mycophenolic-acid and Diabetes-Mellitus--Type-2

Patients with POAG have lower corneal endothelial cell density than healthy controls of the same age. This may be attributed to mechanical damage from elevated IOP and toxicity of glaucoma medications.. Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long-term safety in cats of this dosage regimen is unknown.. T

Topics: Acetylcholine; Acinetobacter baumannii; Actinobacteria; Action Potentials; Adalimumab; Adaptation, Physiological; Adipates; Administration, Oral; Adolescent; Adrenal Glands; Adsorption; Adult; Aged; Aged, 80 and over; Aging; AIDS-Related Opportunistic Infections; Aldosterone; Amino Acids; Ammonia; Amoxicillin; AMP-Activated Protein Kinases; Animals; Antacids; Anti-Bacterial Agents; Antineoplastic Agents; Antirheumatic Agents; Apgar Score; Area Under Curve; ARNTL Transcription Factors; Arterial Pressure; Arthritis, Juvenile; Athletes; Attention; Biodegradation, Environmental; Biofilms; Biofuels; Biological Therapy; Biomass; Biomimetic Materials; Bioreactors; Birth Weight; Bismuth; Blood Flow Velocity; Bone and Bones; Brain Injuries, Traumatic; Calcium; Calcium Channels; Capsaicin; Carbon; Carcinoma, Hepatocellular; Cardiomegaly, Exercise-Induced; Cartilage; Cartilage, Articular; Case-Control Studies; Catalysis; Cats; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Death; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Charcoal; Chemokine CCL2; Child; Child, Preschool; Chondrogenesis; Chronic Disease; Circadian Clocks; Circadian Rhythm Signaling Peptides and Proteins; Clarithromycin; Coccidioides; Coccidioidomycosis; Cognitive Behavioral Therapy; Coinfection; Color; Coloring Agents; Computer Simulation; Computers, Molecular; Consensus; Corticosterone; Cyclic AMP Response Element-Binding Protein; Cytochrome P-450 Enzyme System; Death, Sudden, Cardiac; Density Functional Theory; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dialysis Solutions; Disease Models, Animal; Dogs; Dopamine Agonists; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Electrocardiography; Electrocardiography, Ambulatory; Electrolytes; Endocardium; Endocrine Disruptors; Endocytosis; Endoscopy, Gastrointestinal; Escherichia coli Proteins; Esters; Evolution, Molecular; Executive Function; Feasibility Studies; Female; Ferric Compounds; Fluorescence; Fluorescent Dyes; Fluorine Radioisotopes; Frailty; Free Radical Scavengers; Gabapentin; Geriatric Assessment; Glucaric Acid; Glucocorticoids; Glucose; Glucose Metabolism Disorders; Halogenated Diphenyl Ethers; Heart Rate; Heart Ventricles; HEK293 Cells; Helicobacter Infections; Helicobacter pylori; Hep G2 Cells; Hepatocytes; Humans; Hungary; Hydrogen Sulfide; Hydrogen-Ion Concentration; Immunologic Factors; Immunomodulation; Immunosuppressive Agents; Independent Living; Indocyanine Green; Infant; Infant Formula; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases; Inflorescence; Insulin Resistance; Insulins; International Agencies; Iron; Isotonic Solutions; Kidney Failure, Chronic; Kinetics; Lactones; Leukocytes, Mononuclear; Liver Neoplasms; Macular Edema; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetosomes; Male; Medical Audit; Mesenchymal Stem Cells; Metabolic Syndrome; Metformin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Middle Aged; Molecular Conformation; Molecular Targeted Therapy; Motor Activity; Multiple Sclerosis; Mycophenolic Acid; Netherlands; Neuropsychological Tests; Nuclear Energy; Organs at Risk; Osteoarthritis; Osteoarthritis, Hip; Oxidation-Reduction; Palladium; Pericardium; Perinatal Death; Peritoneal Dialysis; Phantoms, Imaging; Pharmaceutical Preparations; Phospholipids; Phosphorylation; Physical Conditioning, Human; Physical Endurance; Pilot Projects; Polyketides; Polymers; Positron-Emission Tomography; Postoperative Period; Potassium; Powders; Pramipexole; Predictive Value of Tests; Pregabalin; Pregnancy; Pregnancy Outcome; Protein Structure, Secondary; Proton Pump Inhibitors; Puberty; Pulmonary Circulation; Quality Assurance, Health Care; Quantum Dots; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Rats, Sprague-Dawley; Receptors, CCR2; Receptors, Transferrin; Regeneration; Registries; Renal Insufficiency, Chronic; Reproducibility of Results; Research Design; Restless Legs Syndrome; Retina; Retinoid X Receptor alpha; Retrospective Studies; Rhenium; Risk Factors; RNA, Messenger; Severity of Illness Index; Sex Factors; Sodium; Sodium Fluoride; Solvents; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Stroke; Structure-Activity Relationship; Tachycardia, Ventricular; Tetracycline; Tetrahydrofolate Dehydrogenase; Tetrahydronaphthalenes; Thermodynamics; Thiophenes; Time Factors; Tinidazole; Tomography, Optical Coherence; Tomography, X-Ray Computed; Topiramate; Toxoplasma; Toxoplasmosis, Cerebral; Transferrin; Treatment Outcome; Up-Regulation; Upper Extremity; Uremia; Uveitis; Vascular Remodeling; Ventricular Fibrillation; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling; Verapamil; Veterans; Visual Acuity; Vitrectomy; Water Pollutants, Chemical; Zea mays; Zirconium

