Reduced intestinal epithelial cell brush border membrane calcium transport in spontaneously hypertensive rats.
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Animals↗
Biomedical subjects
M Kosch
Publications and source records attributed to M Kosch.
Vessel wall alterations in patients with renal failure.
Cardiovascular complications are a major cause of morbidity and mortality in patients with renal failure. Death due to myocardial infarction and to stroke is more frequent in hemodialysis patients than in the total population. These cardiovascular diseases are mainly the consequence of atherosclerosis and cause decreased life expectancy in patients with renal failure. Ultrasound techniques now make it possible to measure atherosclerotic lesions in big and medium-sized arteries. Thickening of the intima-media-complex is an early sign of atherosclerosis in these vessels. It reduces the distensibility of the arteries during systole. The distensibility of big and medium-sized arteries can be determined using ultrasound-doppler-techniques. In our studies, the intima-media-thickness of the carotid artery was significantly (p< 0.01) increased in patients with chronic renal failure (1.32+/-0.49 mm, n=28) as compared with aged-matched healthy control subjects (0.75 +/- 0.20, n= 29). The distensibility coefficient was higher (p< 0.05) in healthy controls (26 +/- 1.8 10(-3)/kPa, n= 12) than in patients with renal insufficiency (19 +/- 1.7 10(-3)/kPa, n = 12). This demonstrates increased stiffness of the vessel wall resulting in loss of Windkessel function and increased work load of the heart.
Arteries↗
Red blood cell membranes, lipid peroxidation and magnesium in renal insufficiency.
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Erythrocyte Membrane↗
Measurement of skeletal status after renal transplantation by quantitative ultrasound.
BACKGROUND: Osteoporosis remains a major problem following kidney transplantation. Radiographic measures of bone mass are of limited predictive value after transplantation and are complicated by preexisting renal osteopathy. Quantitative ultrasound (QUS) is a new and non-invasive method to assess skeletal status, however, no data exist on ultrasonic bone parameter after kidney transplantation. We evaluated the potential use of this novel method in renal allograft recipients and studied the accuracy compared to normal controls. METHOD: Thirty patients (NTP, age 47.5 +/- 13.0 years) were studied 4.8 +/- 3.2 years after transplantation. Twenty-five healthy control persons (CON) were matched for age and sex. The left and right os calcis were studied by QUS and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were measured. Bone stiffness (BS) was calculated from these parameters and corrected for age (CBS). Differences between right and left os calcis were compared to CON to assess the side variability. RESULTS: Mean +/- SD BS was 75 +/- 22% compared to young adults, age-corrected CBS was decreased in NTP with 86 +/- 25% of normal, indicating a two-fold increased risk of fracture. SOS was 1525 +/- 47.7 m/s, BUA 105 +/- 22 dB/MHz. Mean difference between right and left os calcis was significantly higher in NTP than in CON (7.2 +/- 7.1% vs. 2.1 +/- 2.1%, p < 0.01). Limits of agreement of the measurements (MW of differences +/- 2 SD) according to a Bland-Altmann-type statistic were -16.9% and 20.7%. There was no correlation between CBS and age, cumulative steroid dose, parathyroid hormone concentrations or time after transplantation. CONCLUSION: Our data show altered bone structure expressed by low bone stiffness values measured by quantitative ultrasound in kidney transplant patients. However, because of relatively high inter-feet variance of QUS results we suggest measurement of both ossa calcis to minimize measurement error after transplantation.
Biomechanical Phenomena↗
[Kikuchi-Fusimoto disease: the differential diagnosis of cervical lymphadenitis with recurrent attacks of fever].
HISTORY AND CLINICAL FINDINGS: A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years. Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin. At admission there were several enlarged cervical lymph nodes and subfebrile temperatures. INVESTIGATIONS: Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease. TREATMENT AND COURSE: After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis. CONCLUSION: Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy. Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.
Biopsy↗
Lowered Total Intracellular Magnesium Status in a Subgroup of Hypertensives.
