Imaging features of immune checkpoint inhibitor-related nephritis with clinical correlation: a retrospective series of biopsy-proven cases

Abstract

Objectives: Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes.

Methods: CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained.

Results: Thirty-four patients were included. The total kidney volume was significantly higher at nephritis compared to baseline (464.7 ± 96.8 mL vs. 371.7 ± 187.7 mL; p < 0.001). Fifteen patients (44.1%) had > 30% increase in total kidney volume, which was associated with significantly higher renal toxicity grade (p = 0.007), higher peak creatinine level (p = 0.004), and more aggressive medical treatment (p = 0.011). New/increasing perinephric fat stranding was noted in 10 patients (29.4%) at nephritis. Among 8 patients with contrast-enhanced CT at nephritis, one (12.5%) developed bilateral wedge-shaped hypoenhancing cortical. On PET-CT, the renal parenchymal SUVmax-to-blood pool ratio was significantly higher at nephritis compared to baseline (2.13 vs. 1.68; p = 0.035). The renal pelvis SUVmax-to-blood pool SUVmean ratio was significantly lower at nephritis compared to baseline (3.47 vs. 8.22; p = 0.011).

Conclusions: Bilateral increase in kidney size, new/increasing perinephric stranding, and bilateral wedge-shaped hypoenhancing cortical foci can occur in immunotherapy-related nephritis. On PET-CT, a diffuse increase in radiotracer uptake throughout the renal cortex and a decrease in radiotracer activity in the renal pelvis can be seen.

Key points: • CT features of immune checkpoint inhibitor-related nephritis include an increase in kidney volume, new/increasing perinephric stranding, and bilateral ill-defined wedge-shaped hypoenhancing cortical foci. • FDG-PET features of immune checkpoint inhibitor-related nephritis include an increase in FDG uptake throughout the renal cortex and a decrease in FDG activity/excretion in the collecting system. • > 30% increase in total kidney volume is associated with worse toxicity grade and more aggressive medical management.

Keywords: Immunotherapy; Nephropathy; Radiographic; Radiology; Toxicity.

Figure 1:

Study flow chart. CT: computerized tomography; PET-CT: Positron Emission Tomography-Computerized Tomography.

Figure 2:

Axial CT images of a 66-year-old male with malignant melanoma who developed immune checkpoint inhibitor related nephritis after 3 cycles of a pembrolizumab, ipilimumab and nivolumab. Axial contrast enhanced CT image at baseline (a) and at nephritis (b). His total kidney volume increased from 435 mL at baseline to 726 mL at nephritis (67% increase in total kidney volume). Note the bilateral renal enlargement and new perinephric stranding (arrowheads).

Figure 3:

Axial CT images of a 54-year-old male with lung adenocarcinoma receiving a pembrolizumab at baseline (a), at nephritis (b), one month after nephritis (c) and at 4 months after nephritis (d). He developed immunotherapy related nephritis after 5 cycles of immunotherapy. His total kidney volume increased from 394 mL at baseline to 612 mL at nephritis (55% increase in total kidney volume). Note the wedge shaped hypoenhancing cortical foci seen at nephritis (b) and 1 month post nephritis CT scans (c) (arrowheads). Note the focal cortical thinning and scarring which developed at the sites of these lesions 4 months after management (d) (arrows).

Figure 4:

Maximum intensity projection (MIP) images and fused coronal reformatted F¹⁸-FDG PET-CT images at baseline (a) and at nephritis (b) of a 76-year-old male with lung cancer. Note the bilateral increase in radiotracer uptake throughout the renal parenchyma at nephritis (SUVmax 6.3) compared to baseline (SUVmax 1.7) (arrows). Also note the decrease of FDG activity in the renal pelvis and collecting system at nephritis (SUVmax: 6.3) compared to baseline scan (SUVmax: 17.3) (dotted arrows).