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

Diabetes mellitus is frequent in kidney transplant recipients and is commonly associated with gastrointestinal (GI) complications. Delayed gastric emptying affects 30% to 50% of patients with type 1 or 2 diabetes and can influence oral drug absorption. Time-to-peak concentration of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) is longer in diabetic kidney transplant patients than patients without diabetes. By retaining gut contents in the stomach for longer, this could increase local GI toxicity in diabetic recipients due to an extended duration of exposure to MPA in the stomach. The enteric-coated mycophenolate sodium (EC-MPS) formulation delays the release of MPA until pH is higher than 5.5, such that absorption takes place more distally compared with MMF. Patient-reported outcomes data have been used to assess the effect of conversion to EC-MPS in maintenance kidney transplant patients with diabetes who were experiencing MMF-related GI symptoms. Results indicated that conversion leads to improved GI symptom burden despite higher MPA exposure under the EC-MPS regimen. Improved GI tolerance using EC-MPS has permitted maintenance of optimal MPA exposure in nondiabetic populations. Comparative trials to evaluate the GI symptom burden and maximum achieved MPA dosing using the EC-MPS and MMF formulations in de novo and maintenance diabetic kidney transplant recipients are merited.

Topics: Absorption; Administration, Oral; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gastric Emptying; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tablets, Enteric-Coated; Treatment Outcome

Topics: Adrenal Cortex Hormones; Calcineurin Inhibitors; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Disease Susceptibility; Drug Administration Schedule; Hemolytic-Uremic Syndrome; Humans; Hypertension; Immunocompromised Host; Immunosuppressive Agents; Incidence; Kidney Diseases; Kidney Transplantation; Mycophenolic Acid; Neoplasms; Postoperative Complications; Sirolimus

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is an immunosuppressive agent commonly used after organ transplantation. Because diabetes mellitus may affect disposition of pharmacologic agents, we investigated the influence of diabetes on the pharmacokinetics of MPA, unbound MPA (fMPA) and its phenyl and acyl glucuronide metabolites (MPAG and AcMPAG respectively). The study included 13 diabetic and 11 nondiabetic, stable, kidney-transplant recipients who were receiving a triple maintenance immunosuppressive regimen. Serial plasma samples were obtained predose and at regular intervals for 12 hours. Gastric emptying was assessed using an acetaminophen absorption test and glomerular filtration rate was estimated using iohexol clearance. Treatment groups were well matched. The time to maximum concentration (Tmax) of MPA was 86.4 +/- 41.4 minutes versus 52.8 +/- 31.8 minutes in D and ND patients respectively (P = 0.04) indicating a delay in MMF absorption. Neither the maximum MPA concentration nor the 0- to 12-hour area under the concentration-time curve were different. All parameters derived for fMPA and the MPA metabolites were comparable between the 2 groups, except for the metabolite ratio of MPAG and AcMPAG, which was higher for diabetic patients (P = 0.03). Delayed gastric emptying seemed to have reduced the initial rate but not the extent of MPA absorption in diabetic patients. The profiles of fMPA were similar in both patient groups. With the exception of metabolite concentration ratio, none of the other parameters associated with MPA metabolism were different between the 2 groups.

Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Area Under Curve; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gastric Emptying; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid

The association of different therapeutic approaches with long-term cardiovascular and metabolic outcomes in patients with pemphigus remains to be precisely evaluated.. To assess the risk of long-term cardiovascular and metabolic outcomes and all-cause mortality in patients with pemphigus managed by rituximab compared with those receiving treatment with first-line corticosteroid-sparing agents (azathioprine and mycophenolate mofetil [MMF]).. A global population-based retrospective cohort study compared 961 patients with pemphigus that was managed with rituximab with those treated with azathioprine or MMF (n = 961) regarding the risk of several cardiovascular and metabolic outcomes. Propensity score matching was performed to optimize comparability. Patients were enrolled from the Global Collaborative Network of TriNetX platform.. Risk of myocardial infarction, stroke, peripheral vascular disease, pulmonary embolism, hypertension, hyperlipidemia, type 2 diabetes, obesity, osteoporosis, and avascular bone necrosis.. Of 1602 participants, 855 (53.4%) were women and 747 (46.6%) were men; the mean (SD) age was 54.8 (16.6) years for those treated with rituximab and 54.4 (18.2) years for those treated with azathioprine or MMF. Compared with those treated by azathioprine/MMF, patients treated with rituximab experienced a lower risk of myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P = .01), stroke (RR, 0.42; 95% CI, 0.26-0.69; P < .001), peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P = .003), hypertension (RR, 0.48; 95% CI, 0.38-0.63; P < .001), hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P < .001), type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P < .001), obesity (RR, 0.49; 95% CI, 0.34-0.72; P < .001), and osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P < .001). The all-cause mortality was comparable between patients in both groups (hazard ratio, 0.94; 95% CI, 0.62-1.43; log-rank P = .77).. The results of this cohort study suggest that rituximab was associated with protection against long-term cardiovascular and metabolic outcomes compared with conventional immunosuppressants. This agent might be particularly preferred in individuals with preexisting cardiovascular and metabolic risk factors.

Topics: Azathioprine; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Myocardial Infarction; Pemphigus; Peripheral Vascular Diseases; Retrospective Studies; Rituximab; Stroke

The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

Topics: Adult; Autoimmune Diseases; COVID-19; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Rheumatic Diseases; SARS-CoV-2; Saudi Arabia; Young Adult

This is a report of a case with mucous membrane pemphigoid (MMP) with severe eye involvement and concurrent COVID-19 treated successfully using simultaneous high dose intravenous immunoglobulin (IVIg) and anti-viral treatment as hydroxychloroquine, lopinavir/ritonavir, and ribavirin. He had finished a 2-g cycle of rituximab (RTX) in late January. He was receiving mycophenolate mofetil (MMF) for one month and 30 mg prednisolone for three months until his hospitalization. Prednisolone was tapered to 15 mg when current COVID-19 was suspected, considering his recent cough, dyspnea, and fever.

Topics: Adult; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Deprescriptions; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Humans; Hypertension; Immunoglobulins, Intravenous; Immunologic Factors; Iran; Lopinavir; Male; Mycophenolic Acid; Oseltamivir; Pandemics; Pemphigoid, Benign Mucous Membrane; Pneumonia, Viral; Prednisolone; Ritonavir; Rituximab; SARS-CoV-2; Tomography, Spiral Computed

