Effective cholesterol lowering aftermyocardial infarction in patients with nephrotic syndrome may require amulti-pharmacological approach: A case report

Background Nephrotic syndrome causes severe hypercholesterolaemia due to increased production and altered clearance of lipoproteins from the liver. It is challenging for patients with nephrotic syndrome and coronary heart disease to meet LDL-cholesterol (LDL-C) goals for secondary prevention with conventional lipid-lowering therapy. Case summary We present a man with nephrotic syndrome caused by focal segmental glomerular sclerosis (FSGS) and hypercholesterolaemia. He presented at the emergency room (ER) with an ST-elevation myocardial infarction at the age of 26. On follow-up, the patient had persistent hypercholesterolaemia [LDL-C 3.9 mmol/L and lipoprotein(a) 308 nmol/L] despite a combination of lipid-lowering therapy with atorvastatin 80 mg/day and ezetimibe 10 mg/ day. Addition of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory antibody evolocumab 140 mg bi-monthly did not improve cholesterol levels. However, after addition of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin 10 mg/day on top of other anti-proteinuric treatments, the patient's proteinuria was reduced and a dramatic drop in LDL-C level by 3.2-0.6 mmol/L (-81%) was observed when evolocumab was re-introduced. Discussion We show that target LDL-C levels were obtained in this patient with therapy-resistant FSGS and hypercholesterolaemia following multi-pharmacological treatment with SGLT2 and PCSK9 inhibitors on top of conventional lipidlowering therapy. The SGLT2-inhibitor reduced proteinuria and, speculatively, also reduced urinary loss of PCSK9- antibody. Therefore, in patients with nephrotic syndrome and cardiovascular disease novel therapeutic options to manage proteinuria could be considered to improve the efficacy of the lipid-lowering therapy, especially when the protein-based PCSK9 inhibitors are used.

Sjuls S.1 , Littmann K. 1, 3 , Brinck J. 1, 3 , Jensen U.2 , Bruchfeld A.4, 5
European Society of Cardiology
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  • 1 Department of Endocrinology|Karolinska University Hospital Huddinge
  • 2 Department of Medicine H7|Karolinska Institutet
  • 3 Department of Cardiology
  • 4 Department of Health|Medicine and Caring Sciences|Linköping University
  • 5 Department of Renal Medicine|Karolinska University Hospital and CLINTEC Karolinska Institute
Ключевые слова
case report; evolocumab; Hypercholesterolaemia; nephrotic syndrome; Pcsk9; SGLT2
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