodium-sensitive hypertension, renin profile and genetic predisposition to hypertension have not been fully clarified. The present study aimed to establish the influence of family history of hypertension (at least one of the parents suffering from hypertension) on the renin profile, incidence of sodium-sensitivity of blood pressure and plasma concentration of selected biochemical parameters (creatinine, uric acid, glucose, sodium, potassium, calcium and cholesterol). 85 patients with essential hypertension (38 females, 47 males) were enrolled in the study. Secondary forms of hypertension were excluded in all patients by careful clinical and biochemical examination performed in the Department of Nephrology, Silesian University School of Medicine in Katowice. Plasma renin activity (PRA) was estimated twice: first after administration of a normal sodium diet (100-120 mmol of sodium per day) and 8 hours of supine position (PRA I) and a second time after 3 days of sodium restriction (10-20 mmol of sodium per day) and 3 hours of upright position (PRA II). All other biochemical parameters were measured once. Only patients with urinary sodium excretion lower than 60 mmol per day (after 3 days of low salt diet), were enrolled in the study. Sodium-sensitive hypertension was diagnosed in patients with a decrease of mean arterial blood pressure (MAP) of more or equal to 10 mm Hg after three days of sodium restriction. Reduction of MAP of less than 10 mm Hg was classified as sodium-nonsensitive hypertension. Among 85 patients with essential hypertension 49 (57.6%) had a positive (group I) while 36 (42.4%) a negative family history of hypertension (group II). Using the criteria presented in this study low, normal, high and rigid plasma renin activity were found, in 14.3%, 57.1%, 18.4% and 10.2% respectively of patients of group I. In patients of group II the incidence of the above mentioned renin profiles was similar: 13.9%, 58.3%, 19.4% and 8.4% respectively. In patients of group I 16 (32.7%) had sodium-sensitive and 33 (67.3%) sodium-nonsensitive hypertension, while in patients of group II 16 (44.4%) had sodium-sensitive and 20 (55.6%) sodium-nonsensitive hypertension (difference between group I and group II is statistically not significant). Patients of group I did not differ significantly from patients of group II with respect to : sex, age, blood pressure, sodium urinary excretion and plasma concentration of above mentioned parameters. From results obtained in this study we may conclude, that patients with and without history of essential hypertension do not differ with respect to renin plasma profile, incidence of sodium-sensitivity of blood pressure and other biochemical parameters.
The present paper aimed to assess the influence of EPO-therapy on the requirement of blood transfusion in haemodialysed patients with end-stage renal failure. As shown in this paper, introduction of r-HuEPO into the therapy of uraemic anaemia almost completely eliminated the request for blood transfusion in these patients. EPO therapy did not influence significantly to the serum creatinine concentration and mean arterial blood pressure in these patients.
Acute failure of the transplanted kidney is a major problem in the early posttransplant phase and is recognized as a major cause of graft loss. Early renal transplant dysfunction is mainly due to ischemic damage (acute tubular necrosis), rejection, infection, and cyclosporin A toxicity. Less common causes include bleeding, ureteral obstruction, urinary leak, venous thrombosis, and stenosis or occlusion of the renal transplant artery. Recent advances in both invasive (renal biopsy) and non-invasive (imaging and biochemical) techniques have improved specificity and sensitivity of the diagnosis of the acute renal failure. Several procedures which aim to prevent the kidney transplant failure have recently been introduced. Although they were shown to reduce the incidence of early allograft failure, their influence on the long-term graft survival remains to be proven.
Several factors are involved in the persistence of endocrine alterations after renal transplantation, among which the following are to be mentioned: 1) duration of chronic uraemia before renal transplantation; 2) residual function of the patients' native kidneys; 3) quality of function of the renal graft; 4) modulation of secretion, transport, and degradation of hormones, and/or 5) altered target organ responsiveness to hormones induced by immunosuppressive drugs (glucocorticoids, azathioprine, cyclosporin A) or altered internal environment. In kidney transplant patients the following endocrine abnormalities are to be mentioned: dissociation of the physiological relationship between aldosterone synthesis and function of the renin-angiotensin system, abnormal volumetric regulation of arginine vasopressin secretion, suppressed responsiveness of cortisol secretion to stimulatory manoeuvres, persistent secondary hyperparathyroidism, relative deficiency of insulin (induced by glucocorticoid therapy), with consequent carbohydrate intolerance or even diabetes mellitus, suppressed response of gastrin and pancreatic hormone secretion to a test meal, and reduced responsiveness of atrial natriuretic peptide secretion to central hypervolaemia. Episodes of acute graft rejection are characterized by endocrine alterations similar to those seen in patients with acute or chronic renal failure.
