Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. Most reported cases of parvovirus B19-associated aplastic anemia in renal transplant recipients responded to intravenous immunoglobulin (IVIG) infusion. Tacrolimus is of special interest; it was proposed to be associated with pure red cell aplasia (PRCA) on its own because resolution of anemia on withdrawal of tacrolimus was previously observed. Interaction between parvovirus B19 infection and tacrolimus has not been reported. We report a case of parvovirus B19-associated PRCA in a renal transplant recipient treated with tacrolimus who failed to clear the virus despite repeated courses of IVIG. She showed complete recovery promptly after tacrolimus was switched to cyclosporine A. A well-documented concomitant decrease in serum parvovirus DNA polymerase chain reaction titer was also observed. This shows another mechanism by which tacrolimus can aggravate PRCA because of impaired clearance of parvovirus B19 infection in transplant recipients. For those patients receiving tacrolimus who have parvovirus B19 infection with refractory anemia and who fail to recover with IVIG, replacement of tacrolimus with cyclosporine A can be considered.
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PMID:Parvovirus B19 infection causing red cell aplasia in renal transplantation on tacrolimus. 1058 25

We report an unexplained anemia that persisted for 4 months in a renal transplant patient who was receiving immunosuppression therapy that included prednisolone, tacrolimus and azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts with intranuclear inclusions, characteristic of a parvovirus B19 infection. Both the serum and bone marrow cells were positive by parvovirus B19 DNA PCR. The anemia resolved 6 weeks after the administration of intravenous immunoglobulin (IVIG). Four months later, anemia redeveloped and IVIG was infused again. Hemoglobin levels were, however, still subnormal after 1 month of treatment and tacrolimus was then switched to cyclosporin A, resulting in a clear improvement. A parvovirus B19 infection should be included in the differential diagnosis of renal transplant recipients who present with anemia associated with a low reticulocyte count. Tacrolimus may possibly impair the clearance of a parvovirus B19 infection.
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PMID:A case of persistent anemia in a renal transplant recipient: association with parvovirus B19 infection. 1187 73

Microangiopathic haemolytic anaemia (MAHA) describes intravascular haemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. It is well recognized as a complication of cyclosporin A therapy in solid organ transplantation but has been uncommonly reported in association with tacrolimus therapy and never before in the setting of lung transplantation. Discussed is a 54-year-old female recipient of a left single lung transplant who developed anaemia, thrombocytopenia and red blood cell fragmentation consistent with MAHA following lung volume reduction surgery (VRS) of the native right lung in the setting of high serum tacrolimus levels. Treatment with fresh frozen plasma and plasmapharesis plus supportive therapy with blood and platelet transfusions resulted in successful resolution of the haemolytic process. Cyclosporin A was substituted for tacrolimus and 18 months later there has been no evidence of recurrence. Tacrolimus therapy is a rare cause of MAHA in solid organ transplants but the diagnosis should be considered if there is an unexplained fall in haemoglobin and/or platelet count in the context of high serum tacrolimus levels.
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PMID:Microangiopathic haemolytic anaemia and thrombocytopenia following lung volume reduction surgery in a single lung transplant recipient on maintenance tacrolimus (FK506) therapy. 1275 43

This is a retrospective analysis of 16 children started on tacrolimus with various types of treatment-resistant nephrotic syndrome. There are 13 patients with focal glomerulosclerosis, 1 minimal change disease, and 2 IgA nephropathy with nephrosis. The mean age of the children was 11.4 years (range 3.5-18.1 years) with a mean age at diagnosis of 5.6 years (range 1.6-13.3 years). All patients initially received prednisone 2 mg/kg per day. Other therapies for 15 of 16 included cyclosporine (n=15), chlorambucil (n=5), mycophenolate mofetil (n=5), levamisole (n=3), i.v. methylprednisolone (n=3), and cyclophosphamide (n=2). The major indication for the initiation of tacrolimus included treatment resistance/dependence (n=15) and intolerable side effects from other therapies (n=1). The average time from the diagnosis to initiation of tacrolimus was 5.3 years (range 0.3-13.3 years, median 6 years). The initial dosage of tacrolimus utilized was 0.1 mg/kg per day divided into two doses. The mean follow-up period was 6.5 months (range 2.5-18 months). Thirteen patients (81%) went into a complete remission within an average of 2 months (range 0.5-5.5 months), with 3 patients relapsing while on treatment. Three patients did not respond. Of these, 2 had partial remissions (13%) and 1 failed to respond. Adverse events included anemia (n=1), seizure (n=1), worsening or new-onset hypertension (n=5), and sepsis (n=1). All patients remain on tacrolimus. Tacrolimus is an effective, well-tolerated medication for treatment-resistant forms of nephrotic syndrome in children, with a complete remission rate of 81% and a partial remission rate of 13% (totaling 94%).
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PMID:Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. 1693 33

