mycophenolic-acid and Dyslipidemias

The current standard of care immunosuppressive regimen in kidney transplantation (KT) includes a combination of mycophenolates (MMF/MPA) with a calcineurin inhibitor (CNI).. We designed a systematic review including all randomized clinical trials (RCTs) assessing the outcomes in KT recipients receiving mTORi + CNI compared with regimens containing MMF/MPA or azathioprine with CNI.. A total of 24 studies with 7356 participants were included. The comparison between mTORi-CNI and MMF/MPA-CNI did not show differences in acute rejection, mortality, or graft loss rates. Better graft function was observed using MMF/MPA-CNI than using mTORi + CNI, but this difference was not evident when the mTORi was associated with reduced dose CNI in more recent studies with everolimus. Dyslipidemia, lymphoceles, and impaired wound healing were more frequent with mTORi-CNI and diarrhea and leukopenia were more frequent with MMF/MPA-CNI. Viral infections at any time and malignant neoplasia beyond 2 years were less frequent with mTORi-CNI. Rates of discontinuation because of adverse effects in the mTORi groups varied between 17% and 46% compared to 0%-26.6% in MMF/MPA groups. The current use of lower mTORi dosage has decreased the discontinuation rates.. Efficacy is similar with mTORi + CNI and MMF/MPA-CNI. The safety profile is the predominant difference between the 2 regimens.

Topics: Calcineurin Inhibitors; Diarrhea; Drug Therapy, Combination; Dyslipidemias; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Randomized Controlled Trials as Topic; Standard of Care; TOR Serine-Threonine Kinases; Treatment Outcome

The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant. Acute rejection (AR) occurred significantly less often among those treated with tacrolimus/MMF (12%) than among those treated with tacrolimus/sirolimus (30%) or cyclosporine/sirolimus (28%). Mean estimated GFR was consistently higher in the tacrolimus/MMF arm, especially after controlling for donor age in a multivariable model during the first 36 mo (P ≤ 0.008). The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus (26%) than among those treated with tacrolimus/MMF (12%) or cyclosporine/sirolimus (4%). We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups. Patient noncompliance seemed responsible for 45% (13/29) of observed graft failures, with 11 of these occurring after 36 mo. Significantly more viral infections, protocol violations, and need for antilipid therapy occurred among patients receiving sirolimus, but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes. Taken together, these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus.

Topics: Adolescent; Adult; Aged; Cyclosporine; Diabetes Mellitus; Drug Therapy, Combination; Dyslipidemias; Female; Florida; Graft Rejection; Guideline Adherence; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Young Adult

Although mycophenolate mofetil (MMF) monotherapy has been successfully used in liver transplant recipients suffering from calcineurin-inhibitor (CNI)-related chronic toxicity, still no consensus has been reached on its safety, efficacy and tolerability. We attempted the complete weaning off CNI in 42 individuals presenting chronic renal dysfunction and/or dyslipidemia and/or arterial hypertension and simultaneously introduced 1.5 gm/day MMF. CNI could be completely withdrawn in 41 cases. A total of 32 (75%) patients are currently on

Topics: Adult; Aged; Calcineurin Inhibitors; Cholesterol; Dyslipidemias; Female; Humans; Hypertension; Immunosuppressive Agents; Kidney; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Time Factors; Triglycerides