Moxonidine and related compounds have been recently introduced into antihypertensive therapy. It is thought that these drugs exert their blood pressure lowering effect through interaction with non-adrenergic receptors in the central nervous system, i.e. imidazoline receptors, although the contribution of specific interaction with alpha 2-receptors is still under debate. Imidazoline receptors have recently been documented in the renal proximal tubule. In experimental studies, interaction of imidazolines with these receptors decreased the activity of the Na+/H+ antiporter and induced natriuresis. To quantitate the effect of the imidazoline receptor agonist moxonidine on renal sodium handling and renal haemodynamics in man, we examined ten healthy normotensive males (age 25 +/- 4 years) in a double blind placebo-controlled study using a crossover design. Subjects were studied on a standardized salt intake (50 mmol per day). On the 7th and 10th study day they were randomly allocated to receive either i.v. placebo or i.v. 0.2 mg moxonidine. Urinary electrolyte excretion, lithium clearance (as an index of proximal tubular sodium handling), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal vascular resistance (RVR), mean arterial blood pressure (MAP), plasma renin activity (PRA) and plasma noradrenaline (NA) levels were assessed. Injection of moxonidine did not increase fractional sodium excretion or lithium clearance. Specifically, antinatriuresis was not observed after injection of moxonidine despite a significant decrease in MAP from 91 to 85 mmHg and a significant increase in PRA.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study aimed to assess the function of proximal and distal tubules in patients with simple renal cysts. Thirty-one patients with simple renal cysts and 10 healthy subjects were examined. Based on the cyst fluid/plasma sodium ratio, 25 cysts were found to be of proximal origin and 6 of undetermined origin. In all patients cyst fluid and plasma concentrations of beta-2-microglobulin (beta-2-MG), sodium, potassium, calcium, phosphorus and total protein were assessed. Urinary excretions of sodium, potassium, calcium, phosphorus, beta-2-MG and Tamm-Horsfall protein (THP) were also estimated. Fractional excretion of beta-2-MG was calculated. The concentrations of beta-2-MG in fluid obtained from cysts of proximal origin were significantly higher than in fluid from cysts of undetermined origin (2.26 +/- 0 36 vs. 0.65 +/- 0.13 mg/l, p = 0.0004). Concentrations of THP (6.85 +/- 1.21 vs. 3.14 +/- 1.06 micrograms/ml, p < 0.05), and potassium (4.39 +/- 0.07 vs. 3.13 +/- 0.44 mmol/l, p < 0.05) were also higher in fluid from proximal cysts than in fluid from cysts of undetermined origin. Plasma beta-2-MG concentration was significantly higher in patients with proximal and undetermined cysts than in the control group (4.35 +/- 0.34 and 4.11 +/- 0.74 vs. 1.89 +/- 0.1 mg/l, p < 0.001). Urinary beta-2-MG excretion was also significantly higher in both groups of patients than in healthy subjects (474.8 +/- 165.9 and 346 +/- 94 vs. 100.2 +/- 19.6 micrograms/24 h, p < 0.05). Urinary THP excretion was significantly higher in patients with proximal cysts than in healthy subjects (31.0 +/- 5.1 vs. 16.3 +/- 2.5 mg/24 h, p < 0.05). From the results obtained in this study it seems that patients with simple renal cysts of proximal origin are characterized by abnormal tubular handling of beta-2-MG, and calcium and THP excretion. Thus, in patients with proximal cysts presence of a latent renal tubulopathy seems to be likely.
Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in hemodialyzed patients. Two groups of hemodialyzed patients, each of which comprised 17 subjects, were examined. The first group was treated by EPO (EPO group) while the second one did not receive this hormone (No-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9, and 12 month points of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex- and age-matched healthy subjects. After EPO therapy, an increase of the hematocrit value from 21.8 +/- 0.9 to 32.6 +/- 0.9% was observed, which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the No-EPO group, a significant although less marked rise of the hematocrit value (21.4 +/- 0.4 to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change plasma levels of electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose, and alkaline phosphatase as well as plasma concentrations of calcium-related hormones (PTH, calcitonin, 1,25[OH]2D3), vasopressin, and triiodothyronine. EPO treatment induced a significant decrease in somatotropin, prolactin, follitropin, lutropin, ACTH, cortisol, plasma renin activity, aldosterone, noradrenaline, adrenaline, dopamine, glucagon, pancreatic polypeptide, and gastrin plasma levels and an increase in plasma insulin, estradiol, testosterone, atrial natriuretic peptide, thyrotropin, and thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)
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This study aimed to assess the influence of short-term therapy with recombinant human erythropoietin (rhEPO) on selected parameters of humoral and cell mediated immunity in haemodialyzed uraemic patients (HDP). In 12 HDP before, and after 1 and 3 months of rhEPO therapy the following parameters were assessed: nitroblue tetrazolium (NBT) test, NBT test after latex stimulation, number of B, T and CD4 and CD4- and CD8-positive T lymphocytes, serum concentrations of IgG, IgA and IgM. The number of granulocytes with a positive NBT test was significantly higher after 3 months of rhEPO therapy. The number of granulocytes with a positive NBT test after latex stimulation increase both after 1 and 3 months of rhEPO therapy but significantly only after 3 months of treatment. The number of CD4-positive T lymphocytes increased significantly after 3 months of rhEPO therapy, while the number of CD8-positive lymphocytes decreased significantly after 1 month of therapy. The CD4/CD8 ratio increased significantly after 3 months of rhEPO therapy. Serum IgA concentration increased significantly after 1 and 3 months, while serum IgG level only after 3 months of rhEPO therapy. From the results obtained in this study it follows that rhEPO therapy exerts a positive effect on function of both T and B lymphocytes in haemodialyzed uraemic patients.
