Evaluación histológica del daño renal producido por los inhibidores del punto de control inmunitario

Abstract

Immune checkpoint inhibitors (ICI) constitute the most relevant immunotherapeutic group in the oncology field, but they are not exempt from adverse effects. Renal lesions, although rare, worsen the prognosis. Currently there are combinations of immunotherapy and chemotherapy that improve efficacy but increase the risk of nephrotoxic side effects. The objective was the histological evaluation of renal damage associated with ICI anti-CTLA-4 and anti-PD-1 in combination with cisplatin. An experimental model was designed in C57BL/6 mice treated with the combined therapy of cisplatin (10 mg/kg, single dose) with anti-CTLA-4 or with anti-PD-1 (both 10 or 15 mg/kg/day, for 6 days). Groups with drug monotherapies and a control group were included. Histological kidney damage assessment was performed blindly following a scale-based tissue injury quantification protocol. The data were analyzed with the statistical program IBM SPSS Statistics. The results showed renal tubular damage, more pronounced in the outer cortex, associated with cisplatin treatment, while there were no structural alterations in monotherapy with ICI. Co-treatment potentiated renal structural damage from cisplatin. This potentiation was more evident in the corticomedullary region, so it seems that the drug combination causes a deeper injury in the kidney.