mycophenolic-acid and Abdominal-Pain

Gastrointestinal (GI) symptoms in renal transplant recipients may be caused due to mycophenolic acid (MPA) toxicity. Using small bowel capsule endoscopy (SBCE) we examined the impact of conversion from Mycophenolate Mofetil (MMF) to enteric-coated formulation of Mycophenolate Sodium (EC-MPS) given to treat GI mucosal lesions.. Adult kidney-only recipients at least 30 days after transplant, presenting with GI symptoms while receiving MMF completed a Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, underwent SBCE, and had MMF substituted by EC-MPS. After 30 days, GSRS and SBCE were repeated and findings were compared to baseline values. Patients who were still on EC-MPS 6-24 months post-conversion were contacted for completing a follow-up GSRS questionnaire and SBCE.. Eighteen out of 23 subjects completed the first part of the study. Subjects' median ages and post-transplant time were 47.5 years old and 4.5 months, respectively. Tacrolimus, MMF and prednisone was the main regimen (94%), with a median MMF dose of 750 mg BID. The average baseline GSRS was 2.99 ± 0.81; it significantly decreased to 2.19 ± 0.8 at 30 days post-conversion. At baseline, 50 had gastric and 89% had small bowel lesions. At 30 days, 29 and 62% of the SBCE were still showing gastric and small bowel lesions, respectively. Of 5 patients in the study extension, 4 had abnormal SBCE findings but have been reporting improvement in their symptoms.. Stomach and small bowel mucosal lesions are common in kidney recipients with GI symptoms when treated with MMF. Conversion to EC-MPS for 30 days significantly alleviated the GI symptoms; however, no evident correlation with SBCE findings was found.

Topics: Abdominal Pain; Adult; Aged; Capsule Endoscopy; Diarrhea; Drug Substitution; Dyspepsia; Follow-Up Studies; Heartburn; Humans; Immunosuppressive Agents; Intestine, Small; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Prospective Studies; Stomach; Surveys and Questionnaires; Tablets, Enteric-Coated

Mycophenolate mofetil (MMF) is commonly used in solid organ transplant recipients. MMF is converted to mycophenolic acid (MPA) upon reaching the systemic circulation. Many acidic drugs have altered protein binding in renal failure, and it is possible that MPA protein binding may be decreased. The authors studied 23 renal transplant recipients: 8 transplant patients (7 kidney, 1 kidney/pancreas) with chronic renal insufficiency (CRI) and 15 renal transplant patients with preserved renal function. Plasma was obtained for kinetic profiles of total MPA, free MPA, and its glucuronide metabolite (MPAG). Plasma was obtained from 10 hemodialysis patients and 8 healthy control volunteers to assess in vitro differences in MPA protein binding. Average free fraction of MPA in patients with chronic renal insufficiency was more than double that of patients with normal renal function (5.8 +/- 2.7 vs. 2.5 +/- 0.4, p < 0.01). Free MPAAUC was almost doubled in the patients with chronic renal insufficiency versus controls (2.04 +/- .08 vs. 1.03 +/- 0.6, p < 0.01). MPA protein binding is decreased, and free MPA concentrations are increased in patients with chronic renal failure.

Topics: Abdominal Pain; Adult; Area Under Curve; Enzyme Inhibitors; Female; Humans; IMP Dehydrogenase; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Prodrugs; Protein Binding; Renal Insufficiency

The risk of life-threatening complications, such as visceral disseminated varicella zoster virus (VZV) infection, is greater in immunosuppressed individuals, such as systemic lupus erythematosus (SLE) patients.. Here, a case is reported of a Caucasian woman diagnosed with lupus nephritis and anti-phospholipid syndrome, who was subjected to mycophenolate mofetil and high-dose steroid remission-induction therapy. Two months later she developed abdominal pain followed by a fatal rapid multi-organ failure. As no typical skin rashes were evident, death was initially attributed to catastrophic anti-phospholipid syndrome. However, autopsy and virological examinations on archival material revealed a disseminated VZV infection.. Overall, this case highlights the importance of having a high clinical suspicion of fatal VZV infections in heavily immunosuppressed SLE patients even when typical signs and symptoms are lacking.

Topics: Abdominal Pain; Antiphospholipid Syndrome; Fatal Outcome; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Lupus Nephritis; Middle Aged; Mycophenolic Acid; Real-Time Polymerase Chain Reaction; Steroids

► Abdominal pain ► Lower-leg itching ► Dark urine & yellow eyes.