Tacrolimus (FK506)-induced hematological toxicity, which has rarely been reported in transplant recipients, may result in anemia episodes, reported mainly in kidney and heart transplant recipients, sporadic cases of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, red cell aplasia (4 reported cases), and generalized bone marrow suppression (only 1 reported case). We describe a case of a liver transplant recipient with pancytopenia that appeared during immunosuppressive therapy with tacrolimus. This patient suffered from progressive anemia, leukopenia with severe neutropenia, and mild thrombocytopenia; bone marrow biopsy showed hypoplasia (20% of cellularity) without dysplasia. Bone marrow recovery was made possible by suspending tacrolimus and changing to immunosuppression with cyclosporine A, despite the two drugs being very similar in their mechanism of immunosuppression. Contrary to previously reported cases (pure red cell aplasia and bone marrow hypoplasia), the recovery of hemoglobin and neutrophil values was slow after tacrolimus suspension, even though in the first month transfusions were no longer necessary.
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PMID:Bone marrow hypoplasia complicating tacrolimus (FK506) therapy. 1500 39

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.
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PMID:Anemia in pediatric renal transplant recipients. 1500 19

In the control of acute rejection, attention is being focused more and more on the long-term adverse effects of the immunosuppressive agents used. Since cardiovascular disease is the main cause of death in renal transplant recipients, optimal control of cardiovascular risk factors is essential in the long-term management of these patients. Unfortunately, several commonly used immunosuppressive drugs interfere with the cardiovascular system. In this review, the cardiovascular adverse effects of the immunosuppressive agents currently used for maintenance immunosuppression are thoroughly discussed. Optimising immunosuppression means finding a balance between efficacy and safety. Corticosteroids induce endothelial dysfunction, hypertension, hyperlipidaemia and diabetes mellitus, and impair fibrinolysis. The use of corticosteroids in transplant recipients is undesirable, not only because of their cardiovascular effects, but also because they induce such adverse effects as osteoporosis, obesity, and atrophy of the skin and vessel wall. Calcineurin inhibitors are the most powerful agents for maintenance immunosuppression. The calcineurin inhibitor ciclosporin (cyclosporine) not only induces these same adverse effects as corticosteroids but is also nephrotoxic. Tacrolimus has a more favourable cardiovascular risk profile than ciclosporin and is also less nephrotoxic. It has little or no effect on blood pressure and serum lipids; however, its diabetogenic effect is more prominent in the period immediately following transplantation, although at maintenance dosages, the diabetogenic effect appears to be comparable to that of ciclosporin. The diabetogenic effect of tacrolimus can be managed by reducing the dose of tacrolimus and early corticosteroid withdrawal. The effect of tacrolimus on endothelial function has not been completely elucidated. The proliferation inhibitors azathioprine and mycophenolate mofetil (MMF) have little effect on the cardiovascular system. Yet, indirectly, by inducing anaemia, they may lead to left ventricular hypertrophy. MMF is an attractive alternative to azathioprine because of its higher potency and possibly lower risk of malignancies. Sirolimus also induces anaemia, but may be promising because of its antiproliferative features. Whether the hyperlipidaemia induced by sirolimus counteracts its beneficial effects is, as yet, unknown. It may be combined with MMF, however, initial attempts resulted in severe mouth ulcers.
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PMID:Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. 1534 97

The goal was to study the factors affecting tacrolimus apparent clearance (CL/F) in adult liver transplant recipients. Tacrolimus dose and concentration data (n = 694) were obtained from 67 liver transplant recipients (22 female and 45 male), and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. A 1-compartment pharmacokinetic model with first-order elimination, an absorption rate constant fixed at 4.5 hours, and first-order conditional estimation was used to describe tacrolimus disposition. The predictive performance of the final model was evaluated using data splitting and assessing bias and precision of the estimates. The population estimate of tacrolimus CL/F and apparent volume of distribution (V/F) were found to be 21.3 L/h (95% confidence interval, CI, 18.0-24.6 L/h) and 316.1 L (95% CI 133-495 L), respectively. Neither patient's age, weight, gender, nor markers of liver function influenced tacrolimus CL/F. The final model was TVCL = 21.3 + 9.8 x (1 - HEM) + 3.4 x (1 - ALB) - 2.1 x (1 - DIL) - 7.4 x (1 - FLU), where TVCL, typical estimate of apparent clearance, HEM = 0 if hematocrit <35%, otherwise 1; ALB = 0 if albumin <3.5 g/dL, otherwise 1; DIL = 0 if diltiazem is coadministered, otherwise 1; FLU = 0 if fluconazole is coadministered, otherwise 1. This study identified the factors that significantly affect tacrolimus disposition in adult liver transplant recipients during the early posttransplantation period. This information will be helpful to clinicians for dose individualization of tacrolimus in liver transplant recipients with different clinical conditions including anemia or hypoalbuminemia or in those patients receiving diltiazem or fluconazole.
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PMID:Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients. 1604 97

