Jörg H. Horina

Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: Results in three patients

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Increased susceptibility for CsA-induced hepatotoxicity in kidney graft recipients with chronic viral hepatitis C.

CsA-induced hepatotoxicity is a rare disorder in renal transplant recipients when low doses are administered and whole blood trough levels of CsA are regularly monitored. However, there is controversy about the clinical value of measuring CsA-metabolites, whose contribution to immunosuppression and toxicity is not fully understood. To assess the relation between low-dose CsA therapy and hepatotoxicity, we studied 128 renal transplant recipients attending our nephrology clinic. Eight of these patients had markedly elevated liver function tests. Three patients while receiving very low doses of oral CsA (< 3.8 mg/kg of body weight) presented marked derangements of CsA metabolism with abnormally increased CsA-metabolite levels. Parent drug levels were in the normal range. All 3 patients had chronic infection with hepatitis C virus and revealed histomorphologic evidence of hepatotoxicity. Hepatic dysfunction normalized when CsA was withdrawn or reduced by 50%. It is likely that hepatitis C virus infection interferes with CsA metabolism and/or biliary CsA-excretion and thus is responsible for CsA and/or metabolite-induced hepatotoxicity despite very low doses of CsA.

Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients

Background: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10–14 g/dL in men and 10–12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients. 
Methods: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non‐anemic patients. 
Results: Forty‐three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non‐anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non‐anemic patients (p<0.02). 
Conclusions: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.

Cerebral Hemodynamic Changes following Treatment with Erythropoietin

Adverse hemorheologic effects induced by erythropoietin (EPO) treatment of renal anemia may pose a cerebrovascular risk. We therefore investigated the changes in cerebral perfusion, cerebral blood flow velocity (BFV) and neuropsychologic performance in 11 patients (mean age 37 years) receiving EPO. In response to EPO there was a significant (p less than 0.01) increase in hematocrit (35%), hemoglobin (43%) and whole-blood viscosity (50% at high and 90% at low shear rate). The initially increased blood flow velocity dropped significantly (p less than 0.05) and returned toward normal values in the middle cerebral arteries and the basilar artery (22 and 19% decrease, respectively). Global cerebral blood flow (CBF) decreased by 10% (not significant). The score of the Wechsler Adult Intelligence Scale digit symbol test improved significantly (p less than 0.01) after EPO treatment. None of the patients developed cerebrovascular symptoms or side effects. We conclude that the hematologic and rheologic changes following EPO treatment cause CBF and BFV to return toward normal and improve neuropsychologic performance in patients with end-stage renal disease.

Spontaneous bacterial peritonitis in a patient with nephrogenic ascites during an episode of acute renal transplant rejection

Spontaneous bacterial peritonitis (SBP) is a primary infection of asci tes without signs of perforation or penetration. It occurs most often in patients with liver cirrhosis but can also be diagnosed in patients with ascites from other causes. We report a kidney transplant recipient who developed nephrogenic ascites during an episode of acute rejection. The patient complained of fever, abdominal tenderness, and loose stools and showed all of the signs of peritonitis on physical examination. The patients serum creatinine was elevated, and Duplex sonography of the graft was highly suggestive for acute rejection. Ascites puncture was performed. The ascitic fluid contained 4,000 leukocytes per microliter. No source of infection was detected, so the diagnosis of SBP was made. The patient was treated with ciprofloxacin intravenously and received low-dose steroid pulse therapy. The ascites culture grew Staphylococcus aureus that was highly sensitive to ciprofloxacin. The patient recovered rapidly. We could avoid laparotomy, which is associated with high mortality in patients suffering from SBP. No relapses of SBP occurred. Renal function has improved and remained stable.

Ophthalmological findings in three patients with cholesterol acyltransferase deficiency syndrome before and after kidney transplantation

Familial lecithin cholesterol acyltransferase (LCAT) deficiency syndrome is inherited as an autosomal recessive disorder and is characterized by disturbances of the lipid metabolism. The lack or absence of the enzyme LCAT results in an inability to esterify free cholesterol in the plasma. This is followed by an accumulation of free cholesterol and phospholipids, although total cholesterol may be normal and the concentration of high density lipoprotein cholesterol may be reduced. Clinically this enzymatic defect is characterized by diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure, which is the major cause of morbidity and mortality. We report the ophthalmological findings from three affected siblings (two males and one female). Because of chronic renal failure one of these patients received a kidney transplant 4 years ago. Changes in both the corneal and the fundus before and after transplantation are described in this patient. Corneal opacities resembling arcus lipoides on both eyes were first noticed in a white male at the age of 19 years. Five years later proteinuria was detected by a local general practicioner, but no further diagnostic procedures were performed. In 1981 at the age of 33 years the patient was referred to our hospital because of mild hypercholesterolemia, markedly increased concentration of serum triglyceride and mild normochromic anemia. The ophthalmological examination showed cloudy corneas on both eyes (Fig. 1). In the stroma innumerable minute grayish dots were evenly distributed in all layers over the pupil, with a higher density near by the limbus. Very close to the limbus, however, there was a small zone of almost clear cornea. At that time the patients visual acuity was normal (20/20). No pathological findings were evident concerning the lens, vitreus, or fundus. In 1987 chronic dialysis was necessary because of endstage renal disease. At this time the patient suffered from chronic overhydration and high blood pressure (250/ 120mmHg). A biopsy of his native kidney revealed histomorphological abnormalities affecting mainly the glomeruli. As typical for LCAT deficiency syndrome, widespread lipid deposition and foam cells were found in the mesangium matrix, interstitium, and tubules. The degree of the corneal opacities was further increased. Lipid deposits were again more pronounced at the lirabus without affecting epithelium or endothelium, leaving a narrow zone without stromal dots. The visual acuity was decreased (20/40), and on the fundus arteriolovenous crossing changes, small flame-shaped retinal hemorrhages, and an edema of the macula and the optic disc were observed. Cotton wool exsudates or eyelid xanthelasmas could not be seen. Two and a half years after successful transplantation (creatinine 2.0, blood pressure 140/90) the patient underwent a follow-up ophthalmological examination. His corneas were unchanged, but retinal hemorrhages and the edema of the macula and the optic disc were no longer detectable. Only hypertension-related vascular changes (primarily diminution in diameter of retinal vessels and arteriovenous crossing phenomena) were visible.