tacrolimus and Metabolic-Syndrome

The therapeutic success of renal transplantation has been largely attributable to the development of effective and balanced immunosuppressive treatment regimens. This study provides a meta-analysis of a series of randomized controlled trials that compared the effects of tacrolimus and cyclosporine on metabolic syndrome (MetS) and cardiovascular risk factors after renal transplantation.. We searched various electronic databases and bibliographies, including MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE, for relevant studies published prior to October 2012.. Our meta-analysis included five randomized controlled trials that examined a total of 923 patients. The tacrolimus group and the cyclosporine group exhibited no significant differences in MetS incidence after renal transplantation; risk ratio (RR): 1.06, 95% confidence interval (CI): 0.73-1.55, P = 0.76. Cyclosporine treatment was associated with a higher incidence of hyperlipidemia (RR: 0.50, 95% CI: 0.39-0.64, P < 0.01). Although there were no statistically significant differences, cyclosporine treatment was associated with a higher incidence of hypertension (RR: 0.91, 95% CI: 0.83-1.00, P = 0.06) after renal transplantation compared to tacrolimus treatment, and tacrolimus treatment was associated with a higher incidence of diabetes after renal transplantation (RR: 1.79, 95% CI: 0.98-3.27, P = 0.06) compared to cyclosporine treatment.. Compared to tacrolimus treatment, cyclosporine treatment was associated with a higher incidence of hyperlipidemia. Future large-scale studies are expected to be conducted to further confirm our findings.

Topics: Calcineurin; Cardiovascular Diseases; Cyclosporine; Humans; Hyperlipidemias; Hypertension; Kidney Transplantation; Metabolic Syndrome; Randomized Controlled Trials as Topic; Tacrolimus

Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mammalian target of rapamycin inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study.. After a run-in period, patients (N = 719) were randomized at 30 ± 5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC) (n = 245); (ii) TAC control (n = 243) or (iii) TAC elimination (n = 231). In this post hoc analysis, weight change at 12 and 24 months was compared between groups. Vital signs, lipids, and laboratory parameters at 12 and 24 months and rates of PTMS were assessed.. Mean increase in weight from baseline was higher at month 12 in the TAC control arm (8.15 ± 9.27 kg) than in the EVR + reduced TAC (5.88 ± 12.60 kg, P = 0.056) and the TAC elimination arms (4.76 ± 9.94 kg, P = 0.007). At month 24, the TAC control arm displayed a significantly greater weight increase (9.54 ± 10.21 kg) than either the EVR + reduced TAC (6.69 ± 8.37 kg, P = 0.011) or the TAC elimination groups (6.01 ± 9.98 kg, P = 0.024). Rates of PTMS were similar for the EVR + reduced TAC (71.8%), TAC elimination (70.3%) and TAC control (67.4%) arms (P = NS).. EVR with reduced-exposure TAC attenuated weight gain at 1 and 2 years posttransplant compared with a standard TAC immunosuppression regimen. Rates of PTMS were comparable between EVR-containing and TAC control regimens.

Topics: Adult; Aged; Cardiovascular Diseases; Everolimus; Female; Follow-Up Studies; Glycosylation; Graft Rejection; Graft Survival; Hemoglobins; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver Failure; Liver Transplantation; Male; Metabolic Syndrome; Middle Aged; Obesity; Prospective Studies; Risk Factors; Signal Transduction; Tacrolimus; Weight Gain

The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation.. Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm.. The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm.. This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded.

Topics: Adrenal Cortex Hormones; Adult; Blood Chemical Analysis; Blood Pressure Determination; Body Mass Index; Cyclosporine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Hyperlipidemias; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolic Syndrome; Middle Aged; Monitoring, Physiologic; Mycophenolic Acid; Prognosis; Reference Values; Risk Assessment; Sirolimus; Tacrolimus; Transplantation Immunology

The prevalence of hyperuricemia shows an increasing trend among kidney transplant recipients. The association between metabolic syndrome and hyperuricemia among the recipients of kidney transplants may consequently lead to reduction in graft survival. In this regard, the present study aimed at comparing the kidney transplant recipients with and without metabolic syndrome in terms of the prevalence of hyperuricemia.. This cross-sectional study was carried out on kidney transplant recipients who were referred to the Kidney Transplant Clinic of Montaserieh Organ Transplant Hospital, Mashhad University of Medical Sciences, from 2019 to 2020. The serum uric acid, anthropometric data, renal function, glucose levels, and lipid profile of the study participants were evaluated.. According to our findings, higher mean uric acid levels were reported in recipients with metabolic syndrome (6.9 ± 1.51 mg/dL), compared to recipients without metabolic syndrome (6.11 ± 1.47 mg/dL; P < .001). It was also found that 55.6 and 38.5% of the cases with and without metabolic syndrome had hyperuricemia, respectively (P < .05). Additionally, the results showed no significant association between hyperuricemia and the number of metabolic syndrome criteria (P > .05). A comparison between recipients with and without hyperuricemia revealed significantly lower levels of tacrolimus in the hyperuricemia group (P < .05). Regarding serum Tacrolimus levels, no significant difference was found between recipients with and without metabolic syndrome (P > .05). Moreover, there was no significant difference between recipients with and without hyperuricemia (P > .05) or metabolic syndrome (P > .05) in terms of serum cyclosporine level.. The findings of the current study indicate that kidney transplant recipients suffering from metabolic syndrome have higher mean serum levels of uric acid than those without metabolic syndrome.  DOI: 10.52547/ijkd.7141.