UNLABELLED: The present study aimed assess the relationship between erythropoietin (EPO) and parathormone (PTH) secretion in patients with primary hyperparathyroidism (PHP). Seventeen patients with PHP and 24 patients with uncomplicated cholelithiasis were examined before and during 14 days after surgical treatment. In PHP patients plasma EPO levels were significantly higher than in patients with cholelithiasis (31.5 + 4.3 vs 14.1 + 0.9 mU/ml, p < 0.01). After cholecystectomy transient increase of plasma EPO level was noticed postoperatively during the first 6 days. Such an increase of plasma EPO was absent in PHP patients after removal of the cause of primary hyperparathyroidism. Only in PHP patients a significant negative correlation was found preoperatively between plasma EPO level and Hct value or creatinine clearance respectively. CONCLUSIONS: 1. Patients with PHP are characterized by significantly elevated plasma EPO levels which are related to the degree of anaemia and decrease of GFR. 2. In patients with PHP presence of significant relationship between EPO and PTH secretion could not be proven.
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Using RIA method, serum erythropoietin (EPO) levels were measured in 13 patients undergoing autologous bone marrow transplantation (ABMT) and 4 patients with autologous peripheral blood stem cell transplantation (APBSCT) before and at the end of conditioning regiment as well as at the 3rd, 7th, 10th, 14th, 20th i 30th day after ABMT in correlation with actual haemoglobin (Hb) value. Statistically significant increase in EPO level was observed at days 0 to +14 (p < 0.01) with the maximum at day 3. The correlation between increased EPO level and decreased Hb was observed.
The present study aimed to assess the influence of long-term therapy with recombinant human erythropoietin (rHuEPO) for 12 months on follitropin (FSH), lutropin (LH), testosterone (TE) and estradiol (E2) serum concentrations in hemodialyzed males with chronic renal failure. Two groups of hemodialyzed males with chronic renal failure were examined. The first one consisted of 20 male patients with uraemia and renal anaemia (haematocrit value < 28%). Eleven of them were treated with rHuEPO for 12 months in order to achieve and maintain a target haematocrit value (Hct) of 30-35% (EPO group). The remaining 9 male patients were only carefully monitored both clinically and biochemically (No-EPO group). Patients of both groups (EPO and No-EPO) were intensively supervised according to the same clinical and biochemical protocol. Before (0) and after 3, 6, 9 and 12 months of the study, blood samples were withdrawn for the estimation of blood haemoglobin concentration, Hct, erythrocyte count, serum ferritin concentration, transferrin saturation and serum concentrations of FSH, LH, TE and E2. In patients of the EPO group a marked increase while of the No-EPO group, a slight, but statistically significant increase of the Hct value was found after 9 and 12 months and of E2 concentration after 3, 6, 9 and 12 months of clinical monitoring. In contrast in patients of the EPO group a statistically significant decrease of serum FSH and LH concentrations (during the first 9 months of treatment) and an increase of serum TE and E2 concentrations was observed. From results obtained in this study the following conclusions may be drawn: 1. The degree of anaemia does influence significantly the hormonal profile of the pituitary-gonadal axis in haemodialyzed males with chronic renal failure. 2. rHuEPO therapy for 12 months does exert a significant, although transitory (confined to the first 6-9 months of therapy) suppressive effect on serum follitropin and lutropin levels but increases serum testosterone and estradiol levels in these patients. 3. Alterations of both haematological parameters and of hormone serum levels of the pituitary-gonadal axis observed in EPO treated patients do not seem to be due only to the administration of this hormone.