mycophenolic-acid and Anemia

Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.. We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.. Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N.. Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Topics: Adult; Anemia; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Transplant Recipients; Valganciclovir

Severe anemia requiring multiple blood transfusions in the posttransplant period can trigger rejection. The evaluation of anemia among transplant recipients is a challenging task. Awareness should be continued for tacrolimus to manage pure red cell aplasia, but further evidence is needed to prove whether tacrolimus is a real cause of posttransplant anemia. Our case patient, a 66-year-old male patient with end-stage renal disease due to diabetic nephropathy, underwent a preemptive living donor renal transplant in September 2018. He had received a coronary artery bypass graft with transcatheter aortic valve implantation 3 years before renal transplant. Initially, he was maintained on prednisolone, mycophenolate mofetil, and tacrolimus after basiliximab induction. One month later, he presented with low cardiac output symptoms. His complete blood count showed normocytic normochromic anemia with reticulocytopenia (his hemoglobin level dropped from 112 to 69 g/L), which necessitated regular blood transfusions. His iron profile, serum folate, and vitamin B12 were within normal limits, and he had negative hemolytic and autoimmune screening tests. A bone marrow biopsy revealed acquired pure red cell aplasia, which was most likely drug induced as viral profiles were negative for parvovirus B19, cytomegalovirus, and Epstein-Barr virus. The patient was managed by discontinuing mycophenolate mofetil, and the steroid dose was increased up to 20 mg/day but without improvement. With tacrolimus then considered, 3 weeks after presentation, we replaced tacrolimus with cyclosporine. Complete blood count follow-up showed improvement without any need for further blood transfusions. After 1 month of cyclosporine maintenance, mycophenolate mofetil was resumed with a steady increase of hemoglobin up to 150 g/L and serum creatinine of 122 μmol/L. Pure red cell aplasia is a rare disorder among renal transplant recipients, which could be induced by maintenance tacrolimus therapy.

Topics: Aged; Anemia; Cyclosporine; Epstein-Barr Virus Infections; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus; Transplant Recipients; Treatment Outcome

Fertility in women with kidney failure is restored by transplantation. It requires careful planning and is only advisable in women with good kidney function, controlled blood pressure, and general good health. Immunosuppressive drugs carry risks for the fetus, but the risks of prednisone, azathioprine, cyclosporine, and tacrolimus are surprisingly low. Mycophenolate is teratogenic. The success rate for pregnancy in kidney transplant recipients is lower than in the general population with 70% to 80% of pregnancies resulting in surviving infants. Prematurity, intrauterine growth restriction, and preeclampsia are all increased. Complications are higher and outcomes are worse for women with serum creatinine levels over 1.3 mg/dL. Ten to 15% of women have a temporary or permanent decline in kidney function, particularly if prepregnancy creatinine is high. Transplant-related infections can be serious for the mother and fetus. A multidisciplinary team should coordinate care.

Topics: Anemia; Azathioprine; Cyclosporine; Cytomegalovirus Infections; Female; Herpes Simplex; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Mycophenolic Acid; Preconception Care; Prednisone; Pregnancy; Pregnancy Complications; Tacrolimus; Toxoplasmosis; Urinary Tract Infections

Anemia, leukopenia, and/or thrombocytopenia can occur as a result of non-immune- and immune-mediated mechanisms in patients with systemic lupus erythematosus. Although the differential diagnosis of these cytopenias is broad and warrants a thorough evaluation, lupus disease activity and medications are common etiologic factors. Corticosteroids are the mainstay of initial treatment for immune-mediated hemolytic anemia and severe thrombocytopenia; immunosuppressive agents such as mycophenolate mofetil or azathioprine are often added for their steroid-sparing effects. Rituximab and intravenous immunoglobulin can be considered for refractory cytopenias based on a large body of anecdotal evidence and case series. Newer biologic agents such as belimumab or epratuzumab have yet to be studied specifically in systemic lupus erythematosus-mediated hematologic disorders.

Topics: Anemia; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Leukopenia; Lupus Erythematosus, Systemic; Mycophenolic Acid; Pancytopenia; Rituximab; Thrombocytopenia

B19 virus infection with persistent anaemia has been reported in organ transplant recipients. Detection of B19 virus DNA in serum is the best direct marker of active infection.. The present study evaluated the incidence and clinical role of active B19 virus infection in renal transplant recipients presenting with anaemia.. Forty-eight such recipients were investigated by nested PCR on serum samples. The controls were 21 recipients without anaemia. Active HCMV infection was also investigated as a marker of high immunosuppression.. In 11/48 (23%) patients B19 virus DNA was demonstrated in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had already been seropositive at transplantation and active infection occurred in eight of them during the first 3 months after transplantation. The remaining patient experienced a primary infection 9 months after transplantation. Eight (73%) of these 11 patients displayed a concomitant HCMV infection and four (36%) showed increasing serum creatinine levels but none developed glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11 (73%) needed therapy. In conclusion, the relatively high occurrence (23%) of B19 virus infection in patients presenting with anaemia, suggests that it should be considered in the differential diagnosis of persistent anaemia in renal transplant recipients. Presence of the viral DNA should be assessed early from transplantation and the viral load should be monitored to follow persistent infection and better understand the relation between active infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy and/or immunosuppression reduction in clearing the virus.