We report three-year (interim) effects of combining sirolimus (Siro) vs. mycophenolate mofetil (MMF) as adjunctive therapy with calcineurin inhibitors (CI) in renal transplantation in the three different CI-based regimens.. Between May 2000 and December 2001, 150 recipients of deceased donor (DD) and living donor (LD) kidney transplants were randomized into three groups (n=50/group): Group A (Tacro/Siro), Group B (Tacro/MMF) and Group C (CsA/Siro). This report details drug dosing and monitoring, protocol discontinuance, biopsy-proven rejection, graft failure, other adverse events, and death at 36 months postoperatively.. Actual patient and graft survival respectively in Group A was 90% and 82%, in Group B was 92% and 88%, and in Group C was 96% and 88% (not significant). Biopsy-confirmed acute rejection incidents showed a trend in favor of Group B (10%) vs. Group A (26%) and Group C (20%) combined (P=0.07). The geometric mean */SE serum creatinine concentration and arithmetic mean +/- SE Cockroft-Gault creatinine clearance calculations, respectively, were 1.39*/1.1 and 72.8+/-4.3 for Group A, 1.36*/1.1 and 72.1+/-4.1 for Group B, and 1.60*/1.1 and 61.8+/-3.8 for Group C, a statistically favorable difference for Group B over Group C (P=0.04). There was also less de novo development of posttransplant diabetes mellitus and lipid disorders in Group B vs. A and C (P<0.04).. This three-year (interim) analysis has indicated a trend towards better graft function, fewer endocrine disorders, and fewer acute rejection episodes comparing adjunctive MMF and Tacro vs. Siro and Tacro or Siro and CsA, in the dosages used.

Topics: Adolescent; Adult; Aged; Blood Pressure; Cross-Over Studies; Diabetes Mellitus; Dyslipidemias; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kidney; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Tacrolimus

Cardiovascular (CV) diseases are recognized longterm causes of death after liver transplantation (LT). The objective of this multicenter study was to analyze the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 LT recipients along 5 years after LT. The influence of baseline variables on survival, morbidity, and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow-up. Most CV events (39%) occurred in the first year after LT. Preexisting CV risk factors such as age, pre-LT CV events, diabetes, metabolic syndrome, and hyperuricemia, and mycophenolate-free immunosuppressive therapy, increased post-LT CV morbidity and mortality. The development of new-onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of posttransplant diabetes, whereas cyclosporine increased the risk of arterial hypertension, dyslipidemia, and metabolic syndrome. In conclusion, CV complications and CV mortality are frequent in LT recipients. Preexisting CV risk factors, immunosuppressive drugs, but also the early new onset of obesity and dyslipidemia after LT play an important role on late CV complications. A strict metabolic control in the immediate post-LT period is advisable for improving CV risk of LT recipients. Liver Transplantation 23 498-509 2017 AASLD.

Topics: Adult; Age Factors; Aged; Cardiovascular Diseases; Cyclosporine; Diabetes Mellitus, Type 1; Dyslipidemias; End Stage Liver Disease; Female; Follow-Up Studies; Graft Rejection; Humans; Hypertension; Immunosuppressive Agents; Liver Transplantation; Male; Metabolic Syndrome; Middle Aged; Mycophenolic Acid; Postoperative Complications; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Spain; Survival Analysis; Tacrolimus; Transplant Recipients

Lipid abnormalities (LA) are related to an increased risk for cardiovascular diseases in kidney transplantation patients.. Multivariable logistic regression models were used to estimate the risk of LA associated with potential risk factors, including immunosuppressant use, patient background characteristics, and laboratory data.. In total, 386 patients who were undergoing kidney transplantation were included in the study. Statins were prescribed to 43% of patients. The LA composite outcome was defined as statin use and/or low density lipoprotein cholesterol level ≥120 mg/dL, and 229 patients (59.3%) developed LA as a result. LA was significantly related to everolimus, corticosteroid, age, and estimated glomerular filtration ratio in the multiple logistic regression analysis. The odds ratios were 2.264, 3.119, 1.186, and 0.870, respectively. Mycophenolate mofetil, mizoribine, azathioprine, cyclosporine (CYA), tacrolimus, proteinuria, body mass index, and male sex were not related to LA.. CYA influenced lipid metabolism but was not related to LA in our study. The mean post transplantation period was 8.4 years, and the CYA dose decreased over time. The CYA blood concentration was 70.0 ng/mL, which is relatively low, but it decreased the susceptibility to LA. Serum lipid levels were well controlled by statins, and the estimated glomerular filtration rate was maintained stably.. Everolimus and corticosteroid use, as well as a lower estimated glomerular filtration rate and higher age, were significant risk factors for LA. CYA is known for its adverse LA effects, but it was not a significant risk factor for LA in patients undergoing maintenance phase kidney transplantation.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Azathioprine; Cyclosporine; Dyslipidemias; Everolimus; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Kidney Transplantation; Lipids; Male; Middle Aged; Mycophenolic Acid; Ribonucleosides; Risk Factors; Tacrolimus

We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012) and prednisolone (P = 0.023) doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8-12.2). These findings may aid in predicting a patient's risk of developing dyslipidemia.

