Abstract

Peptide receptor radionuclide therapy (PRRT) is a treatment for neuroendocrine tumours (NET). Renal impairment is a known side effect due to kidney fibrosis. We investigated the association between novel specific fibrosis markers and kidney function following PRRT. We included 38 patients who had all finished PRRT. In serum and urine, we analysed levels of three different fibrosis markers, PRO-C6 (type VI collagen formation), PRO-C3 (type III collagen formation) and C3M (type III collagen degradation). We determined kidney function by the ⁵¹Cr-EDTA plasma clearance. We used Wilcoxon rank sum test and Spearman’s rank correlation to evaluate the association between the fibrosis markers and kidney function. We included 38 NET patients, 25 small-intestinal NET, 6 pancreatic NET, 2 pulmonary NET and 5 other types of NET. Median age was 69 years (IQR: 61–73). Median time from last PRRT to inclusion was 8 months (IQR: 3–20). We found significantly increased levels of serum PRO-C6 (p = .007) and urinary PRO-C6 (p = .033) and significantly decreased levels of urinary C3M (p = .035) in patients with impaired kidney function. Further, we observed a negative association between serum PRO-C6 and kidney function (rho = −0.33, p = .04) and a positive association between urinary C3M and kidney function (rho = 0.37, p = .02). We showed an association between the three fibrosis markers, serum PRO-C6, urinary PRO-C6 and urinary C3M and kidney function. These markers may help to improve the understanding of potential pathological tissue turnover and potentially improve monitoring of kidney function after PRRT in NET patients.

摘要

肽受体放射性核素治疗 (PRRT) 是一种治疗神经内分泌肿瘤 (NET) 的方法。肾功能损害是由肾纤维化引起的已知副作用。我们研究了 PRRT 后新型特异性纤维化标志物与肾功能之间的关联。我们纳入了 38 名全部完成 PRRT 的患者。在血清和尿液中，我们分析了三种不同纤维化标志物 PRO-C6（VI 型胶原形成）、PRO-C3（III 型胶原形成）和 C3M（III 型胶原降解）的水平。^{我们通过51}测定肾功能Cr-EDTA 血浆清除率。我们使用 Wilcoxon 秩和检验和 Spearman 秩相关来评估纤维化标志物与肾功能之间的关联。我们纳入了 38 名 NET 患者、25 名小肠 NET、6 名胰腺 NET、2 名肺 NET 和 5 名其他类型的 NET。中位年龄为 69 岁（IQR：61-73）。从最后一次 PRRT 到纳入的中位时间为 8 个月（IQR：3-20）。 我们发现肾功能受损患者的血清 PRO-C6 ( p  = .007) 和尿 PRO-C6 ( p  = .033) 水平显着升高，尿 C3M ( p = .035) 水平显着降低。此外，我们观察到血清 PRO-C6 与肾功能呈负相关（rho = -0.33，p = .04），尿 C3M 与肾功能呈正相关（rho = 0.37，p  = .02）。我们显示了三种纤维化标志物血清 PRO-C6、尿 PRO-C6 和尿 C3M 与肾功能之间的关联。这些标志物可能有助于提高对潜在病理组织更新的理解，并可能改善 NET 患者 PRRT 后肾功能的监测。