Topics: Anemia; Antibodies, Monoclonal; Antibodies, Viral; Antilymphocyte Serum; Basiliximab; Cyclosporine; Cytomegalovirus Infections; Diagnosis, Differential; Disease Susceptibility; DNA, Viral; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interleukin-1; Kidney Transplantation; Male; Mycophenolic Acid; Parvoviridae Infections; Parvovirus B19, Human; Phosphoproteins; Polymerase Chain Reaction; Postoperative Complications; Prednisone; Recombinant Fusion Proteins; Retrospective Studies; T-Lymphocytes; Tacrolimus; Viral Load; Viral Matrix Proteins; Viremia; Zidovudine

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

Secondary cytopenias are serious complications following hematopoietic cell transplantation. Etiologies include myelotoxic agents, viral infections, and possibly transplant-related factors such as the intensity of the conditioning regimen and the source of stem cells.. We retrospectively analyzed data from 2162 hematopoietic cell transplant recipients to examine the effect of these factors on overall cytopenias occurring after 28 days in hematopoietic cell transplantation.. Advanced age of the patient, recipient cytomegalovirus seropositivity, unrelated donor status, human leukocyte antigen mismatch and lower doses of transplanted CD34(+) cells (≤ 6.4×10(6)/kg) significantly increased the risk of cytopenias after day 28. Non-myeloablative hematopoietic cell transplantation had protective effects on anemia and thrombocytopenia after day 28 (adjusted odds ratio 0.76, probability value of 0.05 and adjusted odds ratio 0.31, probability value of <0.0001, respectively) but not on overall or ganciclovir-related neutropenia. This lack of protection appeared to be due to the use of mycophenolate mofetil in the majority of recipients of non-myeloablative hematopoietic cell transplants. Peripheral blood stem cells did not confer protection from cytopenias when compared to bone marrow.. Elderly patients appear to be more prone to cumulative toxicities of post-transplant drug regimens, but non-myeloablative conditioning, optimized human leukocyte antigen matching, and higher doses of CD34(+) cell infusions may reduce the risk of cytopenia after day 28.

Topics: Adult; Age Factors; Aged; Anemia; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mycophenolic Acid; Neutropenia; Thrombocytopenia; Time Factors; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous

Two recent randomized clinical trials--Fixed Dose Versus Concentration Controlled and the Apomygre--evaluating the benefit of therapeutic drug monitoring of mycophenolate mofetil (MMF) in renal allograft recipients reported conflicting results. In both studies, target mycophenolic acid (MPA) AUC(0-12 h) ranges (ie, values used to guide MMF dosing) were derived from a previous study establishing target MPA AUC(0-12 h) ranges in cyclosporine-treated patients between 30 and 60 mg/L x h(-1). Both studies found an association between MPA exposure and acute rejection. However, only one of the studies found concentration-controlled MMF dosing to be significantly associated with less biopsy-proven acute-rejection episodes compared with fixed dosing. No reduced incidence of MMF-related adverse events (AEs) was observed in either of the 2 trials when MMF concentration-controlled and fixed dosing were compared.. The aim of this study was to assess the clinical utility of target MPA AUC(0-12h) ranges between 30 and 60 mg/L x h(-1) in associating drug exposure with AEs within different time windows after transplantation, thereby identifying patients at increased risk for MMF-related AEs. The effects of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 1A9 (UGT1A9) and MRP2 genes (ie, coding for the UGT1A9 and the multidrug resistance protein transporter MRP2)-both involved in MPA metabolism-on stratified MPA exposure were assessed by applying the current advised target MPA AUC(0-12h) ranges.. We conducted a 5-year clinical follow-up study in renal allograft recipients in whom MPA exposure was measured at 7 days, 6 weeks, 3 months, 1, 3, and 5 years post transplantation using abbreviated AUC measurements. MMF dose adjustments were based on clinical indications (eg, persistent leukopenia, chronic afebrile diarrhea, BK-polyomavirus infection of the renal allograft). Clinicians were blinded to the results of the AUC measurements.. One hundred white de novo renal allograft recipients (59 men, 41 women; mean [SD] age 51.4 [13.8] years) were included in this study. Ninety-eight patients received a renal allograft from a deceased donor. Significantly more episodes of leukopenia were associated with MPA AUC(0-12h) ranges >60 mg/L x h(-1) (P=0.03). Anemia was also significantly associated with higher MPA exposure ranges (incidence of anemia was 40.8%, 52.2%, and 64.3% for MPA AUC(0-12h) ranges <30, 30-60, and >60 mg/L x h(-1), respectively; P=0.004). Mean MPA AUC(0-12h) was significantly higher in the time window immediately preceding or following leukopenia (mean [SD] 59.7 [31.0] vs 46.5 [26.0] mg/L x h(-1); P=0.004) and anemia (mean [SD] hemoglobin <12 g/L x d(-1): 52.5 [30.0] vs 42.2 [21.2] mg/L x h(-1), P=0.002; hemoglobin <10 g/L x d(-1): 56.2 [32.5] vs 45.6 [24.7] mg/L x h(-1), P=0.005). No association was found between incident episodes. of diarrhea or infection and target MPA AUC(0-12 h) ranges. A significantly higher proportion of MPA AUC(0-12 h) measurements in recipients carrying the UGTIA9 T-275A and/or C-2152T SNP were in the low MPA exposure range (23.7%, 16.6%, and 12.6% for MPA AUC(0-12 h) ranges <30, 30-60, and >60 mg/L x h(-1), respectively; P=0.02).. Renal allograft recipients suffering from leukopenia or anemia related to MMF could potentially benefit, at least in part, from MMFdose adjustments based on target therapeutic MPA AUC(0-12 h) ranges between 30 and 60 mg/L x h(-1). This study did not find these target MPA AUC(0-12 h) ranges to be of clinical utility in guiding MMF dosing in patients with gastrointestinal or infectious AEs. Larger prospective studies are necessary to examine the risk for MPA underexposure in patients carrying the UGTIA9 T-275A and/or C-2152T SNP.