A new method to determine total Mg++ content in lymphocytes was developed, offering advantages for routine measurements as compared to fluorescence methods. Intracellular total Mg++ measurements were performed in lymphocytes of 18 healthy subjects and 19 untreated essential hypertensive patients. Mg++ content was referred to lymphocytic and membrane protein, which was determined according to Bradford's method. Mg++ measurements were performed by atomic absorption spectroscopy using a Video 12 apparatus of Thermo Electron Instrumentation Laboratory, Andover, USA. The results show that in patients with essential hypertension total intralymphocytic Mg++ content is significantly lower (0.07 +/- 0.05 mmol/g lymphocytic protein, mean +/- s.d.) as compared to controls (0.11 +/- 0.04 mmol/g lymphocytic protein, mean +/- s.d., p < 0.05). Free intracellular Mg++ content was measured in lymphocytes by the fluorescent indicator mag-fura-II, showing no significant differences in normotensives and hypertensives (0.30 +/- 0.16 versus 0.38 +/- 0.17 mmol/l). Additionally, in platelets free intracellular Mg++ concentrations were not found of significant difference in normotensives and hypertensives (0.52 +/- 0.23 versus 0.47 +/- 0.27 mmol/l) using mag-fura-II. In plasma Mg++ concentrations there was no significant difference in the normotensive and hypertensive group (0.92 +/- 0.07 versus 0.88 +/- 0.07 mmol/l). There was no correlation between plasma or free or total cellular magnesium concentrations in both groups. Furthermore this method seems also suitable for routine measurements of total intracellular Mg++ concentrations in even larger measurements like mag-fur-II. Lowered total intracellular Mg++ concentrations in a subgroup of primary hypertensives may contribute to the development of this disorder, perhaps due to different buffering systems.http://link.springer-ny.com/link/service/journals/00547/bibs/8n3p154.html
Journal Article↗
Flow-mediated vasodilation and distensibility in relation to intima-media thickness of large arteries in mild essential hypertension.
Whether endothelial dysfunction in essential hypertension is a cause or a consequence of structural vessel wall alterations is not known. The purpose of the present study was to compare flow-mediated vasodilation and mechanical vessel wall properties of large arteries between never treated mild essential hypertensive patients with normal intima-media thickness (IMT) and those exhibiting intima-media thickening. We measured brachial and carotid artery diameter and distension by Doppler frequency analysis of vessel wall movements in M-mode in ten essential hypertensive patients with normal carotid artery IMT (HYP1), in ten patients with increased IMT (HYP2), and in 13 normotensive control subjects (CON). Thereafter, we measured changes in brachial artery (BA) diameters during distal reactive hyperemia after 4 min of forearm occlusion. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation, and BA blood flow was estimated using a pulsed Doppler system. Intima-media thickness of the carotid arteries was examined by high resolution B-mode ultrasound. IMT was 0.66 +/- 0.02 mm in the HYP1 group, 0.84 +/- 0.03 mm in the HYP2 group (P < .01 v HYP1, P < .01 v CON), and 0.71 +/- 0.04 mm in the CON group. Forearm occlusion was reduced in both the HYP1 group (3.4% +/- 3.6%, P < .01 v CON) and the HYP2 group (6.4% +/- 1.5%, P < .05 v CON) when compared with the CON group (16.5% +/- 2.8%). Nitroglycerin-mediated vasodilation and BA blood flow were not different between study groups. BA distension (as well as carotid artery distension) was significantly lower in the HYP1 group (52 +/- 6 microm, P < .05 v CON), but not in the HYP2 group (72 +/- 10 microm) when compared with the CON group (88 +/- 13 microm). The data suggest that endothelial dysfunction and reduced distensibility of large arteries in patients with essential hypertension occur in the absence of structural vessel wall alterations.
Adult↗
Studies on cardiac sympathovagal balance and large artery distensibility in patients with untreated essential hypertension.
BACKGROUND: Power spectral analysis of heart rate variability and arterial distensibility are non-invasive measures of cardiac autonomic modulation and mechanical vessel wall properties, respectively. The aim of the present study was to assess cardiac sympathovagal balance, carotid and brachial artery distensibility and a possible relation between these parameters in mildly hypertensive patients as compared to normotensive controls. METHODS: Total power (TP, 0.01 to 0.5 Hz) and spectral components (low frequency 0.04-0.15 Hz, mainly sympathetic cardiac modulation; high frequency 0.15-0.4 Hz, mainly vagal cardiac modulation) and cardiac sympathovagal balance (LF/LH ratio) of short term heart rate variability (ECG-recording) were calculated in 15 untreated essential hypertensive patients (HYP) and 15 age- and sex-matched healthy controls (CON). Brachial and carotid artery distensibility coefficient (DC) was measured with a multigate doppler system (echo-tracking). RESULTS: TP (ms2 x 10(-3)) (11.2 +/- 0.8 vs 13.6 +/- 0.9, P < 0.03), LF/HF ratio (1.07 +/- 0.08 vs 0.75 +/- 0.07, P < 0.01) and HF (ms2 x 10(-3)/%) (0.7 +/- 0.1/49 +/- 2 vs 1.3 +/- 0.2/58 +/- 2, P < 0.01/P < 0.01) were significantly reduced in HYP compared to CON subjects. LF (ms2 x 10(-3)/%) was 0.7 +/- 0.1/50 +/- 2 vs 0.9 +/- 0.1/41 +/- 2, P = 0.16/P < 0.01. Carotid artery DC (15 +/- 2 vs 26 +/- 2, P < 0.001) and brachial artery DC (4.7 +/- 0.6 vs 9 +/- 1.0, P < 0.001) were significantly reduced in HYP. There was a significant correlation between carotid DC and LF/HF (rho = -0.41, P < 0.03). CONCLUSION: The data shows reduced heart rate variability and altered cardiac sympathovagal balance as well as impaired arterial distensibility in untreated mildly hypertensive patients. The relative increase in sympathetic modulation and decreased carotid distensibility appear to be related.
