Department 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.
Department of Clinical Nutrition Science, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan.
J Diabetes Complications. 2022 Nov;36(11):108312. doi: 10.1016/j.jdiacomp.2022.108312. Epub 2022 Sep 24.
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).
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.
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 m/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was -1.888 ml/min/1.73 m/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, α-microglobulin, β-microglobulin, and N-acetyl-β-d-glucosaminidase).
Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.
巨胞饮受体（megalin）是一种近曲小管内吞受体，其可通过两种形式分泌至尿液中：胞外结构域（A-megalin）和全长型（C-megalin）。本研究旨在探索尿 megalin 水平能否作为糖尿病肾病（DKD）进展的独立预后生物标志物。
采用广义估计方程分析基线尿 A-megalin/肌酐（Cr）和/或 C-megalin/Cr 水平与随后估算肾小球滤过率（eGFR）斜率之间的相关性。根据受试者工作特征曲线获得的最佳截断值，将患者分为尿中两种形式 megalin 水平较高或较低的两组。
本研究回顾性分析了 188 例 2 型糖尿病患者。与较低组相比，较高 A-megalin/Cr 组和较高 C-megalin/Cr 组的 eGFR 斜率分别为-0.904 和-0.749 ml/min/1.73 m/年，且 A-和 C-megalin/Cr 均较高组的 eGFR 斜率更陡（-1.888 ml/min/1.73 m/年）。校正已知尿生物标志物（白蛋白、α-微球蛋白、β-微球蛋白和 N-乙酰-β-D-氨基葡萄糖苷酶）后，这些结果仍具有统计学意义。
尿 A-megalin 和 C-megalin/Cr 水平可能是 DKD 进展的独立预后生物标志物，优于其他尿生物标志物。
