Felix Stockenhuber

High-dose Recombinant Human Erythropoietin Stimulates Reticulocyte Production in Patients with Multiple Organ Dysfunction Syndrome

OBJECTIVE To investigate erythropoietin (EPO) production and the erythropoietic potency of recombinant human EPO in the multiple organ dysfunction syndrome. DESIGN Randomized, prospective, controlled clinical trial. MATERIALS AND METHODS Patients received either 600 IU/kg intravenous EPO three times weekly (n = 9) or saline (control, n = 10). MEASUREMENTS EPO levels, circulating soluble receptors for tumor necrosis factor and interleukin-2, levels of interleukin-6 and intercellular adhesion molecule, and early peripheral blood cell progenitors. RESULTS EPO production in the control group remained low. Pharmacologic EPO blood levels were associated with increased reticulocyte counts compared with both controls (p < 0.04) and baseline (p < 0.006). Increased levels of soluble receptors for tumor necrosis factor in the treatment group compared with the controls did not prevent this effect. Interleukin 6 inhibited reticulocyte production. CONCLUSION Despite increased cytokine levels, pharmacologic EPO blood levels were associated with increased reticulocyte counts in patients with multiple organ dysfunction syndrome.

Folic acid supplementation improves erythropoietin response.

Therapy with recombinant human erythropoietin (rhEPO) has become most valuable for the treatment of renal anemia in patients with various chronic renal diseases. For the first time this study presents data showing that rhEPO affects the metabolism of folic acid. There were 13 patients enrolled; they suffered from different chronic renal diseases and showed an impaired responsiveness to rhEPO therapy. Before starting rhEPO therapy the mean corpuscular volume of erythrocytes (MCV) was measured; MCV was 90.4 fl. During rhEPO therapy the MCV increased significantly by 14.8 fl (p < 0.05). The developing macrocytic anemia was overcome when folic acid was administered additionally for a mean period of 3.14 +/- 3 months. Hematocrit (Hct) also responded accordingly. Whereas Hct did not increase adequately during the exclusive treatment with rhEPO, an increase in Hct from 23 +/- 3.3 to 30 +/- 4.2% (p < 0.01) was observed after the addition of folic acid. These results are rather remarkable as folic acid serum levels were clearly within the normal range during the whole study period. So it can be concluded that rhEPO therapy results in an increased demand for folic acid. Even if serum concentrations are within the normal range, the administration of folic acid will enhance the effectiveness of rhEPO therapy so that the rhEPO dosage can be reduced.

Increased serum activity of interleukin-2 in patients with pre-eclampsia.

Pre-eclampsia is a severe complication in pregnancy, manifested by hypertension, proteinuria and oedema, and in the most severe cases leading to fetal death. Immunological mechanisms are generally assumed to be of major importance in the genesis of the disease. Foidart showed anti-laminin antibodies to be involved in preeclampsia. [ 11. Circulating immune complexes [2] and complement activation [3] as well as alterations in T-cell subsets [4] and suppressor activity [5] have also been observed, but still there remains much uncertainty about the pathophysiological mechanisms involved. IL-2 is an important cytokine in the T-cell pathway [6] as it is released by antigenstimulated T cells and enhances alloantigen reactivity by augmentation of cellular cytytoxic function. The question of whether increased cytokine release can be used as a diagnostic marker for an ongoing alteration of maternofetal immune response prompted us to study the serum activity of IL-2 in pregnant women suffering from pre-eclampsia.

Anemia and erythropoietin levels in lung transplant recipients

An evaluation of 26 surviving outpatient lung transplant recipients at one center showed that 65% (17/26) had significant anemia (hemoglobin <11 g/L for women, <14 g/dl for men) at a median follow-up of 13.5 months after transplantation (range, 1–41 months). There were 14 men and 12 women with a mean age of 45.1 years (range, 23.1–66.7 years). Fifteen had a double allograft and 11 had a single allograft. Anemia was normochromic and normocytic/macrocytic with a tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency (transferrin saturation <20%) was found in 35% (6/17) of anemic patients, and two of them also had ferritin levels <15

