mycophenolic-acid and Pneumonia

Pancreas-kidney transplant is an effective treatment for patients with insulin-dependent dabetes and chronic renal failure. Reduction in technical failure loss and early acute rejection rates contributed to prolong pancreas graft survival. However, drug toxicity affects negatively both short- and long-term follow-ups.. This article reviews the existing literature and knowledge of the immunosuppressive drugs that are frequently used in pancreas transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and mycophenolate. The article also discusses the short- and long-term adverse effects of these drugs. The article also reports and discusses the most relevant in vitro studies, providing additional information to in vivo findings. Some clinically relevant drug interactions with immunosuppressive drugs are also highlighted. Over- and underimmunosuppression effects will not be addressed.. Immunosuppressive regimen after pancreas transplant is very effective and contributed to pancreas allograft survival. However, they present several side effects that are potentiated when drugs are combined. Modifiable and non-modifiable risk factors can aggravate metabolic and toxicological effects of immunosuppressive drugs. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.

Topics: Adrenal Cortex Hormones; Bone Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Gastrointestinal Diseases; Graft Rejection; Graft Survival; Hematologic Diseases; Humans; Hyperkalemia; Hyperuricemia; Immunosuppressive Agents; Mycophenolic Acid; Nervous System Diseases; Pancreas Transplantation; Pneumonia; Renal Insufficiency, Chronic; Sirolimus

In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sepsis associated with immunosuppressive medications that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee.. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591.. Immunosuppressed patients, by definition, are susceptible to a wider spectrum of infectious agents than immunologically normal patients and, thus, require a broader spectrum antimicrobial regimen when they present with sepsis or septic shock. Special expertise managing immunosuppressed patient populations is needed to predict and establish the correct diagnosis and to choose appropriate empiric and specific agents and maximize the likelihood that patients will survive these microbial challenges.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibodies, Monoclonal; Antifungal Agents; Antiviral Agents; Aspergillosis; Candidiasis; Consensus Development Conferences as Topic; Evidence-Based Medicine; Hepatitis, Viral, Human; Humans; Immune Tolerance; Immunocompromised Host; Immunophilins; Immunosuppressive Agents; Mycophenolic Acid; Pneumonia; Practice Guidelines as Topic; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

To make an open label prospective trial for comparing the therapeutic effects of mycophenolate mofetil (MMF) vs cyclophosphamide (CYC) pulse therapy on patients with diffuse proliferative lupus nephritis (DPLN).. Forty-six patients with biopsy proven active DPLN were enrolled in this study. Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d (MMF Group). Another 23 cases received conventional intermittent CYC pulse therapy (CYC Group). Supplemental steroid treatment was offered in the same manner to both groups. The age, sex distribution and severity of renal damage were matched in two groups. Therapeutic effects were evaluated at the end of six-month treatment. Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time.. MMF therapy was more effective in reducing proteinuria and hematuria. A 50% reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6% and 91.3% patients in the MMF Group, while only 47.8% and 65.2% in the CYC Group. MMF was more effective in inhibiting autoantibody production (especially anti-dsDNA antibody) and in decreasing serum cryoglobulin levels. Pathologically, the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis, and less microthrombi, less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group. Adverse reactions related to the treatment included gastrointestinal symptoms 26.1% and 43.5% in the MMF and CYC Groups respectively, infection 17.4% in the MMF group and 30.4% in the CYC group.. MMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study.

Topics: Adult; Cyclophosphamide; Female; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Infections; Kidney; Lupus Nephritis; Male; Mycophenolic Acid; Pneumonia; Prospective Studies; Treatment Outcome

Antisynthetase syndrome is a rare autoimmune disease and represents a distinct entity within the idiopathic inflammatory myopathies. Its variable systemic manifestations are composed of myositis, interstitial lung disease, non-erosive arthritis, fever, Raynaud's phenomenon, hyperkeratotic skin changes and the presence of antibodies against aminoacyl-transfer-RNA-synthetases. Interstitial lung disease is the major determinant of morbidity and mortality. The role of lung biopsy remains controversial but it might be considered on an individual basis and may provide information regarding prognosis and treatment response. An integrated clinical, radiological and pathological approach to interstitial lung disease has to be emphasised. Due to the rarity of the disease, no standardised treatment guidelines for antisynthetase syndrome exist. We discuss a patient with anti-Jo1-autoantibody antisynthetase syndrome with proximal myositis and severe, rapid onset, interstitial lung disease with a histopathological pattern of organising pneumonia on surgical lung biopsy and good response to early combined immunosuppressive treatment with corticosteroids, mycophenolate mofetil and rituximab.