Steatosis occurs frequently after liver transplantation (LT). We aimed to determine the prevalence of steatosis in adult LT recipients, to determine the effects of significant (>33%; grades 2-3) steatosis on patient survival, and to identify risk factors for the development of significant steatosis and its effect on fibrosis progression. We retrospectively examined 2360 posttransplant biopsies of 548 LT recipients. Survival was compared between patients with significant steatosis and those with grades 0-1 steatosis. Patients with significant steatosis were compared to controls without steatosis (grade 0) for clinical and laboratory factors and fibrosis progression. Steatosis was found in 309 (56.4%) patients, including 93 (17.0%) patients with significant steatosis. Steatohepatitis (nonalcoholic fatty liver disease activity score ≥ 5) was diagnosed in 57 (10.4%) patients. The prevalence of steatosis increased from 30.3% at 1 year to 47.6% at 10 years after LT (P < 0.001). Survival times did not differ between groups (P = 0.29). On multivariate analysis of pretransplant factors and initial immunosuppression (IS), alcohol-induced cirrhosis (P < 0.001) and high body mass index (BMI; P = 0.002) were associated with the development of significant steatosis, whereas increased levels of alkaline phosphatase (P = 0.01) and mycophenolate mofetil given initially (P = 0.009) appeared to protect against significant steatosis. On multivariate analysis of posttransplant factors, high BMI (P < 0.001), serum triglycerides (P < 0.001), alcohol consumption (P = 0.005), and type 2 diabetes mellitus (P = 0.048) were associated with significant steatosis, whereas high creatinine (P = 0.02) appeared to protect against significant steatosis. Significant steatosis was not associated with a higher fibrosis stage (P = 0.62). Posttransplant steatosis affects 56.4% of LT recipients, and the prevalence increases with time after LT. Recipient factors and types of IS affect the risk for significant steatosis, which is not associated with a higher fibrosis stage or worse patient survival. Liver Transplantation 22 644-655 2016 AASLD.

Topics: Adult; Alcohol Drinking; Alkaline Phosphatase; Biopsy; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Non-alcoholic Fatty Liver Disease; Prevalence; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Triglycerides

Pancreatic islet failure, involving loss of glucose-stimulated insulin secretion (GSIS) from islet β cells, heralds the onset of type 2 diabetes (T2D). To search for mediators of GSIS, we performed metabolomics profiling of the insulinoma cell line 832/13 and uncovered significant glucose-induced changes in purine pathway intermediates, including a decrease in inosine monophosphate (IMP) and an increase in adenylosuccinate (S-AMP), suggesting a regulatory role for the enzyme that links the two metabolites, adenylosuccinate synthase (ADSS). Inhibition of ADSS or a more proximal enzyme in the S-AMP biosynthesis pathway, adenylosuccinate lyase, lowers S-AMP levels and impairs GSIS. Addition of S-AMP to the interior of patch-clamped human β cells amplifies exocytosis, an effect dependent upon expression of sentrin/SUMO-specific protease 1 (SENP1). S-AMP also overcomes the defect in glucose-induced exocytosis in β cells from a human donor with T2D. S-AMP is, thus, an insulin secretagogue capable of reversing β cell dysfunction in T2D.

Topics: Adenosine Monophosphate; Adenylosuccinate Lyase; Adenylosuccinate Synthase; Animals; Cell Line, Tumor; Cysteine Endopeptidases; Diabetes Mellitus, Type 2; Endopeptidases; Enzyme Inhibitors; Exocytosis; Gene Expression Regulation; Glucose; Guanine; Humans; Inosine Monophosphate; Insulin; Insulin Secretion; Insulin-Secreting Cells; Metabolome; Mycophenolic Acid; Patch-Clamp Techniques; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Signal Transduction

Patients with a simultaneous pancreas-kidney transplant (SPKT), especially those with gastroparesis, often have gastro-intestinal (GI) disorders that can modify immunosuppressant pharmacokinetics. We compared the MPA 12-hours area under the curve (AUC(0-12)) in SKPT patients with severe gastroparesis receiving mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS).. Fifteen SKPT patients having a severe gastroparesis were switched, at 182 (69-1523) days post-transplantation, from MMF to EC-MPS because of GI disorders. MPA AUC(0-12) values were obtained before and after the switch, ie, under MMF (500 mg b.i.d.) at 169 (51-1522) days post-transplantation and EC-MPS (360 mg b.i.d.) at 102 (26-355) days after the switch.. Mean MPA AUC(0-12) h did not differ significantly under MMF and EC-MPS, ie, 40.13±14 and 38.24±15.5 mg*h/L, respectively. Trough and maximal MPA concentrations were similar with both MPA formulations. Although all patients had GI disorders under MMF (100%), only 3 had persistent GI disorders under EC-MPS (20%) (p<0.001).. In SKPT patients with severe gastroparesis, exposure to MPA is similar under MMF and EC-MPS. However, the incidence of GI disorders is significantly lower when patients are given EC-MPS.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Follow-Up Studies; Gastroparesis; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pancreas Transplantation; Retrospective Studies; Tablets, Enteric-Coated; Young Adult