Topics: Anemia; Chromatography, High Pressure Liquid; DNA; Drug Resistance, Multiple; Enzyme Inhibitors; Female; Follow-Up Studies; Glucuronosyltransferase; Graft Rejection; Humans; Immunoassay; Kidney Transplantation; Leukopenia; Male; Middle Aged; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Mycophenolic Acid; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prospective Studies; Time Factors; Treatment Outcome; UDP-Glucuronosyltransferase 1A9

Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for the increased risk of gastrointestinal complications in kidney transplant recipients. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. This study evaluated the incidence of post-transplant gastrointestinal complications during screening colonoscopy. Kidney transplant recipients undergoing a colonoscopy for any reasons in the period 2014-2018 were included. Among the 134 patients completing the colonoscopy, 74 patients (56%) had an abnormal finding: an adenoma was found in 25 patients (18.6%), while 19 patients (14.1%) had colitis. Mycophenolic acid/related colitis was the most common colitis (6%), while 7 patients (5.2%) developed a

Topics: Adenoma; Age Distribution; Aged; Anemia; Colitis; Colonoscopy; Colorectal Neoplasms; Diarrhea; Diverticulosis, Colonic; Early Detection of Cancer; Female; Gastrointestinal Hemorrhage; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Time Factors

Topics: Abdominal Pain; Adolescent; Anemia; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Arthralgia; Arthritis; Biopsy; Computed Tomography Angiography; Diagnosis, Differential; Drug Therapy, Combination; Exanthema; Female; Humans; Hypertension; IgA Vasculitis; Immunologic Factors; Kidney; Methylprednisolone; Mycophenolic Acid; Myeloblastin; Nephritis; Pulse Therapy, Drug; Rituximab; Urticaria

Topics: Adult; Anemia; Cyclophosphamide; Dexamethasone; Female; Humans; Mycophenolic Acid; Thrombocytopenia

The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects, such as nephrotoxicity, anemia, leukopenia, and new-onset diabetes after transplantation. In this report, we attempted to identify genetic variants which are associated with these adverse outcomes.. We performed a genome-wide association study, using a genotyping array tailored specifically for transplantation outcomes containing 722 147 single nucleotide polymorphisms, and 2 cohorts of kidney allograft recipients-a discovery cohort and a confirmation cohort-to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes.. Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified.. These results show that adverse effects associated with tacrolimus and mycophenolate are complex, and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors.

Topics: Adult; Aged; Anemia; Diabetes Mellitus; Female; Genome-Wide Association Study; Genotype; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Tacrolimus; United States; Young Adult

Tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. Tacrolimus is also reported to inhibit Plasmodium falciparum growth in vitro. Here, we report that tacrolimus prevented the death from cerebral malaria of Plasmodium berghei ANKA-infected C57BL/6J mice, but not their death from malaria due to the high parasitaemia and severe anaemia. The mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malaria earlier than tacrolimus-treated littermates. Tacrolimus attenuated the infiltration of mononuclear cells including pathogenic CD8

Topics: Anemia; Animals; Brain; CD8-Positive T-Lymphocytes; Cell Movement; Cells, Cultured; Humans; Immunosuppressive Agents; Malaria, Cerebral; Mice; Mice, Inbred C57BL; Mycophenolic Acid; Parasitemia; Plasmodium berghei; Tacrolimus

We compared retrospectively the level of hemoglobin and the percentage of patients with anemia among 59 kidney transplant recipients receiving everolimus, cyclosporine, and corticosteroids and 128 treated with cyclosporine, mycophenolic acid, and corticosteroids. We also compared age at the time of transplantation, sex and ferritine, serum creatinine, creatinine clearance, folic acid, cyanocobalamine levels, use od recombinant erythropoietin, mean corpuscolar volume at the last ambulatory control. Statistical analysis included Student t test, χ(2) test, and logistic regression. The analysis was performed using SPSS software. We observed no difference in terms of hemoglobin levels in patients treated with everolimus (12.9 ± 1.6 vs 12.7 ± 1.5 g/dL). Anemia (defined as hemoglobin <13 g/dL in men and <12 g/dL in women, or need to use erythropoietin) was found in 49% and 45% of patients in the 2 groups respectively (P = .6). The other parameters evaluated were similar except for the mean corpuscular volume, which was significantly lower in the everolimus group. In the multivariate analysis only serum creatinine and estimated glomerular filtration rate influenced the level of hemoglobin. We observed no differences in terms of development of anemia in renal transplanted patients treated with everolimus-based regimen.

Topics: Adult; Aged; Anemia; Cyclosporine; Everolimus; Female; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Retrospective Studies

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV (P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group (P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 (P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders.

