Comparative assessment of KDIGO and CTCAE criteria for detecting renal function deterioration after peptide receptor radionuclide therapy.

Abstract

Renal toxicity after peptide receptor radionuclide therapy (PRRT) is commonly assessed using Common Terminology Criteria for Adverse Events (CTCAE), whereas nephrological classification relies on Kidney Disease: Improving Global Outcomes (KDIGO)-based renal function categories. We compared CTCAE- and KDIGO-derived eGFR_cr-based definitions of renal function deterioration after PRRT and evaluated their predictive value for subsequent long-term renal outcome. 149 gastroenteropancreatic neuroendocrine tumor patients scheduled for PRRT with renal follow-up for at least 12 months after treatment were included. Kidney function was assessed at baseline (BL), after the last cycle (LC) and last available follow-up (FU). Analyzing the time interval from BL to LC, estimated glomerular filtration rate (eGFR_cr)-based KDIGO and CTCAE classifications along with risk factors for recategorization were compared. Clinically relevant KDIGO worsening was defined according to KDIGO 2012 (eGFR_cr category worsening with an additional eGFR_cr decline ≥ 25%). Median eGFR_cr declined from 87 to 68 mL/min/1.73 m² over a median follow-up of 2.2 years (p < 0.0001). From BL to FU, clinically relevant KDIGO worsening was substantially discordant from CTCAE eGFR_cr grading (KDIGO-/CTCAE+: 21 vs. KDIGO+/CTCAE-: 2; p < 0.0001). In multivariable analysis, age (p = 0.0125) and cumulative activity (p = 0.0205) were associated with clinically relevant KDIGO worsening (CTCAE eGFR_cr worsening: age, p < 0.0209). Early CTCAE eGFR_cr worsening during BL to LC predicted subsequent annualized eGFR decline until further FU (β - 6.82; 95% CI - 10.06 to - 3.57; p < 0.0001). Both clinically relevant KDIGO eGFR_cr worsening and absolute eGFR_cr at LC, however, failed to reach significance for long-term outcome prediction of renal function (p > 0.05, each). For evaluation of renal safety under PRRT, clinically relevant KDIGO deterioration and CTCAE grading are not interchangeable. Clinically relevant KDIGO-derived eGFR_cr worsening represents a stricter filtration-based endpoint, whereas early CTCAE eGFR_cr worsening may help identify patients requiring closer post-treatment renal surveillance. Prospective studies integrating serial filtration markers, urine biomarkers, measured GFR, and individualized kidney dosimetry are warranted, especially in light of current ongoing trials investigating PRRT being moved to an earlier stage in the treatment course.