Hypofibrinolysis conferred by the 4G/4G PAI-1 gene variant is a major predisposing factor for AVN in renal transplant patients. The risk is particularly high in obese subjects or patients with persistent hyperparathyroidism. A prospective intervention study of early anticoagulation after renal transplantation is needed to assess whether glucocorticoid-associated AVN can be prevented.
Background. Haemodialysis patients need sustained treatment with intravenous iron because iron deficiency limits the efficacy of recombinant human epoetin therapy in these patients. However, the optimal intravenous iron maintenance dose has not been established yet. Methods. We performed a prospective multicentre clinical trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain the iron status, and to examine the effect on epoetin dosage needed to maintain stable haemoglobin values in these patients. Fifty patients were enrolled in this prospective, open-label, single arm, phase IV study. Results. Forty-two patients (84%) completed the study. After 6 months of intravenous iron sucrose treatment, the mean ferritin value showed a tendency to increase slightly from 405 AE 159 at baseline to 490 AE 275 mg/l at the end of the study, but iron, transferrin levels and transferrin saturation did not change. The haemoglobin level remained stable (12 AE 1.1 at baseline and 12.1 AE 1.5 g/dl at the end of the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46 mg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end of treatment. Conclusions. A regular 50 mg weekly dosing schedule of iron sucrose maintains stable iron stores and haemoglobin levels in haemodialysed patients and allows considerable dose reductions for epoetins. Low-dose intravenous iron therapy may represent an optimal approach to treat the continuous loss of iron in dialysis patients.
Endocrine therapy for hormone-sensitive breast cancer is a well-established treatment option, both in adjuvant and palliative settings. For patients undergoing chronic hemodialysis, only scant pharmacokinetic data have been published for tamoxifen, and no data have been published for anastrozole. We therefore measured plasma levels of tamoxifen, its major metabolite, N-desmethyl tamoxifen, and anastrozole in a breast cancer patient undergoing chronic hemodialysis. Clinical tolerability was good. The blood levels for tamoxifen, N-desmethyl tamoxifen and anastrozole were within the expected therapeutic ranges. From this study, we can conclude that endocrine therapy for breast cancer with tamoxifen or anastrozole seems feasible and safe for patients undergoing chronic hemodialysis.
Voluntary hyperventilation (HV) provokes hemoconcentration due to a loss of fluid from the intravascular space. In 10 healthy male volunteers the hypothesis was tested whether HV increases transcapillary fluid shift into the interstitial compartment. For this purpose, fluorescent light intensity (FLI) alterations after intravenous injection of sodium fluorescein (Na fluorescein) before and during 3 min of HV were determined. Concomitantly, temperature and microvascular skin flux (laser Doppler fluxmetry, LDF) were recorded continuously. Hematocrit and serum proteins, as markers of hemoconcentration, increased significantly from 41.2 ± 2.3 to 42.7 ± 2.0% (p = 0.0023) and from 69.5 ± 3.4 to 72.9 ± 3.0 g/l (p = 0.0005, respectively). Skin temperature and LDF showed no changes during HV compared to baseline levels. Interstitial FLI indicating transcapillary diffusion of Na fluorescein was significantly higher (p < 0.001) during HV compared to the values recorded during the baseline period. The exact mechanism of enhanced transcapillary diffusion of Na fluorescein is not known. The distinct increase in FLI without a significant change in microvascular skin flux suggests an HV-induced increase in capillary pressure or an enhancement in capillary permeability for water and small solutes.
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