Topics: Administration, Intravenous; Adrenal Cortex Hormones; Amino Acyl-tRNA Synthetases; Autoantibodies; Combined Modality Therapy; Enzyme Inhibitors; Female; Humans; Immunologic Factors; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Middle Aged; Mycophenolic Acid; Myositis; Pneumonia; Rituximab; Severity of Illness Index; Treatment Outcome

The development of pulmonary immune-related adverse events (irAEs) in patients undergoing PD-(L)1 targeted checkpoint inhibitors are rare, but may be life-threatening. While many published articles and guidelines are focusing on the presentation and upfront treatment of pulmonary irAEs, the strategy in patients with late-onset pneumonia that are resistant to commonly used immunosuppressive drugs remains unclear.. Here, we report the successful treatment of a mycophenolate-resistant organizing pneumonia (OP) with infliximab in a patient with metastatic melanoma after PD-1 blockade. The patient received two years of PD-1 targeted immunotherapy when he developed multiple nodular lung lesions mimicking a metastatic progression. However, wedge resection of these lesions showed defined areas of OP, which responded well to corticosteroids. Upon tapering, new foci of OP developed which were resistant to high-dose steroids and mycophenolate treatment. The TNFα antagonist infliximab led to a rapid and durable regression of the inflammatory lesions.. This case describes a not well-studied situation, in which a mycophenolate-resistant PD-1 blocker-associated pneumonitis was successfully treated with a TNFα neutralizing antibody. The outcome of this case suggests that infliximab might be the preferable option compared to classical immunosuppressants in the case of steroid-resistant/-dependent late onset pulmonary irAEs.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Immunological; CTLA-4 Antigen; Drug Resistance, Neoplasm; Humans; Immunosuppressive Agents; Infliximab; Ipilimumab; Male; Melanoma; Mycophenolic Acid; Pneumonia; Programmed Cell Death 1 Receptor; Tumor Necrosis Factor-alpha

With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others.. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities.. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil.. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B7-H1 Antigen; Colitis; Exanthema; Hepatitis; Humans; Immunosuppressive Agents; Immunotherapy; Mycophenolic Acid; Neoplasms; Nephritis; Neurodegenerative Diseases; Nivolumab; Pneumonia; Programmed Cell Death 1 Receptor

We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients in 2000-2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen. Compared with the reference ISx (thymoglobulin induction with tacrolimus, mycophenolate, and prednisone maintenance), sirolimus-based ISx was associated with significantly higher three-year risks of pneumonia (adjusted hazard ratio, aHR 1.45; P < 0.0001), sepsis (aHR 1.40; P < 0.0001), diabetes (aHR 1.21; P < 0.0001), acute rejection (AR; adjusted odds ratio, aOR 1.33; P < 0.0001), graft failure (aHR 1.78; P < 0.0001), and patient death (aHR 1.40; P < 0.0001), but reduced skin cancer risk (aHR 0.71; P < 0.001). Cyclosporine-based IS was associated with increased risks of pneumonia (aHR 1.17; P < 0.001), sepsis (aHR 1.16; P < 0.001), AR (aOR 1.43; P < 0.001), and graft failure (aHR 1.39; P < 0.001), but less diabetes (aHR 0.83; P < 0.001). Steroid-free ISx was associated with the reduced risk of pneumonia (aHR 0.89; P = 0.002), sepsis (aHR 0.80; P < 0.001), and diabetes (aHR 0.77; P < 0.001), but higher graft failure (aHR 1.35; P < 0.001). Impacts of ISx over time warrant further study to better guide ISx tailoring to balance the efficacy and morbidity.

