Study
n
Age (years)
Cholesterol > 200 mg/dL (%)
LDL > 100 mg/dL (%)
HDL < 40 mg/dL (%)
TG mean (mg/dL)
Moore et al. [26]
214
44.7
90
97
48
195
Aakhus et al. [27]
403
47
94
18
Brown et al. [28]
100
41.8
83
93
30
163
Etiology of Dyslipidemia in Kidney Transplant Recipients
Many factors influence the prevalence of dyslipidemias in transplant patients.
Potential causes include immunosuppressive medications, diet, obesity, and genetic predisposition.
Some of the primary and secondary causes are summarized below [6, 7]:
1.
Male gender
2.
Genetic predisposition
3.
Increased age
4.
Proteinuria, nephritic syndrome, and hypoalbuminemia
5.
Kidney dysfunction
(a)
Renin–angiotensin system activity
(b)
Abnormal calcium and phosphorus metabolism
(c)
Renal artery stenosis
6.
Immunosuppressive agents
(a)
Calcineurin inhibitors (cyclosporine, tacrolimus)
(b)
Antiproliferative agents (sirolimus)
(c)
Corticosteroids
7.
Other medications like atypical antipsychotics, oral estrogen, protease inhibitors, diuretics, and beta-blockers
8.
Hypothyroidism
9.
Diabetes
10.
Excessive alcohol intake
11.
Chronic liver disease
Immunosuppressive medications, e.g., prednisone, cyclosporine, and sirolimus, are among the several potential remediable causes of dyslipidemias in kidney transplant patients.
Calcineurin Inhibitors
These medications may produce alterations in lipid profile, as early as 1 month within start of therapy. Cyclosporine may have a higher tendency to cause dyslipidemia than tacrolimus. It inhibits the 26-hydroxylase enzyme, leading to a decrease in bile acid synthesis from cholesterol.
Antiproliferative Agents
Mammalian target of rapamycin (mTOR) inhibitors like sirolimus produce dose-dependent significant increases in total cholesterol and triglyceride levels by various mechanisms. They decrease the catabolism of apolipoprotein B100, inhibit insulin and insulin-like growth factor signals, and/or alter hepatocyte synthesis of lipid moieties.
Corticosteroids
These agents induce increases in total cholesterol with variable effects on triglycerides. They increase the activity of acetyl coenzyme A carboxylase and free fatty acid synthetase, downregulate LDL receptor activity, increase the activity of HMG-CoA reductase, and inhibit lipoprotein lipase. They have been associated with increased levels of very low-density lipoproteins (VLDL), total cholesterol (TC), and triglycerides (TG), as well as a decrease in HDL (high-density lipoproteins) levels. In combination with other agents like cyclosporine, these may have additive effects.
Mycophenolic acid and azathioprine These agents do not appear to adversely affect the lipid profile.
Transplantation may be associated with other nontraditional CVD risk factors such as acute rejection episodes which cause endothelial damage and require intensification of immunosuppressive regimens.
Assessment of Dyslipidemia
Kidney transplant patients with dyslipidemia require an individualized approach to screening and management, compared to the general population. Recipients should be monitored for development or worsening of already existing hyperlipidemia that may worsen after transplantation. The evaluation should include an assessment for secondary causes as well.
Screening
Target Population
Frequency of Screening
Traditional guidelines were to screen patients prior to transplant and within the first 6 months of kidney transplantation, at 1-year post-transplant, and at least annually thereafter [4]. The more recent 2013 KDIGO guidelines recommend the initial screening in kidney transplantation, however, follow-up measurement may not be required in the majority of patients [8A]. Any modification in therapy or development of a condition which may be associated with dyslipidemia should prompt more frequent testing, starting within 2–3 months of the intervention or status change.
Screening Method
A complete lipid panel after an overnight fast is the preferred method of screening [4]. The panel should include total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglyceride (TG) levels. Non-HDL cholesterol (calculated as TC minus HDL cholesterol) should also be taken into account.
Treatment
The 2009 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines are based on the 2004 NKF K/DOQI guidelines for managing dyslipidemias in CKD and provide guidance for managing dyslipidemias in renal transplant patients [4, 8]. KDIGO updated their clinical practice guidelines for lipid management in chronic kidney disease in 2013 [8A]. As in general population, controlling the risk factors leading to CVD should be a major component of post-transplant management strategy.
Treatment Goals
The KDIGO and K/DOQI guidelines [4, 8] consider kidney transplant recipients a high-risk group who should be treated like a CVD risk equivalent, unlike the US National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines [9]. By the traditional ‘treat-to-target’ approach, goals of dyslipidemia treatment were to lower LDL, non-HDL, and triglyceride levels while improving HDL level. Based on traditional recommendations, these were the target goals:
Statin | Recommended dose (mg/day) |
|---|---|
Lovastatin | Not done |
Fluvastatin | 80 mg |
Atorvastatin | 20 mg |
Rosuvastatin | 10 mg |
Simvastatin/Ezetmibe | 20 /10 mg |
Pravastatin | 40 mg |
Simvastatin | 40 mg |
Pitavastatin | 2 mg |
LDL cholesterol <100 mg/dL
Non-HDL cholesterol <130 mg/dL
TG <150 mg/dL
However, 2013 KDIGO recommendations revised this approach and suggest a ‘fire-and-forget’ strategy: do not measure LDL unless the results will alter management.
Treatment Strategies
All patients should be counseled about therapeutic lifestyle changes (TLC), which include diet, weight loss, increased physical activity, abstinence from alcohol, and treatment of hyperglycemia, if appropriate. Diet should include <200 mg/day cholesterol, <7 % saturated fat, and increased fiber (10–25 mg/day). Any secondary causes of dyslipidemia should be identified and addressed, if feasible. For example, reducing or eliminating nephritic range proteinuria and treating poorly controlled diabetes or severe hypothyroidism may help with dyslipidemia [8]. Pharmacotherapy plays a major role in the treatment of dyslipidemia, with statins being used the most commonly, based on strong evidence that they reduce LDL cholesterol and cardiovascular events [11]. The 2013 KDIGO Work Group recommends treatment with a statin [8A]. Other agents used include fibrates (fibric acid derivatives), niacin (nicotinic acid), ezetimibe, and bile acid sequestrants. Table 19.3 summarizes the agents used [6].
Medication class/generic name | Typical dosing regimen | Dosing instructions | Major adverse events/drug–drug interactions |
|---|---|---|---|
Statins (HMG-CoA reductase inhibitors) | |||
Atorvastatin | 10–80 mg/day | Given any time of the day | Headache, nausea, sleep disturbance, elevations in hepatocellular enzymes and alkaline phosphatase. Myositis and rhabdomyolysis, primarily when given with gemfibrozil or cyclosporine; myositis is also seen with severe renal insufficiency (CrCl < 30 mL/min). Most statins can also affect digoxin metabolism and levels |
Fluvastatin
Related posts: Live Donor Transplantation
Psychosocial Issues in Renal Transplantation
 The Prevention and Treatment of Coronary Artery Disease in Kidney Transplant Recipients
 Recurrent and De Novo Diseases After Renal Transplantation
 Urologic Issues in the Renal Transplant Patient
 Immunological Assessment of the Transplant Patient
 Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
| |||