Topics: Adult; Aged; Case-Control Studies; Dyslipidemias; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Polymorphism, Single Nucleotide; Prednisolone; Prevalence; Receptors, Glucocorticoid; Risk Factors; Sex Factors

There is continued and significant debate regarding the salient etiologies associated with graft loss and racial disparities in kidney transplant recipients.. This was a longitudinal cohort study of all adult kidney transplant recipients, comparing patients with early graft loss (<5 years) to those with graft longevity (surviving graft with at least 5 years of follow-up) across racial cohorts [African-American (AA) and non-AA] to discern risk factors.. 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). Consistent within both races, early graft loss was significantly associated with disability income [adjusted odds ratio (AOR) 2.2, 95% CI 1.1-4.5], Kidney Donor Risk Index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6). Unique risk factors in AAs included Medicare-only insurance (AOR 8.0, 2.3-28) and BK infection (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control: AAs with a mean systolic blood pressure <150 mm Hg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while low-density lipoprotein <100 mg/dl (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dl (AOR 0.4, 0.2-1.0) and hemoglobin A1C <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but not in non-AA recipients.. AA recipients have a number of unique risk factors for early graft loss, suggesting that controlling cardiovascular comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation.

Topics: Adult; Aged; BK Virus; Black or African American; Cardiovascular Diseases; Cohort Studies; Dyslipidemias; Female; Graft Rejection; Graft Survival; Health Status Disparities; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Longitudinal Studies; Male; Medicare; Middle Aged; Mycophenolic Acid; Odds Ratio; Polyomavirus Infections; Prednisone; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors; United States

This study analyzed the incidence, time course, and risk factors associated with dyslipidemia during the first year after kidney transplantation among patients receiving various immunosuppressive regimens.. The analysis included 474 kidney transplant recipients receiving cyclosporine (CSA) combined with sirolimus (SRL; n=137) or mycophenolate (MMF, n=58) or everolimus (EVR, n=47); or SRL combined with MMF (n=32); or tacrolimus (TAC) combined with SRL (n=86) or MMF (n=114). All patients received prednisone. We evaluated the influence of demographic features, clinical outcomes, and statin use on lipid profiles during the first year after transplantation. total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (hdl-C), low-density lipoprotein cholesterol (ldl-C), non-HDL-C, TC:HDL-C, LDL-C:HDL-C, TG:HDL-C.. Lipid profiles were within the recommended ranges in 28% of patients pretransplantation and in 10% at 1 year; 27% of them received statins. At 1 year, LDL-C<100 mg/dL was observed in 31.8% of patients but more than 35% of these patients still showed other lipid fractions or ratios outside recommended target concentrations. Among all patients with LDL-C>100 mg/dL, almost 70% to 80% had other lipid fractions or ratios within target ranges. A logistic regression analysis showed age, gender, time on dialysis, diabetes, type of calcineurin inhibitor (CSA vs TAC), adjunctive therapy (SRL/EVR vs MMF) and prednisone dose to be associated with dyslipidemia.. Dyslipidemia is frequent at 1 year after transplantation. The lack of agreement among changes observed in lipid fractions and ratios suggests that more studies are necessary to guide therapy besides targeting LDL-C concentrations as recommended by current guidelines.

Topics: Adult; Analysis of Variance; Biomarkers; Brazil; Chi-Square Distribution; Cyclosporine; Drug Therapy, Combination; Dyslipidemias; Everolimus; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lipids; Logistic Models; Male; Middle Aged; Mycophenolic Acid; Odds Ratio; Prednisone; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Tacrolimus; Time Factors; Treatment Outcome