Topics: Adult; Aged; Anemia; Antibodies, Monoclonal; Basiliximab; Case-Control Studies; Cyclosporine; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Glucocorticoids; Humans; Immunosuppressive Agents; Japan; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Prednisolone; Recombinant Fusion Proteins; Ribonucleosides; Viremia; Young Adult

Aim: Pegylated-interferon/ribavirin/simeprevir (PEG-IFN/RBV/SMV) combination therapy is widely used for hepatitis C virus (HCV) treatment after liver transplantation (LT). Here, we observed two cases of extended severe anemia during PEG-IFN/RBV/SMV therapy for HCV serological type 1 re-infected after LT. Immunosuppressants consisted of tacrolimus and mycophenolate mofetil (MMF). Case 1 was a 65-year-old-woman treated with PEG-IFN/RBV/SMV therapy and 500 mg MMF/day 9 months after LT. Her serum hemoglobin (Hb) level decreased from 10 to 8.4 mg/dL on day 25. Despite discontinuing the PEG-IFN/RBV/SMV treatment on day 32, her Hb level decreased to 5.1 mg/dL on day 40. Case 2 was a 61-year-old-woman started on PEG-IFN/RBV/SMV therapy 20 months after LT. Her serum Hb level decreased from 12.2 to 7.1 mg/dL on day 39. The MMF dose was reduced from 1,500 to 1,000 mg/day, and her Hb level was maintained. Red blood cell transfusions were required in both cases, and anemia persisted for 2 months. These patients had the C/C major type inosine triphosphatase (ITPA) polymorphism. In conclusion, MMF induced severe persistent anemia by co-treatment with IFN/RBV in patients who underwent LT. Thus, the immunosuppressant dose should be chosen carefully for patients with the high-risk ITPA allele.

Topics: Aged; Anemia; Antiviral Agents; Erythrocyte Transfusion; Female; Hepatitis C, Chronic; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon-alpha; Liver Transplantation; Middle Aged; Mycophenolic Acid; Recurrence; Ribavirin; Simeprevir; Tacrolimus

Mycophenolate mofetil (MMF) decreases the risk of acute rejection and is associated with improved graft survival in renal transplant recipients. However, MMF-related side effects often necessitate dose reduction, which may expose patients to a higher risk of acute rejection and graft loss. This study's aim was to examine the reasons for MMF dose reduction during the first post-transplant year and its impact on acute rejection, overall and death-censored graft loss.. Single-center retrospective analysis of 749 renal transplant recipients treated with MMF in their initial maintenance immunosuppressive protocol.. In 365 patients (48.7%) a total of 530 MMF dose reductions were done. Reasons for reduction were hematologic toxicity (46.5%), infection (16.1%), gastrointestinal side effects (12.3%), malignancy (2.1%), study protocol (14.6%), and unknown (13.5%). MMF dose reduction as such was not an independent predictor of acute rejection or graft survival, although reductions in ≥ 50% of initial dose were significantly associated with acute rejection.. In this retrospective cohort, by far the most important reason for MMF dose reduction during the first post-transplantation year was hematologic. MMF dose reductions in ≥ 50% increased the risk of acute rejection but did not compromise graft survival.

Topics: Adult; Aged; Anemia; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Pancytopenia; Retrospective Studies; Thrombocytopenia

Anaemia is prevalent in patients with systemic lupus erythematosus (SLE). The anaemia is often a consequence of the disease itself but may also be secondary to drug treatments. Mycophenolate mofetil (MMF) is increasingly used in the management of patients with SLE and its associated anaemia. We describe the case of a 19-year-old girl, who presented acutely with SLE and renal involvement. Her disease was controlled with immunosuppression but she later developed severe transfusion-dependent anaemia. Several causes were considered before a bone marrow biopsy led to the diagnosis of erythroid hypoplasia. In the absence of clinical or laboratory markers of active lupus, MMF was implicated as the cause. Its discontinuation led to a rapid and sustained correction of the anaemia. Red cell aplasia linked to the use of MMF is uncommon and the manufacturers are aware of fewer than 50 cases. This is the first case report of evolving red cell aplasia induced by MMF in SLE.

Topics: Anemia; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Red-Cell Aplasia, Pure; Young Adult

Topics: Anemia; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Male; Mycophenolic Acid; Polymorphism, Single Nucleotide

We studied a case of recurrent PV-B19-associated anemia in a renal transplant child with long-term remission induced by baseline immunosuppression adjusted and intensive IVIG therapy. This was a 15-yr-old boy. Seven wk after transplantation, he experienced acute rejection, which was treated with high-dose steroids, ATG, and plasmapheresis. Ten wk after transplantation (three wk after rejection), his hemoglobin dropped to 54 g/L and serum PV-B19 PCR was positive. After therapy with IVIG and conversion from mycophenolate mofetil to rapamycin, anemia resolved. But the patient had fever on the fourth day of IVIG with mild pulmonary edema and rise in serum creatinine. Two months after the first course of IVIG, anemia recurred and a second course of IVIG (preadministration methylprednisolone) was given, which was followed by the resolution of anemia without side effect and recurrence two months later again. Baseline immunosuppression was adjusted with dual immunosuppression and low doses including prednisolone and tacrolimus. At the same time, monthly course of IVIG was repeated four times. Within the next 23 months, anemia did not recur and renal function remained stable. In conclusion, PV-B19-associated anemia can be recurrent in immunocompromised children and baseline immunosuppression should be carefully adjusted to control PV-B19 infection.

