Plasma concentrations of immunoreactive-endothelin in patients with chronic renal failure treated with recombinant human erythropoietin

1993 ◽  
Vol 84 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Kazuhiro Takahashi ◽  
Kazuhito Totsune ◽  
Yutaka Imai ◽  
Masahiko Sone ◽  
Mitsuru Nozuki ◽  
...  

1. Elevation of blood pressure is one of the major side effects of recombinant human erythropoietin therapy in haemodialysis patients. 2. We investigated the possible involvement of endothelin in the pathogenesis of this recombinant human erythropoietin-induced blood pressure elevation in 51 patients undergoing maintenance haemodialysis. 3. Blood haemoglobin level increased from 7.1 ± 0.1 to 8.8 ± 0.1g/dl (means ± SEM) after 8 weeks of treatment with recombinant human erythropoietin (3000–4500 units/week). An increase in mean blood pressure was found in 19 patients (37%) (n = 9, by 0–10 mmHg; n = 10, by > 10 mmHg). 4. Plasma immunoreactive-endothelin concentration significantly increased from 2.26 ± 0.18 to 3.14 ± 0.31 pmol/l in the 10 patients whose mean blood pressure increased by more than 10 mmHg (P < 0.05), but not in the other patients. Moreover, the increase in plasma immunoreactive-endothelin concentration showed a significant positive correlation with the change in mean blood pressure in 19 patients with elevated mean blood pressure (r = 0.47, P < 0.05). 5. There was no significant correlation between the change in plasma immunoreactive-endothelin concentration and the change in blood haemoglobin level or the change in body weight. 6. These results suggest the possibility that endothelin may contribute to the recombinant human erythropoietin-related rise in blood pressure in some haemodialysis patients.

1991 ◽  
Vol 261 (5) ◽  
pp. E642-E646 ◽  
Author(s):  
P. Eggena ◽  
P. Willsey ◽  
N. Jamgotchian ◽  
L. Truckenbrod ◽  
M. S. Hu ◽  
...  

In humans, blockade of the renin-angiotensin system with angiotensin converting-enzyme inhibitors (ANG CEI) prevents the rise in blood pressure associated with the administration of recombinant human erythropoietin (rhEPO). This study was conducted to determine whether rhEPO elevates blood pressure in normal Wistar rats and whether the renin-ANG system is affected. Groups of 10 rats each were given rhEPO, ANG CEI (enalapril), rhEPO + ANG CEI, or vehicle. Renin and/or renin substrate mRNA was measured in aortas, kidney, and heart; renin activity (PRA), inactive renin, and renin substrate were measured in plasma. rhEPO raised blood pressure in the normal rat without changing the plasma renin system. ANG CEI prevented this blood pressure rise. Renin-specific mRNA was increased by rhEPO in renal tissue, and renin substrate mRNA was significantly elevated in the kidney and aorta. mRNA for renin and renin substrate were not altered in the heart. In both aorta and kidney, a significant correlation was observed between renin substrate mRNA and blood pressure. The data indicate that rhEPO modulates specific tissue renin-ANG systems, which may contribute to blood pressure elevation.


1997 ◽  
Vol 93 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Ryoji Ozono ◽  
Tetsuya Oshima ◽  
Hideo Matsuura ◽  
Katsuhiko Ishibashi ◽  
Mitsuaki Watanabe ◽  
...  

1. We evaluated the effects of the dietary restriction of sodium chloride on blood pressure and systemic calcium metabolism in 19 in-patients with essential hypertension (11 men and 8 women, mean age 49.9 ± 12.1 years). 2. All patients received a high-sodium diet (250 mmol/day) for 1 week, followed by a low-sodium diet (10 mmol/day) for another week. Intake of potassium (100 mmol/day) and of calcium (15 mmol/day) were kept constant throughout the study. 3. Sodium restriction significantly reduced the mean blood pressure (from 114.0 ± 1.9 to 105.0 ± 13.7 mmHg, P < 0.01). Urinary calcium excretion was significantly reduced (from 5.1 ± 2.4 to 2.2 ± 1.0 mmol/day, P < 0.01). 4. The change in mean blood pressure after sodium restriction was not correlated with a change in any parameter of calcium metabolism [whole blood ionized calcium, plasma intact parathyroid hormone, or 1,25-(OH)2 vitamin D3]. 5. Plasma renin activity during a regular sodium diet, an index of renin status, was significantly and inversely correlated with the change in blood pressure during sodium restriction, but not with any change in the parameters of calcium metabolism. 6. We conclude that sodium restriction reduces blood pressure and decreases urinary calcium excretion. However, we observed no significant role of extracellular calcium concentration or of calciotropic hormone concentration in the mechanism of sodium sensitivity.


1996 ◽  
Vol 7 (1) ◽  
pp. 140-144
Author(s):  
J L Teruel ◽  
R Marcen ◽  
J Navarro-Antolin ◽  
A Aguilera ◽  
G Fernandez-Juarez ◽  
...  

