Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the risk of chronic kidney disease progression in patients with type 2 diabetes.

Aims: Preclinical studies have associated proprotein convertase subtilisin/kexin type 9 (PCSK9) with the pathogenesis of kidney disease. We aim to study whether plasma PCSK9 predicts the risk of chronic kidney disease (CKD) progression in patients with type 2 diabetes.

Materials and methods: A total of 1902 outpatients with type 2 diabetes from a regional hospital and a primary care facility were included in this prospective study. Baseline plasma PCSK9 was measured by immunoassay. CKD progression was defined as a composite of incident end stage kidney disease (ESKD, sustained eGFR < 15 mL/min/1.73 m², maintenance dialysis or renal death) or doubling of serum creatinine.

Results: A total of 226 renal events were identified during a median of 7.2 years of follow-up. The Cox regression model showed that one standard deviation (SD) increment of plasma PCSK9 was associated with a 1.27 (95% CI 1.10-1.48) fold increased risk for the composite renal outcome after adjustment for known cardio-renal risk factors. As a categorical variable, participants with PCSK9 in the top tertile had a 1.47 (95% CI 1.02-2.12) fold adjusted risk for the renal outcome compared to those in the lowest tertile. Consistent data were obtained when ESKD was taken as the study outcome or non-renal death was taken as a competing risk.

Conclusion: A high level of plasma PCSK9 is independently associated with an increased risk of CKD progression, suggesting the need to further elucidate the role of PCSK9 in diabetic kidney disease. Future studies are warranted to explore whether PCSK9 is a potential target for prevention and treatment of kidney disease.