Adult↗
Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients.
BACKGROUND: Alterations of large artery function and structure are frequently observed in renal allograft recipients. However, endothelial function has not yet been assessed in this population. METHODS: Flow-mediated vasodilation is a useful index of endothelial function. We measured the diameter and distensibility of the brachial artery at rest using high-resolution ultrasound and Doppler frequency analysis of vessel wall movements in the M mode. Thereafter, changes in brachial artery diameter were measured during reactive hyperemia (after 4 min of forearm occlusion) in 16 cyclosporine-treated renal allograft recipients and 16 normal controls of similar age and sex ratio. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation. Brachial artery blood pressure was measured using an automatic sphygmomanometer, and brachial artery flow was estimated using pulsed Doppler. RESULTS: Distensibility was reduced in renal allograft recipients (5.31 +/- 0. 74 vs. 9.10 +/- 0.94 x 10-3/kPa, P = 0.003, mean +/- sem), while the brachial artery diameter at rest was higher (4.13 +/- 0.14 vs. 3.25 +/- 0.14 mm, P < 0.001). Flow-mediated vasodilation was significantly reduced in renal allograft recipients (0.13 +/- 0.08 vs. 0.60 +/- 0.08 mm or 3 +/- 2 vs. 19 +/- 3%, both P < 0.001). However, nitroglycerin-mediated vasodilation was similar in renal allograft recipients and controls (0.76 +/- 0.10 vs. 0.77 +/- 0.09 mm, NS, or 19 +/- 3 vs. 22 +/- 2%, NS). There were no significant differences in brachial artery flow at rest and during reactive hyperemia between both groups. The impairments of flow-mediated vasodilation and distensibility in renal allograft recipients remained significant after correction for serum cholesterol, creatinine, parathyroid hormone concentrations, end-diastolic diameter, as well as blood pressure levels, and were also present in eight renal allograft recipients not treated with cyclosporine. Flow-mediated vasodilation was not related to distensibility in either group. CONCLUSIONS: The results show impaired endothelial function and reduced brachial artery distensibility in renal allograft recipients. The impairments of flow-mediated vasodilation and distensibility are not attributable to a diminished brachial artery vasodilator capacity, because endothelium-independent vasodilation was preserved in renal allograft recipients.
Adult↗
Histiocytic, necrotizing lymphadenitis as rare cause of cervical lymphadenopathy and fever of unknown origin--a case of biopsy proven recurrence over 19 years.
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Biopsy↗
A case with renovascular hypertension.
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Angiography, Digital Subtraction↗
Decreased membrane Mg2+ concentrations in a subgroup of hypertensives: membrane model for the pathogenesis of primary hypertension.
Intracellular Mg2+ measurements were performed in erythrocyte membranes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ concentrations were determined by atomic absorption spectroscopy using a Video 12 apparatus. The results show that in patients with essential hypertension total Mg2+ content in erythrocyte membranes was significantly decreased as compared with the control group (0.28 +/-0.05 v 0.52+/-0.15 mmol/g membrane protein; mean+/-SD, P < .001). Additionally, plasma and free intracellular Mg2+ content of lymphocytes and platelets showed no significant difference in normotensives and hypertensives. Lowered total membrane Mg2+ concentrations in a subgroup of primary hypertensives may contribute to the development of this disorder, perhaps due to different buffering or membrane transport systems.
Adult↗
A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients.