Topics: Cross-Sectional Studies; Humans; Hyperuricemia; Kidney Transplantation; Metabolic Syndrome; Tacrolimus; Uric Acid

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

The evolution of metabolic and cardiovascular disease (CVD) complications after liver transplantation (LT) is poorly characterized. We aim to illustrate the prevalence of obesity and metabolic syndrome (MS), define the cumulative incidence of CVD, and characterize risk factors associated with these comorbidities after LT. A retrospective review of 455 consecutive LT recipients from 1999 to 2004 with an 8- to 12-year follow-up was performed. Obesity increased from 23.8% (4 months) to 40.8% (3 years) after LT. Increase in body mass index predicted MS at 1 year after LT (odds ratio, 1.1; P < 0.001, per point). CVD developed in 10.6%, 20.7%, and 30.3% of recipients within 1, 5, and 8 years, respectively. Age, diabetes, hypertension, glomerular filtration rate < 60 mL/minute, prior CVD, ejection fraction < 60%, left ventricular hypertrophy, and serum troponin (TN) > 0.07 ng/mL were associated with CVD on univariate analysis. Age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06; P = 0.019), diabetes (HR, 1.78; 95% CI, 1.09-2.92; P = 0.022), prior history of CVD (HR, 2.46; 95% CI, 1.45-4.16; P < 0.001), and serum TN > 0.07 ng/mL (HR, 1.98; 95% CI, 1.23-3.18; P = 0.005) were independently associated with CVD in the long term. Smoking history (ever), sex, hyperlipidemia, and serum ferritin levels were not predictive of CVD. Tacrolimus use versus noncalcineurin-based immunosuppression (HR, 0.26; 95% CI, 0.14-0.49; P < 0.001) was associated with reduced risk of CVD but not versus cyclosporine (HR, 0.67; 95% CI, 0.30-1.49; P = 0.322). CVD is common after LT. Independent of MS, more data are needed to identify nonconventional risk factors and biomarkers like serum TN. Curbing weight gain in the early months after transplant may impact MS and subsequent CVD in the long term.

Topics: Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Comorbidity; Cyclosporine; Diabetes Complications; End Stage Liver Disease; Female; Glomerular Filtration Rate; Humans; Hypertension; Immunosuppression Therapy; Incidence; Liver Transplantation; Male; Metabolic Syndrome; Middle Aged; Obesity; Odds Ratio; Prevalence; Proportional Hazards Models; Retrospective Studies; Risk Factors; Tacrolimus

Insulin resistance is common posttransplantation and contributes to both new onset diabetes after transplantation and the metabolic syndrome. Insulin resistance indexes have never been validated in transplant recipients on tacrolimus compared with cyclosporine, although it is more diabetogenic. We aimed to assess these indexes in renal transplant recipients on tacrolimus as primary immunosuppressant.. Retrospective analysis of 76 frequently sampled, intravenous glucose tolerance tests (for insulin sensitivity) in 38 nondiabetic renal transplant recipients on tacrolimus-centered immunosuppression. Indexes tested were fasting glucose/insulin ratio, homeostasis model assessment (HOMA) index, 1/HOMA, log (HOMA), quantitative insulin sensitivity check index, and the McAuley's index. Indexes were also compared against waist/hip ratio and C-reactive protein (CRP). Multivariate linear regression analysis was performed to determine independent variables predictive for insulin resistance.. Insulin sensitivity successfully correlated with all indexes: fasting glucose/insulin ratio (r=0.246, P=0.033), HOMA index (r=-0.240, P=0.038), 1/HOMA (r=0.282, P=0.014), log (HOMA) (r=-0.316, P=0.006), quantitative insulin sensitivity check index (r=0.320, P=0.005), and McAuley's index (r=0.323, P=0.005). McAuley's index also correlated strongest with waist/hip ratio (r=-0.425, P<0.001). All indexes failed to correlate with CRP. Variables independently associated with insulin sensitivity were HbA1c (r=0.189, P=0.019), pulse pressure (r=0.146, P=0.021), and CRP (r=0.210, P=0.010).. Insulin resistance indexes are valid in transplant recipients taking tacrolimus, with McAuley's index the strongest surrogate.

