Association between fibrosis markers and kidney function following peptide receptor radionuclide therapy in patients with neuroendocrine tumours

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.

Keywords:

• Fibrosis
• biomarkers
• kidney
• neuroendocrine tumours
• cancer

Disclosure statement

D.G.K.R., who performed the measurements of the fibrosis markers, is employed at the Danish biomarker company, Nordic Bioscience, who have developed the analysis method of the fibrosis markers. D.G.K.R., M.A.K. and F.G. are full-time employees at Nordic Bioscience. Nordic Bioscience is a privately-owned, small–medium size enterprise partly focused on the development of biomarkers. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. D.G.K.R., M.A.K. and F.G. hold stocks in Nordic Bioscience. The patents for the ELISAs used to measure the biomarker levels are owned by Nordic Bioscience. The funder provided support in the form of salaries for authors D.G.K.R., M.A.K. and F.G., but did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Henning Grønbaek is on advisory board at Ipsen and has received research grants from Abbvie, Intercept, ARLA and the NOVO Nordisk Foundation.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

This work was supported by the Danish Research Foundation.