Topics: Adolescent; Adrenal Cortex Hormones; Anemia; Combined Modality Therapy; Follow-Up Studies; Graft Rejection; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Parvoviridae Infections; Parvovirus B19, Human; Plasmapheresis; Postoperative Complications; Recurrence; Risk Assessment; Severity of Illness Index; Time Factors; Transplantation Immunology; Treatment Outcome

Mycophenolate-related anemia and leukopenia are well-known toxicities after transplantation. Toxicity leads to dose reduction, addition of colony-stimulating factors or erythropoietin, or discontinuation of immunosuppressive therapy. The causes of and risk factors associated with toxicity are unclear.. We studied the association between mycophenolate-related anemia and leukopenia and 2724 single nucleotide polymorphisms (SNP) in 978 patients undergoing living or deceased donor kidney transplant. Patients were followed up to time of first anemia (hemoglobin<10 gm/dL or hematocrit<30%) or first leukopenia (white blood cell [WBC] count <3000 cells/mm), which required clinical intervention in the first 6 months after transplant.. Anemia occurred in 87 (9.5%) subjects and leukopenia in 224 (22.9%). In single SNP analyses, none of the SNPs were associated with time to leukopenia at a false discovery rate (FDR) of 20%. However, SNPs from the IL12A, HUS, CYP2C8 genes were associated with time to anemia, allowing for an FDR of 20%. To assess the independence of these SNPs as predictors of anemia, we conducted a multi-SNP analysis including one SNP from each of the three genes. All three SNPs were associated with time to anemia, after adjusting for recipient age, weight, posttransplant dialysis and antiviral drug use, and stratifying by clinical center.. Although these SNPs require validation in an independent population, our results suggest that genetics may play a role in risk of mycophenolate-related hematologic toxicity. This may ultimately provide for better management of maintenance immunosuppression and gives insights into potential mechanism(s) by which toxicity occurs.

Topics: Adult; Aged; Anemia; Aryl Hydrocarbon Hydroxylases; Cell Cycle Proteins; Cytochrome P-450 CYP2C8; Female; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents; Interleukin-12 Subunit p35; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors

Clinical studies suggest that the immunosuppressant mycophenolate mofetil is associated with anemia. However, the mechanism for this is not known. Here, we studied the effect of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, on erythropoiesis in vitro.. Both UT-7 cells and primary murine bone marrow cells were studied. Cells were initially treated with erythropoietin and MPA and proliferation and caspase-3 assays were performed. The effect of guanosine-5'-triphosphate, guanosine, and caspase inhibitors was also investigated.. MPA was found to decrease the proliferation of UT-7 cells and erythropoiesis in murine bone marrow cells. This inhibition was associated with an increase in caspase-3 activity in the UT-7 cells. Inhibition was reversed in UT-7 cells and in murine bone marrow by guanosine, but not by caspase inhibitors. The apoptosis induced by MPA was also reversed by guanosine. UT-7 cells treated with MPA showed a decreased inosine-5'-monophosphate dehydrogenase activity.. These results suggest that MPA inhibits inosine-5'-monophosphate dehydrogenase activity in erythroid cells and that this is a likely mechanism of action of anemia in MPA-treated patients.

Topics: Adult; Anemia; Animals; Bone Marrow Cells; Caspase 3; Cell Differentiation; Cell Proliferation; Cells, Cultured; Enzyme Inhibitors; Erythropoietin; Female; Hematopoiesis; Humans; IMP Dehydrogenase; Mice; Mycophenolic Acid; Young Adult

Sarcoidosis is a multisystem granulomatous disease that may involve the bone marrow, with resultant fever, anemia, and leukopenia. Although generally effective in treating the clinical manifestations of bone marrow sarcoidosis, systemic corticosteroids are not warranted for long-term therapy because of their well-known adverse effects. Therefore, alternative corticosteroid-sparing therapeutic regimens are desired.. A 41-year-old man sought treatment for cutaneous and bone marrow sarcoidosis resulting in fatigue, anemia, and leukopenia refractory to conventional therapies and mycophenolate mofetil. We initiated combination immunosuppressive therapy with methotrexate sodium and mycophenolate mofetil, which resulted in a safe and prolonged quiescence of cutaneous disease and resolution of anemia and leukopenia throughout a 34-month follow-up period.. We present this case to highlight the growing body of evidence supporting combination immunosuppressive therapy to treat refractory sarcoidosis. In our patient, sarcoidal bone marrow involvement responded dramatically to a combined regimen of methotrexate and mycophenolate mofetil with no significant adverse effects, despite previously having been refractory to conventional agents and mycophenolate mofetil alone. This report provides evidence that combination immunosuppressive therapy is a potential treatment of refractory bone marrow sarcoidosis and highlights important issues about combined immunosuppressive therapy.

Topics: Adult; Anemia; Bone Marrow Diseases; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Leukopenia; Male; Methotrexate; Mycophenolic Acid; Sarcoidosis; Skin Diseases

Anemia is a known adverse effect of sirolimus (SRL) therapy. Sirolimus may contribute to anemia by a direct antiproliferative effect or by increasing inflammation, worsening kidney function, or decreasing iron utilization. After observing the need for high dose exogenous erythropoietin dosage in some patients on SRL, we hypothesized that SRL therapy may influence anemia by inducing a state of erythropoietin resistance.. Twenty-five stable renal transplant patients on maintenance tacrolimus and SRL therapy were enrolled in a prospective trial with conversion from SRL to enteric coated mycophenolate sodium. Measurement of plasma erythropoietin and red cell indices were performed pre- and postconversion.. Renal function remained unchanged after conversion. Serum hemoglobin (Hb) increased in 18/21 (86%) of patients after conversion. Endogenous erythropoietin level decreased from a median of 28.3 (11.5-374) to 16.6 (3.1-78.8) mIU/mL, (P<0.001); and the erythropoietin:Hb ratio dropped from 2.7 (0.7-34.3) to 1.2 (0.2-6.7), (P<0.001); indicating less erythropoietin resistance after conversion. Mean corpuscular volume increased after conversion, but transferrin saturation and ferritin did not change. Conversion was complicated by posttransplant erythrocytosis in two patients.. Conversion from SRL to enteric coated mycophenolate sodium led to an increase in Hb and a decrease in erythropoietin resistance in stable kidney transplant recipients. Increase in Hb seemed to be independent of renal functional changes or changes in iron sequestration.