Topics: Adolescent; Adult; Cyclosporine; Diabetes Mellitus; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Pneumonia; Renal Insufficiency; Risk; Sepsis; Sirolimus; Tacrolimus; United States; Young Adult

Topics: CD4-Positive T-Lymphocytes; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Pneumonia; Retrospective Studies; Rheumatic Diseases; Risk Factors

The tolerance of mycophenolate mofetil (MMF; Shanghai Roche, China) in Lee Classes III, IV, and V immunoglobulin A nephropathy (IgAN) remains unclear. This article reports nine cases of severe pneumonia (SP), including pneumocystis pneumonia (PCP) and cytomegalovirus (CMV) pneumonia, and its risk factors in MMF plus low-dose corticosteroid-treated patients with Lee Classes III, IV, and V IgAN. Fifty-three patients with IgAN were included in this single-center study. The treatment regimen was MMF (1-1.5 g/d) plus low-dose corticosteroids (0.5 mg/kg/d). SP was defined as diffuse bilateral lung infiltrate with respiratory failure. PCP was diagnosed by detecting the organisms in the sputum and bronchoalveolar lavage. CMV infection was diagnosed through serum screening for CMV-IgG and IgM antibodies and CMV-DNA testing by a real-time polymerase chain reaction assay. The risk factors of SP were analyzed. Nine cases (16.9%) of SP occurred in this study. All SP developed at approximately the 10(th)-14(th) week after the initiation of the regimen: PCP was diagnosed in four cases and CMV infection in two cases. Renal function impairing was more serious in patients with SP than in those without SP, as evidenced by estimated glomerular filtration rate (p = 0.019) and serum creatinine level (p = 0.016). Six of the nine SPs occurred in MMP plus low-dose methylprednisolone group, which was statistically higher than that in the MMF plus low-dose prednisone group (p = 0.000). The incidence of SP in this study was 16.9%. Chronically impaired renal function and the use of methylprednisolone may be the risk factors for SP.

Topics: Adrenal Cortex Hormones; Adult; Female; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pneumonia; Pneumonia, Pneumocystis; Prednisone; Retrospective Studies; Risk Factors

Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function.

Topics: Acute Disease; Adult; Antibodies, Monoclonal; Basiliximab; Coinfection; Cystic Fibrosis; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lung Transplantation; Male; Mycophenolic Acid; Pneumonia; Prednisone; Recombinant Fusion Proteins; Recovery of Function; Renal Dialysis; Respiratory Insufficiency; Tacrolimus

Here, we report on a patient after kidney transplantation, who developed fever and pneumonitis due to mycophenolic acid (MPA) treatment. Decreasing MPA dosages improved the symptoms, but after rechallenge with higher MPA doses the symptoms recurred. Discontinuation of MPA resulted in a complete resolution of fever within 24 h and a rapid improvement in pneumonitis. In vitro, the patient's polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MPA and N-formyl Met-Leu-Phe. We first report on MPA-induced pneumonitis and show that MPA can induce a pro-inflammatory response in kidney-transplanted patients. These pro-inflammatory changes might be due to paradoxical activation of PMNs.

Topics: Fever; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Neutrophils; Pneumonia; Respiratory Burst; Tablets, Enteric-Coated

Topics: Adrenal Cortex Hormones; Adult; Azathioprine; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; Diarrhea; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Metronidazole; Mycophenolic Acid; Pneumonia; Pneumonia, Bacterial; Pneumonia, Viral; Postoperative Complications; Sirolimus; Tacrolimus; Tomography, X-Ray Computed