The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6-12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 +/- 3/80 +/- 2 mm Hg at entry and 133 +/- 3/82 +/- 2 mm Hg after 2 years in the normotensive group, 146 +/- 4/90 +/- 3 mm Hg at entry and 145 +/- 3/87 +/- 2 mm Hg after 2 years in the hypertensive group (P < 0.01, normotensives vs hypertensives). The distensibility coefficient (DC) decreased significantly after 2 years in the hypertensive group (DC 18.3 +/- 1.3 10(-3)/kPa before, 15.1 +/- 1.2 10(-3)/kPa after 2 years, P < 0.05) whereas no significant change was observed in the normotensive group (DC 19.0 +/- 1.4 10(-3)/kPa before, DC 17.8 +/- 1.3 10(-3)/kPa after 2 years, NS). There was a significant correlation between the change of the distensibility coefficient after 2 years and mean arterial pressure (n = 48, r = 0.42, P < 0.01). The results show that the decrease of arterial distensibility after 2 years is accelerated in hypertensive renal transplant recipients despite effective anti-hypertensive treatment. Since BP levels were not different at entry into the study and after 2 years, differences in distending pressure along cannot explain the more pronounced decrease of arterial distensibility over time in hypertensive renal transplant recipients.
Adult↗
Effect of hyperparathyroidism on arterial distensibility in renal transplant recipients.
BACKGROUND: The cushioning function of the arterial system is altered in patients with end-stage renal failure. The role of hyperparathyroidism for the altered vessel wall properties of large arteries not known. METHODS: To exclude the confounding effects of fluid volume changes and hypercirculation as well as uremic toxicity on vessel wall properties from those of hyperparathyroidism, the present study was conducted in 54 normotensive renal transplant recipients with good graft function, three to six months after transplantation. The vessel wall properties of the common carotid artery were investigated in 32 of them, who had increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter, SEM), and compared to those of 22 control recipients of same age with normal plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by Doppler analysis of the vessel wall movements, blood pressure was determined by sphygmomanometry. RESULTS: Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in patients with normal plasma iPTH levels (NS). There was no difference in enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal transplant recipients with hyperparathyroidism as compared with the control patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28 microns, P < 0.05) and distensibility coefficient of the common carotid artery (15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared with the control patients. Multiple regression analysis showed that the distensibility coefficient of the common carotid artery was negatively correlated with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH levels (P < 0.05). The effects of plasma iPTH levels were not related to serum calcium concentrations or to differences in the enddiastolic diameter of the common carotid artery. CONCLUSIONS: The data suggest that secondary hyperparathyroidism can affect the cushioning function of larger arteries in patients with end-stage renal failure independently of high blood pressure.
Adult↗
Progressive heterogeneity of myocardial perfusion in heart transplant recipients detected by thallium-201 myocardial SPECT.
UNLABELLED: Progressive graft atherosclerosis is a serious complication in long-term survivors after heart transplantation. Coronary angiography is insensitive with regard to the early and characteristic alterations. We evaluated the progression of these abnormalities and the influence of former rejection episodes. METHODS: Early after transplantation, 43 patients (34 men, mean age 53.7 +/- 10.7 yr) underwent stress and redistribution 201Tl myocardial SPECT after treadmill exercise. Twenty patients were followed-up to the second postoperative year, and 13 patients to the third postoperative year. Thallium-201 distribution and kinetic abnormalities were documented in a scheme enclosing 20 myocardial segments. Additionally, a score was developed that measured the degree of inhomogeneity of 201Tl distribution and the severity of perfusion defects, respectively. RESULTS: Regarding scintigraphy, pathologic results could be found in 40% of segments (redistribution, 25%; reverse redistribution, 30%; persistent defects, 49%). Score values in heart transplant recipients differed significantly from normal controls (p < 0.001) and were comparable to patients with single vessel disease of their native hearts. Thallium-201 inhomogeneity in recipients after treatable rejection episodes did not differ from results in recipients without any biopsy-proven rejection. The follow-up of cardiac transplant patients revealed a significant increase of score values up to the third year after transplantation (p < 0.02), despite reproducible normal angiography. There was no direct correlation between score values and IVUS results, although there was a parallel trend in 10 of 12 follow-ups. CONCLUSION: Despite normal coronary angiography, 201Tl myocardial SPECT frequently revealed pathologic results in heart transplant recipients. Scintigraphic results did not correlate with intimal thickening of epicardial coronary arteries accessible to intravascular ultrasonography in the early phase after transplantation. The presented score of inhomogeneity might reveal progressive disease possibly caused by small vessel alterations.
Case-Control Studies↗
Can Tl-201 myocardial SPECT abnormalities in orthotopic heart recipients be explained by coronary vessel wall alterations assessed by intravascular ultrasound?
