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

Tomomichi Iida1, Michihiro Hosojima2, Hideyuki Kabasawa2

  • 1Department of Applied Molecular Medicine, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan; Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan.

Journal of Diabetes and Its Complications
|October 13, 2022
PubMed
Abstract

Insights

Urinary megalin, in both ectodomain (A-megalin) and full-length (C-megalin) forms, shows promise as an independent prognostic biomarker for diabetic kidney disease (DKD) progression.

Area of Science:

  • Nephrology
  • Endocrinology
  • Biomarker Discovery

Background:

  • Diabetic kidney disease (DKD) is a major complication of diabetes.
  • Early and accurate prognostic biomarkers are crucial for managing DKD progression.
  • Megalin, a proximal tubular receptor, is excreted in urine in two forms: A-megalin and C-megalin.

Purpose of the Study:

  • To investigate the potential of urinary megalin levels as independent prognostic biomarkers for DKD progression.
  • To assess the association between urinary A-megalin/creatinine and C-megalin/creatinine levels and the estimated glomerular filtration rate (eGFR) slope.

Main Methods:

  • Retrospective analysis of 188 patients with type 2 diabetes.
  • Generalized estimating equation used to analyze associations between urinary megalin levels and eGFR slope.
  • Patients categorized into higher/lower groups based on ROC curve-derived cutoff values for A-megalin/Cr and C-megalin/Cr.

Main Results:

  • Higher urinary A-megalin/Cr and C-megalin/Cr levels were associated with steeper eGFR decline (-0.904 and -0.749 ml/min/1.73 m²/year, respectively).
  • Combined higher levels of both forms showed a significantly steeper eGFR slope (-1.888 ml/min/1.73 m²/year).
  • These associations remained significant after adjusting for other urinary biomarkers.

Conclusions:

  • Urinary A-megalin/Cr and C-megalin/Cr are potential independent prognostic biomarkers for DKD progression.
  • Megalin levels in urine may offer valuable insights into DKD trajectory beyond traditional biomarkers.
Keywords:
Diabetic kidney diseaseEstimated glomerular filtration rateMegalin

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