Department and Clinic of Pediatric Nephrology, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2020 May;29(5):603-609. doi: 10.17219/acem/121519.
Treatment with cyclosporine A (CsA), a calcineurin inhibitor, is effective in children with difficult idiopathic nephrotic syndrome (INS). Prolonged CsA treatment can result in several adverse effects, the most significant being nephrotoxicity (CsAN). The plasma and urine levels of the proteins annexin V (AnV) and uromodulin (UM) were investigated in order to assess their usefulness as indicators of early-stage CsAN. Uromodulin is considered a distal tubular damage marker. Annnexin V is present in the distal tubules.
To measure AnV in children with INS receiving CsA treatment and to assess the usefulness of this biomarker for monitoring CsAN and as an indicator of changes in the distal tubules of the nephron.
The prospective study included 30 patients with INS and 22 controls. Plasma and urinary AnV levels were measured 3 times: before CsA treatment, and after 6 and 12 months of therapy. The AnV levels were compared to those of UM.
The urinary AnV and UM levels were significantly higher in the INS patients before CsA therapy in comparison to the reference group. A progressive increase of urinary AnV was observed after 6 and 12 months of therapy. Urinary UM only increased after 6 months. No significant correlations were found between plasma and urinary concentrations of the proteins studied.
The increased urinary excretion of AnV in children with INS receiving CsA treatment may suggest its usefulness as an early marker of subclinical CsAN. Annexin V seems to be a more sensitive indicator of tubular damage in the course of CsA therapy than UM, though large, multicenter studies are needed.
环孢素 A(CsA)是一种钙调神经磷酸酶抑制剂,对治疗难治性特发性肾病综合征(INS)儿童有效。长期 CsA 治疗可导致多种不良反应,最显著的是肾毒性(CsAN)。本研究旨在探讨抗钙蛋白 V(AnV)和尿调蛋白(UM)在血浆和尿液中的水平,以评估其作为早期 CsAN 指标的有用性。尿调蛋白被认为是远端肾小管损伤的标志物。AnV 存在于远端肾小管中。
测量接受 CsA 治疗的 INS 儿童的 AnV,并评估该生物标志物对监测 CsAN 的有用性,以及作为肾单位远端小管变化的指标。
前瞻性研究纳入 30 例 INS 患儿和 22 例对照者。分别在 CsA 治疗前、治疗后 6 个月和 12 个月 3 次测量血浆和尿液 AnV 水平。将 AnV 水平与 UM 进行比较。
与对照组相比,CsA 治疗前 INS 患儿的尿 AnV 和 UM 水平显著升高。治疗后 6 个月和 12 个月时,尿 AnV 水平逐渐升高。尿 UM 仅在治疗 6 个月后升高。未发现研究蛋白的血浆和尿液浓度之间存在显著相关性。
接受 CsA 治疗的 INS 儿童尿液中 AnV 的排泄增加,可能提示其作为亚临床 CsAN 的早期标志物有用。与 UM 相比,AnV 似乎是 CsA 治疗过程中肾小管损伤的更敏感指标,但需要进行更大规模、多中心的研究。