Hyperglycemia is a common adverse event of immunosuppressive drugs used in organ transplant. Because cyclosporine is less diabetogenic than tacrolimus is, cyclosporine may be preferred in patients with pre-existing diabetes mellitus type 2, to prevent insulin treatment after a transplant.. From March 2005 to June 2011, adult renal transplant patients with pre-existing diabetes mellitus type 2, who were not treated with insulin before a transplant, were treated with cyclosporine in combination with mycophenolate mofetil and corticosteroids. For comparison, we used historical controls who were treated with tacrolimus instead of cyclosporine.. Of the 16 patients treated with cyclosporine, only 4 remained free of insulin treatment after a follow-up of least 1 year, compared with 2 of 12 patients who were treated with tacrolimus (25% vs 17%; P = .67). Almost all patients required insulin treatment within 2 months of the transplant, and patients required comparable doses of insulin at different times after the transplant in both groups. None of the baseline characteristics could sufficiently predict the need to start insulin treatment.. Cyclosporine cannot be preferred over tacrolimus to minimize either the chance of requiring insulin treatment posttransplant or the dosage of insulin in patients with pre-existing diabetes mellitus type 2.

Topics: Adrenal Cortex Hormones; Aged; Blood Glucose; Calcineurin Inhibitors; Case-Control Studies; Cyclosporine; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Tacrolimus; Time Factors; Treatment Outcome

Type 2 diabetes mellitus (DM) is the commonest cause of end-stage renal disease (ESRD) worldwide. Renal transplantation (RTx) is the best therapeutic modality for such patients. First-degree relatives of patients with type 2 DM have high risk of diabetes/pre-diabetes. Parents are often too old to be suitable donors, and siblings/children/spouse are either not suitable/acceptable or do not come forward for organ donation. This leaves deceased donation (DD) as only suitable donors. Data scarcity on DDRTx outcome in diabetic nephropathy (DN) prompted us to review our experience. This retrospective single-center 10-year study was undertaken to evaluate patient/graft survival, graft function, rejection episodes, and mortality in these patients.. Between January 2001 and March 2011, thirty-five DN-ESRD patients underwent DDRTx in our center following cardiac fitness assessment of recipients. All patients received single-dose rabbit-anti-thymocyte globulin for induction and steroids, calcineurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression. Mean recipient age was 49.66 ± 6.76 years, and 25 were men. Mean donor age was 50 ± 16.45 years, 23 were men.. Over a mean follow-up of 2.28 ± 2.59 years, patient and graft survival rates were 68.5% and 88.5%, respectively, with mean SCr of 1.9 ± 0.62 mg/dl. Delayed graft function was observed in 34.3% patients, and 25.7% had biopsy-proven acute rejection; 31.5% patients died, mainly because of infections (22.8%), coronary artery disease (2.86%), and cerebrovascular events (5.7%).. DDRTx in patients with DN has acceptable graft function and patient/graft survival over 10-year follow-up in our center and, therefore, we believe it should be encouraged.

