Urinary A- and C-megalin predict progression of diabetic kidney disease: an exploratory retrospective cohort study

Aims: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (Amegalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD).Methods: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin.Results: We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/ Cr and higher C-megalin/Cr groups were - 0.904 and -0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was -1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, alpha 1-microglobulin, beta 2-microglobulin, and N-acetyl-beta-Dglucosaminidase).Conclusions: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.