Topics: Anemia; Drug Resistance; Erythropoietin; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Function Tests; Kidney Transplantation; Mycophenolic Acid; Sirolimus; Tablets, Enteric-Coated

Anaemia is common following renal transplantation and is associated with the development of congestive heart failure (CHF). However the prevalence of anaemia in the first year following transplantation and the association between anaemia occurring early and the development of CHF have been understudied.. In this study, 132 incident patients undergoing tacrolimus and mycophenolate mofetil-based renal transplantation were studied for the prevalence of, and risk factors for, anaemia and CHF in the early period post transplantation.. Anaemia occurred in 94.5% and 53.1% of patients at 1 week and 12 months, respectively, and was associated with allograft dysfunction, hypoalbuminaemia, higher mycophenolic acid (MPA) levels, bacterial infection and hypoalbuminaemia. The association with hypoalbuminaemia may reflect the presence of chronic inflammation post-transplantation. Of patients displaying haemoglobin <11 g/dl, 41.1% and 29.4% were treated with erythropoiesis stimulating agents (ESAs) at 1 and 12 months respectively. CHF developed in 26 patients beyond 1 month post-transplantation, with echocardiographic left ventricular systolic function preserved in all but one. CHF was associated with anaemia and lower haemoglobin, allograft dysfunction, duration of dialysis and left ventricular hypertrophy on echocardiography prior to transplantation, suggesting the aetiology of CHF may involve the interplay of diastolic cardiac dysfunction, pre-load mismatch and after-load mismatch.. Modification of risk factors may improve anaemia management post transplantation. Reducing the prevalence of anaemia may in turn reduce the incidence of CHF-these observations support the need for clinical trials to determine how anaemia management may impact CHF incidence.

Topics: Adult; Anemia; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Hypoalbuminemia; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Recombinant Proteins; Risk Factors; Tacrolimus; Time Factors

The impact of posttransplant anemia (PTA) upon patient and graft survival remains controversial. The aim of this study was to assess the incidence of PTA 1 year after transplantation in patients treated with calcineurin inhibitors and mycophenolate mofetil, and to determine the impact of 1-year PTA upon long-term patient and graft survival.. Between January 1, 1999, and December 31, 2003, all patients with a functioning graft at 1 year, and who were receiving an immunosuppressive regimen based on calcineurin inhibitors and mycophenolate mofetil, were included in the study (n=339). Anemia was defined according to the World Health Organization criteria, that is, hemoglobin levels less than 13 g/dL for men and less than 12 g/dL for women.. One hundred and eight of 339 were anemic at 1 year after transplantation (31.85%; group I). Independent predictors for 1-year anemia are donor's age and serum creatinine at 6 months. At last follow-up, that is, 69.4+/-17.7 months after transplantation, there had been a significant number of deaths in group I (n=7; 6.9%) compared with nonanemic patients (group II) (n=4; 1.73%; P=0.04). Mean allograft survival was significantly better in group II (70.7+/-17.1 months) compared with group I (66.4+/-18.7 months; P=0.03). Also, 12 graft losses (11.1%) were observed in group I and seven occurred in group II (3%; P=0.004). Independent predictors for allograft loss included delayed graft function and serum creatinine at 1 year.. After kidney transplantation, the occurrence of PTA at 1 year is harmful, in the long term, to patient survival.

Topics: Adult; Aged; Anemia; Calcineurin Inhibitors; Cohort Studies; Female; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prevalence; Risk Factors

Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors.. Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems.. Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb)<12 g/dl, females Hb<11 g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 micromol/l vs 131.0 micromol/l, P<0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P<0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8%, P=0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R=-0.29, P<0.001), but not between EPO levels and eGFR (R=0.02, P=0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis.. Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Azathioprine; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Predictive Value of Tests

Anemia remains frequent in the first month following renal transplantation and is a risk factor for cardiovascular accidents. The purpose of this study was to analyze the prevalence of anemia during this period notably among different immunosuppressive treatment groups.. In this study, we entered the patients who had received a renal allograft in our transplant unit from 1993 to 2003, including patients who had received azathioprine (AZA) from 1993 to 1996 and mycophenolate mofetil (MMF) from 1996 to 2003. No patient received rHu-erythropoietin after transplantation during that period. A mathematical model normalized the hemoglobin (Hb) threshold level at which blood transfusion was decided and Hb on admission.. One hundred and eighty-eight patients on AZA and 223 on MMF were included in the analysis. The mean age +/- SD was 41 +/- 12 years in the AZA group, and 45 +/- 12 years in the MMF group (P < .006). Before the transplantation, Hb was higher in the MMF group (11.4 +/- 1.9 vs 10.2 +/- 2 g/dL, P < .0001). After normalization at a threshold level of transfusion of 7 g/dL, transfusions were more frequent among the MMF group (72% vs 48%, P < .0001). Double therapy with MMF (1500 mg/d) + steroids or therapy with MMF (750 mg/d) + tacrolimus + steroids increased the risk of transfusion compared to the AZA group. MMF (750 mg/d) + cyclosporine conferred a similar risk of transfusion compared with the AZA group.. MMF alone or in association with tacrolimus is associated with an increased risk of anemia and transfusion in the immediate posttransplantation period.

