Abstract Background and Aims The most current lines of cancer treatment aim to increase efficacy and decrease adverse effects. In this sense, one of the main therapeutic strategies is immunotherapy. Immune checkpoint inhibitors (ICIs) constitute the most relevant immunotherapeutic pharmacological group in the clinical setting. Despite their greater safety than conventional therapies, these agents still cause adverse events. Renal effects, although rare, have been shown to worsen the prognosis of patients. In addition, immune and chemotherapy combination have been approved nowadays. Although they have improved efficacy, they have increased risk of suffering nephrotoxic side effects. Our hypothesis is that kidney damage caused by ICIs could be subclinical, and therefore, not evidenced by the classic clinical biomarkers (plasma creatinine and urea). The aim of this work was the histological evaluation of renal damage associated with anti-CTLA-4 in combination with cisplatin. Method An experimental model was designed in C57BL/6 mice treated with the combined therapy of cisplatin (10 mg/kg, single dose) and anti-CTLA-4 (10 or 15 mg/kg/day, for 6 days) administrated by intraperitoneal injection. In addition, groups treated with drug monotherapies and a control group were included. On the day of sacrifice (day 6) the kidneys were collected and histological sections were made and stained with hematoxylin-eosin. Histological quantification of kidney damage was performed blindly following a tissue damage quantification protocol. For this, 10 photos were taken per kidney (600X), 5 of the external cortex and 5 of the corticomedullary region. Each photo was segmented into 6 areas and a score was assigned to each area as follows. 0: no damage, 1: damage up to 1/3 of the area, 2: damage between 1/3 and 2/3 of the area, and 3: damage over 2/3 of the area. Subsequently, the mean scores of the kidneys from the same experimental group were calculated, as well as the standard error of the mean. Data was analyzed with the statistical software SPSS®. Results Our results showed tubular renal damage associated with cisplatin treatment. It was more pronounced in the external cortical area. However, no structural alterations associated with ICI treatment were found. Co-treatment with both drugs potenciated renal structural damage from cisplatin. Conclusion This potentiation was more evident in the corticomedullary region, so it seems that the drugs combination causes a deeper lesion in the kidney than cisplatin monotherapy. Our study suggests that the combined therapy of anti-CTLA-4 and cisplatin could induce generalized tubular lesions.