Lipoprotein(a) in systemic lupus erythematosus is associated with history of proteinuria and reduced renal function

Abstract

Objective Proteinuria is the clinical expression of lupus nephritis and despite recent advances in the therapeutic armamentarium for lupus nephritis, morbidity and mortality rates remain high. Therefore, the identification of factors that predict lupus nephritis is paramount in preventing damage accrual and disease progression. Lipoprotein (a) (Lp[a]) is a primarily genetically inherited plasma lipoprotein with pro-thrombotic and pro-atherosclerotic effects. Elevated Lp(a) has been observed at early stages of renal impairment in the general population and is associated with the development of chronic kidney disease. However, little is known about renal implications of Lp(a) in SLE. Thus, we evaluated Lp(a) and atherosclerotic events, thrombotic events, renal disease, and disease activity in patients with SLE. Methods SLE patients fulfilling the revised American College of Rheumatology (ACR) or SLICC classification criteria with a measurement of Lp(a) were included in the analysis. A cutoff of 125 nmol/L was chosen based on expert opinion. Chi-square test was used to compare the differences between patient characteristics and Lp(a) levels. Logistic regression or linear regression were used, where appropriate, to assess the association between Lp(a) values and the measured outcomes. Results Lp(a) levels from 562 patients were analyzed. There was an association between elevated Lp(a) and a history of proteinuria (OR 1.58, p-value = 0.02). This association remained significant following adjustment for age, sex, race, low C3, and elevated anti-dsDNA (OR = 1.55, p-value = 0.04). There was also an association with eGFR < 60 ( p = 0.02). Patients with elevated Lp(a) had higher physician global activity ( p = 0.01) and erythrocyte sediment rate ( p = 0.03). Conclusion Elevated Lp(a) was associated with proteinuria, independent of known factors associated with lupus proteinuria, as well as reduced eGFR and physician global activity. Our findings highlight the potential role of Lp(a) as a noninvasive biomarker for early renal disease in SLE.