To compare the healthcare expenditure associated with mycophenolate mofetil (MMF)-based immunosuppression in contrast to conventional therapy in patients with lupus nephritis.. Our retrospective single-center study compared the major healthcare costs during the first 24 months of treatment incurred by immunosuppressive medications, hospitalization, and complications in patients with severe lupus nephritis who had been treated with prednisolone and either MMF or sequential cyclophosphamide induction followed by azathioprine maintenance (CTX-AZA).. Forty-four patients were studied (22 in each group). Baseline demographic and clinical measures, and remission rates after treatment, were similar between the 2 groups. Immunosuppressive drug cost was 13.6-fold higher in the MMF group (US$4168.3+/-1176.5 per patient, compared with $285.0+/-70.6 in the CTX-AZA group, mean difference $3883.2+/-251.3; p<0.001). MMF treatment was associated with a lower incidence of infections (12.0 episodes/1000 patient-months, compared with 32.4 in the CTX-AZA group; p=0.035). Combined cost of hospitalization and treatment of infections was 82.5% lower in the MMF group (mean difference -2208.7+/-1700.6; p=0.120). Overall treatment expenditure on immunosuppressive drugs, hospitalization, and treatment of infections was 1.57-fold higher in the MMF group (mean US $4635.9 compared with $2961.5 in the CTX-AZA group; p<0.001).. While the cost of MMF treatment for severe lupus nephritis is much higher compared with CTX-AZA, the increased drug cost is partially offset by savings from the reduced incidence of complications.

Topics: Adult; Azathioprine; Cyclophosphamide; Drug Costs; Female; Hospital Costs; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infections; Lupus Nephritis; Male; Middle Aged; Mycophenolic Acid; Pneumonia; Young Adult

Mycophenolate mofetil (MMF), a relatively new immunosuppressant, is widely used in the field of transplantation and also for autoimmune diseases with good tolerance. It has been reported that MMF possesses potent activity against pneumocystis pneumonia (PCP). This study investigated the effects of this treatment on the occurrence of severe pneumonia (SP) including PCP and its risk factors.. This was a retrospective cohort study. Of 850 IgA nephropathy (IgAN) patients that were followed up in our renal centre, 32 received MMF (1-1.5 g/day) and 47 were treated with cyclophosphamide (CTX; 50-100 mg/day). All the patients also received prednisone. SP was defined as diffuse bilateral lung infiltrate with respiratory failure, and PCP was diagnosed by detecting organisms in sputum and bronchoalveolar lavage.. Patients given MMF or CTX did not differ in their distribution of age, sex, renal function or prednisone dosage. However, 6 of the 32 patients developed SP around the third month after the initiation of MMF administration: 3 were diagnosed with PCP, 2 with suspected PCP and in the other PCP could not be excluded. SP did not occur in patients treated with CTX. Most SP cases (five of six) presented with abrupt onset and rapidly progressed to respiratory failure, from which four died. The deterioration of renal function was strongly associated with the occurrence of SP. Six patients (6 of 16) with chronic renal function impairment (eGFR < 60 ml/min/1.73 m(2)) developed SP while none of the patients with eGFR > 60 ml/min/1.73 m(2) did. Absolute lymphocyte counts decreased significantly in patients with eGFR < 60 ml/min/1.73 m(2) after 3 months of MMF treatment compared to the counts before MMF was initiated (1.71 +/- 0.23 versus 2.43 +/- 0.17 x 10(9)/l, P = 0.04). This effect was more pronounced in patients with SP, which had significantly lower counts than patients without SP (0.22 +/- 0.04 versus 1.91 +/- 0.20 x 10(9)/l, P = 0.001). The occurrence of SP or PCP in patients with chronically impaired renal function was also associated with lymphopenia.. This study is the first report of delayed SP including PCP following MMF plus corticosteroids in patients with IgAN. Chronically impaired renal function might be a risk factor for severe infection, and lymphocyte counts may serve as useful and convenient tools for monitoring the intendance of the occurrence of PCP. This finding and its risk factors need to be further evaluated.

Topics: Adult; Cyclophosphamide; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunosuppressive Agents; Lymphocyte Count; Male; Middle Aged; Mycophenolic Acid; Pneumonia; Pneumonia, Pneumocystis; Prednisone; Retrospective Studies; Risk Assessment; Time Factors

Topics: Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pneumonia