Topics: Diabetes Mellitus; Female; Glomerular Filtration Rate; Glucose Tolerance Test; Graft Rejection; Humans; Immunosuppressive Agents; Insulin Resistance; Kidney Transplantation; Male; Metabolic Syndrome; Middle Aged; Patient Selection; Renal Replacement Therapy; Retrospective Studies; Tacrolimus; Wales; White People

New-onset diabetes after transplantation (NODAT) is a major posttransplant complication associated with lower allograft and recipient survival. Our objective was to determine whether metabolic syndrome pretransplant is independently associated with NODAT development.. We recruited 640 consecutive incident nondiabetic renal transplant recipients from three academic centers between 1999 and 2004. NODAT was defined as the use of hypoglycemic medication, a random plasma glucose level more than 200 mg/dL, or two fasting glucose levels more than or equal to 126 mg/dL beyond 30 days posttransplant.. Metabolic syndrome was common pretransplant (57.2%). NODAT developed in 31.4% of recipients 1 year posttransplant. Participants with metabolic syndrome were more likely to develop NODAT compared with recipients without metabolic syndrome (34.4% vs. 27.4%, P=0.057). Recipients with increasing number of positive metabolic syndrome components were more likely to develop NODAT (metabolic syndrome score prevalence at 1 year: 0 components-0.0%, 1-24.2%, 2-29.3%, 3-31.0%, 4-34.8%, and 5-73.7%, P=0.001). After adjustment for demographics, age by decade (hazard ratio [HR] 1.34 [1.20-1.50], P<0.0001), African American race (HR 1.35 [1.01-1.82], P=0.043), cumulative prednisone dosage (HR 1.18 [1.07-1.30], P=0.001), and metabolic syndrome (HR 1.34 [1.00-1.79], P=0.047) were independent predictors of development of NODAT at 1 year posttransplant. In a multivariable analysis incorporating the individual metabolic syndrome components themselves as covariates, the only pretransplant metabolic syndrome component to remain an independent predictor of NODAT was low high-density lipoprotein (hazard ratio [HR] 1.37 [1.01-1.85], P=0.042).. Metabolic syndrome is an independent predictor for NODAT and is a possible target for intervention to prevent NODAT. Future studies to evaluate whether modification of metabolic syndrome factors pretransplant reduces NODAT development are needed.

Topics: Blood Glucose; Diabetes Mellitus; Fasting; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Polycystic Kidney Diseases; Prevalence; Regression Analysis; Tacrolimus

We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year.. We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index.. Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P=.004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P=.035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation.. There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of these entities, which are related to poor cardiovascular outcomes.

Topics: Adult; Diabetes Mellitus; Female; Humans; Immunosuppressive Agents; Incidence; Insulin; Kidney Transplantation; Male; Metabolic Syndrome; Middle Aged; Retrospective Studies; Risk Factors; Tacrolimus

Topics: Adolescent; Adult; Body Mass Index; Child; Graft Survival; Humans; Immunosuppressive Agents; Insulin Resistance; Kidney Transplantation; Metabolic Syndrome; Obesity; Risk; Tacrolimus

To investigate the risk factors of insulin resistance (IR) and the role of IR and metabolic syndrome in the pathogenesis of chronic allograft nephropathy (CAN).. One hundred and twenty-seven kidney transplant recipients with normal renal function and no proteinuria at the 6th month after transplantation, and without the experience of acute rejection, calcinurine intoxication and severe infection, were involved in the study. Their primary disease of ESRF was chronic glomerulonephritis but not diabetes mellitus and hypertension. Half year and one year after transplantation, blood and urine biochemical determinations and physical examination were performed in the recipients, and HOMA calculated. 200 ordinary community residents were randomized selected as controls.. The incidence of MS in the recipients was significantly higher than controls. The incidences of obesity and overweight between recipients and controls were no significant difference. While the insulin resistance level and urine albumin level, and the incidence of MS and microalbuminuria (MAU) were significantly higher in recipients with obesity or overweight than that in recipients without obesity or overweight. The insulin resistance level in tacrolimus-treated recipients was markedly higher than CsA-treated recipients, and there was a positive correlation between the blood concentration of tacrolimus and insulin resistance level. MAU positive recipients had higher insulin resistance levels than the recipients without MAU. The recipients with metabolic syndrome had higher insulin resistance levels compared to recipients without metabolic syndrome, and higher insulin resistance levels existed in recipients with hypertriglyceridemia or hypercholesterolemia, hypertension.. It is shown in the study that obesity or overweight, tacrolimus (especially when its blood concentration was high) were risk factors resulting in insulin resistance in kidney transplant recipients. It is suggested in the study that insulin resistance often accompanied with hypertriglyceridemia, hypercholesterolemia and hypertension in kidney transplant recipients might be involved in the pathogenesis of the pathogenesis of CAN.

Topics: Adult; Chronic Disease; Cyclosporine; Female; Glomerulonephritis; Humans; Incidence; Insulin Resistance; Kidney Transplantation; Male; Metabolic Syndrome; Middle Aged; Overweight; Risk Factors; Tacrolimus