Topics: Adult; Aged; Antilymphocyte Serum; Azathioprine; Cadaver; Calcineurin Inhibitors; Creatinine; Delayed Graft Function; Developing Countries; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; India; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Steroids; Treatment Outcome

Several landmark studies have recently been published in nephrology. In summary, mycophenolate mofetil is superior to azathioprine in maintaining remission and preventing relapse in lupus nephritis. For patients with type I diabetes, long-term renal function is better preserved when optimal glycaemic control is obtained with intensive diabetes therapy from the onset of disease, and in patients with type 2 diabetes treatment with bardexolone may increase renal function. With respect to chronic kidney disease, the association of simvastatine and ezetimibe is effective in improving cardiovascular outcomes. There is no need to initiate dialysis in asymptomatic patients, and daily haemodialysis seems better than three times weekly hemodialysis. Finally, N-acetylcysteine does not prevent contrast nephropathy.

Topics: Anticholesteremic Agents; Azathioprine; Azetidines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Kidney Failure, Chronic; Lupus Nephritis; Mycophenolic Acid; Nephrology; Renal Dialysis; Secondary Prevention; Simvastatin; Treatment Outcome

Glucocorticoids have never been studied in a placebo-controlled manner in giant cell arteritis (GCA), but their effectiveness is well established. However, evidence for the efficacy of immunosuppressant drugs as steroid-sparing agents in this disease is highly desirable, especially in elderly patients. We report the use of mycophenolate mofetil (MMF) as a steroid-sparing agent in three patients (mean age 78 years) with GCA, at high risk of longterm high dose glucocorticoids because of type II diabetes mellitus, obesity, hypertension or osteoporosis.. clinical monitoring and assessment of laboratory parameters were carried out weekly (first month) and then patients were seen in the clinic every 2 weeks. Vascular lesions were also monitored at the onset and during the follow-up by Doppler ultrasonography (every 3 months).. all three patients showed clinical benefit, and were also able to taper steroid use to a more rapid regimen compared with the recently suggested steroid reduction approach. MMF was well tolerated, and no signs of toxicity were observed in a mean of 21.6 months (12-29) of follow-up.. mycophenolate mofetil may be considered a steroid-sparing agent in elderly patients with GCA but, before results of controlled trials become available, MMF may be considered only for patients who do not improve or stabilize with conventional therapy, or in patients for whom reduced steroid dosage is highly recommended.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Giant Cell Arteritis; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Steroids

Anti-insulin antibodies have been described in two contexts: in insulin-naive individuals (so-called 'insulin autoimmune syndrome') and in patients with insulin-treated diabetes, in whom antibodies are rarely of clinical significance. We report the case of an 68-year-old woman who exhibited a local allergic reaction to subcutaneous insulin followed by severe insulin resistance, evidenced by poor glycaemic control despite treatment with > 3.5 U/kg of insulin per day. She was found to have circulating polyclonal anti-insulin antibodies of the IgG subtype and responded clinically to a course of plasma exchange and immunosuppression with mycophenolate mofetil and, subsequently, intravenous immunoglobulin. Falling titres of antibodies on this regimen correlated with improved glycaemic control. This case suggests that clinicians should be alert to the possibility of insulin resistance due to anti-insulin antibodies and that immunosuppression in this situation may be a valuable therapeutic option.

Topics: Aged; Antigen-Antibody Reactions; Diabetes Mellitus, Type 2; Female; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Insulin; Insulin Antibodies; Insulin Resistance; Mycophenolic Acid; Plasma Exchange

Our aim was to evaluate the frequency and risk factors of posttransplant diabetes mellitus (PTDM) at our kidney transplant center, and to compare graft and patient outcomes between the kidney recipients with and without PTDM.. We studied 203 kidney transplant recipients with a negative history of diabetes mellitus before transplantation. We examined them for PTDM and made diagnosis on the basis of the American Diabetes Association criteria. Measurements of plasma glucose were carried out from 3 months to 24 months after transplantation. All data including recipient and donor demographics, cause of end-stage renal disease, cytomegalovirus and hepatitis C virus antibody tests, and patient and graft outcomes were assessed in relation to PTDM.. High fasting plasma glucose was seen in 24 (11.8%), 19 (9.4%), 16 (7.9%), and 13 (6.4%) patients at 3, 6, 12, and 24 posttransplant months, respectively. Moreover, impaired glucose tolerance was seen in 17 (8.4%), 16 (7.9%), 17 (8.4%), and 19 (9.4%) patients at the corresponding times, respectively. Accordingly, 39 patients (19.2%) were diagnosed to have PTDM. The mean age of the kidney recipients with PTDM was 46.5 +/- 12.3 years as compared to 38.6 +/- 13.4 years in nondiabetic kidney recipients (P = .02). The 5-year patient and graft survival rates were not significantly different between the kidney recipients with and without PTDM.. This study showed that PTDM is a common metabolic disorder in our kidney transplant patients. We recommend a less diabetogenic immunosuppressive protocol, especially for our older recipients.

