Urinary collagen degradation marker may predict kidney function decline during peptide radionuclide therapy | Research

The takeaway

Urinary C3M (type III collagen degradation marker) was significantly lower at specific time points in NET patients who subsequently lost >25% kidney function during PRRT, suggesting potential as a prognostic biomarker.

uC3M predicts kidney decline
Lower urinary collagen degradation marker after first PRRT treatment identified patients who subsequently lost >25% kidney function

What the researchers found

uC3M significantly lower in kidney-decline patients after 1st treatment (74 vs 135 ng/mg) and 3 months post-EOT (56 vs 118 ng/mg). 43% (6/14) had >25% kidney function decline. Median follow-up 12 months. Other fibrosis markers (PRO-C3, PRO-C6) not significantly different.

Why it matters

Kidney damage from PRRT is irreversible. A urine biomarker that predicts who will lose kidney function could enable protective interventions or dose adjustments before permanent damage occurs.

How the study worked

Prospective cohort of 14 NEN patients undergoing PRRT. Serum and urine fibrosis markers (PRO-C3, PRO-C6, C3M) measured before and after each treatment. Kidney function tests through 24 months post-EOT. Linear mixed models.

What this study cannot tell us

Very small sample (14 patients). Exploratory analysis. Overall mixed model only marginally significant (p=0.078). Needs larger validation study.

How to read the evidence

Small exploratory prospective study. Promising biomarker signal needing validation in larger cohorts.

When this study was published

Published in 2025.

The bigger picture

Biomarker-guided PRRT could personalize treatment intensity—protecting kidneys in susceptible patients while maintaining oncological efficacy.

Questions still open

Can uC3M guide dose adjustments during PRRT?
Should routine uC3M monitoring be implemented for PRRT patients?
Would kidney-protective strategies (hydration, amino acid infusion) help patients with low uC3M?

Common questions

Can PRRT damage the kidneys?

Yes, kidney function decline is a recognized side effect of PRRT because the radiolabeled peptides are filtered through the kidneys. In this study, 43% of patients lost more than 25% of kidney function. A urine test (C3M) may help identify at-risk patients early.

What is C3M?

C3M is a fragment released when type III collagen is broken down. Lower levels in urine suggest less collagen degradation (fibrolysis) and potentially more fibrosis accumulation in the kidneys. Patients with lower uC3M after PRRT were more likely to lose kidney function.

Read the original research

Fibrosis markers as prognostic markers of decline in kidney function in patients with neuroendocrine neoplasms undergoing peptide receptor radionuclide therapy.

Frontiers in endocrinology, 16, 1495369

View on PubMed ↗Publisher’s paper ↗

Citation

Stemann Lau, Tobias; Bossen, Lars; Rasmussen, Daniel Guldager Kring; Genovese, Federica; Karsdal, Morten; Arveschoug, Anne Kirstine; Grønbæk, Henning; Dam, Gitte. (2025). Fibrosis markers as prognostic markers of decline in kidney function in patients with neuroendocrine neoplasms undergoing peptide receptor radionuclide therapy.. Frontiers in endocrinology, 16, 1495369. https://doi.org/10.3389/fendo.2025.1495369