Role of excretory graft function for erythropoietin formation after renal transplantation

Eckardt, Kai‐Uwe; Frei, Ulrich; Kliem, Volker; Bauer, Christian; Koch, K. M.; Kurtz, Armin

doi:10.1111/j.1365-2362.1990.tb01927.x

Cited by 18 publications

(12 citation statements)

References 23 publications

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“…It is also of note that blood gases did not change following PTx. Secondly, the data on serum iEPO levels obtained after renal allotransplantation by others [31] and ourselves [32] also suggest that surgery has no effect perse on serum EPO levels. It is the lag time and the amplitude of the increase of serum EPO levels that are significantly different between renal transplantation and PTx.…”

Section: Discussionmentioning

confidence: 99%

Serum Erythropoietin and Erythropoiesis in Primary and Secondary Hyperparathyroidism: Effect of Parathyroidectomy

Ureña

Eckardt

Sarfati

et al. 1991

Nephron

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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 dicussion. 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 < 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 ± 13,317 to 86,533 ± 13,462/mm³ (p < 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 after PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 ± 3,000 to 40,827 ± 4,080/mm³ (p < 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 μg/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 < 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.

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Section: Discussionmentioning

confidence: 99%

Serum Erythropoietin and Erythropoiesis in Primary and Secondary Hyperparathyroidism: Effect of Parathyroidectomy

Ureña

Eckardt

Sarfati

et al. 1991

Nephron

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“…Observations in the early posttransplantation period indicate that excretory kidney function and the ability to produce EPO may dissociate. 22 Tubular function is probably a prerequisite for the adaptation of EPO formation to changes in blood oxygen content. 23,24 In fact, it is possible that, as a result of the lack of tubular oxygen consumption, renal oxygen tensions in diseased kidneys are higher than in intact kidneys 25 ; however, other evidence points toward an important role of hypoxia in the progression of kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD

Bernhardt¹,

Wiesener²,

Scigalla³

et al. 2010

Journal of the American Society of Nephrology

304

250

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The reasons for inadequate production of erythropoietin (EPO) in patients with ESRD are poorly understood. A better understanding of EPO regulation, namely oxygen-dependent hydroxylation of the hypoxia-inducible transcription factor (HIF), may enable targeted pharmacological intervention. Here, we tested the ability of fibrotic kidneys and extrarenal tissues to produce EPO. In this phase 1 study, we used an orally active prolyl-hydroxylase inhibitor, FG-2216, to stabilize HIF independent of oxygen availability in 12 hemodialysis (HD) patients, six of whom were anephric, and in six healthy volunteers. FG-2216 increased plasma EPO levels 30.8-fold in HD patients with kidneys, 14.5-fold in anephric HD patients, and 12.7-fold in healthy volunteers. These data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production. Furthermore, the data indicate that deranged oxygen sensing-not a loss of EPO production capacity-causes renal anemia.

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“…Its secretion is stimulated by anemia and hypoxia [1], The production of EPO is insuffi cient in uremia, and this is the major cause of renal anemia [1], Successful renal transplantation is usually followed by resolution o f the anemia in a few months [2] and the feed back loop between hematocrit (Hct) and EPO can be rees tablished [3], The system may be disturbed by graft failure and by posttransplant polycythemia, in which both sup pressed [4] and elevated serum EPO (s-EPO) […”

Section: Introductionmentioning

confidence: 99%

Increased Serum Erythropoietin Level during Azathioprine Treatment in Renal Transplant Recipients

Jensen

Hansen²,

Pedersen³

1994

Nephron

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One hundred and six renal transplant patients were studied. During the first 12 months after renal transplantation all patients were treated with cyclosporine (Cy) and prednisone. At 12 months after transplantation the patients were randomly allocated to either conventional treatment with azathioprine (Az) and prednisone (group Az) or to continued treatment with Cy and prednisone (group Cy). Serum erythropoietin (s-EPO), glomerular filtration rate (GFR) and hematocrit (Hct) were measured at 12,18 and 24 months after transplantation. s-EPO rose in the group Az from 19 U/l (mean) at 12 months to 28 U/l (p < 0.01) at 18 months and remained elevated at 24 months at 29 U/l compared with baseline level and with healthy subjects without anemia 18 U/l (p < 0.01). There was no significant change in s-EPO in group Cy during the study. The Hct in the two groups was not significantly different. GFR was the same in the two groups at 12 months and after 24 months. In conclusion, a switch from Cy to Az 1 year after renal transplantation results in a sustained rise in s-EPO which may in part represent a compensatory phenomenon to bone marrow suppression.

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Role of excretory graft function for erythropoietin formation after renal transplantation

Cited by 18 publications

References 23 publications

Serum Erythropoietin and Erythropoiesis in Primary and Secondary Hyperparathyroidism: Effect of Parathyroidectomy

Serum Erythropoietin and Erythropoiesis in Primary and Secondary Hyperparathyroidism: Effect of Parathyroidectomy

Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD

Increased Serum Erythropoietin Level during Azathioprine Treatment in Renal Transplant Recipients

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