Akimoto T, Kimura T, Watanabe Y, Ishikawa N, Iwazu Y, Saito O, Muto S, Yagisawa T, Kusano E
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Transplant Proc. 2013 Jan-Feb;45(1):134-6. doi: 10.1016/j.transproceed.2012.07.150.
Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long extracellular domain, which can be cleaved and released as a soluble form. However, information regarding the origins and kinetics of soluble serum Klotho remains poorly understood. We evaluated serial changes in serum Klotho levels among living donors before and after retroperitoneoscopic nephrectomy as well as in their renal transplant recipients.
The levels of soluble Klotho in serum obtained from 10 living donors and their renal transplant recipients were determined using a sandwich enzyme-linked immunosorbent assay system.
Serum soluble Klotho was detectable in all subjects. The baseline serum Klotho concentrations in the living donors ranged from 726.4 to 1417.1 pg/mL (median, 909.8 pg/mL; interquartile ranges [IR], 754.8-1132.4), whereas that in the concomitant renal transplant recipients ranged from 397.5 to 1047.2 pg/mL (median, 613.0 pg/mL; IR, 445.9-750.8; P = .003). The levels of soluble serum Klotho measured 5 days after retroperitoneoscopic nephrectomy (median, 619.0 pg/mL; IR, 544.6-688.5; P = .001) were significantly lower than the baseline values. Among the renal transplant recipients, no significant changes in serum Klotho levels were observed during the observation period.
Our data regarding soluble serum Klotho levels obtained from living donors support the idea that the kidneys are a major source of soluble serum Klotho in human subjects without a deterioration of renal function. In recipients, concomitant acute kidney injuries and immunosuppressive protocols might modulate the release of soluble Klotho from the grafts into the circulation.
klotho是一种单次跨膜蛋白，主要在肾脏、甲状旁腺和脑脉络丛中表达，其胞质尾短，胞外区长，可被切割并以可溶性形式释放。然而，关于可溶性血清klotho的来源和动力学的信息仍知之甚少。我们评估了活体供者在腹膜后肾切除术前、术后以及其肾移植受者血清klotho水平的系列变化。
使用夹心酶联免疫吸附测定系统测定从10名活体供者及其肾移植受者获得的血清中可溶性klotho的水平。
所有受试者血清中均可检测到可溶性klotho。活体供者的基线血清klotho浓度范围为726.4至1417.1 pg/mL（中位数，909.8 pg/mL；四分位间距[IR]，754.8 - 1132.4），而同期肾移植受者的基线血清klotho浓度范围为397.5至1047.2 pg/mL（中位数，613.0 pg/mL；IR，445.9 - 750.8；P = 0.003）。腹膜后肾切除术后5天测得的可溶性血清klotho水平（中位数，619.0 pg/mL；IR，544.6 - 688.5；P = 0.001）显著低于基线值。在肾移植受者中，观察期内血清klotho水平未观察到显著变化。
我们从活体供者获得的关于可溶性血清klotho水平的数据支持以下观点，即肾脏是人类受试者中可溶性血清klotho的主要来源，且肾功能无恶化。在受者中，并发的急性肾损伤和免疫抑制方案可能会调节可溶性klotho从移植物释放到循环中的过程。
