tacrolimus and Dyslipidemias

To compare new onset dyslipidaemia in live-related renal transplant recipients taking cyclosporine versus tacrolimus after 3 months of therapy.. The randomised controlled trial was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Karachi, from September 2010 to April 2011, and included 182 End Stage Renal Disease patients on maintenance haemodialysis with pre-transplant normal lipid profile. The patients, who had live-related renal transplant, were randomly allocated to two equal groups using lottery. Group A received cyclosporine (3 mg/kg) and group B was treated with tacrolimus (0.1 mg/kg). All patients had pre-transplant fasting lipid profile checked when they were on maintenance haemodialysis and 3 months after renal transplantation. Serum fasting lipid profile was collected by taking 5 ml blood by venipuncture after an overnight fast of 9-12 hours. SPSS 10 was used for statistical analyses.. Of the 182 patients, 144 (79.1%) were males and 38 (20.9%) were females. The overall mean age was 30.18 +/- 9.57 years, and the mean weight was 54.41 +/- 11.144 kg. Significant difference was not observed between the two groups regarding age and weight of the patients. Dyslipidaemia was found in 115(63.2%) subjects; 61(67%) in group A and 54 (59.3%) in group B. There was no statistical difference (p=0.28) when comparison was done after 3 months of therapy.. The occurrence of new onset hyperlipidaemia is similar in renal transplant recipients receiving either cyclosporine or tacrolimus in first 3 months post-transplant, but there is room for more research in this field as dyslipidaemia following successful renal transplantation is a frequent and persistent complication.

Topics: Adult; Cyclosporine; Dyslipidemias; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Tacrolimus; Young Adult

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

Subclinical inflammation is related to adverse events in patients with coronary artery disease. In the present study, we determined the changes in hemostatic parameters and inflammatory markers in a large cohort of dyslipidemic cardiac transplant recipients compared with dyslipidemic healthy controls, and the effect of cyclosporin microemulsion (CsA) vs. tacrolimus immunoprophylaxis on these parameters.. Stable cardiac transplant recipients (n=129) aged 56.7+/-10.1 years, 79+/-42 months postcardiac transplantation, and 26 mildly dyslipidemic healthy control subjects had serum measurements for lipids and lipoproteins, hemostatic parameters, and selected inflammatory markers. Transplant recipients were randomized to either continuation of CsA maintenance or conversion to tacrolimus immunoprophylaxis and were reassessed after six months.. CsA-maintained cardiac transplant recipients exhibited a significant elevation in Factor VIII, Von Willebrand factor, fibrinogen and PAI-I compared with healthy control subjects (all P<0.05). Similarly, cardiac transplant patients yielded a significantly elevated C-reactive protein (CRP) (4.11+/-6.25 [transplant group (TX)] vs. 2.09+/-2.21 mg/L [control group (CTL)]; P=0.0195), and homocysteine (19.2+/-8.8 [TX] vs. 9.70+/-2.45 microM [CTL]; P<0.001). VCAM, ICAM, E- and P-selectins were also significantly higher in transplant patients than in controls (all P<0.05). The conversion from CsA to tacrolimus resulted in a significant decrease in uric acid, total- and LDL-cholesterol, apolipoprotein B, creatinine, and homocysteine levels (all P<0.05).. Stable long-term CsA-maintained cardiac transplant patients exhibit a significant and general increase in hemostatic parameters and markers for subclinical inflammation. Tacrolimus conversion improved the patient lipid profile and decreased serum creatinine, uric acid, and homocysteine without any significant effect on the other markers.

Topics: Adult; Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Cyclosporine; Dyslipidemias; Emulsions; Heart Transplantation; Hemostasis; Humans; Immunosuppressive Agents; Inflammation; Middle Aged; Postoperative Complications; Tacrolimus; Thrombosis

Topics: Animals; Dyslipidemias; Fatty Acid Synthases; Glucocorticoids; Liver; Liver Transplantation; Male; Mice; Mice, Inbred C57BL; RNA; RNA Stability; Tacrolimus

