#1795 Diverse histological findings of kidney injury in cancer patients on immunotherapy- impact on clinical management
Authors: Fokas Stavros , Gerakis Alexander , Kaitantzoglou Christine , Giatras Ioannis , Palamaris Kostas , Gakiopoulou Harikleia 
Published: May 2024

Abstract

Background and Aims
Immune checkpoint inhibitors (CPIs) are becoming rapidly more used to treat various types of cancer. Acute interstitial nephritis (AIN) is considered the most common pattern of kidney injury in these patients, however other distinct histological lesions are increasingly reported. The aim of this study is to assess the histological findings and the value of kidney biopsy in the management of patients with CPI-associated nephrotoxicity.

Method
All records from patients treated with CPIs and kidney injury that underwent a kidney biopsy during the last 4 years were retrospectively assessed.

Results
We included 16 biopsied patients treated with CPIs and kidney injury, 8 males and 8 females. The mean age at the time of renal biopsy was 68 (± 8.2) years and the median follow up time was 11.5 (8-29) months. The most common primary malignancy was non-small cell lung cancer (n = 8), followed by melanoma (n = 3), endometrial cancer (n = 2), renal cell carcinoma (n = 1), breast cancer (n = 1) and hepatocellular carcinoma (n = 1). At the time of kidney biopsy eleven patients were treated with pembrolizumab, three patients with ipilimumab and nivolumab combination, one patient with ipilimumab and one patient with atezolizumab. Eleven patients were on immune-chemo combined therapy. Twelve patients presented with acute kidney injury (AKI), two with nephrotic syndrome, one with nephrotic range proteinuria and one with acute onset of hypertension and subnephrotic proteinuria [Urine Protein (UPr): 3 g/24 h]. The median time to developing kidney injury from CPI initiation was 9 (4.25-21.5) months. The prevalent histologic lesion was AIN (n = 5), followed by three cases of mixed AIN with acute tubular injury (ATI), and two cases of pure ATI. We recorded three cases of CPI-associated glomerulonephritis including membranous nephropathy (MN) with a lupus-like pattern on immunofluorescence, AA amyloidosis and Focal Segmental Glomerulosclerosis (FSGS) cellular variant. Two patients had diabetic nephropathy (DN) with ATI and one patient had thrombotic microangiopathy (TMA) with ATI. Immunotherapy was temporarily withheld in all patients at the time of kidney biopsy. After the establishment of the histological diagnosis: we continued treatment with corticosteroids in nine patients (five cases with AIN, one case with mixed AIN/ATI, one case with MN, one case with FSGS and one case with TMA/ATI). Withdrawal of corticosteroids was decided in five cases (two patients with diabetic nephropathy, two patients with mixed ATI/AIN and one with ATI). The patient with AA amyloidosis was treated with colchicine and cortisone with partial remission of nephrotic syndrome (UPr: 1.2 g/24 h). In one case with pure ATI, corticosteroids, and the concomitant chemotherapeutic agent (pemetrexed) were withdrawn with complete response of AKI. Partial remission of proteinuria occurred in the patient with FSGS (UPr: 1.3 g/24 h). At the end of follow up, kidney recovery occurred in all 12 patients with AKI (among them one patient who required renal replacement therapy at the time of biopsy). Rechallenge with a CPI was attempted in 8 patients. After rechallenging, one patient experienced relapse of nephrotic syndrome (MN) and immunotherapy was withdrawn. The other seven patients continued CPI treatment without recurrence of kidney injury. The overall patient survival was 62.5%.

Conclusion
AIN is only one of the possible causes of nephrotoxicity in patients receiving CPIs. Kidney biopsy establishes the accurate diagnosis of CPI-associated AKI. In selected cases it allows the continuation of immunotherapy and can prevent the unnecessary use of corticosteroids.