PCSK9 in diabetic kidney disease

Chronic Kidney Disease (CKD) and, specifically, diabetic kidney disease (DKD)+, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches, since protection offered by statins in CKD patients is not satisfactory. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) promotes hypercholesterolemia and may be targeted therapeutically. Adding anti-PCSK9 agents to standard lipid lowering therapy further reduces the incidence of cardiovascular events.

We studied plasma PCSK9 in a cross-sectional study of 134 diabetic kidney disease patients with estimated glomerular filtration rate (eGFR) categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma PCSK9 in this population.

Mean±SD plasma PCSK9 levels were 309.8±113.9 ng/ml. Plasma PCSK9 was not influenced by eGFR or albuminuria, but was higher in patients on lipid lowering therapy. In univariate analysis, plasma PCSK9 showed a significant positive correlation with serum total iron binding capacity, vitamin E, plasma renin and phosphaturia, and there was a trend towards a positive correlation with total serum cholesterol. In multivariate models, only therapy with fibrate and statin, and renin remained independently correlated with plasma PCSK9. However, multivariate models explained very little of the PCSK9 variability.

In DKD, therapy with lipid lowering drugs and specially the fibrate/statin combination were independently associated with higher PCSK9 levels. The biomarker potential of PCSK9 levels to identify DKD patients that may benefit from anti-PCSK9 strategies should be studied.