Topics: Abdominal Pain; Acne Vulgaris; Adolescent; Analgesics; Antipruritics; Chemical and Drug Induced Liver Injury; Female; Glucocorticoids; Humans; Immunologic Factors; Minocycline; Mycophenolic Acid; Prednisolone; Pruritus; Treatment Outcome; Urine; White People

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: Abdominal Pain; Adolescent; Antibiotics, Antineoplastic; Aorta; Carotid Arteries; Computed Tomography Angiography; Diagnosis, Differential; Glucocorticoids; Humans; Male; Mycophenolic Acid; Prednisone; Takayasu Arteritis; Weight Loss

Topics: Abdomen; Abdominal Pain; Acute Kidney Injury; Administration, Intravenous; Adult; Anti-Inflammatory Agents; Ascites; Asthenia; Contrast Media; Creatinine; Disease Progression; Edema; Enzyme Inhibitors; Female; Humans; Jejunum; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Prednisone; Tomography, X-Ray Computed; Ultrasonography; Vomiting

Topics: Abdominal Pain; Child; Diarrhea; Humans; IgA Vasculitis; Immunosuppressive Agents; Male; Mycophenolic Acid; Recurrence; Treatment Outcome

Topics: Abdominal Pain; Endosonography; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphadenitis; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycophenolic Acid; Prednisone; Tomography, X-Ray Computed

Diarrhea is considered to be a common side effect after renal transplantation, due to a number of infective or drug-related causes. Over the past decade the etiology has perhaps changed with the evolution of immunosuppression. In an attempt to minimize early acute rejection and potential steroid use, the recent introduction of mycophenolic acid-based therapies has increased the incidence of diarrheal symptoms. Histologic and macroscopic appearance of mycophenolate-induced colitis is not well documented.. Three patients with immunosuppression-induced colitis had received deceased-donor renal transplantations and presented with diarrhea and/or abdominal pain. All patients made a full recovery after decreasing the dose or withdrawing mycophenolate mofetil or myfortic with corticosteroid-free regimens.. Patients with immunosuppression-induced colitis require prompt intervention by dose reduction or withdrawal. Both myocophenolate mofetil and myfortic can induce a Crohn's-like colitis even after a long period of exposure. The symptoms may require 6 months to resolve, suggesting that surgery should be considered only as a last resort after a significant period off therapy.

Topics: Abdominal Pain; Adrenal Cortex Hormones; Biopsy; Crohn Disease; Diarrhea; Drug Substitution; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid

The porphyrias are a group of disorders of the heme biosynthesis pathway that may present with acute life-threatening attacks, commonly exacerbated by a wide variety of medications. Many newer immunosuppressive medications, which are in use following kidney transplantation, have not been fully explored in acute porphyrias.. A 53-year-old woman received a kidney from a deceased donor, after being on hemodialysis for 4 years. Hereditary coproporphyria was diagnosed at age 19 years. We administered tacrolimus, mycophenolate mofetil and steroid immunosuppression. In the immediate post-transplant periods she displayed abdominal pain and transient uroporphyrin elevation in parallel with slightly elevated (15 ng/mL) tacrolimus concentrations. As the target tacrolimus level was achieved, these findings disappeared.. Tacrolimus, mycophenolate- mofetil, and steroid therapy for hereditery coproporphyri was safe, in the long term.

Topics: Abdominal Pain; Coproporphyria, Hereditary; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Risk Factors; Tacrolimus; Treatment Outcome

Topics: Abdominal Pain; Adult; Anti-Bacterial Agents; Cephalosporins; Everolimus; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Lymphocele; Male; Mycophenolic Acid; Prednisolone; Radiography; Scapula; Sirolimus; Tacrolimus; Ultrasonography

Topics: Abdominal Pain; Adult; Antibodies, Fungal; Biopsy; C-Reactive Protein; Child; Crohn Disease; Female; Humans; IgA Vasculitis; Immunosuppressive Agents; Mycophenolic Acid; Pyoderma Gangrenosum; Saccharomyces cerevisiae; Skin; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Abdominal Pain; Crohn Disease; Humans; Ileitis; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid

A 50-year-old woman with Beçhet's disease presented with episodic diarrhoea and generalised abdominal pain. She was on regular mycophenolate maintenance therapy, being intolerant of both ciclosporin and azathioprine. Previous rectal biopsy was consistent with colitis, probably associated with Beçhet's disease. During this admission, she began passing faecal matter per vaginam. Digital rectal examination confirmed the presence of a large rectovaginal fistula. She underwent urgent laparotomy for a subtotal colectomy with end ileostomy. Although there were no signs of septicaemia preoperatively, small perforations were identified in the caecum and at the splenic flexure on laparotomy. Histopathology confirmed the presence of multiple shallow ulcers throughout the colon with features suggestive of Beçhet's colitis.

