Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report

Kido, Kazuhiko; Evans, Rickey A.; Gopinath, Anil; Flynn, Jeremy D.

doi:10.1177/0897190017692920

Cited by 11 publications

(12 citation statements)

References 10 publications

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“…44 Severe hypertriglyceridemia with the use of mTOR inhibitors has been reported. 45,46 Clinical trials comparing mTOR inhibitors with CNIs have also shown that mTOR inhibitors are associated with higher levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), and total cholesterol. [47][48][49] It remains unclear if mTOR inhibitor-induced hypertriglyceridemia is directly related to exposure (area under curve) or drug trough levels; however, regardless of this controversy, transplant recipients are at an increased risk of hypertriglyceridemia with mTOR inhibitors.…”

Section: Hypertriglyceridemia In Ktrsmentioning

confidence: 99%

New Approaches to Cardiovascular Disease and Its Management in Kidney Transplant Recipients

et al. 2022

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Cardiovascular events, including ischemic heart disease, heart failure, and arrhythmia, are common complications after kidney transplantation and continue to be leading causes of graft loss. Kidney transplant recipients have both traditional and transplant-specific risk factors for cardiovascular disease. In the general population, modification of cardiovascular risk factors is the best strategy to reduce cardiovascular events; however, studies evaluating the impact of risk modification strategies on cardiovascular outcomes among kidney transplant recipients are limited. Furthermore, there is only minimal guidance on appropriate cardiovascular screening and monitoring in this unique patient population. This review focuses on the limited scientific evidence that addresses cardiovascular events in kidney transplant recipients. Additionally, we focus on clinical management of specific cardiovascular entities that are more prevalent among kidney transplant recipients (ie, pulmonary hypertension, valvular diseases, diastolic dysfunction) and the use of newer evolving drug classes for treatment of heart failure within this cohort of patients. We note that there are no consensus documents describing optimal diagnostic, monitoring, or management strategies to reduce cardiovascular events after kidney transplantation; however, we outline quality initiatives and research recommendations for the assessment and management of cardiovascular-specific risk factors that could improve outcomes.

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Section: Hypertriglyceridemia In Ktrsmentioning

confidence: 99%

New Approaches to Cardiovascular Disease and Its Management in Kidney Transplant Recipients

et al. 2022

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“…Expert opinion and anecdotal case reports provide hints on how to proceed [22]. Kido et al reported on a pharmacological approach in an index patient without signs of hyperviscosity syndrome [32]. Furthermore triglyceride levels were lower (4425 mg/dl).…”

Section: Discussionmentioning

confidence: 99%

Sirolimus-Induced Severe Hypertriglyceridemia Presenting with Signs of Hyperviscosity Syndrome and as Pink Colored Blood: A Case Report

2022

Ann Case Report

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Background: Inhibitors of the mammalian target of rapamycin have proven as potent immunosuppressive drugs effective in prevention of graft-versus-host-disease (GvHD). However severe disturbances of lipid metabolism are possible with the risk of developing hypertriglyceridemia-induced hyperviscosity syndrome. Clinical experience in the management of this potentially life-threatening complication is limited. Case presentation: We report a case of a patient with myelodysplastic syndrome complicated by chronic GvHD after allogeneic hematopoietic stem cell transplantation on second line sirolimus maintenance therapy while developing hyperviscosity syndrome due to severe hypertriglyceridemia of 138mmol/l presenting as pink colored blood. Plasmapheresis was initiated alongside fenofibrates to lower triglycerides. Importantly only serial therapeutic intervention with daily plasmapheresis over five days resulted in persistent therapeutic success. Triglyceride levels dropped to 7.02 mmol/l on day 8 after admission. Conclusions: The index case is notable due to symptomatic sirolimus-induced excessive hypertriglyceridemia with signs of hyperviscosity syndrome. Furthermore, we provide evidence that only after repeated plasma exchanges a satisfying decrease of lipid levels is achieved.

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“…The effect of cyclosporine on triglyceride levels is relatively mild, increasing by 50 mg/dl in one study (103), but triglyceride levels were >400 mg/dl in 14% to 25% of patients with sirolimus in one report of renal transplant recipients (104) and in another in 28% of sirolimus and 35% of everolimus treated patients (105). Both sirolimus and everolimus have been associated with the development of severe HTG (106,107). These agents increase APOC3 levels and inhibit LPL (108,109).…”

Section: Immunosuppressive Agentsmentioning

confidence: 97%

A Comprehensive Update on the Chylomicronemia Syndrome

Goldberg

Chait

2020

Front. Endocrinol.

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The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When due to very rare monogenic mutations in the genes encoding the enzyme, lipoprotein lipase, or its regulators, APOC2, APOA5, GPIHBP1, and LMF1, it is referred to as the familial chylomicronemia syndrome. Much more frequently, the chylomicronemia syndrome results from a cluster of minor genetic variants causing polygenic hypertriglyceridemia, which is exacerbated by conditions or medications which increase triglyceride levels beyond the saturation point of triglyceride removal systems. This situation is termed the multifactorial chylomicronemia syndrome. These aggravating factors include common conditions such as uncontrolled diabetes, overweight and obesity, alcohol excess, chronic kidney disease and pregnancy and several medications, including diuretics, non-selective beta blockers, estrogenic compounds, corticosteroids, protease inhibitors, immunosuppressives, antipsychotics, antidepressants, retinoids, L-asparaginase, and propofol. A third uncommon cause of the chylomicronemia syndrome is familial forms of partial lipodystrophy. Development of pancreatitis is the most feared complication of the chylomicronemia syndrome, but the risk of cardiovascular disease as well as non-alcoholic steatohepatitis is also increased. Treatment consists of dietary fat restriction and weight reduction combined with the use of triglyceride lowering medications such as fibrates, omega 3 fatty acids and niacin. Effective management of aggravating factors such as improving diabetes control, discontinuing alcohol and replacing or reducing the dose of medications that raise triglyceride levels is essential. Importantly, many if not most cases of the chylomicronemia syndrome can be prevented by effective identification of polygenic hypertriglyceridemia in people with conditions that increase its likelihood or before starting medications that may increase triglyceride levels. Several new pharmacotherapeutic agents are being tested that are likely to considerably improve treatment of hypertriglyceridemia in people at risk.

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Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report

Abstract: Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.

Cited by 11 publications

References 10 publications

New Approaches to Cardiovascular Disease and Its Management in Kidney Transplant Recipients

New Approaches to Cardiovascular Disease and Its Management in Kidney Transplant Recipients

Sirolimus-Induced Severe Hypertriglyceridemia Presenting with Signs of Hyperviscosity Syndrome and as Pink Colored Blood: A Case Report

A Comprehensive Update on the Chylomicronemia Syndrome

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