Dyslipidemia exhibits a high incidence after liver transplantation, in which tacrolimus, a widely used immunosuppressant, plays a fundamental role. MicroRNAs and related circRNAs represent a class of noncoding RNAs that have been recognized as important regulators of genes associated with lipid metabolism. However, their transcriptional activities and functional mechanisms in tacrolimus-related dyslipidemia remain unclear. In this study, we observed that tacrolimus could induce triglyceride accumulation in hepatocytes by stimulating sterol response element-binding proteins (SREBPs) and miR-33a. Our in silico and experimental analyses identified miR-33a as a direct target of circFASN. Tacrolimus could downregulate circFASN and result in elevated miR-33a in vivo and in vitro. Overexpression of circFASN or silencing of miR-33a decreased the promoting effects of tacrolimus on triglyceride accumulation. Clinically, the incidence of dyslipidemia in liver transplant recipients with elevated serum miR-33a after liver transplantation was higher than that in patients without elevated serum miR-33a (46.3% vs. 18.8% p = 0.012, n = 73). Our results showed that the circFASN/miR-33a regulatory system plays a distinct role in tacrolimus-induced disruption of lipid homeostasis. MiR-33a is likely a risk factor for tacrolimus-related dyslipidemia, providing a potential therapeutic target to combat tacrolimus-induced dyslipidemia after liver transplantation.

Topics: Animals; Dyslipidemias; Gene Expression Regulation; Hep G2 Cells; Hepatocytes; Homeostasis; Humans; Immunosuppressive Agents; Lipid Metabolism; Liver; Liver Transplantation; Mice; MicroRNAs; Risk Factors; RNA, Circular; Tacrolimus; Triglycerides

Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Serum adiponectin levels inversely correlate with CVD-related outcomes, but the relationship between hypoadiponectinemia and CVD after LT is unknown. Thus, the aim of the present study was to prospectively evaluate this relationship in LT recipients (LTR).. LTR were prospectively enrolled (N = 130) between January 1, 2012, and January 1, 2014. Baseline adiponectin levels were drawn at enrollment and patients were followed for CVD events. Hypoadiponectinemia was defined as serum adiponectin <10 µg/mL. The primary endpoint was a composite CVD outcome consisting of myocardial infarction, angina, need for coronary revascularization, stroke, or cardiac death.. The mean age was 58 ± 11 years and prevalence of obesity, diabetes, and dyslipidemia was 40%, 35%, and 40%, respectively. A total of 20 CVD events were noted, after median follow up of 45 months. Hypoadiponectinemia was significantly associated with future risk of CVD events (hazard ratio, 3.519; 95% confidence interval, 1.180-10.499, P = 0.024). This association was independent of traditional CVD risk factors including age, gender, obesity, hypertension, diabetes, and choice of immunosuppression.. Hypoadiponectinemia is a strong independent predictor of future cardiovascular events in LTR, which can be incorporated in clinical practice to assess CVD risk assessment after LT.

Topics: Adiponectin; Aged; Cardiovascular Diseases; Cyclosporine; Diabetes Complications; Dyslipidemias; End Stage Liver Disease; Female; Humans; Immunosuppression Therapy; Insulin Resistance; Liver Transplantation; Male; Metabolism, Inborn Errors; Middle Aged; Obesity; Proportional Hazards Models; Prospective Studies; Risk Assessment; Tacrolimus; Transplant Recipients; Treatment Outcome

This study aims to verify the new-onset diabetes after kidney transplant (NODAT) incidence in recipients within 1 year after kidney transplantation from a single center in Southern Brazil and to assess the associated conditions.. A retrospective study of 258 post-renal transplant patients was performed. Demographic (gender, age, ethnic background) and clinical (origin of graft, associated infections, body mass index (BMI) at transplant time and 6 and 12 months after, causes of renal failure, and comorbidities) data were analyzed. All patients were on tacrolimus, mycophenolate mofetil, and prednisone treatment. Patients with and without NODAT were compared.. A NODAT incidence of 31.2% was noted 1 year post transplantation. In the univariate analysis, patients with NODAT were older (p = 0.001), mostly had African-American ethnic background (p = 0.02), and had renal failure secondary to high blood pressure (HBP) (p = 0.001). The group of patients with NODAT also had more incidence of post-transplant HBP (p = 0.01), heart failure (p = 0.02), and dyslipidemia (p = 0.001). Logistic regression showed that African-American ethnic background, post-transplant HBP, and dyslipidemia were independently associated with NODAT.. This study shows a NODAT incidence that is greater in patients with African-American ethnic background and that is associated with HBP and dyslipidemia.

