Chronic Kidney Disease Complicated With Hypertriglyceridemia, The Latest Treatment Progress Inventory

For a long time, cardiovascular disease (CVD) has been the leading cause of death in chronic kidney disease (CKD), and hypertriglyceridemia (HTG) is the most common CKD dyslipidemia closely related to the residual risk of CVD. However, China still lacks a consensus on the management of CKD-HTG. What new knowledge needs to be mastered on CKD-HTG[1]?

What are the current problems in the management of CKD-HTG?

Chinese statistics show that the prevalence rates of dyslipidemia, HTG, and hypercholesterolemia among residents over the age of 18 are 40.4%, 13.1%, and 4.9%, respectively [2].

Click to cistanche examine for CKD

Among Chinese CKD patients, the probability of dyslipidemia is significantly higher than that of the general population [3]. Patients with CKD typically present with HTG and low HDL, with normal LDL. Among them, HTG is the most important form of dyslipidemia in CKD patients.

Although statins are currently the first-line treatment option for dyslipidemia in CKD patients, the residual risk of HTG-related CVD after treatment is still not low. There is still considerable room for improvement in the clinical intervention and management of CKD-HTG.

What are the hazards of HTG?

In the past, CVD was often thought to be related to the abnormality of low-density lipoproteins. In fact, all lipoproteins with a diameter of<70nm and containing ApoB can pass through the arterial vessel wall, thereby promoting atherosclerosis. These lipoproteins are also called rich in The lipoprotein of TG should be paid attention to clinically.

HTG promotes atherosclerosis and increases the risk of CKD-CVD. At the same time, HTG is associated with a decrease in high-density lipoprotein and an increase in small, dense low-density lipoprotein (referring to a smaller, denser subcomponent of low-density lipoprotein). The reason why CKD patients are prone to HTG is mainly related to the increased synthesis and decreased clearance of TG [5], which leads to the increase of plasma TG in CKD patients in the early stage, and reaches the highest level in the end-stage renal disease stage.

For the kidney, TG deposits in podocytes, mesangial cells, and proximal tubule epithelial cells cause lipid nephrotoxicity, which is reflected in the stimulation of podocyte detachment and apoptosis, mesangial cell proliferation, and glomerulosclerosis. It can be seen that HTG is very harmful to CKD, and the prevention and treatment of CKD-HTG have to be put on the agenda.

HTG Diagnosis and Treatment Collection

According to the "Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China (2016 Revision)", the appropriate level of TG should be<1.7mmol/L on an empty stomach (fasting for more than 12 hours), and an increase should be TG≥2.3mmol/L (Figure 4).

Among them, those with serum TG>2.3mmol/L have an increased risk of atherosclerotic cardiovascular disease (ASCVD). /L should seek multidisciplinary consultation.

For CKD-HTG, the Improving Global Kidney Outcomes Organization (KDIGO) recommended therapeutic lifestyle intervention (TLC) in 2013 [7], namely:

Improve diet: The dietary adjustment principle for CKD patients is to control the total energy and reasonably select the composition ratio of each nutrient on the basis of meeting the daily essential nutritional requirements [8]: control the total energy intake at 25-35kcal/kg; low-fat and low-sugar diet; Mediterranean diet; increase intake of omega-3 unsaturated fatty acids.

Keep moving: Regular moderate-intensity exercise can significantly reduce TG levels. However, according to the different CKD conditions and stages, the exercise program should be adjusted: HTG patients should maintain moderate-intensity aerobic exercise 5 days a week, 45 minutes a day, for at least 8 consecutive weeks; CKD-HTG patients should avoid sitting for a long time. 5 days a week, 30 minutes of aerobic exercise per day; dialysis HTG patients performed simple home-based individualized exercise after evaluating their physical function, such as walking slowly for 20 minutes every 2 days.

Weight control: Non-dialysis patients should aim to reduce body weight by 5%-10%, while dialysis patients are not recommended to reduce weight, but both need to control abdominal obesity.

Limit alcohol consumption: Patients with mild to moderate alcohol consumption do not need to quit alcohol, and patients with no history of alcohol consumption are not recommended to drink alcohol, and long-term excessive alcohol consumption should be avoided.