Topics: Adult; Age Factors; Cyclosporine; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Hospitals, University; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Prospective Studies

The obese Zucker rat has metabolic condition resembling type II diabetes, including hyperlipidemia, obesity, insulin resistance, and hyperglycemia. With advancing age, the obese Zucker rat develops glomerulosclerosis, proteinuria, and renal failure. Since immune cells play a central role in the development of chronic renal injury, we evaluated the potential benefit of mycophenolate mofetil (MMF), alone and in combination with angiotensin receptor type 1 blockade (ARB) in the obese Zucker rat.. Thirteen-week-old male obese Zucker rats (fa/fa) were randomly assigned to four experimental groups (five rats each) that received the following treatments for 3 months: (1) losartan (100 mg/L in the drinking water), (2) MMF (20 mg/kg/day), (3) MMF and losartan, and (4) placebo. Lean Zucker rats (N = 5) were included as normal controls. Renal function, biochemical parameters, renal histology, and immunohistology were evaluated.. The placebo-treated obese Zucker rats exhibited proteinuria and significant glomerular and tubulointerstitial injury in association with renal immune cell infiltration. Proteinuria, histologic damage, and renal immune cell infiltration were all reduced by MMF treatment alone or in combination with ARB. The improvement of proteinuria and structural damage was more pronounced in the group that received the combination of MMF and losartan.. MMF treatment alone, and especially in combination with ARB, improves nephropathy in the obese Zucker rat.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Immunosuppressive Agents; Losartan; Male; Mycophenolic Acid; Obesity; Rats; Rats, Zucker

The present study investigated the incidence of posttransplant diabetes mellitus (PTDM) and calculated the risk of developing PTDM under a tacrolimus-based immunosuppression based on clinical characteristics, tacrolimus pharmacokinetics, and genetic polymorphisms related to tacrolimus pharmacokinetics or diabetes mellitus.. Seventy nondiabetic adult kidney recipients were studied. Patients with continuous high plasma glucose levels, over 6.5 mg/dl of hemoglobin A1c, or requiring insulin and/or oral antidiabetic agents for more than 3 months after transplantation 6 months postoperatively were diagnosed as having PTDM. Twelve genomic polymorphisms were assessed.. Six months after transplantation, 10 recipients (14.3%) developed PTDM. Positive risk factors were age (P=0.019) and body mass index (P=0.038). There were no significant differences in acute rejection rate, total steroid doses, tacrolimus pharmacokinetics or its related to genetic polymorphisms between the two groups. The frequency of PTDM was significantly higher in patients with the vitamin D receptor (VDR) TaqI t allele than in those with the TT genotype (P=0.013). On multivariate analysis, age over 50 years (odds ratio 9.28, P=0.003) and the presence of the VDR TaqI t allele (odds ratio 7.05, P=0.048) were correlated with the development of PTDM.. The incidence of PTDM was 14.3% in our cohort. Age over 50 years was a risk factor. The presence of the VDR TaqI t allele may also be a risk factor for PTDM, suggesting that genotyping of diabetes-related polymorphisms is a possible method of predicting a patient's risk for developing PTDM and would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals.

Topics: Adiponectin; Adult; Azathioprine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Diabetes Mellitus, Type 2; Female; Genes, MDR; Humans; Immunosuppressive Agents; Incidence; Ion Channels; Kidney Transplantation; Male; Membrane Transport Proteins; Middle Aged; Mitochondrial Proteins; Multivariate Analysis; Mycophenolic Acid; Peptidyl-Dipeptidase A; Polymorphism, Genetic; PPAR gamma; Receptors, Calcitriol; Risk Factors; Tacrolimus; Uncoupling Protein 2