Topics: Adult; Brazil; Diabetes Mellitus; Dyslipidemias; Female; Humans; Hypertension; Immunosuppressive Agents; Incidence; Kidney Transplantation; Logistic Models; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Statistics, Nonparametric; 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

Cardiovascular diseases induce long-term morbidity and mortality of adult LT recipients. The aim of this retrospective study was to assess CVRF, lipid abnormalities, and atherosclerosis (appraised by c-IMT), more than 10 yr after pediatric LT. Thirty-one children who underwent LT between December 1990 and December 2000 were included. Median age at LT was 14 months (range 4-64), and median follow-up after LT was 11.9 yr (range 9.0-17.3). In our cohort, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients was smoker or diabetic. High TC and TG were both observed in 6.5% of the patients. The mean c-IMT for male patients was 1.22 ± 1.55 and 1.58 ± 1.23 mm in female patients. Seven patients (22%) had a mean c-IMT above +2 s.d. Values below the 5th percentile were noted for LDL-cholesterol (58.1%), HDL-cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL-cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05). In conclusion, our results suggest that pediatric LT patients do not present significant CVRF; moreover, instead of hyperlipidemia, hypocholesterolemia (LDL-C) is frequent and immunosuppressive therapy is probably the cause.

Topics: Adolescent; Apolipoprotein A-I; Apolipoproteins B; Biopsy; Cardiovascular Diseases; Child; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Cyclosporine; Dyslipidemias; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Infant; Liver; Liver Failure; Liver Transplantation; Male; Retrospective Studies; Risk Factors; Tacrolimus; Transplant Recipients; Treatment Outcome

The CONCERTO study results showing the beneficial effects of conversion from cyclosporine to tacrolimus prolonged-release (tacrolimus PR) in stabilised patients after kidney transplantation, were first published in 2011. This communication describes our first experience of conversion from cyclosporine to tacrolimus PR in stabilised kidney transplant patients. The aim was to determine whether it could be used in routine clinical practice in the Czech and Slovak Republics.. Evaluation was carried out at five transplantation centres in the Czech Republic and Slovakia. In all participating Centres, the drug conversion was conducted according to the ICH/GCP guidelines. A total of 104 patients stabilised after kidney transplantation were converted from maintenance therapy with cyclosporine to treatment with tacrolimus PR. The data were collected 26 weeks after the switch. The primary endpoint was change in kidney graft function measured from the estimated glomerular filtration rate (GFR). The effect of conversion on blood pressure, metabolic parameters and cosmetic changes was also recorded. Special attention was paid to the safety and tolerability of treatment with tacrolimus PR.. GFR increased after six months by 10 % (P = 0.040). In addition a significant decrease in serum creatinine and triglycerides level was found together with major reduction in the incidence and severity of gingival hyperplasia and hirsutism. 3% of patients developed new onset of diabetes mellitus. Otherwise, the switch was very well-tolerated, without serious adverse events or acute rejections.. Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.

Topics: Cyclosporine; Delayed-Action Preparations; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Substitution; Dyslipidemias; Female; Gingival Hyperplasia; Glomerular Filtration Rate; Hirsutism; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Tacrolimus; Treatment Outcome

Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long‑term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK‑52E, were cultured either with oxidized low‑density lipoprotein (ox‑LDL), FK506, ox‑LDL combined with FK506, or vehicle, respectively. Changes in cell morphology and changes in the levels of lectin‑like ox‑LDL receptor‑1 (LOX‑1), reactive oxygen species (ROS), hydrogen peroxide and fibrosis‑associated genes were evaluated at 24, 48 and 72 h. In separate experiment, total of 60 Sprague‑Dawley rats were divided randomly into four groups, which included a high‑fat group, FK506 group, high‑fat combined with FK506 group, and control group. After 2, 4 and 8 weeks, the serum lipid levels, the levels of ox‑LDL, ROS, and the expression levels of transforming growth factor (TGF)‑β1 and connective tissue growth factor were determined. The in vitro and in vivo models revealed that lipid metabolism disorder and FK506 caused oxidative stress and a fibrogenic response. In addition, decreased levels of LOX‑1 markedly reduced the levels of TGF‑β1 in the in vitro model. Taken together, FK506 and dyslipidemia were found to be associated with CRAD following transplantation.

