Cisplatin Nephrotoxicity Might Have a Sex Difference. An analysis Based on Women's Sex Hormone Changes

Abstract

Background: A sex difference in cisplatin-induced nephrotoxicity (CIN) has been reported in human and animal studies. We examined in humans whether it is associated with sex-hormone changes. Methods: In this retrospective nationwide cohort study, we used Taiwan's National Health Insurance Research Database (NHIRD) to identify patients with a history of malignancy and cisplatin treatment. Patients diagnosed with kidney disease before cisplatin treatment and those with sex-organ malignancies were excluded. A diagnosis of kidney disease within 90 days after the first administration of cisplatin was the study outcome. Risk factors were estimated using a Cox regression model. Subgroup analyses were performed based on different women's estrogen levels in phases of childbearing, perimenopause, and postmenopause. Results: A retrospective analysis of the records of 3973 men (mean age: 56.15 ± 12.85 years) and 1154 women (mean age: 56.31 ± 12.40 years) showed that 1468 (36.95%) men and 451 (39.08%) women had a new diagnosis of kidney disease. The risk factors were being > 55 years old, a high comorbidity score, and a history of aminoglycoside treatment. Only postmenopausal women had a significantly higher risk of kidney injury (hazard ratio: 1.28; 95% CI: 1.02-1.61) than did men. Conclusions: Perimenopausal women have a significantly higher risk of CIN than do men, which might be explained by women's higher levels of estrogen. Additional studies on the underlying mechanisms of the sex difference of CIN are needed.

Keywords: acute kidney disease; chronic kidney disease; cisplatin; nephrotoxicity; sex difference.

Figure 1

The cumulative incidence rate of kidney injury within 90 days after first cisplatin administration.

Figure 2

The cumulative incidence rate of kidney injury within 90 days after first cisplatin administration in different life stage of women: (A) childbearing stage 20-45 years old (B) perimenopause stage 45-55 years old (C) postmenopause stage (>55 years old) This figure had been presented at ASN Kidney Week 2016 in Chicago, IL. More information can be found at www.asn-online.org.