Immunohistochemical Evaluation of Renal Biopsy with Anti-PD1 and p53 to Solve the Dilemma between Platinum- and Pembrolizumab-Induced AKI: Case Report and Review

Author:

Mancianti Nicoletta1,Tripodi Sergio Antonio2ORCID,Pascucci Alessandra3,Calatroni Marta4ORCID,La Porta Edoardo5,Guarnieri Andrea1,Garosi Guido1

Affiliation:

1. Department of Medical Science, Nephrology, Dialysis and Transplantation Unit, University Hospital of Siena, 53100 Siena, Italy

2. Department of Oncology, Pathology Unit, University Hospital of Siena, 53100 Siena, Italy

3. Center for Immuno-Oncology Medical Oncology and Immunotherapy, Division Oncology Department, University Hospital of Siena, 53100 Siena, Italy

4. Nephrology and Dialysis Division, IRCCS Humanitas Research Hospital, 20089 Milan, Italy

5. UO Nephrology Dialysis and Transplant, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy

Abstract

Introduction: The combination therapy of platinum and pembrolizumab looks like a promising treatment in advanced non-small-cell lung cancer. However, both platinum-based chemotherapy and pembrolizumab can lead to AKI. AKI can occur due to acute tubular necrosis or interstitial nephritis. It is essential to identify the drug responsible for renal damage. For this purpose, we used new immunohistochemistry markers (p53 and anti-PD1 analysis). Case Description: A 77-year-old female patient with advanced non-small-cell lung cancer received the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy carboplatin. The patient, after 60 days, experienced AKI. A kidney biopsy was performed, and two new immunohistochemical techniques for p53 (experimental markers of ATN from platinum) and anti-PDL1 (experimental markers of PD-1 inhibitors nephritis) were employed. Renal biopsies revealed severe tubular damage. No infiltration was detected, and the immunohistochemical assessment of PDL-1 was negative. The expression of p53 was positive. The renal biopsy suggested platinum-induced acute tubular necrosis. After discontinuing steroids and reducing carboplatin, the patient continued with pembrolizumab, and their renal function returned to normal within two months. Discussion: Combining checkpoint inhibitors and platinum-based therapies may result in AKI. The standard method of examining kidney tissue may not provide sufficient information about the effects of these drugs on the kidneys. To address this issue, we recommend incorporating an assessment of the analysis of the expression of PDL1 and p53. This personalized approach will help identify the best treatment option for the patient while ensuring the best possible cancer treatment plan.

Publisher

MDPI AG

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