Topics: Allografts; Animals; Connective Tissue Growth Factor; Disease Models, Animal; Dyslipidemias; Fibrosis; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lipid Metabolism; Lipoproteins, LDL; Mice; Rats; Reactive Oxygen Species; Scavenger Receptors, Class E; Tacrolimus; Transforming Growth Factor beta1

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

Since the introduction of monitoring levels of immunosuppressive medications in our service in July 2000, 1088 kidney transplant patients were received for therapeutic drug monitoring and regular follow-up. The aim of this study was to retrospectively analyze the data on these renal graft patients in Algeria and correlate with our 12 years' experience with calcineurin inhibitor (CNI) measurements. In addition, during this period, we also examined other bioche-mical parameters. The analysis was focused on the difference of effect of cyclosporin A (CsA; 623 patients) and Tacrolimus (Tac; 465 patients) on lipid and glucose metabolism and their side-effects, if any, on the renal function. The mean age at the time of transplantation was 36.1 years. A great majority of the transplanted kidneys had been taken from living related donors (88.6%). Three-quarters of all grafts were transplanted in our country (79.5%). Dyslipidemia and renal dysfunction were the most common adverse effects of CsA and Tac exposure, with a frequency of 21.4% and 10.3%, respectively. Both the CNIs had a similar effect on the lipid levels. The highest incidence occurred at 3-12 months after renal graft. Tac seemed to have more side-effects on glycemia, causing the onset of diabetes mellitus more than two-fold than CsA (6.9% vs. 3.1%). A significant difference was observed during 12-24 months after transplantation. However, Tac was associated with the most favorable effects on renal function estimated with the Modification of Diet in Renal Disease (MDRD) formula.

Topics: Adult; Algeria; Biomarkers; Blood Glucose; Chi-Square Distribution; Cyclosporine; Diabetes Mellitus; Drug Monitoring; Dyslipidemias; Female; Hospitals; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Lipids; Male; Middle Aged; Retrospective Studies; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

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

The principal risk factors for cardiovascular mortality posttransplantation are hyperglycemia, hypertriglyceridemia, obesity, and smoking.. Among 115 patients, we assessed the risk factors for new-onset diabetes (NODM) and dyslipidemia (NODL), and their effects on the function and histopathologic changes in the allografts at 1 year posttransplantation.. When evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal vs NODM patients (P=.004), normal versus NODL patients (P=.002), and normal versus NODL + NODM patients (P=.0001). The difference in body mass index (BMI) was significant when comparing normal with NODM + NODL patients (P=.003). In regard to immunosuppressive therapy, NODM was significantly more frequent among/prescribed tacrolimus (tac; P=.005), whereas subjects who received cyclosporine (CsA) showed a significantly higher incidence of NODL (P=.001). The triglyceride levels were 3.02 ± 1.51 mmol/L among those on CsA versus 2.15 ± 1.57 mmol/L for (P=.004). The difference also proved to be significant for total cholesterol level: 5.43 ± 1.23 mmol/L versus 4.42 ± 1.31 mmol/L respectively (P=.001). In regard to allograft function a significant difference was noted at 1 year after transplantation between the NODM + NODL and the normal group in serum creatinine level (P=.02) as well as the estimated glomerular filtration rate (P=.004). Among diabetic patients, the serum creatinine level measured at posttransplant year 5 was significantly higher than that in 1 year (212.43 vs 147.00 μmol/L; P=.0003). When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy in all 3 groups compared with normal function patients.. Our clinical study suggested that at 1 year after transplantation allograft function is already impaired in the presence of both medical conditions (NODM and NODL). However, in regard to morphology, a single condition (NODM or NODL) was sufficient to produce histologic changes in the kidney.

