Gene Expression in Urinary Sediment Cells as an Indicator of the Contribution of Plasma Lipids to Diabetic Kidney Disease.

BACKGROUND

In individuals with Type 1 diabetes mellitus (T1D) who maintain good glycemic control and are free of chronic complications, lipid profiles are generally within normal ranges. However, impaired renal function or albuminuria alters this profile, contributing to the progression of diabetic kidney disease (DKD). This study hypothesized that, in urinary sediment cells from T1D individuals (n = 87), the mRNA expression of genes related to free fatty acid (FFA) uptake (CD36, FABP1, SCL27A1, SLC27A2, and SLC27A4, which encode FATP1, FATP2, and FATP4, respectively), albumin uptake (LRP2 and CUBN), inflammation (IL1B and IL18), and fibrosis (TGFB1) would vary depending on the degree of renal function decline and of urinary albumin excretion (UAE) and correlate with each other and with plasma lipid concentrations.

RESULTS

CD36 expression was higher in urinary sediment cells of individuals with relevant renal function decline compared to those without relevant decline. CD36, IL1B, TGFB1, and SLC27A4 (at the limit of statistical significance) expressions were higher in individuals with UAE > 11 mg/g versus UAE ≤ 11 mg/g creatinine (cohort median value). CD36 expression positively correlated with IL1B (r = 0.46) and TGFB1 (r = 0.45) expressions, and LRP2 expression positively correlated with IL18 (r = 0.44) and TGFB1 (r = 0.30). Expression of SLC27A genes also correlated with inflammatory and profibrotic genes. Plasma FFA concentrations positively correlated with CD36 (r = 0.27) and IL1B (r = 0.30) expressions, while plasma triglyceride (TG) concentrations positively correlated with CD36 (r = 0.22) and negatively correlated with FABP1 (r = -0.28) expressions. Urinary sediment gene expression was modulated by statin (IL18) and angiotensin II receptor blockers (LRP2, CUBN, and FABP1) use.

CONCLUSIONS

The expression of lipid metabolism-related genes in urinary sediment cells, correlated with proinflammatory and profibrotic genes, as well as with plasma FFA and TG, and associated with clinical indicators of renal function, provides indirect evidence for the involvement of lipids in the pathogenesis of DKD.