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

J Diabetes Complications. 2022 Nov;36(11):108312. doi: 10.1016/j.jdiacomp.2022.108312. Epub 2022 Sep 24.

Abstract

Aims: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) 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, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase).

Conclusions: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

Keywords: Diabetic kidney disease; Estimated glomerular filtration rate; Megalin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / urine
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / urine
  • Diabetic Nephropathies* / diagnosis
  • Disease Progression
  • Glomerular Filtration Rate
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Retrospective Studies

Substances

  • Low Density Lipoprotein Receptor-Related Protein-2
  • Biomarkers