Topics: Adult; Analysis of Variance; Atrophy; Biomarkers; Biopsy; Body Mass Index; Case-Control Studies; Chi-Square Distribution; Creatinine; Cyclosporine; Diabetes Mellitus; Dyslipidemias; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Graft Survival; Humans; Hungary; Immunosuppressive Agents; Kidney; Kidney Transplantation; Lipids; Logistic Models; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome

We studied the mechanisms by which immunosuppressants result, in dyslipidemia among human kidney transplant recipients.. Seventy-five living donor kidney transplant recipients were enrolled in our study with informed consent and the approval of out Institutional Ethics Committee. Each donor-recipient pair were relatives, there were no prisoners. The serum lipid profile, the expression of CD36 on peripheral blood monocytes, and the whole blood concentrations of cyclosporine (CsA) or tacrolimus (FK506) were determined at various times after transplantation.. CsA significantly increased serum lipid concentrations. The CsA concentration correlated positively with low-density lipoprotein cholesterol (LDL) levels, whereas FK506 showed no significant effect on serum lipid level. There was a positive correlation between the CsA concentrations and the expression of CD36; FK507 showed no significant effect on CD36 expression.. Hyperlipidemia in kidney transplant recipients treated with CsA was associated with overexpression of CD36 on peripheral blood monocytes.

Topics: Adult; CD36 Antigens; Cyclosporine; Dyslipidemias; Female; Humans; Kidney Transplantation; Male; Middle Aged; Monocytes; Tacrolimus

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

Immunosuppression has improved graft and recipient survival in transplantation but is accompanied by several adverse effects like dyslipidemia and cardiovascular disease. Herein, we performed an observational, descriptive study to analyze the relationship of dyslipemia (hypercholesterolemia [hypercho] and hypertriglyceridemia [hypertg]) and cardiovascular disease with two different immunosuppressive regimens in liver transplantation: cyclosporine treatment based upon C2 levels (CsA2) and tacrolimus (Tac), both in combination with steroids. Seventy-four liver transplantation patients were included during a 2-year period: 35 with CsA2 and 39 with Tac. The mean follow-up was 40 months. There were no significant differences between the groups in terms of age, gender, Model for End-stage Liver Disease Score, Child stage, and indication for transplantation. The distribution of patients with HyperCho and HyperTg was independent of the immunosuppressive agent (P = NS), both in a global and in a stratified analysis at 6, 12, 24, and 60 months. The analysis of cardiovascular events revealed no differences between the groups (CsA2 14.3%; Tac 18.9%; P = NS). We suggest that CsA monitoring using C2 levels shows a safety profile similar to that of Tac with regard to the development of dyslipidemia and cardiovascular events.

Topics: Cyclosporine; Dyslipidemias; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Immunosuppressive Agents; Lipids; Liver Transplantation; Male; Tacrolimus

Lipid-lowering therapy with statins has been associated with decreased mortality and morbidity in heart transplant recipients. Among the available drugs, pravastatin, fluvastatin or low-dose simvastatin have been recommended due to the low risk of pharmacokinetic interaction. However, these first-line statins possess a rather modest lipid-lowering effect and selection of alternative statins is limited due to interactions with cyclosporine (CsA). The aim of this prospective study was to evaluate the safety and efficacy of conversion to tacrolimus and atorvastatin in CsA-treated heart transplant recipients and dyslipidemia refractory to fluvastatin.. Thirty heart transplant recipients taking CsA and fluvastatin 40 to 80 mg/day, with total cholesterol levels of >211 mg/dl, were recruited. After baseline assessment, they were converted to tacrolimus and atorvastatin at a starting dose of 20 mg/day and underwent clinical and laboratory follow-up at 1, 4, 7, 10 and 13 months.. During 13 months of follow-up, treatment with tacrolimus and atorvastatin was tolerated in 24 patients (80%). No case of myotoxicity, liver toxicity or new-onset diabetes was observed. After conversion, the mean cholesterol level (as averaged from levels at 1, 4, 7, 10 and 13 months) was lower than before conversion (183 +/- 24 vs 231 +/- 33 mg/dl, p < 0.0001). When compared with baseline values, conversion also resulted in lower mean LDL-cholesterol levels (92 +/- 25 vs 130 +/- 38 mg/dl, p < 0.0001) and lower mean triglyceride levels (166 +/- 60 vs 220 +/- 101 mg/dl, p < 0.0001).. Conversion to tacrolimus and atorvastatin appears to be a safe and effective lipid-lowering therapy in CsA-treated heart transplant recipients with dyslipidemia refractory to fluvastatin.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Cohort Studies; Cyclosporine; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Heart Transplantation; Heptanoic Acids; Humans; Immunosuppressive Agents; Indoles; Male; Middle Aged; Prospective Studies; Pyrroles; Tacrolimus; Treatment Outcome; Triglycerides