Successful Treatment of Hemodialysis-Related Porphyria cutanea tarda with Deferoxamine

mUg/L. In addition, vitamin B12 was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels were significantly decreased in anemic lung transplant recipients as compared with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1–41 mU/ml, vs. 53 mU/ml, 15–88 mU/ml; P<0.05). In nonanemic lung transplant recipients, erythropoietin levels were decreased too, as compared with normal controls (median, 2 mU/ml, range 1–21 mU/ml, vs. 5 mU/ml, 3–32 mil/ ml; P<0.05). Investigation of peripheral stem cells in 9 patients showed normal stimulation of erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128–1898 cells/ml) independent of erythropoietin concentrations. Analysis of putative prognostic factors, such as age, surgical procedure (double vs. single lung allograft), indication for transplantation, time after transplantation, infection status, presence of bronchiolitis obliterans, immunosuppression (

Transient hyperoxaluria after ingestion of chocolate as a high risk factor for calcium oxalate calculi.

pM azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial partial pressure of oxygen, did not demonstrate any difference in erythropoietin concentrations. Only the sex variable revealed a trend to higher levels in women than in men (median, 4 mU/ml, range 1–41 mU/ml, vs. 1 mU/ml, 1–16 mU/ml; P>0.05). The causes for low erythropoietin levels are not quite understood yet; however, they offer a rationale for the treatment of chronic anemia with recombinant human erythropoietin.

Comparison of Duplex sonography and color Doppler imaging in renal allograft evaluation: a prospective study

End-stage renal failure and long-term hemodialysis treatment promote the development of genetically conditioned porphyria cutanea tarda (PCT). The clinical manifestation is triggered off by unknown factors coexisting with renal insufficiency and hemodialysis. Iron overload is often associated with the disease and is thought to play a key role in its pathogenesis. Iron removal by deferoxamine infusions is regarded as the treatment of choice for patients who cannot undergo repeated phlebotomy procedures and has been successfully used in patients with normal renal function. We report a case of hemodialysis-related PCT and iron overload in whom repeated venesections were contraindicated on account of severe anemia and treatment with deferoxamine led to a striking improvement of symptoms.

Myocardial calcinosis associated with hemodialysis

In 6 male subjects the diurnal variation of urinary oxalic acid excretion was studied after ingestion of chocolate, a food stuff rich in oxalic acid. The ingestion of chocolate caused a striking but transient increase in urinary oxalic acid excretion due to its absorption in the upper gastrointestinal tract. The peak excretion rates occurred 2-4 h after the intake of the chocolate. The peak values were 235% of the fasting excretion rate in the trial with 50 g chocolate and 289% in the trial with 100 g chocolate and reached the amounts found in cases with primary hyperoxaluria. The administration of ranitidine had no influence on oxalic acid absorption. The transient hyperoxaluria observed seems to be an important factor for the formation of calcium oxalate calculi in patients on risk for stone disorders.

Serum concentrations of immune parameters during acute cardiogenic pulmonary edema.

A prospective study compared the diagnostic capability of quantitative Duplex sonography (DS) and color Doppler imaging (CDI) in 49 consecutive patients with 50 renal allografts. Sixty five DS examinations and 65 CDI examinations were performed by two independent investigators on two different machines on the same day. The resistive index (RI) was calculated and the color flow of renal arteries was observed up to the arcuate arteries. There was good correlation of RI values obtained by DS and CDI at all vascular sites. Thirty one allografts were functioning stably and 19 were in a state of dysfunction, defined by histology (n = 17). Forty allografts presented with a RI less than 0.9 and normal color flow. All five allografts with a pathologic RI greater than or equal to 0.9 showed abnormal color flow (missing flow in arcuate and/or interlobar arteries). Five allografts had a RI less than 0.9 but abnormal color flow, possibly due to atrial fibrillation, hypertension, heart failure or a combination of these. A normal color flow pattern excludes severe vascular compromise to the allograft. In addition, CDI revealed three biopsy-related vascular lesions; two of them had been missed by DS.

Serum-Erythropoietin Concentration During Acute Cardiogenic Pulmonary Edema

Abstract Increased plasma oxalic acid concentrations have been found in patients with chronic renal failure. Secondary oxalosis in patients on chronic hemodialysis is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. 1,2 The oral or intravenous administration of ascorbic acid aggravates the elevated plasma oxalic acid in patients on hemodialysis. 3 As a consequence of increased plasma oxalic acid levels, calcium oxalate deposits have been found in myocardium and other organs. 4 We report a patient treated with chronic hemodialysis with diffuse calcinosis in the myocardium at autopsy. In this patient, who had undergone parathyroidectomy, a high intake of ascorbic acid led to increased oxalic acid synthesis and calcium deposits in many tissues.