According to this facility's protocol for the treatment of anemia in hemodialyzed patients, androgens were administered to male patients aged over 50 yr and recombinant human erythropoietin was administered to male patients below 50 yr of age and to female patients. In the study presented here, both therapeutic approaches have been prospectively analyzed. Patients were divided into two groups. Group A was composed of 18 patients, aged 62 +/- 12 yr, treated with nandrolone decanoate (200 mg/wk im) for 6 months; Group B was composed of 22 patients (6 men, 16 women) aged 47 +/- 15 yr, treated with subcutaneous recombinant human erythropoietin (initial dose, 6000 IU/wk) for 6 months. The increases of hemoglobin were similar in both groups; Group A, from 7.3 +/- 0.8 to 10.8 +/- 1.7 g/dL (P < 0.001), and Group B, from 7 +/- 0.6 to 10.4 +/- 1 g/dL (P < 0.001). In Group A, increases of triglycerides (159 +/- 71 versus 267 +/- 153 mg/dL, P < 0.001), serum albumin (3.9 +/- 0.3 versus 4.2 +/- 0.3 g/dL, P < 0.05), and dry weight (62.1 +/- 9.8 versus 64.9 +/- 10.1 kg, P < 0.001) were observed, which remained unmodified in Group B. Blood pressure control worsened in one patient (6%) from Group A, and in ten patients (45%) from Group B (P < 0.05). In conclusion, androgens produced an improvement in anemia in selected patients, similar to that achieved by use of recombinant human erythropoietin but at a lower cost. Androgens also have an appreciable anabolic effect and did not increase the blood pressure.


1994 ◽  
Vol 5 (5) ◽  
pp. 1208-1215
Author(s):  
F Schaefer ◽  
B van Kaick ◽  
J D Veldhuis ◽  
G Stein ◽  
K Schärer ◽  
...  

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 71 (1) ◽  
pp. 261-65
Author(s):  
Muhammad Sajid Hussain ◽  
Qasim Raza ◽  
Muhammad Omer Aamir ◽  
Nadia Murtaza ◽  
Sadia Naureen ◽  
...  

Objective: To determine the effect of subcutaneous recombinant human erythropoietin on blood pressure in predialysis chronic kidney disease (CKD) patients. Study Design: Case-series descriptive study. Place and Duration of Study: Combined Military Hospital Peshawar, from Mar 2016 to Sep 2016. Methodology: A total of 100 cases were enrolled. Inclusion criteria was patients of 18 to 60 years of both gender & estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 having Hb <10g/dL and pre-dialysis while Exclusion Criteria was pregnancy or lactation, BP more than 140/90 mmHg, patients on Haemodialysis and worsening renal function. Baseline BP, body weight and eGFR of anaemic chronic kidney disease patients were recorded prior to EPO Alpha therapy. Erythropoiesis-stimulating agents (ESAs) i.e. EPO Alpha (50-100 Units/kg thrice or once weekly) was administered subcutaneously. Subsequent blood pressure, body weight and eGFR monitoring was done after 2 and 4 weeks post EPO Alpha injection. Results: Mean age range was 46.71 years with range of 20-60 years, 73 (73%) were male while 27 (27%) werefemales. Mean ± SD for other quantitative variables like eGFR was 23.12 ± 5.28, Hb levels (g/dL) was 8.62 ± 0.85,Weight (kg) was 56.66 ± 6.62 and duration of CKD was 9.87 ± 4.02. Frequency of Hypertension (post EPO) was 2(2%) and p-value was 0.453. Conclusion: We concluded that the frequency of hypertension in pre-dialysis patients with chronic kidney disease (CKD) receiving recombinant human erythropoietin (rhEPo) subcutaneously (SC) in low doses, is very low, so rhEPo can be used subcutaneously......................


2019 ◽  
Vol 4 (1) ◽  
pp. e000185 ◽  
Author(s):  
Peter K Kaiser ◽  
Laurent Kodjikian ◽  
Jean-Francois Korobelnik ◽  
Julia Winkler ◽  
Albert Torri ◽  
...  

ObjectiveExplore relationships between systemic exposure to intravitreal aflibercept injection (IAI) and systemic pharmacodynamic effects via post hoc analyses of clinical trials of IAI for neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DME).Methods and analysisAdults from VGFT-OD-0702.PK (n=6), VGFT-OD-0512 (n= 5), VIEW 2 (n=1204) and VIVID-DME (n=404) studies were included. Validated ELISAs were used to measure concentrations of free and bound aflibercept (reported as adjusted bound) in plasma at predefined time points in each study. Non-compartmental analysis of concentration–time data was obtained with dense sampling in VGFT-OD-0702.PK and VGFT-OD-0512. Sparse sampling was used in VIEW 2 and VIVID-DME. Blood pressure or intrarenal function changes were also investigated.ResultsFollowing intravitreal administration, free aflibercept plasma concentrations quickly decreased once maximum concentrations were achieved at 1–3 days postdose; pharmacologically inactive adjusted bound aflibercept concentrations increased over a longer period and reached plateau 7 days postdose. Ratios of free and adjusted bound aflibercept decreased over time. There were no meaningful changes in systolic/diastolic blood pressure over the duration of each study at all systemic aflibercept exposure levels. For all treatment arms in VIEW 2, there was no clinically relevant change in mean intrarenal function from baseline at week 52. Overall, incidence of systemic adverse events in VIEW 2 and VIVID-DME was low and consistent with the known safety profile of IAI.ConclusionIAI administration was not associated with systemic effects in patients with nAMD or DME as measured by blood pressure or intrarenal function, two known pharmacologically relevant effects of anti-vascular endothelial growth factor.


1991 ◽  
Vol 9 (11) ◽  
pp. 1085 ◽  
Author(s):  
S D Roger ◽  
A C McMahon ◽  
L A Miller ◽  
A B S Dawnay ◽  
A E G Raine

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