The triglyceride to HDL-cholesterol ratio and chronic graft failure in renal transplantation

BACKGROUND: Transplant vasculopathy (TV) is a major contributing factor to chronic graft failure in renal transplant recipients (RTR). TV lesions resemble atherosclerosis in several ways, and it is plausible to believe that some risk factors influence both atherosclerotic plaque formation and formation of TV. OBJECTIVE: The objective of this prospective longitudinal study was to determine if dyslipidemia reflected by the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is prospectively associated with death censored chronic graft failure in RTR. METHOD: 454 prospectively included RTR with a functioning graft for at least one year, were followed for a median of 7 years. RTR were matched based on propensity scores to avoid potential confounding and subsequently the association of the TG/HDL-C ratio with the endpoint chronic graft failure, defined as return to dialysis or re-transplantation, was investigated. RESULTS: Linear regression analysis showed that concentration of insulin, male gender, BMI and number of antihypertensives predict the TG/HDL-C ratio. Cox regression showed that the TG/HDL-C ratio is associated with chronic graft failure (HR = 1.43, 95%CI = 1.12-1.84, p = 0.005) in competing risk analysis for mortality. Interaction testing indicated that the relationship of the TG/HDL-C ratio with graft failure is stronger in subjects with a higher insulin concentration. CONCLUSION: Our results demonstrate that the TG/HDL-C ratio has the potential to act as a predictive clinical biomarker. Furthermore, there is a need for closer attention to lipid management in RTR in clinical practice with a focus on triglyceride metabolism. (c) 2021 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Hypertriglyceridaemia: Aetiology, Complications and Management

The bulk of plasma triglycerides are carried by chylomicrons in the fed and very low-density lipoproteins in the fasted state. These triglyceriderich lipoproteins are metabolised to remnant lipoproteins by lipoprotein lipase (LPL). Hypertriglyceridaemia results if triglyceride-rich lipoproteins accumulate either due to defective clearance, overproduction or a combination of both mechanisms. Genetic and environmental factors interact in the genesis of hypertriglyceridaemia but occasionally a single factor may be dominant. At a molecular level the most common cause of severe primary hypertriglyceridaemia is loss of function mutations in both alleles of LPL. The most common environmental contributors include diabetes, diet, alcohol and medications (including oestrogen, steroids, retinoids and protease inhibitors). Severe hypertriglyceridaemia can trigger acute pancreatitis while mild to moderate hypertriglyceridaemia is an independent cardiovascular risk factor. Treatment strategies are determined by the severity and aetiology of hypertriglyceridaemia as well as the patient’s cardiovascular risk profile. General strategies include lifestyle modifications with restriction of dietary fat intake, cessation of alcohol intake and increased exercise. Contributing metabolic disorders should be controlled and aggravating medications withdrawn or reduced where possible. Moderate hypertriglyceridaemia may be treated with high doses of omega-3 fatty acids (4 g/day), fibrates, niacin or statins. Fibrates are the agents of choice in severe hypertriglyceridaemia.Keywords: triglycerides; pancreatitis; fibrates; lipoprotein lipase; eruptive xanthomat

Feasibility of the MELD score as a screening tool for pharmacists to identify patients with impaired hepatic function at hospital admission