UNLABELLED: The aim of this study was to compare findings on coronary intravascular ultrasound and thallium-201 SPECT in patients following orthotopic heart transplantation. BACKGROUND: No data are available on whether pathological thallium scintigraphic findings in heart recipients are based on coronary vessel wall alterations identifiable by intravascular ultrasound. METHODS: 29 patients (mean age: 50.9 +/- 11.5 years; male n = 23) were investigated by means of intravascular ultrasound of selected coronary segments and thallium-201 myocardial SPECT. Patients were investigated 11.6 +/- 5.4 weeks post transplantation, a subgroup of 13 patients was re-investigated 70.2 +/- 18.4 weeks following transplantation. A total of 214 cross-sectional areas of the left coronary artery were examined using a 3.5 French intravascular ultrasound catheter to measure intimal index and the circumferential extension of a three-layer appearance of the vessel wall. Shortly after catheterisation, an ergometric stress-test was performed to examine all recipients by means of thallium-201 SPECT. In each patient, 20 segments of the left ventricle were evaluated using a score system of differentiate between persistent defects, redistribution, and reverse redistribution. A score was developed that measured the degree of inhomogeneity and severity of perfusion defects, respectively. Findings on scintigraphy were correlated to coronary intravascular ultrasound findings. RESULTS: At first investigation, mean intimal index of all evaluated coronary cross-sectional areas was 0.06 +/- 0.1. Sixty-four cross-sectional areas demonstrated a three-layer appearance of the vessel wall, mean circumferential extension was 72 +/- 122 degrees. Thallium scintigraphy demonstrated a total of 336 (40%) pathological left ventricular segments; 168 (20%) were regarded as permanent defects, 67 (8%) demonstrated redistribution and 101 (12%) showed reverse redistribution. The score of inhomogeneity was calculated as 5.8% +/- 2.6%. In the subgroup of patients at the follow-up study, the score was 6.4 +/- 2.8%. There was no correlation between intimal index and the score, nor could any correlation be confirmed between the score and the circumferential extension of a three-layer appearance of the vessel wall. At second investigation, no significant differences of intimal index (0.05 +/- 0.07) or circumferential extension of a three-layer appearance of the vessel wall (74 +/- 118 degrees) could be confirmed. The score was slightly, but significantly increased to 8.1 +/- 4.5% at the second investigation (P < 0.05). CONCLUSION: Early after orthotopic heart transplantation, pathologic thallium distribution patterns of the left ventricle could be observed. These pathological patterns did not correlate with the extent of diffuse coronary vessel wall alterations identifiable by intravascular ultrasound. After more than 1 year, the degree of scintigraphic abnormalities increased significantly, not accompanied by an increase of diffuse coronary vessel wall alterations.
Adult↗
Preparation and properties of sterically stabilized hexadecylphosphocholine (miltefosine)-liposomes and influence of this modification on macrophage activation.
The aim of the study was to investigate for the first time the preparation, physical properties and macrophage activating effect of sterically stabilized liposomes made from hexadecylphosphocholine (HPC, Miltefosine) using different poly(ethylene glycol) lipids for coating. We could demonstrate that it is possible to prepare different liposomal vesicle types (MLV, SUV and LUVET) without any problem and with a high stability in buffer (release of hydrophilic marker was < 5% after half a year) and in plasma (t1/2 up to several days). The preparation method, including size of polycarbon membrane filter used for the preparation of LUVETs had the main influence on vesicle size and size distribution. The addition of a charged lipid like DCP and different amounts of PEG-lipid up to 10% had no effect on size and stability of PEG-LUVETs. A comparison of activating potency of PEG-HPC-vesicles with commonly used HPC-liposomes was performed with mouse peritoneal macrophages. HPC-liposomes induced a clear release of NO and TNF from mouse peritoneal macrophages especially in a synergistical action with LPS. On the contrary the effect of PEG-liposomes was similar to control cells after a combined activation in vivo/in vitro. The reduced interaction of these liposomes with the MPS was also demonstrated by an unchanged carbon ink uptake after treatment of mice (i.p.) with liposomes prepared with and without PEG-lipid. PEG-HPC-liposomes combine the advantages of HPC, liposomes and PEG-coating, resulting in a promising preparation for treatment of mammary cancers.
Animals↗
Iron management in renal failure patients--how do we achieve the best results?
The majority of patients with renal insufficiency suffer from a normochromic, normocytic anaemia. This renal anaemia affects the quality of life of these patients and reduces their chance of survival. Despite the availability of recombinant human erythropoetin for the treatment of renal anaemia, many patients do not achieve the target haemoglobin concentration of more than 11 g/dl. A major factor contributing to suboptimal correction of renal anaemia and reduced responsiveness to epoetin is a lack of iron availability to the stimulated erythropoesis.Thus, forthe majority of patients with renal insufficiency intravenous iron therapy will be the treatment of choice to replete and maintain adequate iron stores.
Anemia, Iron-Deficiency↗