Early Renal Effects After Radioactive Iodine Therapy in Differentiated Thyroid Cancer: A Prospective Observational Study

Background/Objectives: Radioactive iodine (RAI) therapy is widely used after thyroidectomy for differentiated thyroid cancer, but early renal tubular changes may not be reflected by conventional renal function parameters. We prospectively evaluated urinary tubular biomarker changes across three administered RAI activities. Methods: We included 120 patients, with 40 in each activity group (1.11, 3.70, and 5.55 GBq). Blood was collected at baseline and day 7, and urine at baseline, day 1, and day 7. Urinary kidney injury molecule-1, netrin-1, cystatin C, and β2-microglobulin were measured by enzyme-linked immunosorbent assay; conventional renal parameters were also assessed. Results: All four biomarkers increased significantly from baseline to Day 1 in all activity groups. Percentage increases were numerically greater at higher administered activities; however, baseline-adjusted mixed-effects analysis showed no significant activity-group effect or activity group × time interaction. Absolute biomarker levels partially declined by Day 7 and remained numerically above baseline, whereas urinary creatinine-normalized biomarker ratios remained significantly elevated. Serum creatinine decreased and creatinine-based eGFR increased by Day 7, whereas urinary albumin, protein, and phosphate showed no consistent changes across the activity groups. Conclusions: The concordant early changes observed in urinary tubular biomarkers, without deterioration in conventional renal function parameters, support an early subclinical tubular response following RAI therapy. Although percentage increases were numerically greater at higher administered activities, baseline-adjusted mixed-effects analyses did not support an independent activity-related effect. Therefore, these findings should not be interpreted as evidence of clinically significant renal injury. Longer-term studies are needed to determine the persistence, reversibility, and clinical significance of these findings.