WHAT IS KNOWN AND OBJECTIVE Hepatic impairment (HI) is a known risk factor for drug safety. The MELD score (Model-for-endstage-liver-disease), calculated from serum creatinine, bilirubin and International Normalized Ratio (INR), is a promising screening tool corresponding to Child-Pugh Score (CPS) for drug adjustment. We tested the feasibility of MELD as an automatic screening tool accounting for correct calculation, interfering factors (IF) and detection of patients corresponding to CPS-B/C potentially requiring drug adjustment. METHODS We retrospectively calculated MELD for a 3-month cohort of surgical patients and assessed need for adjustment of MELD parameters to standard values. IF for INR (oral anticoagulants) and serum creatinine (renal insufficiency (RI; eGFR\textless60~ml/min/1.73m²); as well as drugs elevating creatinine levels (DECL)) and the number of patients with MELD scores corresponding to CPS-B/C were analysed. For MELD \geq7.5, liver and bile diagnoses were recorded. RESULTS AND DISCUSSION Of 1183 patients, MELD was calculable for 761 (64%; median 7.5, range 6.4-36.8). Parameters had to be adjusted for 690 (91%) patients. IF of parameters were RI in 172 (23%), INR-elevating drugs in 105 (14%) and DECL in 33 (4%) patients. Of 335 (44%) patients with MELD \geq7.5, 122 (36%) had documented liver or bile diagnoses. MELD 10-\textless15 (corresponding to CPS-B) was found for 105 (14%), MELD \geq15 (corresponding to CPS-C) for 66 (9%) of the 761 patients with a calculated MELD. Referred to all patients, drug adjustments due to possible HI were recommendable for 14% of patients with suspected CPS-B/C. WHAT IS NEW AND CONCLUSION MELD is a feasible screening tool for HI as a risk factor for drug safety at hospital admission when appropriately considering correct parameter adjustment and RI and INR-elevating drugs as IF. Further evaluation of sensitivity and specificity is needed

Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats

BACKGROUND: Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats. METHODS: Male SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits. RESULTS: The marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance. CONCLUSION: The results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience

Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes

Management of dyslipidemias with fibrates, alone and in combination with statins: role of delayed-release fenofibric acid

Cardiovascular disease (CVD) represents the leading cause of mortality worldwide. Lifestyle modifications, along with low-density lipoprotein cholesterol (LDL-C) reduction, remain the highest priorities in CVD risk management. Among lipid-lowering agents, statins are most effective in LDL-C reduction and have demonstrated incremental benefits in CVD risk reduction. However, in light of the residual CVD risk, even after LDL-C targets are achieved, there is an unmet clinical need for additional measures. Fibrates are well known for their beneficial effects in triglycerides, high-density lipoprotein cholesterol (HDL-C), and LDL-C subspecies modulation. Fenofibrate is the most commonly used fibric acid derivative, exerts beneficial effects in several lipid and nonlipid parameters, and is considered the most suitable fibrate to combine with a statin. However, in clinical practice this combination raises concerns about safety. ABT-335 (fenofibric acid, Trilipix®) is the newest formulation designed to overcome the drawbacks of older fibrates, particularly in terms of pharmacokinetic properties. It has been extensively evaluated both as monotherapy and in combination with atorvastatin, rosuvastatin, and simvastatin in a large number of patients with mixed dyslipidemia for up to 2 years and appears to be a safe and effective option in the management of dyslipidemia

Innovative Lipid Biomarkers and Long-Term Outcomes:studies in patients treated with renal replacement therapy and in the general population

Cardiovascular disease is the leading cause of mortality in the developed world. Atherosclerosis, the main driving factor behind cardiovascular disease, is largely influenced by lipids. Patients with a decreased kidney function, such as dialysis patients or patients who have undergone a kidney transplantation are at a particularly high risk of cardiovascular disease. Furthermore, they can develop atherosclerotic lesions in the (transplanted) kidney, leading to further function decline and eventually kidney failure. Low density lipoproteins (LDL), the ‘bad’ cholesterol, and triglycerides promote the formation of atherosclerotic plaques. High density lipoprotein (HDL), the ‘good’ cholesterol is able to break down atherosclerosis and thereby lowers the risk of cardiovascular disease. In this thesis this process was evaluated in dialysis patients, which showed that they have a decreased ability of HDL to perform this protective effect. Furthermore, a novel protective effect of HDL was described, namely the ability to lower inflammation. This protective effect indeed leads to a lower risk of cardiovascular disease in the general population. A different way of describing lipid abnormalities, by using a ratio of triglycerides to the HDL, is better at identifying patients who are at risk of cardiovascular disease of kidney disease. Furthermore, a risk score developed for cardiovascular disease is also able to predict kidney disease, which lends evidence to the fact that both processes are driven by atherosclerosis. In conclusion, this thesis identified novel biomarkers for atherosclerosis and shows how important close attention to lipid control is in both kidney disease patients and the general population

2015 Korean Guidelines for the Management of Dyslipidemia: Executive Summary (English Translation)

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