Sirolimus is a potent immunosuppressive drug that has been shown to decrease the incidence of rejection post renal transplantation. Dyslipidemia is a well recognized side effect of sirolimus therapy, which may have an impact on patient survival and post-transplant cardiac morbidity and mortality. It is unknown whether sirolimus-induced dyslipidemia is aggravated by concomitant use of tacrolimus which may also affect lipid profile. To compare sirolimus induced dyslipidemia in tacrolimus based vs. tacrolimus free regimens in renal transplant recipients.. Patients who received sirolimus post kidney transplantation for at least nine sequential months were included in our retrospective study. Forty-eight renal transplant recipients were divided into 2 groups based on the immunosuppressive regimen; Group 1 received prednisone, sirolimus and mycophenolate mofetil, while Group 2 received prednisone, sirolimus, mycophanolate mofetil and tacrolimus. Lipid profile was assessed pre-transplantation and at one, three, six and nine months post sirolimus therapy.. Both groups showed significant but comparable elevation in total cholesterol, LDL-C and triglycerides with sirolimus therapy. The elevation was evident starting from the first month of sirolimus administration and remained to the ninth month at the end of the follow up period. At first month, mean triglycerides was 2.68 and 2.6 mmol/L (P>0.1) and mean total cholesterol was 6.3 and 5.7 mmol/L in group 1 and 2 (P>0.1); respectively. By the ninth month, triglycerides level was 2.6 and 3.9 mmol/L (P>0.1) while mean total cholesterol level was 6.2 and 6.1 mmol/L (P>0.1) in group 1 and 2 respectively. Lipid-lowering agents and total steroids dose were similar in both groups.. Hypercholesterolemia and hypertriglyceridemia secondary to sirolimus therapy is independent from concomitant tacrolimus use. Lipid-profile should be monitored in all renal transplant recipients receiving sirolimus as early as first month regardless of the immunosuppressive regimen used.

Topics: Adult; Cohort Studies; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Renal Insufficiency; Retrospective Studies; Sirolimus; Tacrolimus

Lipid abnormalities including increased total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) have been frequently reported in renal transplantation and could be involved in the high frequency of cardiovascular diseases in this population.. Two hundred ninety-five patients were transplanted between January 1995 and October 2000 in our center. Two hundred two patients were included in this study. Seventy-six patients received tacrolimus (Tac), and 126 patients cyclosporine (CsA). Lipid parameters were assessed the day of transplantation and 1 year posttransplantation.. Serum lipids were similar between the two groups at D0. At M12, TC and LDL-C were significantly higher in the CsA group (6.14 +/- 1.37 vs 5.28 +/- 1.32 mmol/L; P < .05 and 3.98 +/- 1.05 vs 3.26 +/- 1.03 mmol/L; P < .05 CsA vs Tac, respectively). TG were comparable in both groups (1.86 +/- 1.07 vs 1.62 +/- 0.92 mmol/L; P = .55; CsA vs Tac). Incidence of de novo hypercholesterolemia was significantly higher in the CsA group (28 vs 8%) whereas incidence of hyperTG was similar in both groups. Prevalence of LDL-C was significantly higher in the CsA group (65% vs 31%; P < .001), whereas there was no difference in high density lipoprotein (HDL)-C levels.. Mean serum lipid levels and incidence and prevalence of hyperTC, especially LDL-C, was significantly higher in patients receiving CsA when compared with Tac. TG and HDL-C levels were similar. Although the study was retrospective, our results confirm that CsA increases lipid levels, whereas Tac does not.. Lipid disorders are frequently observed in renal transplant recipients. CsA, but not Tac, significantly increases incidence and prevalence of high TC and LDL-C.

Topics: Adult; Body Mass Index; Cholesterol; Cyclosporine; Dyslipidemias; Hemoglobins; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Lipids; Middle Aged; Postoperative Complications; Prevalence; Retrospective Studies; Tacrolimus; Triglycerides