Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Sci Rep. 2024 Jun 5;14(1):12901. doi: 10.1038/s41598-024-62246-1.
Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of - 0.9, + 1906, - 7.1, - 38.3, - 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: - 1.1, - 2.3, - 0.7, - 1.6 and - 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.
早期肾损伤可通过尿标志物检测出来，如β-2 微球蛋白 (B2M)、金属蛋白酶组织抑制剂-2 (TIMP-2)、胰岛素样生长因子结合蛋白 7 (IGFBP7)、肾损伤分子-1 (KIM-1) 和/或中性粒细胞明胶酶相关脂质运载蛋白 (NGAL)。然而，这些生物标志物的信息在健康和患病人群中的病理生理学和参考范围都很匮乏。在 REnal Protection Against Ischaemia-Reperfusion in transplantation 研究中，我们比较了 38 位活体供肾者在肾切除术前 24 小时和术后 24 小时的尿 B2M、TIMP-2、IGFBP7、KIM-1 和 NGAL 水平。线性回归用于评估肾切除术后 1 年时基线生物标志物浓度与肾功能之间的关系。供者肾切除术前 24 小时尿肌酐和肌酐标准化 B2M、TIMP-2、IGFBP7、KIM-1、NGAL 和白蛋白的中位数水平分别为 9.4mmol/L、14μg/mmol、16pmol/mmol、99pmol/mmol、63ng/mmol、1390ng/mmol 和 0.7mg/mmol，术后 24 小时分别降低了 -0.9、+1906、-7.1、-38.3、-6.9、+2378 和 +1.2。在基线时，B2M、TIMP-2、IGFBP7、KIM-1 和 NGAL 的每标准差增加，供者 eGFR 在 12 个月后的变化分别为 -1.1、-2.3、-0.7、-1.6 和 -2.8。尿 TIMP-2 和 IGFBP7 的排泄在肾切除术后减半，与尿肌酐相似，提示这些标志物主要反映肾小球滤过。B2M 和 NGAL 的排泄显著增加，与白蛋白相似，表明肾切除术后近端肾小管重吸收减少。肾切除术后 KIM-1 变化不大。尽管这些生物标志物均与供者长期 eGFR 无强相关性，但这些结果为这些尿生物标志物的病理生理学提供了有价值的见解。
