P0449SERUM PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) IN NON-DIABETIC ASIANS WITH NEPHROTIC SYNDROME

Background and Aims Nephrotic syndrome is associated with hypercholesterolemia, while its treatment, often involving high-dose glucocorticosteroids, may cause hyperglycemia. Proprotein convertase subtilisin /kexin type 9 (PCSK9) regulates plasma cholesterol and is associated with post-transplant diabetes. Although a potential therapeutic target in nephrotic syndrome, the relationships between PCSK9 and lipid parameters are not well established. We aimed to characterize serum PCSK9 and metabolic parameters among individuals with nephrotic syndrome. Method Single-center prospective cohort study of non-diabetic adults newly-diagnosed with nephrotic syndrome and subsequently treated with immunosuppressant. Fasting serum PCSK9 was measured using ELISA at diagnosis. Clinical history, blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) and biochemistry (fasting glucose and lipid, HbA1c and fasting serum PCSK9) were obtained at diagnosis and at 3 months during immunosuppression therapy. Spearman’s correlation was used to evaluate for associations between PCSK9 and glycemic and lipid parameters. Results Among 15 adults with nephrotic syndrome, the majority was female (60%) and Chinese (80%). Median age was 40 (IQR 26, 51) years. The most frequent diagnoses were minimal change disease or focal segmental nephrosclerosis (n=7) and lupus nephritis (n=5); the minority had IgA nephropathy, membranous nephropathy or vasculitis. At diagnosis, median eGFR was 97.9 (59.5, 120.9) ml/min/1.73 m2, UPCR 7.6 (6.1, 10.4) g/g, LDL-cholesterol 4.6 (3.1, 6.7) mmol/L and fasting serum PCSK9 317.6 (276.8, 470.1) ng/ml. PCSK9 correlated positively with hypertriglyceridemia (r=0.55, p=0.03) at baseline. Most patients (n=14, 93%) were treated with prednisolone (monotherapy or in combination with other immunosuppressant) and 1 received tacrolimus monotherapy. At 3 months, the majority (n= 11, 73%) had achieved clinical remission. Fasting serum PCSK9 was higher at 3 months [median 430.6 (283.1, 496.0) ng/ml] compared to baseline, although the difference was not statistically significant. At 3 months, PCSK9 correlated positively with age (r=0.58, p=0.03), LDL-cholesterol (r=0.90, p=0.04) and change in BMI (r=0.72, p=0.01). Conclusion PCSK9 is associated with metabolic parameters at diagnosis and during the treatment course in patients with nephrotic syndrome treated with immunosuppressant.