A two year-old female who had underwent ABO-incompatible heart transplantation at four months of age was admitted with unexplained anemia and renal dysfunction. The patient also had evidence of moderate liver dysfunction. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and prednisolone. Tacrolimus was held on day 2 for five days because of an elevated trough blood concentration. The patient required one fourth of her maintenance dose to keep trough concentrations within the target range. Nadolol and amiodarone were prescribed on day 7 to control ventricular arrhythmias. Sirolimus was prescribed on day 11. A precautionary (non-steady-state) sirolimus trough concentration was grossly elevated. Sirolimus was held and tacrolimus was discontinued. Sirolimus blood concentrations remained above the target range for fourteen days despite successive dose manipulations. The patient succumbed from complications of ECMO on day 42. Amiodarone and cyclosporine interactions in the solid organ transplant population have been previously described. To our knowledge, there are no cases of amiodarone and sirolimus or tacrolimus interactions reported in English literature. Both tacrolimus and sirolimus are metabolized through the same enzyme system as cyclosporine, and the chance of a similar interaction occurring is high. Sirolimus is also a substrate of p-glycoprotein and thus may be significantly affected by amiodarone. We have described a potential interaction with sirolimus, tacrolimus and amiodarone. If amiodarone is deemed the most appropriate choice for the patient, clinicians should consider prospectively decreasing sirolimus and tacrolimus doses. Blood concentrations should also be monitored more frequently in order to minimize prolonged periods of supratherapeutic concentrations and related toxicities.
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PMID:Amiodarone-sirolimus/tacrolimus interaction in a pediatric heart transplant patient. 1691 99

Arterial hypertension develops in up to 80% of renal transplant recipients. Uncontrolled hypertension induces left ventricular hypertrophy, heart failure and death, but also promotes deterioration of allograft function. Cadaveric transplantation, delayed graft function, renal artery stenosis, presence of native kidneys, increased body weight and therapy with calcineurin inhibitors and steroids have been associated with an increased incidence of hypertension after kidney transplantation. Cyclosporine increases both systemic and renal vascular resistance, enhances sympathetic activation, endothelin production and, possibly, decreases vascular relaxation by decreasing the generation of nitric oxide. Tacrolimus has less pronounced prohypertensive role after renal transplantation. Corticosteroids contribute to the development of hypertension, since their withdrawal results in a significant decrease of blood pressure in the majority of patients. Renal artery stenosis occurs in almost 12% of hypertensive renal transplant recipients. It is a correctable cause of hypertension, and for this reason should be investigated in all suspected patients. Doppler ultrasonography is used as the screening method that is highly sensitive and specific in the hands of a well-experienced investigator. However, dependence of the method on the experience of the investigator is its major drawback. Magnetic resonance angiography and spinal computed tomography angiography are useful noninvasive methods, but arteriography remains a method for establishing the definitive diagnosis. Percutaneous balloon angioplasty, with or without placement of the stent, is successful in the majority of patients, but with a high incidence of restenoses (20%). Surgery is indicated for stenoses that cannot be treated with angioplasty or that recur. Auto-transplantation of the kidney with complex stenoses of graft arteries is useful in selected cases. Posttransplant hypertension should be aggressively treated to prevent the development of end-organ damage. Every effort should be invested in reducing immunosuppression when appropriate, together with salt restriction and weight reduction. Calcium channel blockers have good antihypertensive properties accompanied with minimization of cyclosporine-induced renal vasoconstriction. Angiotensin-converting enzyme inhibitors (ACEi) should be used in patients with proteinuria. Renal function should be carefully monitored after their introduction since they may cause transitory deterioration of glomerular filtration and/or hyperkaliemia. ACEi can induce anemia in renal transplant recipients, side effect that is often used in the treatment of posttransplant erythrocytosis. All other antihypertensive drugs could be used, with minoxidil being the most potent one. Patients with resistant hypertension should be investigated for the presence of renal artery stenosis. After exclusion of rejection, renal artery stenosis and recurrent disease, in cases of severe hypertension, native kidneys laparoscopic nephrectomy should be considered.
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PMID:[Arterial hypertension in renal transplant recipients]. 1836 9


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