Topics: Abdominal Abscess; Abdominal Pain; Behcet Syndrome; Colitis; Colitis, Ulcerative; Colon; Diarrhea; Female; Humans; Ileostomy; Immunosuppressive Agents; Intestinal Perforation; Middle Aged; Mycophenolic Acid; Rectovaginal Fistula

Topics: Abdominal Pain; Diagnosis, Differential; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glucocorticoids; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Middle Aged; Mycophenolic Acid; Prednisone

Topics: Abdominal Pain; Child; Glucocorticoids; Humans; IgA Vasculitis; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisolone; Radiography; Recurrence; Time Factors; Treatment Outcome

Topics: Abdominal Pain; Drug Interactions; Family; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Mycophenolic Acid; Tacrolimus

Mycophenolate mofetil (MMF) is a prodrug that is hydrolyzed to the active immunosuppressant mycophenolic acid (MPA). The drug is now widely prescribed for adult renal transplant recipients and its use has been extended to pediatric patients, although pharmacological data in this age group are limited. Nine pediatric renal transplant recipients received MMF with corticosteroids and either cyclosporine or tacrolimus a median of 55 months (range 7.5-124 months) months after transplantation. The pharmacokinetic parameters of MPA and MPA glucuronide (MPAG) were determined at steady state by high-performance liquid chromatography after administration of MMF at the oral dose of 494+/-142 mg/m(2) twice daily. MPA was rapidly absorbed, with a peak concentration at 1.4 h. The mean plasma concentration of MPA at steady state was 4.7+/-1.3 microg/ml. The areas under the plasma concentration-time curves (AUCs) over 12 h (between two administrations) were 57.0+/-15.3 microg.h/ml for MPA and 1,515+/-722 microg.h/ml for MPAG, and the apparent oral clearance was 11.7+/-7.0 and 0.5+/-0.4 l/h for MPA and MPAG, respectively. Assuming that the pharmacokinetics of MPA was dose dependent, the mean concentration at steady state and the AUC for MPA were calculated for the recommended dosage schedule of 600 mg/m(2) every 12 h and were 6.3+/-2.7 microg/ml and 75.2+/-32.9 microg.h/ml, respectively. The tolerance of MMF was studied prospectively with a follow-up of 1.1+/-0.2 years. Gastrointestinal disorders requiring dosage reduction or discontinuation of therapy, observed in five of nine patients, occurred at an incidence higher than expected from adult data. Our results suggest that the dose of 600 mg/m(2) every 12 h extrapolated from adult data for use in pediatric patients would be associated with plasma levels and AUCs higher than expected and may be associated with a higher incidence of side-effects, primarily gastrointestinal.

Topics: Abdominal Pain; Adolescent; Child; Cyclosporine; Diarrhea; Glucuronates; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Prospective Studies

Abdominal pain occurs frequently in renal transplant recipients receiving mycophenolate mofetil (MMF) therapy. The cause of this abdominal pain has not been fully elucidated, but may involve local irritation, as well as inhibition of rapidly dividing cells of the gastrointestinal (GI) tract. This milieu of inflammation and added immunosuppression is conducive to activation of cytomegalovirus (CMV). We therefore sought to find the prevalence of active CMV in patients presenting with abdominal pain on maintenance MMF therapy. All patients receiving a renal transplant at our center from March 1, 1997, to September 1, 1997, were studied. Any patient presenting with midepigastric pain for greater than 3 days underwent esophagogastroduodenoscopy (EGD) with biopsy. CMV was diagnosed by the presence of inclusion bodies and immunohistochemical studies. Ten patients presented with persistent midepigastric pain; nine of these patients had evidence of GI CMV. Patients who were CMV negative and received an allograft from CMV-positive donors and those with leukopenia were at significantly increased risk for the development of abdominal pain. In our study population, the majority of patients on maintenance MMF therapy who presented with persistent midepigastric pain had evidence of active CMV infection in the upper gastrointestinal tract.

Topics: Abdominal Pain; Adult; Cytomegalovirus Infections; Digestive System; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Logistic Models; Male; Mycophenolic Acid; Prevalence; Risk Factors