Bone Morphogenetic Proteins (BMPs), Extracellular Matrix Metalloproteinases Inducer (EMMPRIN), and Macrophage Migration Inhibitory Factor (MIF): Usefulness in the Assessment of Tubular Dysfunction Related to Chronic Kidney Disease (CKD)

Abstract

Bone morphogenetic proteins (BMP), extracellular matrix metalloproteinases inducer (EMMPRIN), and macrophage migration inhibitory factor (MIF) are known to be closely connected to renal tubule damage by experimental data; however, this has not been analyzed in children with chronic kidney disease (CKD). The aim of this study was to determine their usefulness in the assessment of CKD-related tubular dysfunction. The study group consisted of 61 children with CKD stages 1–5 and 23 controls. The serum and urine concentrations of BMP-2, BMP-6, EMMPRIN, and MIF were assessed by ELISA and their fractional excretion (FE) was calculated. The serum and urine concentrations of BMP-2, BMP-6, EMMPRIN, and MIF were significantly elevated in children with CKD vs. controls. The FE of BMP-2, FE BMP-6, and EMMPRIN increased significantly in CKD stages 1–2, but exceeded 1% in CKD stages 3–5. FE MIF became higher than in controls no sooner than in CKD 3–5, but remained below 1%. The FE values for BMP-2, BMP-6, and EMMPRIN of <1% may result from the tubular adaptive mechanisms, whereas those surpassing 1% suggest irreversible tubular damage. The analysis of serum/urinary concentrations and fractional excretion of examined parameters may allow the assessment of CKD-related tubular dysfunction.