HTG Drug Therapy Progress Inventory

In addition, drug therapy is also an important part of HTG intervention. It is recommended to use statins as the first line, and it is recommended to use TG-lowering drugs in combination (fibrates, omega-3 fatty acids, niacin, and its derivatives)[9]:

For the currently available fibrates, it is recommended to be used in CKD patients with severely elevated TG (over 11.3mmol/L), and the dosage must be adjusted at any time according to renal function. It is not recommended to use fibrates and statins in CKD patients at the same time: Fibrate drugs mainly reduce serum TG levels and increase high-density lipoprotein levels by activating peroxisome proliferator-activated receptor α (PPARα) and lipoproteins, which can significantly reduce TG by about 38% and TG by 27%-40% CVD risk, but at the same time, the incidence of eGFR decline increases by about 9%, so severe renal impairment (including dialysis), active liver disease, etc. are contraindications, and the risk of combining statin myopathy and rhabdomyolysis in patients with renal failure will increase [10].

For CKD patients with high TG after statin therapy or other high cardiovascular risk groups, omega-3 fatty acid drugs combined with statin therapy are recommended to reduce TG levels: omega-3 drugs can activate PPARα and enhance lipoprotein Two pathways of lipase are used to lower lipids, which are not metabolized by the kidneys, and the kidneys are safe. Common adverse reactions are only mild gastrointestinal reactions, which can reduce TG levels in CKD patients by 11%-26%. Low-level evidence confirms that it can reduce the risk of vascular death by 55%. It can also slow down the decline in renal function and reduce proteinuria[11-12 ]. There is no drug-drug interaction between these drugs and statins, nor does it increase their respective adverse reactions.

Niacin drugs have limited research in CKD patients, do not improve renal and cardiovascular outcomes, and have high safety risks. Niacin drugs combined with statins are not recommended for the treatment of HTG in CKD patients.

For special patients, HTG intervention is also different:

Nephrotic syndrome: Currently, statins are the most commonly used drugs for the treatment of nephrotic syndrome with dyslipidemia. Patients with nephrotic syndrome who still have HTG after statin therapy can be treated with gemfibrozil, fenofibrate, or omega-3 drugs. Treatment [13] requires the early intervention of hypercholesterolemia and HTG (positively correlated with the degree of proteinuria), abnormal blood lipids can accelerate the progression of CVD and kidney disease.

Diabetic nephropathy: About 22.3% suffer from HTG at the same time. When TG>5.6mmol/L, TG-lowering drugs (such as omega-3 and fibrates) can be the first choice based on lifestyle intervention to reduce the risk of acute pancreatitis; It is recommended to use fenofibrate alone or in combination with statins to treat patients with diabetic nephropathy stage 3a or earlier to reduce the risk of progressive microvascular events; it is not recommended to use fibrates alone or in combination with statins to treat patients with diabetic nephropathy stage 3b-5 [14].

Non-dialysis patients with CKD stage 4-5: It is recommended to take 2 g/d omega-3 drugs to reduce TG levels; it is not recommended to take fibrates to reduce TG levels.

Dialysis patients with stage 5 CKD: It is recommended to take 1.3g/d~4g/d omega-3 drugs to reduce TG levels.

Kidney transplant patients: For HTG patients who cannot use statins or who are poorly treated by statins, replacement or combination of omega-3 drugs or fibrates should be considered; immunosuppressants have nephrotoxicity, and fibrates include fenofibrate mainly It is mainly excreted by the kidneys, and the interaction with immunosuppressants may lead to deterioration of renal function. The risks and benefits of combined use should be carefully weighed.

Summarize

HTG is the most common disorder of lipid metabolism in CKD patients, which is closely related to residual cardiovascular risk. HTG has toxic effects on glomerular mesangial cells, endothelial cells, podocytes, and renal tubular cells, leading to the onset and progression of CKD, increased CVD, and all-cause death.

Therefore, attention must be paid to HTG treatment. Intervention lifestyle treatment should be given first in the treatment, and triglyceride-lowering treatment should be added on this basis. At present, there are three types of triglyceride-lowering drugs, and the development of new drugs is also on the way.

for more information:ali.ma@wecistanche.com