mycophenolic-acid and Anemia--Iron-Deficiency

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.

Topics: Anemia; Anemia, Iron-Deficiency; Azathioprine; Bone Marrow; Child; Erythropoiesis; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus

Oral administration of ferrous-sulfate was reported to decrease intestinal absorption of mycophenolate mofetil (MMF) in healthy Japanese individuals by 90%.. We examined the effect of a single oral dose of ferrous sulfate on steady-state mycophenolic acid pharmacokinetics in 10 iron-deficient (hypochromic red blood cells >2.5%), Caucasian, long-term kidney graft recipients using a randomized, open-label, crossover design. On days A and B, MMF (1,000 mg) was given orally at 8:00 am. On day C, MMF and ferrous sulfate (105 mg) were coadministered at 8:00 am. On day D, MMF was given at 8:00 am and ferrous sulfate was given orally 4 hours later.. The interindividual variability of the 12-hour area under the plasma mycophenolic acid concentration versus time curves (AUC(0-12)) under control conditions was small (89.5 +/- 27.8 and 87.6 +/- 39.1 mg x h/L, respectively). Concomitant or subsequent administration of MMF and ferrous sulfate did not affect the bioavailabilty of MMF (AUC(0-12), 91.9 +/- 30.4 mg x h/L and 96.0 +/- 31.7 mg x h/L).. Oral therapy of iron deficiency using ferrous sulfate in long-term kidney graft recipients does not impede intestinal absorption of MMF; hence, exposure to this immunosuppressive agent is not reduced.

Topics: Administration, Oral; Anemia, Hypochromic; Anemia, Iron-Deficiency; Area Under Curve; Biological Availability; Cross-Over Studies; Drug Interactions; Erythrocytes; Female; Ferrous Compounds; Humans; Intestinal Absorption; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Time; Time Factors

Topics: Anemia, Iron-Deficiency; Diabetic Nephropathies; Humans; Ileitis; Ileum; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Single-Balloon Enteroscopy; Ulcer

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.

Topics: Adolescent; Anemia; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Body Mass Index; Child; Child, Preschool; Cross-Sectional Studies; Erythropoietin; Female; Graft Rejection; Growth; Hemoglobins; Humans; Immunosuppressive Agents; Iron; Kidney Function Tests; Kidney Transplantation; Male; Mycophenolic Acid; Recombinant Proteins; Tacrolimus