Elevated human epididymis protein 4 levels in chronic kidney disease compromise the accuracy of the risk of ovarian malignancy algorithm

The present study aimed to compare the diagnostic accuracy of the risk of ovarian malignancy algorithm (ROMA) for differentiating ovarian tumors in patients with and without chronic kidney disease (CKD), using postoperative histopathological findings as the reference standard among patients who underwent surgery after ROMA testing. The retrospective study included 1,122 patients, including 21 with CKD, who met the inclusion criteria and underwent surgery for ovarian tumors at Gangneung Asan Hospital between August 2015 and August 2025. In patients with CKD, human epididymis protein 4 (HE4) levels were elevated in both benign and malignant groups compared with normal levels, with progressively higher levels observed with increasing CKD severity. Among patients with benign ovarian tumors, median HE4 levels were higher in those with CKD than in those without CKD (210.00 vs. 41.10 pmol/l). Cancer antigen 125 (CA125) levels did not differ significantly according to CKD status. Because of the elevated HE4 levels, ROMA scores were significantly higher in patients with CKD, resulting in low specificity {0.200 [95% confidence interval (CI), 0.066‑0.470]} and reduced overall accuracy [0.429 (95% CI, 0.240‑0.640)]. Receiver operating characteristic curve analysis demonstrated superior predictive performance of ROMA in patients without CKD [area under the curve (AUC), 0.724; 95% CI, 0.680‑0.768] compared with those with CKD (AUC, 0.467; 95% CI, 0.217‑0.717). In conclusion, in patients with CKD and ovarian tumors, ROMA should be interpreted with caution, and CA125 and imaging findings should be considered alongside other clinical information when assessing the risk of ovarian malignancy.