Topics: Adult; Anemia; Azathioprine; Blood Transfusion; Cytomegalovirus Infections; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Postoperative Complications; Postoperative Period; Retrospective Studies

Mycophenolate mofetil (MMF) is an immunosuppressive drug used in renal transplantation, lupus nephritis and pemphigus vulgaris patients. An apparent link is described between the use of MMF with prednisone to treat pemphigus vulgaris and the development of red blood cell anemia. Specifically, after initiation of 500 mg MMF twice a day given in conjunction with the long-standing use of prednisone, which had been tapered to a dose of 10 mg daily, the patient's red blood cell count dropped by 17% over 7 weeks. To put this into perspective, total aplasia of red blood cells for 40 days would result in a drop of 30-33% in the red blood cell count. In the transplantation literature, MMF has been noted to lower red blood cell counts. One previous study of four transplant patients whose immediate post-transplantation immunosuppression utilized corticosteroids, cyclosporine, MMF, and anti-T-lymphocyte globulin noted anemia in 13% of them. The dermatology literature heretofore has not noted that anemia is a side effect of patients taking MMF to treat pemphigus. This report suggests that anemia can occur due to MMF, in particular when it is given with prednisone, a side effect well documented in the transplantation literature when the triple combination of MMF, cyclosporine and prednisone is used. It would therefore seem prudent to monitor red and white blood cell counts in patients taking MMF. A review of the literature also reveals that MMF is a safe medication that appears to have a more favorable side effect profile than azathioprine, although it is more expensive than azathioprine.

Topics: Anemia; Drug Therapy, Combination; Erythrocyte Count; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Pemphigus; Prednisone

After liver transplantation, reinfection of the newly engrafted liver with hepatitis C virus is essentially universal in patients who are viremic at the time of transplantation. Treatment with interferon preparations with or without ribavirin is recommended in patients with marked histologic injury; however, hematologic toxicity associated with therapy has been reported, which is usually treated with growth factor support, including erythropoietin analogues. We present the first reported case of anti-erythropoietin antibody-mediated pure red cell aplasia arising in the setting of hepatitis C virus therapy in a patient who underwent living donor liver transplantation.

Topics: Anemia; Antibodies; Antiviral Agents; Epoetin Alfa; Erythropoietin; Graft Rejection; Hematinics; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Polyethylene Glycols; Prednisone; Recombinant Proteins; Red-Cell Aplasia, Pure; Ribavirin; Secondary Prevention; Tacrolimus

Anemia is a phenomenon frequently observed after kidney transplantation and differential diagnosis is broad.. A 39-year-old woman who had been transplanted a kidney of her father 11 months ago was admitted to the hospital because of severe and worsening anemia (hematocrit [Hct] 0.24). She was under a standard posttransplant immunosuppressive protocol consisting of tacrolimus, mycophenolate mofetil (MMF) and prednisolone. Kidney function was excellent (serum creatinine 118 micromol/l), clinical symptoms of anemia included vertigo, fatigue and low blood pressure. Striking laboratory features were reticulocytopenia (1 per thousand), high ferritin (3,486 microg/l) and low folic acid (4.8 nmol/l), other parameters remained in the normal or therapeutic range. Endoscopic examinations did not reveal any pathologic finding. Bone marrow biopsy, however, showed giant pronormoblasts and the missing of more mature forms as a possible hint to a lack of, e. g., vitamin B(12) (whose serum level was normal, though). After all, the most probable cause of the anemia seemed to be a toxic drug effect and MMF as a possible causative agent was significantly reduced. Nonetheless, the red blood cell count continued to fall (lowest Hct 0.18). On a later outpatient visit all of a sudden positive IgM and IgG antibodies against parvovirus B19 could be detected. Due to a high virus load short-term immunoglobulin treatment was instituted, after which Hct levels rose to normal and virus load decreased to a low degree although still detectable.. An infection with parvovirus B19 should always be taken into account as a possible cause of anemia in immunosuppressed patients. Establishing the diagnosis in the acute stage of the disease can be difficult, as antibodies are often negative in these patients and viremia remains the only proof. In most cases a substantial reduction of immunosuppressive therapy is necessary, the infection's relevance for the development of a potentially life-threatening myocarditis is still a matter of debate.

Topics: Acute Disease; Adult; Anemia; Biopsy; Bone Marrow; Diagnosis, Differential; Erythroblasts; Female; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Opportunistic Infections; Parvoviridae Infections; Parvovirus B19, Human; Postoperative Complications; Viral Load

Although posttransplantation anemia (PTA) is common in the mycophenolate mofetil era, its impact on patient survival is unknown. This retrospective cohort study characterized factors that are associated with PTA 12 mo after transplantation in mycophenolate mofetil-treated kidney recipients and explored whether 12-mo PTA affects outcomes. The records of 626 kidney recipients were examined for presence of anemia (hemoglobin <12 g/dl). Multivariate regression models, fit with covariates that had unadjusted relationships, investigated both risk factors for 12-mo PTA and whether 12-mo PTA contributes to mortality. Anemia prevalence was 72, 40, and 20.3% at 1, 3, and 12 mo, respectively. By multivariate logistic regression, anemia at 3 mo (odds ratio [OR] 10.0; 95% confidence interval [CI] 5.3 to 17.1; P = 0.0001), donor age (OR 1.0; 95% CI 1.1 to 1.3; P = 0.005), and 3-mo creatinine (OR 2.0; 95% CI 1.2 to 3.3; P = 0.044) were associated with 12-mo PTA. The PTA cohort had inferior patient survival (P = 0.02, log rank) and a higher proportion of cardiovascular deaths (6.3 versus 2.2%; P = 0.017) than nonanemic patients. By Cox regression, 12-mo PTA (hazard ratio [HR] 3.0; 95% CI 1.3 to 6.7; P = 0.009), 12-mo creatinine (HR 1.3; 95% CI 1.1 to 1.4; P = 0.008), age at transplantation (HR 1.1; 95% CI 1.1 to 1.2; P = 0.004), and hepatitis C seropositivity (HR 2.8; 95% CI 1.1 to 7.0; P = 0.03) were associated with mortality. There was no interaction between 12-mo PTA and serum creatinine. In conclusion, 12-mo PTA is associated with an increased risk for patient death. The presence of anemia 3 mo after kidney transplantation is a major determinant of 12-mo PTA. PTA in kidney recipients therefore should be defined by its persistence or occurrence beyond the third posttransplantation month.

