Subclinical tubular kidney injury associated with immune checkpoint inhibitors and cisplatin treatment: Diagnosis through urinary biomarkers

Abstract

Immune checkpoint inhibitors (ICIs) represent a major advance in cancer treatment due to their efficacy and safety profile. However, they are not free of side effects, including nephrotoxicity, which worsens prognosis. Diagnosis of renal injury based on clinical findings has limitations in predicting and identifying the type of damage. Biopsy remains the only definitive technique, though it is invasive and carries risks. Thus, new diagnostic approaches using urinary biomarkers are needed. Our hypothesis is that the renal damage associated with ICIs could be subclinical and not detectable by the tests used in clinical practice. Therefore, the aim was to associate the excretion of urinary biomarkers with subclinical renal damage in an experimental mouse model of treatment with ICIs and chemotherapy. A pathophysiological study was also performed to interpret the relationship between the biomarkers and the type of damage. Our results showed that the combined therapy of ICIs and cisplatin causes subclinical tubular damage, as evidenced by the excretion of albumin, NGAL and KIM-1, and suggest that cisplatin-induced renal damage is potentiated by the administration of ICIs. Diagnosis using these urinary biomarkers could be an optimal tool to detect damage at an earlier stage and improve patient management. In turn, ICIs promote an inflammatory process, as demonstrated by the biomarkers TNF-α, IL-9, CD8 and CD3, which would be involved in the development of kidney damage. Our findings open the possibility of studying their usefulness as differential diagnostic tools to identify characteristic inflammatory lesions of acute tubulo-interstitial nephritis, avoiding renal biopsy.