Topics: Adult; Anemia; Cohort Studies; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Factors; Time Factors

Renal transplantation in children has traditionally required immunosuppression with multiple medications including glucocorticoids. Data collected over almost 30 yr suggest that although glucocorticoids are efficacious as part of a regimen to minimize the incidence of acute rejection episodes, their use is associated with increased risk for post-transplant hypertension, hyperlipidemia, and reduced growth rates. We desired to reduce these complications and thus used an immunosuppressive protocol including daclizumab, tacrolimus, and mycophenolate mofetil and study the efficacy of this protocol in a population with a high percentage of African-American recipients. No patient received glucocorticoids at any time post-transplant. Our results show that at 1 yr post-transplant, glomerular filtration rate, serum glucose, calcium and phosphorous metabolism, serum magnesium, and serum lipids were similar in patients receiving steroid-free and those receiving steroid-based immunosuppression. The incidence of acute rejection was similar in the two groups. Hematocrit and white blood count levels were lower 1 month after transplant in the steroid-free patients but these levels increased within several months. Systolic blood pressure was similar in the two groups, although this was achieved, in part, in the patients who received steroids by the administration of medications to lower blood pressure. Finally, tacrolimus levels were similar in the two groups, but patients receiving steroids required higher doses of tacrolimus at several time points studied during the first post-transplant year. Taken together, our data suggests that at one-year follow-up, steroid-free immunosuppression is safe, and efficacious in pediatric renal transplant recipients.

Topics: Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Blood Glucose; Blood Pressure; Calcium; Child; Daclizumab; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Lipids; Male; Mycophenolic Acid; Phosphorus; Tacrolimus; Thrombocytopenia

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

ABSTRACT. Anemia has long been known to be a complication of end-stage renal disease (ESRD), and it has been linked to cardiovascular morbidity and mortality. Although kidney transplant recipients (KTR) are prone to experiencing cardiovascular outcomes, little is known about the epidemiology of anemia in this population. With few exceptions, studies to date have not fully evaluated the associations between posttransplant anemia (PTA) and medications commonly used in KTR, particularly immunosuppressant drugs, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB). The authors aimed to specifically investigate possible associations between these drugs and PTA. Detailed medical information was retrospectively collected on 374 consecutive KTR from our transplant clinic. Univariate/multivariate linear regression models were used to test for associations between hematocrit (HCT) and other covariates, and logistic regression models were used to detect independent predictors of PTA, defined as HCT <33%. The mean time since transplantation was 7.7 yr, and mean creatinine was 2.2 mg/dl. The prevalence of PTA was 28.6%. Ten percent of all patients were on erythropoietin therapy, but only 41.6% of patients whose HCT was <30 received this treatment. From multivariate analyses, the authors found that female gender and lower renal function were associated with lower HCT (both P < 0.001). Patients on ACEI had significantly lower HCT (P = 0.005) compared with patients without such treatment. In addition, a significant curvilinear dose-response relationship was found between ACEI dose and HCT. Among the immunosuppressant drugs, mycophenolate mofetil (P = 0.05) and tacrolimus (P = 0.02) were associated with a lower HCT. The authors conclude that PTA is prevalent and undertreated in KTR. Several medications that are possibly modifiable correlates of PTR deserve further study.

Topics: Adult; Anemia; Angiotensin-Converting Enzyme Inhibitors; Erythropoietin; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Prevalence; Retrospective Studies; Sex Distribution; Tacrolimus

Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal.. An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls.. Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months.. Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

Topics: Adolescent; Adult; Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biopsy; Child; Cohort Studies; Daclizumab; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Hyperlipidemias; Hypertension; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Infections; Kidney; Kidney Transplantation; Male; Mycophenolic Acid; Postoperative Complications; Prospective Studies; Steroids; Survival Analysis; Tacrolimus

Topics: Adult; Anemia; Antibodies, Viral; Azathioprine; Bone Marrow Cells; DNA, Viral; Drug Therapy, Combination; Erythrocyte Transfusion; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Mycophenolic Acid; Parvoviridae Infections; Parvovirus B19, Human; Polymerase Chain Reaction; Postoperative Complications; Reticulocyte Count

The efficacy and safety of mycophenolate mofetil (MMF) in combination with CsA and prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD, respectively) after BMT and PBSCT from HLA-mismatched and -matched donors was evaluated in an open single center trial. Twenty-four patients, 17-48 years of age, with acute (n = 17) and chronic GVHD (n = 7) were treated with 2 g MMF daily in addition to CsA and prednisolone. Overall grade improvement of aGVHD was found in 11 of 17 (65%) patients treated with MMF. MMF therapy in the treatment of cGVHD led to moderate improvement in three of six patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n = 6), anemia (n = 4) and thrombocytopenia (n = 3). Hematological adverse events were not severe and did not require the discontinuation of MMF. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in significant dose reduction of prednisolone for the treatment of GVHD.

Topics: Acute Disease; Adolescent; Adult; Anemia; Bone Marrow Transplantation; Chronic Disease; Cyclosporine; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Prednisolone